bluuebunny/crossref_metadata_2025 huggingface dataset:
A tribute to Loránd Eötvös
Authors: Kubbinga Henk
Published: September 2020

The last decades of the 19th century Hungary came to flourish as an independent part of the Austrian-Hungarian Monarchy; 1867 was a crucial year, a year of ‘Ausgleich’, ‘Compromise’. József Eötvös, Hungary’s leading intellectual and Cabinet Minister, reorganized science. He sent his son to Heidelberg, where junior learned physics from i.a. Bunsen, Helmholtz and Kirchhoff. What more could a youngster wish for? Roland Eötvös returned home with a predilection for fundamental matters, most of all for the nature of gravity and its relation to inertia. Geophysics, Hungary’s pride, finally took centre stage.
Partition Markov Model for Covid-19 Virus
Authors: García Jesús Enrique , González-López Verónica Andrea , Tasca Gustavo Henrique
Published: September 2020

In this paper, we investigate a specific structure within the theoretical framework of Partition Markov Models (PMM) [see García Jesús and González-López, Entropy 19, 160 (2017)]. The structure of interest lies in the formulation of the underlying partition, which defines the process, in which, in addition to a finite memory o associated with the process, a parameter G is introduced, allowing an extra dependence on the past complementing the dependence given by the usual memory o. We show, by simulations, how algorithms designed for the classic version of the PMM can have difficulties in recovering the structure investigated here. This specific structure is efficient for modeling a complete genome sequence, coming from the newly decoded Coronavirus Covid-19 in humans [see Wu et al., Nature 579, 265–269 (2020)]. The sequence profile is represented by 13 units (parts of the state space’s partition), for each of the 13 units, their respective transition probabilities are computed for any element of the genetic alphabet. Also, the structure proposed here allows us to develop a comparison study with other genomic sequences of Coronavirus, collected in the last 25 years, through which we conclude that Covid-19 is shown next to SARS-like Coronaviruses (SL-CoVs) from bats specimens in Zhoushan [see Hu et al., Emerg Microb Infect 7, 1–10 (2018)].
Big Data‚ KI und Maschinenlernen auf dem Weg zur Precision-Psychiatry – wie verändern sie den therapeutischen Alltag?
Authors: Winter Nils Ralf , Hahn Tim
Published: September 2020

Derzeit sehen wir verstärkt Ansätze in der psychiatrischen Forschung, die sich mit prognostischen Modellen und einer individualisierten Diagnosestellung und Therapieauswahl beschäftigen. Vor diesem Hintergrund strebt die Precision-Psychiatry, wie auch andere Teildisziplinen der Medizin, eine präzisere Diagnostik und individualisierte Therapie durch Big Data an. Die elektronische Patientenakte, Datenerfassung durch Smartphones und technische Fortschritte in der Genotypisierung und Bildgebung ermöglichen eine detaillierte klinische und neurobiologische Beschreibung einer Vielzahl von Patienten. Damit diese Daten tatsächlich zu einem Paradigmenwechsel in der Behandlung psychischer Störungen führen, braucht es eine Personalisierung der Psychiatrie durch Maschinelles Lernen (ML) und Künstliche Intelligenz (KI). Neben der Digitalisierung der Klinik müssen wir daher eine KI-Infrastruktur etablieren, in der maßgeschneiderte KI- und ML-Lösungen entwickelt und nach hohen Validierungsstandards evaluiert werden können. Zusätzlich müssen Modellvorhersagen und detaillierte Patienteninformationen in KI-basierte Clinical-Decision-Support-Systeme (CDSS) integriert werden. Nur so können Big Data, Maschinelles Lernen und Künstliche Intelligenz den Behandler im therapeutischen Alltag aktiv und effizient unterstützen und eine personalisierte Behandlung erreichen.
Atualização no estadiamento dos sarcomas ósseos e das partes moles
Authors: Guedes Alex , Oliveira Marcelo Bragança dos Reis , Costa Flávia Martins , de Melo Adelina Sanches
Published: September 2020

