bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway nitrite is increased in extremely preterm infants with bronchopulmonary dysplasia
Authors: Gentle Samuel J. , Freeman Amelia , Patel Rakesh P. , Ambalavanan Namasivayam , Lal Charitharth V.
Published: September 2020

Rationale

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and significantly contributes to mortality and morbidity with few predictive biomarkers. Given that nitrites have been implicated in pathways associated with lung disease, we hypothesized that nitrite levels would be altered in the airways of premature infants diagnosed with BPD.

Methods

This was a prospective cohort study of extremely low birth infants (< 28 weeks’ gestation) at the University of Alabama at Birmingham. Nitrite levels from tracheal aspirates (TAs) were compared between intubated and ventilated infants with BPD and gestation matched full term (FT) controls. TA derived nitrite levels from day one after birth were also compared between preterm infants who did and did not develop BPD.

Results

Infants with BPD were found to have significantly elevated nitrite levels in their tracheal aspirates compared to gestation matched FT controls (p < 0.05). There was a trend for increased nitrite levels on postnatal day one in infants that developed BPD compared to infants that did not develop BPD (p = 0.05).

Conclusions

In conclusion, nitrite levels are significantly increased in airways of infants with BPD. Data from a larger cohort are needed to further support the utility of nitrite for BPD prediction.

Trial registration

Not applicable.
Correction to: The therapeutic effect to eldecalcitol + bisphosphonate is superior to bisphosphonate alone in the treatment of osteoporosis: a meta-analysis
Authors: Zheng Zaoqian , Luo Jinyu
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Plants expressing murine pro-apoptotic protein Bid do not have enhanced PCD
Authors: Manara Anna , Imanifard Zahra , Fracasso Linda , Bellin Diana , Crimi Massimo
Published: September 2020

Objectives

The purpose of this study was to explore whether plant programmed cell death (PCD) cascade can sense the presence of the animal-only BH3 protein Bid, a BCL-2 family protein known to play a regulatory role in the signaling cascade of animal apoptosis.

Results

We have expressed the mouse pro-apoptotic protein Bid in Arabidopsis thaliana and in Nicotiana tabacum. We did not obtain any transformed plant constitutively expressing the truncated protein (tBid—i.e. the caspase-activated form) whereas ectopic expression of the full-length protein (flBid) does not interfere with growth and development of the transformed plants. To verify whether the presence of this animal pro-apoptotic protein modified stress responses and PCD execution, both N. tabacum and A. thaliana plants constitutively expressing flBid have been studied under different stress conditions triggering cell death activation. The results show that the presence of flBid in transgenic plants did not significantly change the responses to abiotic stress (H2O2 or NO) and biotic stress treatments. Moreover, the finding that no Bid active form was present in treated tobacco plants suggests an absence of a proper activation of Bid.
Low-dose DNA demethylating therapy induces reprogramming of diverse cancer-related pathways at the single-cell level
Authors: Takeshima Hideyuki , Yoda Yukie , Wakabayashi Mika , Hattori Naoko , Yamashita Satoshi , Ushijima Toshikazu
Published: September 2020

Background

Epigenetic reprogramming using DNA demethylating drugs is a promising approach for cancer therapy, but its efficacy is highly dependent on the dosing regimen. Low-dose treatment for a prolonged period shows a remarkable therapeutic efficacy, despite its small demethylating effect. Here, we aimed to explore the mechanisms of how such low-dose treatment shows this remarkable efficacy by focusing on epigenetic reprograming at the single-cell level.

Methods

Expression profiles in HCT116 cells treated with decitabine (DAC) were analyzed by single-cell RNA-sequencing (scRNA-seq). Functional consequences and DNA demethylation at the single-cell level were analyzed using cloned HCT116 cells after DAC treatment.

Results

scRNA-seq revealed that DAC-treated cells had highly diverse expression profiles at the single-cell level, and tumor-suppressor genes, endogenous retroviruses, and interferon-stimulated genes were upregulated in random fractions of cells. DNA methylation analysis of cloned HCT116 cells revealed that, while only partial reduction of DNA methylation levels was observed in bulk cells, complete demethylation of specific cancer-related genes, such as cell cycle regulation, WNT pathway, p53 pathway, and TGF-β pathway, was observed, depending upon clones. Functionally, a clone with complete demethylation of CDKN2A (p16) had a larger fraction of cells with tetraploid than parental cells, indicating induction of cellular senescence due to normalization of cell cycle regulation.

