bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies
Authors: Vijay Suresh , Brassier Anais , Ghosh Arunabha , Fecarotta Simona , Abel Florian , Marulkar Sachin , Jones Simon A.
Published: January 2021

Background

If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6 months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2/3 Survival of LAL-DInfantsTreated With SebelipaseAlfa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa.

Results

The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan–Meier estimates of survival to 12 months and 5 years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2 years in VITAL and 3.2 years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-agezscores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3–16.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7–19.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity.

Conclusions

The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic parameters, and liver parameters, and was generally well tolerated, with an acceptable safety profile.
A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide
Authors: Mehta Atul , Ramaswami Uma , Muenzer Joseph , Giugliani Roberto , Ullrich Kurt , Collin-Histed Tanya , Panahloo Zoya , Wellhoefer Hartmann , Frader Joel
Published: January 2021

Background

Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs.

Methods

The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company.

Results

As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year.

Conclusions

The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.
Executive function is inversely correlated with physical function: the cognitive profile of adult Spinal Muscular Atrophy (SMA)
Authors: Mix Lucas , Schreiber-Katz Olivia , Wurster Claudia D. , Uzelac Zeljko , Platen Sophia , Gipperich Christina , Ranxha Gresa , Wieselmann Gary , Osmanovic Alma , Ludolph Albert C. , Petri Susanne , Lulé Dorothée
Published: January 2021

Background

Spinal muscular atrophy (SMA) issues from mutations in the survival of motor neuron (SMN) 1 gene. Loss or reduction of the SMN protein results in progressive muscle weakness. Whether this protein deficiency also affects cortical function remains unclear. While no data on adult patients exists so far, prior studies in children with SMA indicate cognitive abilities equal or even superior to healthy controls. This may suggest a possible compensatory—neuropsychological and interactional—process. The goal of this study was to assess the cognitive profile of adult patients with SMA, with a special focus on social cognition as a potential candidate for enhanced cognitive function through compensatory processes.

Methods

In a cross-sectional design, N = 31 adult SMA patients (types II and III) were assessed for language, verbal fluency, memory, visuospatial abilities and executive function with the Edinburgh Cognitive and Behavioural ALS Screen and for social cognition with the Reading the Mind in the Eyes Test. Physical function was evaluated using the Hammersmith Functional Motor Scale Expanded. N = 19 neurologically healthy controls were matched with patients for age, sex and years of education.

Results

In none of the abovementioned cognitive domains significant differences between SMA patients and controls were found. Among patients, no differences between type II SMA and type III SMA were detected for any domain. However, a trend towards better social cognition in patients with type II SMA, compared to those with type III SMA was observed. Furthermore, a significant inverse correlation of physical function and executive function was detected: lower motor function was associated with a better executive function.

Conclusions

This study shows cognitive abilities in adult SMA in the normal range for all assessed domains. Thus, reduction of SMN protein has no obvious negative impact on cognitive function. Executive functions are identified as the only cognitive domain correlated with disease severity. Therefore, executive functions may play a role in the adaptation to physical restrictions in SMA, making them a promising target for future research.
Living with a recalled implant: a qualitative study of patients’ experiences with ASR hip resurfacing arthroplasty
Authors: Bitar Christian , Krupic Ferid , Felländer-Tsai Li , Crnalic Sead , Wretenberg Per
Published: January 2021

Background

Total hip arthroplasty is the traditional treatment for osteoarthritis in the hip joint. Hip resurfacing arthroplasty, with metal on metal bearing, is a modern concept initially developed mainly for young active people. The metal-on-metal hip arthroplasty implant, Articular Surface Replacement (ASR), was implanted in approximately 93,000 patients before it was recalled in 2010 due to a high complication rate. This study aimed to evaluate patients’ own experiences living with an implant that they knew had a high complication rate and had been recalled from the market.

Methods

A total of 14 patients, still living with the implant, of a cohort of 34 patients were available for follow-up. Qualitative semi-structured interviews were conducted with 14 patients where a majority actively sought for metal-on-metal hip resurfacing arthroplasty (HRA), and subsequently underwent HRA with an ASR prosthesis between 11/21/2006 and 09/28/2009. The responses were analyzed using content analysis described by Graneheim and Lundman to compress text and identify categories and subcategories.