Os sarcomas ósseos e das partes moles consistem em grupo heterogêneo de neoplasias malignas de origem mesenquimal que podem ocorrer em qualquer faixa etária. O estadiamento preciso destas lesões determina as melhores estratégias terapêuticas e estimativas de prognóstico. Dois sistemas de estadiamento são os mais frequentemente empregados no manejo destas neoplasias: o sistema proposto pelo grupo da Universidade da Flórida, liderado pelo Dr. William F. Enneking (1980), adotado pela Musculoskeletal Tumor Society (MSTS) e o sistema desenvolvido pela American Joint Committee on Cancer (AJCC) (1977) que se encontra em sua 8a edição (2017). O presente artigo busca atualizar o leitor a respeito do estadiamento dos sarcomas ósseos e das partes moles que acometem o sistema musculoesquelético.
Incidência e fatores de risco das complicações da cirurgia de Latarjet
Authors: Cohen Marcio , Fonseca Raphael , Gribel Bernardo , Galvão Marcus Vinicius , Monteiro Martim , Motta Filho Geraldo
Published: September 2020

Objetivo A cirurgia de Latarjet é bem estabelecida para o tratamento da instabilidade anterior do ombro. Apresenta complicações específicas com taxas de até 30%. Nosso objetivo é avaliar a incidência e os fatores de risco associados às complicações após a cirurgia de Latarjet.

Métodos Analisamos retrospectivamente 102 pacientes submetidos ao procedimento. Dividimos as complicações em três tipos: clínicas, relacionadas ao enxerto e relacionadas aos implantes. Todos os pacientes foram submetidos a radiografias e tomografia computadorizada (TC). Os fatores de risco analisados foram gênero, idade, cirurgia prévia, epilepsia e experiência do cirurgião.

Resultados Um total de 102 pacientes consecutivos (108 casos) foram avaliados. A média de idade foi 33,7 anos (18 a 61 anos), com 88 homens e 14 mulheres. A taxa de complicações foi de 21,2%, sendo 12% clínicas, 7,4% relacionadas ao enxerto e 2,7% relacionadas ao implante. As mais frequentes foram apreensão anterior (oito casos) e posicionamento lateral do enxerto, em seis casos. A TC foi realizada com o mínimo de 6 meses em 79 casos (73%), evidenciando a consolidação do enxerto em 75 pacientes (94.9%). Nenhum caso de não união apresentou instabilidade. Dez pacientes (9.2%) precisaram de cirurgia de revisão. Os fatores de risco relacionados às complicações foram epilepsia (p = 0.0325), experiência do cirurgião (p = 0.0499) e pacientes ≥ 40 anos (p = 0.0151). Não houve correlação com gênero e cirurgia prévia.

Conclusão A taxa de complicações após a cirurgia de Latarjet foi de 21,2%, com 9% necessitando de revisão cirúrgica. Epilepsia, idade > 40 anos e experiência do cirurgião foram fatores de risco.
Sevoflurano tópico en infección superficial por SARM tras artroplastia de rodilla. Caso Clínico
Authors: Nova Ainara Achaerandio-de , Losa-Palacios Sergio , San Martín-Martínez Alfredo , Gerónimo-Pardo Manuel
Published: September 2020

Intentar el tratamiento retentivo de material protésico ante heridas quirúrgicas infectadas por gérmenes resistentes es objeto de debate, especialmente cuando el agente causal es un Staphylococcus aureus resistente a meticilina (SARM). Una paciente diabética y con obesidad tipo I sufrió infección de la herida quirúrgica tras artroplastia de rodilla que no evolucionó bien con antibioterapia empírica y terapia hiperosmolar. Se planificó una reintervención que fue demorada por motivos extramédicos (falta de terapia de presión negativa para cubrir la herida postoperatoria, pues se preveía no poder realizar cierre primario). Mientras se conseguía este material, y tras obtener el consentimiento de la paciente, se iniciaron irrigaciones de la herida con sevoflurano tópico off-label, pues ese fármaco ha mostrado capacidad antimicrobiana. La evolución clínica fue excelente desde el inicio a pesar de que en el cultivo se aisló un SARM resistente a la antibioterapia empírica, por lo que se desestimó la reintervención y se continuó con sevoflurano tópico junto a la antibioterapia dirigida por antibiograma, lográndose la curación completa de la herida tras 6 semanas. Durante ese tiempo, la paciente no experimentó ningún efecto adverso atribuible al sevoflurano. El sevoflurano tópico aparece como una valiosa nueva opción terapéutica ante heridas postoperatorias infectadas, especialmente cuando los gérmenes causantes son resistentes a los antibióticos convencionales.
Clinical Decision Support for Worker Health: A Five-Site Qualitative Needs Assessment in Primary Care Settings
Authors: Ash Joan S. , Chase Dian , Baron Sherry , Filios Margaret S. , Shiffman Richard N. , Marovich Stacey , Wiesen Jane , Luensman Genevieve B.
Published: September 2020