Conclusions

Epigenetic reprogramming of specific cancer-related pathways at the single-cell level is likely to underlie the remarkable efficacy of low-dose DNA demethylating therapy.
Energy efficiency in an integrated agro-ecosystem within an acidic soil area of the Mekong Delta, Vietnam
Authors: Thao Nguyen Thi Thu , Van Tung Tra , Thao Nguyen Thi Phuong , Le Thanh Son , Braunegg Sibylle , Braunegg Gerhart , Schnitzer Hans , Hai Le Thanh
Published: September 2020

Background

Both exergy and energy analysis methodologies are used for analysing energy efficiencies in various processes, including agriculture. This study focuses on the connection of three main process components (husbandry-crop-fishpond) in a typical farming household located within an acid soil region of rural Vietnam. The concept of exergy analysis is used to underline the potential for resource efficiency in alternative processes in the agricultural system. For development of an integrated ecological system aiming towards zero emissions, the analytical methods of material cycles and energy flows utilized a set of indicators of resource efficiency in a sustainable agriculture.

Results

The design of the ideal integrated farming system “Agro-Industrial Zero Emissions Systems” (AIZES) can increase the system efficiency by making use of indigenous natural materials and waste reuse/recycling. Recycling waste produce energy, fish feed and fertilizer can result in a decreased environmental load of approximately half. Using exergy analysis to calculate an indicator non-renewable yield ratio (NRYR), the systems verified sustainability of agriculture production.

Conclusions

The farming household will be able to subsidize their fuel and electricity consumption by utilizing biogas. Surplus biogas will be distributed to proximate households, further creating sustainable goals. Biochar, created by mixing the biomass residues with local plants, will improve soil quality and pig sludge, mixed with biomass residue, will create high-quality fertilizer.
SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease
Authors: Gustavsson Tobias , Syvänen Stina , O’Callaghan Paul , Sehlin Dag
Published: September 2020

Background

Alzheimer’s disease (AD) immunotherapy with antibodies targeting amyloid-β (Aβ) has been extensively explored in clinical trials. The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants – RmAb158, the recombinant murine version of BAN2401, which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients, and the bispecific RmAb158-scFv8D3, which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis.

Methods

A single intravenous injection of iodine-125 (125I)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice (tg-ArcSwe). In vivo single-photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks. Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβ and CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with Aβ.

Results

Despite faster blood clearance, [125I]RmAb158-scFv8D3 displayed higher brain exposure than [125I]RmAb158 throughout the study. The brain distribution of [125I]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology, while [125I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times. Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for [125I]RmAb158-scFv8D3, whereas [125I]RmAb158 displayed retention and Aβ interactions in lateral ventricles.

Conclusions

The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging. Moreover, it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy.
Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer’s disease
Authors: Xu Jin , Bankov Giulia , Kim Min , Wretlind Asger , Lord Jodie , Green Rebecca , Hodges Angela , Hye Abdul , Aarsland Dag , Velayudhan Latha , Dobson Richard J. B. , Proitsi Petroula , Legido-Quigley Cristina ,   on behalf of the AddNeuroMed Consortium
Published: September 2020

Background

There is an urgent need to understand the pathways and processes underlying Alzheimer’s disease (AD) for early diagnosis and development of effective treatments. This study was aimed to investigate Alzheimer’s dementia using an unsupervised lipid, protein and gene multi-omics integrative approach.

Methods

A lipidomics dataset comprising 185 AD patients, 40 mild cognitive impairment (MCI) individuals and 185 controls, and two proteomics datasets (295 AD, 159 MCI and 197 controls) were used for weighted gene co-expression network analyses (WGCNA). Correlations of modules created within each modality with clinical AD diagnosis, brain atrophy measures and disease progression, as well as their correlations with each other, were analyzed. Gene ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD phenotypes. Lipid species were annotated in the lipid modules associated with AD phenotypes. The associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also explored.

Results

Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis, brain atrophy measures and disease progression. The lipid modules comprising phospholipids, triglycerides, sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid metabolism. The five protein modules involved in positive regulation of cytokine production, neutrophil-mediated immunity, and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism (the APOE ε4 genotype).

Conclusions

Modules of tightly regulated lipids and proteins, drivers in lipid homeostasis and innate immunity, are strongly associated with AD phenotypes.
Anterior skull base reconstruction using nasoseptal flap: Cadaveric feasibility study and clinical implication [SevEN-001]
Authors: Sung Kyoung Su , Lim Jaejoon , Na Minkyun , Lee Sanghun , Kim Ju-Seong , Hong Je Beom , Hong Chang-Ki , Moon Ju Hyung
Published: September 2020

Background

Pedicled nasoseptal flap (PNSF) has significantly improved the surgical outcomes of endoscopic endonasal approach (EEAs) by reducing cerebrospinal fluid (CSF) leakage. The purpose of this study is to assess the feasibility of using a PNSF for anterior skull base (ASB) reconstruction and to describe a method to compensate for a short flap based on our results.

Methods

In this cadaveric study, ASB dissection without sphenoidotomy was performed using 10 formalin-fixed and 5 fresh adult cadaver specimens, and the sufficiency of the PNSF to cover the ASB was assessed. After the sphenoidotomy, the length by which the PNSF fell short in providing coverage at the posterior wall of the frontal sinus (CPFS), and the extent of the anterior coverage from the limbus (CL) of the sphenoid bone was measured.