Results

The results showed that most patients had already decided that they wanted a metal-on-metal HRA implant before meeting the surgeon. They expressed that the implant made it possible to live an active life. A majority did not think about the fact that they had a hip implant, because they lacked subjective pain. Most of the patients were positive about the annual exams at the hospital and wanted them to continue. None of them felt that their trust towards the healthcare system had changed after the implant recall. They expressed a belief that they would need new surgery sooner than they first thought.

Conclusions

Despite all the attention when the ASR prosthesis was recalled, patients with ASR-HRA did not report themselves negatively affected by the recall in this group of patients where a majority had actively sought for an HRA procedure. The healthcare system has an obligation to continue the annual exams, even if the implant provider does not continue reimbursement.
Chromosome Y as a marker for sex discrepancies in patients with organ transplants: a case report
Authors: Balaguer Nuria , Mateu-Brull Emilia , Naja Roy P. , Nagi Jara B. , Milán Miguel
Published: January 2021

Background

Organ transplantations cause discrepancy in results from cell-free DNA (cfDNA) testing, but scientific literature is scarce.

Case

A 33-year old gravida underwent cfDNA testing, which showed high levels of Y chromosome (ChrY) in the maternal bloodstream. The ChrY pattern was comparable to an adult male reference. As a result, cfDNA testing was only informative for autosomes. Routine 20-week ultrasound scan showed no structural alterations and the presence of female external genitalia. Post-clinical research revealed that the patient received a bone marrow transplant from a male donor several years before. Fluorescence in situ hybridization showed that 100% of nuclei analysed from the patient’s lymphocytes presented a ChrY.

Conclusion

This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.
Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort
Authors: Liang Xiao , Cheng ShiQiang , Ye Jing , Chu XiaoMeng , Wen Yan , Liu Li , Qi Xin , Jia YuMeng , Zhang Feng
Published: January 2021

Objective

To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.

Methods

The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.

Results

We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10–5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10–8) interacting with total testosterone for fluid intelligence.

Conclusion

Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer—study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II
Authors: Gugerell Alfred , Gouya-Lechner Ghazaleh , Hofbauer Helmut , Laggner Maria , Trautinger Franz , Almer Gabriele , Peterbauer-Scherb Anja , Seibold Marcus , Hoetzenecker Wolfram , Dreschl Christiane , Mildner Michael , Ankersmit Hendrik Jan
Published: January 2021

Background

Diabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients.

Methods/design

APOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint.

Conclusion

We consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial.

Trial registration

EudraCT 2018-001653-27. Registered on 30 July 2019. ClinicalTrials.gov NCT04277598. Registered on 20 February 2020. Title: “A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)”
Identifying student opinion leaders to lead e-cigarette interventions: protocol for a randomized controlled pragmatic trial
Authors: Chu Kar-Hai , Matheny Sara , Furek Alexa , Sidani Jaime , Radio Susan , Miller Elizabeth , Valente Thomas , Robertson Linda
Published: January 2021

Background

After the US Surgeon General declared youth electronic cigarette (e-cigarette) use an epidemic in 2018, the number of youth e-cigarette users continued to surge, growing from 3.8 million in 2018 to over 5 million 2019. Youth who use e-cigarettes are at a substantially higher risk of transitioning to traditional cigarettes, becoming regular cigarette smokers, and increasing their risk of developing tobacco-related cancer.

A majority of youth are misinformed about e-cigarettes, often believing they are not harmful or contain no nicotine. Middle school students using e-cigarettes have been affected by its normalization leading to influence by their peers. However, social and group dynamics can be leveraged for a school-based peer-led intervention to identify and recruit student leaders to be anti-e-cigarette champions to prevent e-cigarette initiation. This study outlines a project to use social network analysis to identify student opinion-leaders in schools and train them to conduct anti-e-cigarette programming to their peers.