Background Although patients who work and have related health issues are usually first seen in primary care, providers in these settings do not routinely ask questions about work. Guidelines to help manage such patients are rarely used in primary care. Electronic health record (EHR) systems with worker health clinical decision support (CDS) tools have potential for assisting these practices.

Objective This study aimed to identify the need for, and barriers and facilitators related to, implementation of CDS tools for the clinical management of working patients in a variety of primary care settings.

Methods We used a qualitative design that included analysis of interview transcripts and observational field notes from 10 clinics in five organizations.

Results We interviewed 83 providers, staff members, managers, informatics and information technology experts, and leaders and spent 35 hours observing. We identified eight themes in four categories related to CDS for worker health (operational issues, usefulness of proposed CDS, effort and time-related issues, and topic-specific issues). These categories were classified as facilitators or barriers to the use of the CDS tools. Facilitators related to operational issues include current technical feasibility and new work patterns associated with the coordinated care model. Facilitators concerning usefulness include users' need for awareness and evidence-based tools, appropriateness of the proposed CDS for their patients, and the benefits of population health data. Barriers that are effort-related include additional time this proposed CDS might take, and other pressing organizational priorities. Barriers that are topic-specific include sensitive issues related to health and work and the complexities of information about work.

Conclusion We discovered several themes not previously described that can guide future CDS development: technical feasibility of the proposed CDS within commercial EHRs, the sensitive nature of some CDS content, and the need to assist the entire health care team in managing worker health.
Comparison of Safety between Different Kinds of Heparins in Patients Receiving Intra-Aortic Balloon Counterpulsation
Authors: Guan Xiaonan , Chen Mulei , Li Yanbing , Zhang Jianjun , Xu Li , Sun Hao , Zhang Dapeng , Wang Lefeng , Yang Xinchun
Published: September 2020

Background The present study aimed to compare the effectiveness and safety of low molecular-weight-heparin (LMWH) and unfractionated heparin (UFH) in acute myocardial infarction (AMI) patients receiving intra-aortic balloon counterpulsation (IABP).

Materials and Methods We retrospectively analyzed a total of 344 patients receiving IABP for cardiogenic shock, severe heart failure, ventricular septal rupture, or mitral valve prolapse due to AMI. A total of 161 patients received UFH (a bolus injection 70 U/kg immediately after IABP, followed by infusion at a rate of 15 U/kg/hour and titration to for 50 to 70 seconds of activated partial thromboplastin time. A total of 183 patients received LMWH (subcutaneous injection of 1.0 mg/kg every 12 hours for 5 to 7 days and 1.0 mg/kg every 24 hours thereafter). Events of ischemia, arterial thrombosis or embolism, and bleeding during IABP were evaluated. Major bleeding was defined as a hemoglobin decrease by >50 g/L (vs. prior to IABP) or bleeding that caused hemodynamic shock or life-threatening or requiring blood transfusion.

Results Subjects receiving UFH and LMWH did not differ in baseline characteristics. Ischemia was noted in five (3.1%) and two (1.1%) subjects in UFH and LMWH groups, respectively. Arterial thromboembolism occurred in three (1.9%) subjects in the UFH group, but not in the LMWH group. Logistic regression analysis failed to reveal an association between ischemia or bleeding with heparin type. Major bleeding occurred in 16 (9.9%) and six (3.3%) patients in the UFH and LWMH groups, respectively (p = 0.014). Regression analysis indicated that LMWH is associated with less major bleeding.