Results

Without sphenoidotomy, the mean length of the remaining PNSF after the coverage of the posterior wall of the frontal sinus was 0.67 cm. After sphenoidotomy, the PNSF fell short by a mean length of 2.10 cm, in providing CPFS. The CL was 1.86 cm. Based on these findings, defects resulting from an endoscopic resection of ASB tumors were reconstructed using PNSF without total sphenoidotomy in 3 patients. There were no postoperative CSF leaks or complications.

Conclusions

The use of PNSF for ASB reconstruction may be insufficient to cover the entire ASB defect after removal of large lesions which need total sphenoidotomy. When possible, by leaving some portion of the anterior sphenoid wall for supporting the PNSF, successful ASB reconstruction could be achieved in endoscopic resection of ASB tumors. Additional methods might be needed in some cases of large ASB lesions wherein the anterior sphenoid wall should be removed totally and the ASB defect is too large.
The three-dimensional morphology of mandible and glenoid fossa as contributing factors to menton deviation in facial asymmetry—retrospective study
Authors: Oh Min-Hee , Cho Jin-Hyoung
Published: September 2020

Background

The aim of this study is to evaluate whether the three-dimensional (3D) morphology of the mandibular condyle, glenoid fossa, and mandible correlated with menton deviation in facial asymmetry.

Subjects and methods

Thirty adults (15 males and 15 females; mean age, 23.2 ± 3.8 years) with facial asymmetry were included. Linear, angular, and volumetric measurements of the 3D morphology of the mandibular condyle, glenoid fossa, and mandible were recorded using computed tomography (CT) images. The right/left differences were obtained by subtracting the left value from the right value, and an independent t test was used to compare the differences between the females and males. Multiple regression analysis was performed to identify the correlation between the right/left difference of the 3D morphology and menton deviation.

Results

The results of the comparative analysis did not show any statistical difference between the females and males (P > .05), so the females and males were combined. Multiple regression analysis for the mandibular condyle, glenoid fossa, and mandible showed that neck length, ramus length, and frontal ramal inclination had positive influences on menton deviation, with 76.5% of explanatory power. The neck length and head volume of the mandibular condyle when only the mandibular condyle was considered, and the ramus length and frontal ramal inclination when only the mandible was considered had positive influence on menton deviation with 69.9% and 68.6% explanatory power, respectively. On the other hand, when only considering glenoid fossa, the glenoid fossa had little effect on menton deviation with 15.7% of explanatory power.

Conclusions

In facial asymmetry, the right/left differences in mandibular condyle and mandible have more impact on the menton deviation than the right/left differences in glenoid fossa.

Trial registration

CNUDH, CNUDH-EXP-2017-016. Registered 28 September 2017
School learning climate in the lens of parental involvement and school leadership: lessons for inclusiveness among public schools
Authors: Alinsunurin Jason
Published: September 2020

Prior literature has shown that school learning climate is critical in helping individual learners meet their educational objectives. In this paper, the role of parental involvement in shaping the school learning climate is explored within a multilevel and hierarchical modeling framework using data from the 2015 PISA round.

As the schools’ social and relational character, we find that reducing learning barriers is a critical challenge for school leadership. A welcoming environment for parents, as well as the effective design of effective forms of two-way communications, are positively associated with a substantial reduction in the barriers to improving teacher management’s learning climate.

We also find that public schools facing social and educational inclusiveness challenges can dramatically enhance their learning environment by activating specific parental involvement mechanisms. Similarly, principal’s leadership in framing and communicating goals and curricular development to the school is also found to be significant for inclusiveness.

However, parental involvement is also found to have potential tensions with school management. The worsening of the learning climate may arise due to pressures brought about by laws requiring parental involvement in schools. Because the learning climate is composed of a wide variety of relationships between and within schools, this work demonstrates that parental involvement is an integral part of school leadership and the school improvement process. Further research attention is encouraged to understand the tensions between teacher roles, principal leadership, and parental involvement through employing other quantitative or qualitative research designs.
Assessing the acceptability of a text messaging service and smartphone app to support patient adherence to medications prescribed for high blood pressure: a pilot study
Authors: Kassavou Aikaterini , A’Court Charlotte Emily , Chauhan Jagmohan , Brimicombe James David , Bhattacharya Debi , Naughton Felix , Hardeman Wendy , Mascolo Cecilia , Sutton Stephen
Published: September 2020

Aims and objectives

This paper describes a pilot non-randomised controlled study of a highly tailored 56-day text messaging and smartphone app prototype intervention to increase adherence to anti-hypertensive medication in primary care. The aim of this study was to evaluate the acceptability of the intervention and obtain patients’ views about the intervention content, the delivery mode, and the mechanisms by which the intervention supported medication adherence.