Methods

In the 2019–2020 academic school year, 6th grade students from nine schools in the Pittsburgh area were recruited. A randomized controlled trial (RCT) was conducted with three arms—expert, elected peer-leader, and random peer-leader—for e-cigarette programming. Sixth grade students in each school completed a network survey that assessed the friendship networks in each class. Students also completed pre-intervention and post-intervention surveys about their intention-to-use, knowledge, and attitudes towards e-cigarettes. Within each peer-led arm, social network analysis was conducted to identify peer-nominated opinion leaders. An e-cigarette prevention program was administered by (1) an adult content-expert, (2) a peer-nominated opinion leader to assigned students, or (3) a peer-nominated opinion leader to random students.

Discussion

This study is the first to evaluate the feasibility of leveraging social network analysis to identify 6th grade opinion leaders to lead a school-based e-cigarette intervention.

Trial registration

ClinicalTrials.govNCT04083469. Registered on September 10, 2019.
Enhanced methane production from cellulose using a two-stage process involving a bioelectrochemical system and a fixed film reactor
Authors: Sasaki Kengo , Sasaki Daisuke , Tsuge Yota , Morita Masahiko , Kondo Akihiko
Published: January 2021

Background

It is desirable to improve the anaerobic digestion processes of recalcitrant materials, such as cellulose. Enhancement of methane (CH4) production from organic molecules was previously accomplished through coupling a bioelectrochemical system (BES); however, scaling-up BES-based production is difficult. Here, we developed a two-stage process consisting of a BES using low-cost and low-reactive carbon sheets as the cathode and anode, and a fixed film reactor (FFR) containing conductive material, i.e., carbon fiber textiles (CFTs) (:BES → FFR). By controlling the cathodic current at 2.7 μA/cm2 without abiotic H2 production, the three-electrode BES system was operated to mimic a microbial electrolysis cell.

Results

The thermophilic BES (inlet pH: 6.1) and FFR (inlet pH: 7.5) were operated using hydraulic retention times (HRTs) of 2.5 and 4.2 days, respectively, corresponding to a cellulose load of 3555.6 mg-carbon (C)/(L day). The BES → FFR process achieved a higher CH4 yield (37.5%) with 52.8 vol% CH4 in the product gas compared to the non-bioelectrochemical system (NBES) → FFR process, which showed a CH4 yield of 22.1% with 46.8 vol% CH4. The CH4 production rate (67.5 mM/day) obtained with the BER → FFR process was much higher than that obtained using electrochemical methanogenesis (0.27 mM/day). Application of the electrochemical system or CFTs improved the yields of CH4 with the NBES → FFR or BES → non-fixed film reactor process, respectively. Meta 16S rRNA sequencing revealed that putative cellulolytic bacteria (identified as Clostridium species) were present in the BES and NBES, and followed (BES→ and NBES→) FFR. Notably, H2-consuming methanogens, Methanobacterium sp. and Methanosarcina sp., showed increased relative abundances in the suspended fraction and attached fraction of (BES→) FFR, respectively, compared to that of (NBES→) FFR, although these methanogens were observed at trace levels in the BES and NBES.

Conclusions

These results indicate that bioelectrochemical preprocessing at a low current effectively induces interspecies H2 transfer in the FFR with conductive material. Sufficient electrochemical preprocessing was observed using a relatively short HRT. This type of two-stage process, BES → FFR, is useful for stabilization and improvement of the biogas (CH4) production from cellulosic material, and our results imply that the two-stage system developed here may be useful with other recalcitrant materials.
Zygomatic implants placed in atrophic maxilla: an overview of current systematic reviews and meta-analysis
Authors: Ramezanzade Shaqayeq , Yates Julian , Tuminelli Frank J. , Keyhan Seied Omid , Yousefi Parisa , Lopez-Lopez Jose
Published: January 2021

Background

Zygomatic implants are a treatment option for severely atrophic maxilla.

Main text

This study aimed to summarize and evaluate systematic reviews assessing the clinical outcomes of zygomatic implants including survival/failure rate and complications. PubMed-MEDLINE, Google Scholar, LILACS, and the Cochrane Database were searched up to April 2020. Risk of bias assessment was conducted by the AMSTAR tool. Initial searches yielded 175 studies. These were assessed, and following title abstract and full-text evaluation, 7 studies (2 meta-analyses) were included in the final review. According to the AMSTAR tool, 1 was deemed high quality, 4 were classified as medium, and 2 as low quality. The mean AMSTAR score (±SD) was 5.28 of 9 (±2.36) ranging from 2/9 to 9/9. The reported survival rates ranged from 95.2 to 100% except for resected maxillas, which established higher failure rates up to 21.43%. Concerning the complications with the zygomatic implants, various surgical and prosthetic complications were reported with sinusitis being the most frequently observed complication. Zygomatic implants appears to offer a promising alternative to formal bone grafting techniques with lower costs, less complications, less morbidity, shorter treatment times, and comparably high survival rates.