Conclusion LMWH could reduce the risk of major bleeding in patients receiving IABP. Whether LMWH could reduce arterial thromboembolism needs further investigation.
Resultados a longo prazo de osteotomia varizante femoral distal (OVFD) com cunha de abertura lateral para artrose do compartimento lateral do joelho utilizando navegação computadorizada
Authors: Kandhari Vikram , Angadi Darshan , Myat Darli , Fritsch Brett , Parker David , Coolican Myles
Published: September 2020

Objetivo O objetivo principal do presente estudo foi avaliar os resultados a longo prazo, incluindo a sobrevivência em Osteotomia Varizante Femoral Distal com Cunha de Abertura Lateral (OVFD-CAL) utilizando navegação computadorizada. O objetivo principal do presente estudo foi avaliar os resultados a longo prazo, incluindo a sobrevivência.

Métodos Foi realizada uma análise retrospectiva dos dados coletados prospectivamente de pacientes com artrite do compartimento lateral submetidos a OVFD-CAL por navegação de dezembro de 2006 a novembro de 2012. As pontuações International Knee Documentation Committee (IKDC, na sigla em inglês) e Knee Injury and Osteoarthritis Outcome Score (KOOS, na sigla em inglês) foram analisadas para medição de resultados. Conversão para artroplastia durante o acompanhamento foi o ponto final.

Resultados Um total de 19 OVFD-CAL foram realizados em 17 pacientes com média de idade de 46,6 ± 6,5 anos formaram a coorte do estudo. O alinhamento coronal foi corrigido a partir de uma média de 7,1° (2–11°) de valgo para uma média de 2,1° (0,5°–3°) de varo. As pontuações do IKDC melhoraram de uma média pré-operatória de 39 para 53 no acompanhamento de médio de longo prazo de 9,1 anos. Os escores do KOOS no acompanhamento a longo prazo foram: dor 71, sintomas 56, atividades da vida diária 82, esportes e recreação 59, qualidade de vida 43. A sobrevivência do OVFD-CAL foi de 78,9% em um acompanhamento de 9,1 anos. Presença de degeneração da cartilagem segundo a Sociedade Internacional de Reparação de Cartilagem (International Cartilage Repair Society [ICRS, na sigla em inglês])≥ grau 2 no compartimento medial do joelho e deformidade pré-operatória em valgo > 7° fortemente correlacionado com a conversão para artroplastia total do joelho (ATJ) no acompanhamento a longo prazo (r – 0,66).

Conclusões A OVFD-CAL por navegação computadorizada apresentou resultados clínicos satisfatórios e sobrevida de 79% no acompanhamento a longo prazo. Presença de alterações degenerativas ICRS ≥ grau 2 no compartimento medial do joelho com > 7° de deformidade pré-operatória em valgo afeta negativamente a sobrevivência da OVFD-CAL no acompanhamento de longo prazo.
Structure of two-dimensional electron clusters with various shapes, at low temperatures
Authors: Syvokon V. E.
Published: September 2020

The molecular dynamics method is used to study the structure of two-dimensional clusters that can be created in electronic systems above the surface of superfluid helium, using triangular, square, hexagonal and round holding electrode geometries. Clusters with a fixed surface density of 108 cm−2, but different numbers of particles (from 3 to 406) are considered. The spatial configurations of particles in clusters are calculated corresponding to a temperature of 10−2 K. The shape of the cluster significantly affects the arrangement of the electrons inside. If the symmetry of the cluster is consistent with the triangular symmetry of the electronic crystal, then for some numbers of particles, clusters with ideal defect-free packing are possible; otherwise, the clusters contain defects. An additional external field applied to the cluster significantly changes the configuration of its particles.
Liveweight and carcass characteristics of White Dorper and Crossbred lambs grazing lucerne, subterranean clover, biserrula or a choice of subterranean clover plus biserrula in southern Australia
Authors: McGrath Shawn R. , Sandral Graeme A. , Sundermann Louise , Quinn Jane C. , Weston Leslie A. , Friend Michael A.
Published: September 2020