Methods

Patients diagnosed with hypertension were invited and recruited to the study via general practice text messages and attended a face to face meeting with a member of the researcher team. Participants were asked to test the text messaging intervention for 28 consecutive days and switch to the smartphone app for 28 more days. Participants completed baseline and follow-up questionnaires and took part in semi-structured telephone interviews. Digital log files captured patients’ engagement with the intervention. Participant transcripts were analysed using thematic analysis. Descriptive statistics were used to summarise data from questionnaires and log files. A mixed methods analysis generated data to respond to the research questions.

Results

Seventy-nine patients expressed interest to participate in this study, of whom 23 (64% male, 82% above 60 years old) were registered to take part. With one drop-out, 22 participants tested the text messaging delivery mode (with 20 being interviewed) and four of them (17%) switched to the app (with 3 being interviewed). All participants engaged and interacted with the text messages and app notifications, and all participants found the intervention content and delivery mode acceptable. They also self-reported that the interactive elements of the intervention motivated them to take their medications as prescribed.

Conclusion

This study provides evidence that the digital intervention is acceptable by hypertensive patients recruited in primary care. Future research could usefully investigate its feasibility and effectiveness using rigorous research methods.

Trial registration

ISRCTN12805654
Bifurcation analysis of a composite cantilever beam via 1:3 internal resonance
Authors: Sayed M. , Mousa A. A. , Alzaharani D. Y. , Mustafa I. H. , El-Bendary S. I.
Published: September 2020

In this paper, we study a multiple scales perturbation and numerical solution for vibrations analysis and control of a system which simulates the vibrations of a nonlinear composite beam model. System of second order differential equations with nonlinearity due to quadratic and cubic terms, excited by parametric and external excitations, are presented. The controller is implemented to control one frequency at primary and parametric resonance where damage in the mechanical system is probable. Active control is applied to the system. The multiple scales perturbation (MSP) method is implemented to obtain an approximate analytical solution. The stability analysis of the system is obtained by frequency response (FR). Bifurcation analysis is conducted using various control parameters such as natural frequency (ω1), detuning parameter (σ1), feedback signal gain (β), control signal gain (γ), and other parameters. The dynamic behavior of the system is predicted within various ranges of bifurcation parameters. All of the stable steady state (point attractor), stable periodic attractors, unstable steady state, and unstable periodic attractors are determined efficiently using bifurcation analysis. The controller’s influence on system behavior is examined numerically. To validate our results, the approximate analytical solution using the MSP method is compared with the numerical solution using the Runge-Kutta (RK) method of order four.
The feasibility of direct adductor canal block (DACB) as a part of periarticular injection in total knee arthroplasty
Authors: Bagaria Vaibhav , Kulkarni Rajiv V. , Valavi Anisha , Choudhury Himanshu , Dhamangaonkar Anoop , Sahu Dipit
Published: September 2020

Background

Adductor canal block (ACB) is one of the preferred methods of analgesia in total knee arthroplasty (TKA). However, conventionally its use is time-consuming, requires ultrasound guidance, a trained anaesthesia team and adherence to strict asepsis by members of the allied teams. This study was done to assess the feasibility and safety of direct adductor canal block (DACB) as a part of surgeon-administered periarticular infiltration.

Materials and methods

Thirty computed tomography (CT) angiography films of the patients were retrospectively reviewed. The trajectory of the needle placement for a DACB in relation to the target region of the adductor block was determined. Fourteen knees in seven cadavers, were dissected through a medial parapatellar approach to perform TKA. After administering the DACB using the technique based on CT data, dissection was carried out to ascertain the correct placement of the dye by visualising the stained areas.

Results

The angle of approach in the coronal plane from the entry point to the medial high point and to the adductor hiatus was 10.2° (8−14°) and 6° (3.8−11°), respectively. The angle of approach in the sagittal plane from the entry point to the medial high point and to the adductor hiatus was 7° (5−10.5°) and 29° (19−43°), respectively. In all the 14 cadaveric knees, we confirmed the correct placement of the methylene blue dye as demonstrated by the staining of the adductor canal.

Conclusion

The study demonstrates the feasibility of the DACB. This surgeon-driven technique is likely to reduce the cost of the procedure, reduce operating room time and also eliminate the risks of surgical-site contamination.
Role of diffusion-weighted MRI in characterization of mediastinal masses
Authors: Raafat Tarek Ahmed , Ahmed Shimaa Mohamed , Seif Emam Mohamed Abo , Mikhael Hisham Samir Wahba , Awad Ahmed Sayed
Published: September 2020

Background

Diffusion MR imaging (DWI) is a widely available non-invasive non-contrast functional MR imaging technique with short acquisition time. It helps in the analysis of tissue characteristics based on the diffusion of water protons within the tissue. Quantitative assessment of a mass is possible by calculating its apparent diffusion coefficient (ADC) value which is inversely correlated with tissue cellularity. So, DWI has diagnostic potential to distinguish benign from malignant tumors because of the tendency of the latter to show lower ADC values and more restricted diffusion. The aim of our work is to evaluate the use of DWI and ADC value measurement in differentiation between benign and malignant mediastinal tumors.