Conclusion

Complications were rare and usually easy to manage. However, the treatment should be directed by appropriately trained clinicians with noticeable surgical experience.
Cross-Sectional International Survey to Determine the Educational Interests of Spanish-Speaking Latin American Radiation Oncologists
Authors: Mailhot Vega Raymond B. , De La Mata Dolores , Amendola Beatriz , Li Benjamin , Poitevin Adela , Sarria Gustavo , Sole Sebastian , Sher David J. , Hardenbergh Patricia
Published: January 2021

PURPOSE

With the existing oncology disparities in Latin America, physician expertise has been cited as a possible contributor to inferior oncologic outcomes in some cancers. As two-dimensional radiotherapy rapidly evolved to intensity-modulated radiation therapy in Latin America, adequate contouring education is an actionable target to improving physician knowledge and clinical outcomes. Yet, topics of interest to Latin American radiation oncologists are underreported. We assessed Latin American interest in a virtual platform for case discussion and identified the educational topics of most interest to them.

MATERIALS AND METHODS

A Spanish-language online survey was designed by a team of Latin American educators. The questions assessed professional nationality, desire for an online educational platform for case presentation, career length, and topics of interest. Educational topics included head and neck (H&N), CNS, GI, lung, gynecologic, breast, and pediatric cancers, lymphoma, sarcoma, stereotactic body radiotherapy (SBRT), brachytherapy, and medical physics.

RESULTS

One hundred thirty-three surveys were included for analysis. Overall, 127 respondents (98%) affirmed interest in participating in a virtual platform for case discussion and treatment advances. The most popular educational themes were H&N cancers (24%), SBRT (14%), and CNS cancers (13%). Of countries with > 10 respondents, the most popular educational topic remained H&N cancers for Argentina, Chile, and Mexico, but the most popular topic among Peruvian respondents was CNS cancer (27%).

CONCLUSION

With international collaboration and a large sample size, we present the first survey results describing Latin American radiation oncology educational interests. Participants were overwhelmingly interested in a virtual platform, and most were specifically interested in H&N cancer education. These results can be used for focused didactic preparation in Latin America. Future efforts should expand on improving representation and outreach among Central American radiation oncologists.
Rapid toxin sequestration modifies poison frog physiology
Authors: O'Connell Lauren A. ,   LS50: Integrated Science Laboratory Course, O'Connell Jeremy D. , Paulo Joao A. , Trauger Sunia A. , Gygi Steven P. , Murray Andrew W.
Published: January 2021

Poison frogs sequester chemical defenses from their diet of leaf litter arthropods for defense against predation. Little is known about the physiological adaptations that confer this unusual bioaccumulation ability. We conducted an alkaloid-feeding experiment with the Diablito poison frog (Oophaga sylvatica) to determine how quickly alkaloids are accumulated and how toxins modify frog physiology using quantitative proteomics. Diablito frogs rapidly accumulated the alkaloid decahydroquinoline within 4 days, and dietary alkaloid exposure altered protein abundance in the intestines, liver and skin. Many proteins that increased in abundance with decahydroquinoline accumulation are plasma glycoproteins, including the complement system and the toxin-binding protein saxiphilin. Other protein classes that change in abundance with decahydroquinoline accumulation are membrane proteins involved in small molecule transport and metabolism. Overall, this work shows that poison frogs can rapidly accumulate alkaloids, which alter carrier protein abundance, initiate an immune response, and alter small molecule transport and metabolism dynamics across tissues.
A UNIFIED SYSTEM FOR DISTRIBUTING AND RETRIEVING INFORMATION FOR A MULTILEVEL HIERARCHY OF USERS IN AN INSTITUTION
Authors: Cherevko Igor , Pertsov Andriy
Published: January 2021