Results

This study included 44 cases of mediastinal masses: 27 males and 17 females. The mean ADC value of malignant mediastinal lesions was significantly lower than the mean ADC value of benign mediastinal lesions, with mean ADC 1.39 ± 0.26 in benign mediastinal lesions and mean ADC 0.86 ± 0.35 in malignant mediastinal lesions. This study also revealed that the cut-off threshold of ADC value for the differentiation between malignant and benign lesions was 1.11 × 10-3 mm2/s, with an area under ROC curve of 0.93. The sensitivity and specificity of our cutoff ADC values were 90.9% and 100%, with 100% positive predictive value and 76.9% negative predictive value.

Conclusion

DWI with calculation of ADC value is functional MR imaging technique used in the analysis of tissue characteristics and quantitative assessment of a mediastinal mass. So, it can distinguish benign from malignant tumors because of the tendency of the malignant lesions to show more restricted diffusion and lower ADC values.
Can loss of agency and oppositional perturbation associated with antidepressant monotherapy and low-fidelity psychological treatment dilute the benefits of guideline-consistent depression treatment at the population level?
Authors: Ormel Johan , Bosker Fokko J. , Hollon Steven D. , Ruhe Henricus G.
Published: September 2020

Despite major expansions of evidence-based treatments of common mental disorders in recent decades, especially antidepressant medication, the point prevalence of depression has not decreased; instead it probably increased in young adults. We question whether antidepressants (AD)-monotherapy and low-fidelity-to-guideline psychological treatment (PT) might have no effect or even adverse effects in some patients and contexts that dilute the benefits of treatment at the population level, making it harder for population-based studies to detect treatment-driven prevalence reductions. Randomized Clinical Trial (RCT)s have not identified these effects because AD-monotherapy and low-fidelity PT are uncommon in RCTs where treatment protocols are specified and carefully monitored, unlike treatment in real-world settings. Second, RCTs may have missed the bigger picture of ultimate outcomes due to too short follow-ups. We elaborate two mechanisms through which AD-monotherapy and low-fidelity PT could produce adverse effects on long-term illness course. Both mechanisms are speculative and we outline how to test.
Clinical Pan-Cancer Assessment of Mismatch Repair Deficiency Using Tumor-Only, Targeted Next-Generation Sequencing
Authors: Albayrak Adem , Garrido-Castro Ana C. , Giannakis Marios , Umeton Renato , Manam Monica Devi , Stover Elizabeth H. , Porter Rebecca L. , Johnson Bruce E. , Liaw Kai-Li , Amonkar Mayur , Church Alanna J. , Janeway Katherine A. , Nowak Jonathan A. , Sholl Lynette , Lin Nancy U. , Johnson Jason M.
Published: September 2020

PURPOSE

Given regulatory approval of immune checkpoint inhibitors in patients with mismatch repair–deficient (MMR-D) cancers agnostic to tumor type, it has become important to characterize occurrence of MMR-D and develop cost-effective screening approaches. Using a next-generation sequencing (NGS) panel (OncoPanel), we developed an algorithm to identify MMR-D frequency in tumor samples and applied it in a clinical setting with pathologist review.

METHODS

To predict MMR-D, we adapted methods described previously for use in NGS panels, which assess patterns of single base-pair insertion or deletion events occurring in homopolymer regions. Tumors assayed with OncoPanel between July 2013 and July 2018 were included. For tumors tested after June 2017, sequencing results were presented to pathologists in real time for clinical MMR determination, in the context of tumor mutation burden, other mutational signatures, and clinical data.

RESULTS

Of 20,301 tumors sequenced, 2.7% (553) were retrospectively classified as MMR-D by the algorithm. Of 4,404 samples with pathologist sign-out of MMR status, the algorithm classified 147 (3.3%) as MMR-D: in 116 cases, MMR-D was confirmed by a pathologist, five cases were overruled by the pathologist, and 26 were assessed as indeterminate. Overall, the highest frequencies of OncoPanel-inferred MMR-D were in endometrial (21%; 152/723), colorectal (9.7%; 169/1,744), and small bowel (9.3%; 9/97) cancers. When algorithm predictions were compared with historical MMR immunohistochemistry or polymerase chain reaction results in a set of 325 tumors sequenced before initiation of pathologist assessment, the overall sensitivity and specificity of the algorithm were 91.1% and 98.2%, respectively.

CONCLUSION

We show that targeted, tumor-only NGS can be leveraged to determine MMR signatures across tumor types, suggesting that broader biomarker screening approaches may have clinical value.
Transitioning From Intrathecal Hydromorphone to Sublingual Buprenorphine–Naloxone Through Microdosing: A Case Report
Authors: Crum Isaiah T. , Meyer Karre VaKara M. , Balasanova Alëna A.
Published: September 2020

A 76-year-old woman with chronic noncancer pain and an intrathecal hydromorphone–bupivacaine pump was admitted for acute exacerbation of heart failure. Her pump was unable to be replaced due to medical comorbidities. She was unable to tolerate oral opioids due to ventilatory depression. Tapering hydromorphone resulted in opioid withdrawal due to physiological dependence. Microdosing of sublingual buprenorphine–naloxone was initiated while decreasing intrathecal hydromorphone. This successfully weaned the patient off intrathecal hydromorphone with adequate pain relief and prevented both opioid withdrawal and ventilatory depression. To our knowledge, microdosing buprenorphine-naloxone to assist with discontinuing intrathecal opioids has not been previously reported in the literature.
Pursuing Medicaid Block Grants with the Healthy Adult Opportunity Initiative: Dressing Up Old Ideas in New Clothes
Authors: Miller Edward Alan , Huberfeld Nicole , Jones David K.
Published: September 2020

The Trump administration's Healthy Adult Opportunity waiver follows a long history of Republican attempts to retrench the Medicaid program through block grants and to markedly reduce federal spending while providing states with substantially greater flexibility over program structure. Previous block grant proposals were promulgated during the presidential administrations of Ronald Reagan and George W. Bush and majorities in Congress led by House Speaker Newt Gingrich and House Budget Committee Chair and then Speaker Paul Ryan. Most recently, Medicaid block grants featured prominently in Republican efforts to repeal and replace the Affordable Care Act. This essay traces the history of Republican Medicaid block grant proposals, culminating in the Trump administration's Healthy Adult Opportunity initiative. It concludes that the Trump administration's attempt to convert Medicaid into a block grant program through the waiver process is illegal and, if implemented, would leave thousands of people without necessary medical care. This fact, combined with failed legislative efforts to block grant Medicaid during the last forty years, highlights the substantial roadblocks to radically restructuring a popular program that helps millions of Americans.
A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
Authors: Wong Tatianna Wai Ying , Ahmed Abdalla , Yang Grace , Maino Eleonora , Steiman Sydney , Hyatt Elzbieta , Chan Parry , Lindsay Kyle , Wong Nicole , Golebiowski Diane , Schneider Joel , Delgado-Olguín Paul , Ivakine Evgueni A. , Cohn Ronald D.
Published: September 2020

Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches.
Nefarious Presentism: A Recourse to Primitivism
Authors: Ajiboro Aderonke
Published: September 2020

Presentism is one of the various views in the discourse on the existence of time and spatio-temporal reality which holds that only the present is real and also that only present things exist. Neil McKinnon characterizes presentism in some ways that are all problematic, although he claims that the most appealing of all is the statement that “only present entities exist.” This view permeates all thoughts about presentism, and it has led to problems about the formulation of presentism. The link between accepting the existence of a temporal part (present) and the events that have that part as its spatio-temporal reference creates a hub of debate among presentists, and this raises a lot of issues not just in metaphysics, but in other areas of philosophical discourse as well. Tallant and Ingram take a challenging position on this issue as presentists in their own right. For them, the requisite status of a presentist properly so-called should be of a commitment to the reality of the present exclusively. In this paper, I engage the views of Tallant and Ingram on the problems of presentism such as triviality and truthmaking as regards ontological implications. I will argue that the avoidance of ontological commitment in nefarious presentism does appear to avoid the problem of truthmaking, which implies avoiding an analysis of truth in order to solve the problem of truthmaking. I will also argue that this avoidance to address the principle of un-analyzability of thisness is a recourse to primitivism.
What Makes Free Will Free: The Impossibility of Predicting Genuine Creativity
Authors: Erinakis Nikos
Published: September 2020

In this paper I argue that Mill’s ‘Doctrine of Philosophical Necessity’ regarding the human will and action cannot apply on all cases, and that the human mind has potentially the capacity to create freely a will or action that, no matter what kind of knowledge we possess, cannot be predicted. More precisely, I argue against Mill’s attempt of conjunction between the freedom of the will and the ‘Doctrine of Philosophical Necessity’ while I attempt a comparison with the relevant Kantian approach. I then claim that a will cannot be free and be predicted at the same time, as both the elements of freedom and unpredictability of the will are founded on the very process of its formulation as an outcome of genuine creativity. I, thus, attempt to propose a more substantially free view of free will and action than the ones presented by the prominent conceptions.
Making Sense of Dignity: A Starting Point
Authors: Peonidis Filimon
Published: September 2020