This article presents a specific model of the distribution of the messages and retrieving information for a multilevel hierarchy of users that was recently proposed by the authors. The main channels and messengers of communication between users were analyzed and compared. A Telegram messenger bot has been developed to automate the sending of information messages, divided into hierarchical levels of recipients in educational institutions. C# programming language and .NET Core technology, Entity Framework Core, ASP.NET Web API Core, PostgreSQL database were used for development. They are implemented in the VisualStudio environment appropriate application in the form of a web application API.
DEVELOPMENT OF CHILDREN'S RIGHTS IN POLAND – SELECTED ASPECTS
Authors: Kmak Malgorzata
Published: January 2021

Children’s rights are human rights, they result from the personal dignity and uniqueness of the child as a person. They apply to every child, they cannot be stripped away or renounced. It also means that if a child has a right, the state must ensure that it can be exercised. Further, if the child has a certain right, it means that there must also be procedures to enforce it. The beginning of the international movement for the protection of children's rights dates back to 1874, when the first organization for the protection of children's rights, the New York Society for the Prevention of Cruelty to Children, was founded in The United States. In Europe, at a similar time, since 1880, international societies of criminologists, youth court judges, care for abandoned and homeless children were being established to work on relaxing the criminal law for minors or establishing educational and care facilities for children. It was in the 19th century when the rights of the child were discussed in Poland for the first time. Moral, religious, or customary norms regulated children’s place in the community. However, the development of these rights was a long process that had started in Poland much earlier. The article aims to present selected historical situations affecting the development process and the current state of children's rights in Poland.
APPLICATION OF CLOUD TECHNOLOGIES IN ACCOUNTING
Authors: Lapitkaia Liudmila
Published: January 2021

Traditional accounting in modern conditions of digitalization of the economy requires significant changes in terms of the use of new information tools. One of these opportunities is the use of new information technologies in accounting. These new information technologies include cloud technologies, which are a specific environment (for storing, processing, and protecting information) that combines technical tools, software, communication channels, and technical support. Services that may be based on technology (MCloud) are software as a service (SaaS), infrastructure as services (IaaS), platform as services (PaaS). From the point of view of an accounting organization, the most convenient of these three types of services is the service as a software. Cloud technologies are the storage and processing of information on servers on the Internet. The positive aspects of using cloud technologies include the fact that accountants do not need to purchase, install the program on their computer, maintain it in working order, and ensure data protection and security. All this can be done in the cloud. Cloud storage - is online storage where information is stored on the network on servers provided by an information service provider for the use of customers. At the same time, cloud providers provide services for renting a server from various companies based on cloud technologies. The article analyzes the opportunities that cloud technologies provide in accounting, considers the advantages and disadvantages of using such technologies.
INDICES OF ENVIRONMENTAL PERFORMANCE OF THE COMPАNIES FROM THE AUTOMOBILE SECTOR IN THE CONTEXT OF INTEGRATED REPORTING
Authors: Yosifova Desislava , Petrova-Kirova Magdalena
Published: January 2021

Until very recently business operations were most strongly motivated by the ambition to maximize financial return and the purpose of the corporate accounting statements was to present information mainly on the cash flow, the financial and the asset position, as well as the financial outcome of the company. The development of the world economy and the thereby arising positive and negative effects on society is not fully covered by conventional accounting and financial reporting system. The insufficiency of such information obstructs satisfying the information needs of various interested parties, resulting in growing expectations and pressure over the companies to accept not only the positive, but also the negative effect on their behaviour in the economic, environmental, and social aspect. All of the above prerequisites, along with the capital restriction the companies are facing, require a change towards an appropriate upgrade of traditional corporate reporting. This problem is particularly significant for Bulgaria, which, being a member state of the EU, is expected to apply all European Directives for implementation of environmental requirements essentially related to the transport sector. In addition, the country’s geostrategic position, through which territory 5 of the ten Pan-European transport corridors run through, makes the problems related to the development and the application of methodologies and the toolkit for covering, registering, and reporting the effect of transport companies’ activities (especially those in the automobile sector) on the environment, people, and society as a whole, particularly important. Integrated reporting is ready to face these challenges and to solve a significant part of the problematic fields, which, in complex with the data and the indicators, registered and accounted for by traditional financial reporting, can provide together, to a sufficient and full extent, the demand for information in the implementation of environmental policy on a national, local and global scale.
Ectoderm to mesoderm transition by down-regulation of actomyosin contractility
Authors: Kashkooli Leily , Rozema David , Espejo-Ramirez Lina , Lasko Paul , Fagotto François
Published: January 2021