Although appeals to human dignity became quite popular after the end of War World II in various moral and legal settings, the term retained an air of semantic indeterminacy, and scholars are of opposing minds concerning its usefulness and significance. In this essay I intend to offer a sketch of a “deflationary” account of human dignity – viewed as one moral value among many others – according to which it is conceived as the minimal respect we prima facie owe to our own personality, as well as to the personality of everyone else without any restriction or exception. This account is accompanied by a justification, which does not presuppose the endorsement of a particular moral theory, and envisages dignity as a bulwark to counter the morally abhorrent consequences of many categorical and normatively tainted dichotomies western societies have created.
Workplace exposure to carbon dioxide during routine laparoscopy – is it safe?
Authors: af Petersens Malin , Andersson Fenger-Krog Fritiof , Jakobsson Jan G.
Published: September 2020

Background: Minimally invasive surgeries have increased dramatically during the last decades. Carbon dioxide (CO2) is the gas used for insufflation during laparoscopies, creating space and visibility. The CO2 leaks into ambient air through ports where instruments are inserted. If the CO2 reaches a certain concentration it affects personnel health. There are national occupational exposure limits (OEL) for CO2, including a level limit value (LLV) of 5000 ppm. We are not aware of any previous studies addressing occupational exposure to CO2 during laparoscopies. The aim of this study was to assess the compliance to national OELs for CO2 during laparoscopies.

Methods: A gas detector was placed in the breathing zone of personnel in the operating theatre. The detector measured CO2 concentrations every tenth minute during laparoscopies in three locations.

Results: During 27 laparoscopies, the measured CO2 reached a maximum concentration of 1100 ppm, less than one fourth of the LLV. Median CO2 concentration was 700 ppm.

Conclusion: Results show that the occupational exposure to CO2 during laparoscopies is well below set OELs. Our findings support personnel safety associated with routine use of CO2 during laparoscopies.
Information protection and information security
Authors: Sychev Yuriy
Published: September 2020

The textbook is developed in accordance with current standards at a high methodological level and can be used to study the following subjects: "Fundamentals of information security", "Information security", "information Protection", "threats to information security", "Malware", "Antivirus programs", "Technology for building secure automated systems".
Meets the requirements of Federal state educational standards of higher education of the latest generation.
The material presented in the textbook is tested in the classroom and is intended for students studying in the direction of training 10.03.01 "Information security" (bachelor's level). It can also be used in preparation for admission to the master's program.
Current problems of intellectual property law
Authors: Goncharenko Lyubov' , Kuleshova Inna , Loseva Ol'ga , Pavlov Vladimir , Rahmatulina Rimma , Ruzakova Ol'ga , Ruchkina Gul'nara , Sviridova Ekaterina , Fabrichnyy Sergey
Published: September 2020

The textbook covers current issues of legal regulation of intellectual property. The book deals with topical issues of copyright, related rights, patent law, intellectual property assessment, as well as topical issues of the emergence, implementation and protection of non-traditional intellectual property objects, implementation and protection of rights to means of individualization, international legal regulation and taxation of intellectual property. Special attention is paid to topical issues of legal regulation of intellectual property rights turnover.
For better assimilation of the material, each paragraph of the textbook ends with questions for self-control, practical tasks and lists of recommended literature.
Meets the requirements of Federal state educational standards of higher education of the latest generation.
It is intended for use in the educational process in the direction of training 40.04.01 "Jurisprudence".
Geotechnology: underground mine workings and their fixing
Authors: Komarov Evgeniy
Published: September 2020

The textbook describes the basic concepts of underground mine workings, assessment of their stability, modern methods of fastening and protection during the entire life of mines and mines. Examples of calculating the rational cross-sectional area of mine workings and questions for self-testing aimed at consolidating the knowledge and competencies obtained by students are given.
It is intended for students of all specializations studying in the field of Mining and studying the disciplines " Underground Geotechnology "and" Construction Geotechnology", since it is a basic informative carrier of professional knowledge and competencies.
Foreign policy of Ancient Rome during the period of the kings and the early Republic
Authors: Panischev Aleksey
Published: September 2020

The monograph is devoted to the foreign policy of Ancient Rome during the period of the kings and the early Republic. The paper draws attention to the fact that at these stages of its development, Rome did not create a state in the modern sense, but rather a Federation, and with a developed self-government of its participants. Thanks to a system of mutually beneficial treaties, Rome became a political center among the peoples of Ancient Italy. At the same time, remnants of tribal relations were preserved in Ancient Rome for a long time. Attention is also paid to the development of military Affairs in Rome. It is noted that in Ancient Rome for a long time there were no defensive walls, which predisposed the Romans to an offensive type of warfare. The Romans created battle tactics that would be consistent with the characteristics of the soldiers ' weapons and would allow for rapid military training among recruits, which provided the Romans with high mobilization capabilities. However, classically represent the soldier in the Lorica of segmentata in the tsarist period was not.
An important role in the development of Rome as the center of international politics of Ancient Italy, the center of the Federation was played by the high moral standards postulated by the ancient Roman society and invested in the concept of the Republic. All these diplomatic, ethical, and military features of Ancient Rome combined to determine the success of Roman civilization. However, it is worth noting that the disorganization of these principles caused the fall of Rome.
For anyone interested in the historical processes of Ancient Italy and Ancient Rome.
ALGORITHMS OF STRUCTURAL AND PARAMETRICAL TUNING OF ADAPTIVE OBSERVERS
Authors: Mukhanov Konstantin
Published: September 2020

This paper deals with the identification of nonlinear systems of adaptive observers (AO). The process of building an AH consists of two stages – structural and parametric. At the structural stage, the class of nonlinearity and its structural parameters are estimated. In the process of parametric identification, the adjustment of the obtained parameters of the nonlinear system takes place. Considered two cases of application of structural information. The main focus is on the case of insufficient structural information. Adaptive algorithms for setting the parameters of AO are proposed. A procedure for estimating uncertainty is proposed.
Methods of preparing children to learn Russian at school
Authors: Biba Anna
Published: September 2020

The textbook is aimed at developing professional competencies in preparing preschool children to learn Russian at school.it reveals the current content of preparing preschoolers to learn reading and writing in primary school, contains a method for teaching them sound word analysis, reading syllables and words in accordance with a scientifically based sound analytical and synthetic method, a technique for teaching children to print letters and syllables, and describes opportunities for cognitive development of preschool children in the process of speech work. The methodological material is accompanied by examples from the speech of preschool children and their training practices. A test is offered for professional self-control over the assimilation of the corresponding methodology in General. The appendices contain methodological illustrative and reference material.
Meets the requirements of Federal state educational standards of higher education of the latest generation.
For undergraduate students in the field of "Pedagogical education", it can also be used by undergraduates in the study of a course on the cognitive development of preschool children and in the process of professional development and retraining of employees of preschool educational institutions and primary school teachers.
A Branch-and-Price-and-Cut Algorithm for the Cable-Routing Problem in Solar Power Plants
Authors: Luo Zhixing , Qin Hu , Cheng T. C. E. , Wu Qinghua , Lim Andrew
Published: September 2020

A solar power plant is a large-scale photovoltaic (PV) system designed to supply usable solar power to the electricity grid. Building a solar power plant needs consideration of arrangements of several important components, such as PV arrays, solar inverters, combiner boxes, cables, and other electrical accessories. The design of solar power plants is very complex because of various optimization parameters and design regulations. In this study, we address the cable-routing problem arising in the planning of large-scale solar power plants, which aims to determine the partition of the PV arrays, the location of combiner boxes, and cable routing such that the installation cost of the cables connecting the components is minimized. We formulate the problem as a mathematical programming problem, which can be viewed as a generalized capacitated minimum spanning tree (CMST) problem, and then devise a branch-and-price-and-cut (BPC) algorithm to solve it. The BPC algorithm uses two important valid inequalities, namely the capacity inequalities and the subset-row inequalities, to tighten the lower bounds. We also adopt several acceleration strategies to speed up the algorithm. Using real-world data sets, we show by numerical experiments that our BPC algorithm is superior to the typical manual-based planning approach used by many electric power planning companies. In addition, when solving the CMST problem with unitary demands, our algorithm is highly competitive compared with the best exact algorithm in the literature.
EXPEDIENTE - v20n3
Authors: Leme Vanessa Barbosa Romera
Published: September 2020

EXPEDIENTE - v20n3
Um Estudo sobre Denúncias de Violência Registradas no Disque 100 - Pessoas com Deficiência
Authors: Lima Márcia De , Maia Luciana Maria
Published: September 2020

As pessoas com deficiência, quando comparadas a seus pares sem deficiência, são mais vulneráveis a sofrerem violência. O presente trabalho tem por objetivo analisar os dados relativos às denúncias de violência contra pessoas com deficiência disponibilizados pelo Disque Direitos Humanos - Disque 100. Utilizou-se como fonte de dados o Disque 100 - Balanço Anual 2017 - Pessoas com Deficiência, sendo analisados os dados referentes à agressão (frequência, tipo de violação e local); às características da vítima (deficiência, etnia, idade e sexo) e dos agressores (relação com a vítima, idade, sexo e etnia); quem foi o denunciante. Verificou-se um número considerável de denúncias entre os anos de 2011 e 2017 (M=8800, dp=2879), sendo que a maior parte dos casos (35,8%) foi de negligência (abandono, alimentação, amparo, higiene, medicamentos/assistência à saúde). As violações ocorreram no espaço privado do lar (85,6%) e as vítimas eram em sua maioria mulheres (52,8%), pardas (29,7%), com idade entre 18 a 50 anos (76,9%) e deficiência intelectual (65,8%). A maioria dos perpetradores era familiares (57,1%), homens (57,6%), com idade entre 18 a 50 anos (39,6%). Tal quadro sinaliza a necessidade de ações para a prevenção da violência cometidas contra pessoas com deficiência.