Collective migration of cohesive tissues is a fundamental process in morphogenesis and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In theXenopusembryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, high for mesoderm. Surprisingly, we find that these seemingly deep differences can be accounted for simply by differences in Rho-kinases (Rock)-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on two negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the two regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favor more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behavior of the mesoderm. We propose that the “ectoderm to mesoderm transition” is a prototypic case of collective migration driven by a down-regulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial-to-mesenchymal transition.
Cell cycle-dependent and independent mating blocks ensure fungal zygote survival and ploidy maintenance
Authors: Vještica Aleksandar , Bérard Melvin , Liu Gaowen , Merlini Laura , Nkosi Pedro Junior , Martin Sophie G.
Published: January 2021

To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeastSchizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating.
Insights into mobile health application market via a content analysis of marketplace data with machine learning
Authors: Aydin Gokhan , Silahtaroglu Gokhan
Published: January 2021

Background

Despite the benefits offered by an abundance of health applications promoted on app marketplaces (e.g., Google Play Store), the wide adoption of mobile health and e-health apps is yet to come.

Objective

This study aims to investigate the current landscape of smartphone apps that focus on improving and sustaining health and wellbeing. Understanding the categories that popular apps focus on and the relevant features provided to users, which lead to higher user scores and downloads will offer insights to enable higher adoption in the general populace. This study on 1,000 mobile health applications aims to shed light on the reasons why particular apps are liked and adopted while many are not.

Methods

User-generated data (i.e. review scores) and company-generated data (i.e. app descriptions) were collected from app marketplaces and manually coded and categorized by two researchers. For analysis, Artificial Neural Networks, Random Forest and Naïve Bayes Artificial Intelligence algorithms were used.

Results

The analysis led to features that attracted more download behavior and higher user scores. The findings suggest that apps that mention a privacy policy or provide videos in description lead to higher user scores, whereas free apps with in-app purchase possibilities, social networking and sharing features and feedback mechanisms lead to higher number of downloads. Moreover, differences in user scores and the total number of downloads are detected in distinct subcategories of mobile health apps.

Conclusion

This study contributes to the current knowledge of m-health application use by reviewing mobile health applications using content analysis and machine learning algorithms. The content analysis adds significant value by providing classification, keywords and factors that influence download behavior and user scores in a m-health context.
Implementation of the new integrated algorithm for diagnosis of drug-resistant tuberculosis in Karnataka State, India: How well are we doing?
Authors: Shankar S. Uma , Kumar Ajay M. V. , Venkateshmurthy Nikhil Srinivasapura , Nair Divya , Kingsbury Reena , R. Padmesha , Velu Magesh , P. Suganthi , Gupta Joydev , Ahmed Jameel , G. Puttaswamy , Hiremath Somashekarayya , Jaiswal Ravi K. , Kokkad Rony Jose , N. Somashekar
Published: January 2021

Background

As per national policy, all diagnosed tuberculosis patients in India are to be tested using Xpert® MTB/RIF assay at the district level to diagnose rifampicin resistance. Regardless of the result, samples are transported to the reference laboratories for further testing: first-line Line Probe Assay (FL-LPA) for rifampicin-sensitive samples and second-line LPA(SL-LPA) for rifampicin-resistant samples. Based on the results, samples undergo culture and phenotypic drug susceptibility testing. We assessed among patients diagnosed with tuberculosis at 13 selected Xpert laboratories of Karnataka state, India, i) the proportion whose samples reached the reference laboratories and among them, proportion who completed the diagnostic algorithm ii) factors associated with non-reaching and non-completion and iii) the delays involved.

Methods

This was a cohort study involving review of programme records. For each TB patient diagnosed between 1st July and 31st August 2018 at the Xpert laboratory, we tracked the laboratory register at the linked reference laboratory until 30th September (censor date) using Nikshay ID (a unique patient identifier), phone number, name, age and sex.

Results

Of 1660 TB patients, 1208(73%) samples reached the reference laboratories and among those reached, 1124(93%) completed the algorithm. Of 1590 rifampicin-sensitive samples, 1170(74%) reached and 1104(94%) completed the algorithm. Of 64 rifampicin-resistant samples, only 35(55%) reached and 17(49%) completed the algorithm. Samples from rifampicin-resistant TB, extra-pulmonary TB and two districts were less likely to reach the reference laboratory. Non-completion was more likely among rifampicin-resistant TB and sputum-negative samples. The median time for conducting and reporting results of Xpert® MTB/RIF was one day, of FL-LPA 5 days and of SL-LPA16 days.

Conclusion

These findings are encouraging given the complexity of the algorithm. High non-reaching and non-completion rates in rifampicin-resistant patients is a major concern. Future research should focus on understanding the reasons for the gaps identified using qualitative research methods.
Occult hepatitis B virus infection in a Kenyan cohort of HIV infected anti-retroviral therapy naïve adults
Authors: Salyani Adil , Shah Jasmit , Adam Rodney , Otieno George , Mbugua Evelyn , Shah Reena
Published: January 2021

Background

Occult hepatitis B virus (HBV) infection (OBI) is a phase of HBV infection characterised by the presence of HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg). OBI is of concern in the HIV-infected due to high prevalence and risk of HBV reactivation. The prevalence and clinico-demographic characteristics of OBI in anti-retroviral therapy (ART) naïve HIV infected adults in Kenya is unknown.

Methods

A cross sectional study carried was out at three sites in Kenya. HIV infected ART naïve adults were enrolled and demographic data collected. Blood samples were assayed for HBsAg, HBV DNA, alanine aminotransferase, aspartate aminotransferase, antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). Data on CD4 count, HIV viral load and platelet count were obtained from medical records.

Results

Of 208 patients, 199 (95.7%) did not report HBV vaccination, 196 (94.2%) were HBsAg negative, 119 (57.2%) had no HBV markers, 58 (27.9%) had previous HBV infection (anti-HBc positive) and 11 (5.3%) had OBI. All 11 (100%) OBI patients were anti-HBc positive. OBI patients comprised 19.0% of HBsAg negative, anti-HBc positive patients. There was no difference in clinico-demographic characteristics between the overt HBV, OBI and HBV negative patients.

Conclusion

This was the first study on OBI in ART naïve HIV infected adults in Kenya. The lower OBI prevalence compared to other sub-Saharan African countries could be attributed to lower HBV exposure. Most patients were HBV unexposed and unimmunized, outlining the need to implement guideline recommended immunization strategies.
Sustentabilidade Ambiental e Práticas Turísticas na Praia de Bilene - Uma Leitura Interpretativa das Principais Mudanças
Authors: Bernardo Bernardino Jose , Neves José Lourenço
Published: January 2021

A presente pesquisa intitulada:  A sustentabilidade ambiental e práticas turísticas na praia de Bilene - Uma leitura interpretativa das principais mudanças, tem por objectivo avaliar a dinâmica da actividade turística e a sua influencia na sustentabilidade ambiental na praia de Bilene. A pesquisa privilegiou a abordagem qualitativa apoiada pelo método de revisão bibliográfica, observação directa, método cartográfico e técnica de entrevista a 60 indivíduos, seguido da análise e síntese. O estudo revela que o turismo é o principal sector de actividade socioeconómica e que mais cresce no município. Por sua vez, este crescimento tem sido acompanhado por fortes alterações de sistemas ambientais que sustentam esta actividade, como por exemplo a praia, dunas e biodiversidade local. O estudo conclui que a actividade turística na praia de Bilene tende à sustentabilidade embora persistem alguns desafios referentes a degradação da paisagem. O estudo sugere a necessidade de uma Educação ambiental aos intervenientes, a comunidade, operadores, turistas, líderes locais, representantes locais do estado e estruturas municipais de forma a reduzir os riscos do equilíbrio dos ecossistemas locais. Sugere ainda a intensificação da fiscalização da costa, das lagoas, das dunas, da fauna endémica, em particular as Tartarugas marinha e outros é extremamente necessária de forma a reduzir os riscos do equilíbrio dos ecossistemas e infra-estruturas locais.
A Geodiversidade do Baixo Umbelúzi, usos e impactos sócio-ambientais: Caso do Bairro 7 de Setembro, Boane – Moçambique
Authors: Bernardo Bernardino Jose , Ombe Zacarias , De Jesus Octávio Manuel , Chichango David Benjamin
Published: January 2021

A Geologia de Moçambique está repartida em dois grandes terrenos, o Pré-câmbrico e Fanerozóico. Estes dois complexos geológicos são responsáveis por uma diversidade de recursos naturais, dentre eles os recursos da geodiversidade, que são variedades de elementos da geologia (rochas, minerais, fósseis, solos) e os elementos da geomorfologia (formas de relevo), e esses recursos são aplicados para vários fins. O objectivo desta pesquisa consiste em analisar os impactos sócio - ambientais derivados dos usos da geodiversidade do baixo Umbelúzi no Bairro 7 de Setembro em Boane, entre os anos 2005 e 2018. Esta pesquisa, apoiou-se na abordagem qualiquanti e nos métodos descritivos, explicativo, observação, cartográfico, análise e síntese. Os resultados demonstram que as actividades de uso e extracção da geodiversidade presente (areias inertes, solos mistos, cascalho, argila e sebes vivas) levam a degradação ambiental e alteração da paisagem. Consta também que as mesmas actividades apresentam impactos sociais como produção de alimentos, geração de empregos, produção de material de construção civil, pastoreio entre outros. Contudo, o crescimento da população e pressões económicas, algumas ligadas a crise global tem o seu impacto negativo na disponibilidade destes recursos e na emergência de desafios ligados ao uso da terra havendo muitas vezes sobreposição de interesses de uso sobre o mesmo espaço. Desta forma, a pesquisa recomenda um uso sustentável dos recursos que perpassa por um zoneamento ecológico.

Palavras-chave: Geodiversidade, Baixo Umbelúzi, Usos e Impactos.
Ricardo Tesch
Authors: Alonso Aurelio A. , Conti Ana Cláudia de Castro Ferreira , Conti Paulo César R. , Grossmann Eduardo , Zwir Liete , Furquim Bruno , Tesch Ricardo
Published: January 2021

Ricardo Tesch se graduou pela UFRJ (Universidade Federal do Rio de Janeiro), em 1992. Especializou-se em Ortodontia, pela Associação dos Cirurgiões-Dentistas de Campinas (SP), em 1999. De lá, seguiu para a vida acadêmica, fazendo o mestrado e o doutorado, em Medicina, com área de concentração em Cirurgia de Cabeça e Pescoço, pelo Hospital Higienópolis (SP) e Clínica Médica, em Neurologia, pela UFRJ, respectivamente. É professor adjunto da Unifase (Faculdade de Medicina de Petrópolis), onde exerce também o cargo de coordenador dos cursos de Especialização em DTM e Dor Orofacial e Ortodontia, além de ser diretor do Centro de Medicina Regenerativa. Ele coordena, também, o curso de especialização em DTM e Dor Orofacial da PUC, na República Dominicana.
Desgastes Incisais e Ortodontia
Authors: Seixas Mayra , Câmara Carlos Alexandre
Published: January 2021

INTRODUÇÃO: O aumento do número de pacientes adultos trouxe para o ortodontista alguns desafios importantes: alterações periodontais e dentárias como unidades ausentes, perdas ósseas e de papilas, desarmonias no contorno gengival e desgastes incisais são muito frequentes. Esses últimos podem trazer significativas consequências estéticas e funcionais, requerendo um diagnóstico cuidadoso e, na imensa maioria dos casos, abordagens transdisciplinares. OBJETIVOS: Analisar os tipos e características dos desgastes incisais, suas implicações histológicas, estéticas e funcionais, assim como as más oclusões com as quais estão mais frequentemente associados; e conhecer como diagnosticar e utilizar ferramentas gráficas para o planejamento restaurador, além dos aspectos importantes relacionados com a estabilidade e longevidade das restaurações incisais.