Context Biserrula (Biserrula pelecinus L.) is a relatively new legume species in Australia that has been shown to maintain higher quality forage late in the season than subterranean clover (Trifolium subterraneum L.). Aim This study investigated the suitability of lucerne (Medicago sativa L.), subterranean clover and biserrula, or a choice of both biserrula and subterranean clover, for finishing White Dorper and White Suffolk × Merino lambs during spring. Methods An experiment was established near Wagga Wagga, NSW, in 2013 in a randomised complete block design with three replicates and four pasture treatments grazed by lambs during late spring and early summer. Liveweight, carcass weight and GR fat depth of White Dorper and White Suffolk × Merino lambs grazing lucerne, subterranean clover, biserrula or a choice of subterranean clover plus biserrula were compared. Key results Lambs grazing lucerne had significantly (P < 0.05) higher final liveweight, carcass weight and GR fat depth than lambs grazing other pasture treatments. After 61 days of grazing, mean liveweight of lambs grazing lucerne, subterranean clover and subterranean clover plus biserrula was higher than of lambs grazing biserrula monoculture. In vitro digestible organic matter digestibility and crude protein content indicated that lambs grazing biserrula should have achieved growth rates at least as high as lambs grazing subterranean clover. Sheep genotype and pasture type affected final liveweight. Final liveweight was higher for White Dorper lambs when grazing the subterranean clover plus biserrula treatment than the subterranean clover monoculture (45.6 vs 44.5 kg; P < 0.05) but was similar for White Suffolk × Merino lambs grazing these treatments (47.3 vs 47.2 kg; P > 0.05). Conclusions Provision of a companion species or mixture of species when lambs graze biserrula during late spring to summer appears to offer benefits for lamb growth rate over this period.
On the nature of AA question1
in Yi2 and related problems
Authors: Zhang Heyou , Wuni Muji
Published: September 2020

This paper aims to study a kind of interrogative in Yi which surfaces as an AA form commonly viewed as
AA/Reduplicative Question. It explores the interrogative motivation, question type, generative mechanism and syntactic derivation
of AA Question. We first assume that (i) AA question in Yi is a kind of alternative question, which is reduced successively from
A-or-not-A and A-not-A question and (ii) the [+Q] feature of AA question does not result from reduplication but from other
reasons. To justify these two assumptions, we use tests including adverb tests, modal tests, tag question tests, SFP tests, Q
& A tests, and cross-language investigation and sociolinguistic survey. The findings include (i) the [+Q] feature of AA
question results from the existence of an abstract interrogative morpheme, (ii) the phenomenon of reduplication is just a kind of
byproduct with the syntactic derivation of AA question and (iii) AA question, diachronically speaking, is essentially a kind of
alternative question, which is reduced successively from A-or-not-A and A-not-A question to meet the economic principle of
language.
Speech acts in corpus pragmatics
Authors: Weisser Martin
Published: September 2020

In corpus pragmatics, most of the research into speech acts still tends to be limited to working with the original, highly
abstract, speech-act taxonomies devised by ordinary language philosophers like Austin and Searle. The aim of this article is to illustrate
how the use of such restricted taxonomies may lead to oversimplified or potentially misleading impressions regarding the communicative
functions expressed in spoken interaction, and to demonstrate how a more elaborate taxonomy, the DART taxonomy (Weisser, 2018), may help us gain better insights into the pragmatic strategies that occur in dialogues. To this end,
I will draw on a small sample of dialogues, both from a task-oriented domain and unconstrained interaction, and contrast selected speech-act
categorisations on the basis of Searle’s and the DART taxonomy, demonstrating the advantages that arise from using a more fine-grained
taxonomy to describe complex verbal exchanges.
Assessing impact of channel selection on decoding of motor and cognitive imagery from MEG data
Authors: Roy Sujit , Rathee Dheeraj , Chowdhury Anirban , McCreadie Karl , Prasad Girijesh
Published: September 2020

Objective. Magnetoencephalography (MEG) based brain–computer interface (BCI) involves a large number of sensors allowing better spatiotemporal resolution for assessing brain activity patterns. There have been many efforts to develop BCI using MEG with high accuracy, though an increase in the number of channels (NoC) means an increase in computational complexity. However, not all sensors necessarily contribute significantly to an increase in classification accuracy (CA) and specifically in the case of MEG-based BCI no channel selection methodology has been performed. Therefore, this study investigates the effect of channel selection on the performance of MEG-based BCI. Approach. MEG data were recorded for two sessions from 15 healthy participants performing motor imagery, cognitive imagery and a mixed imagery task pair using a unique paradigm. Performance of four state-of-the-art channel selection methods (i.e. Class-Correlation, ReliefF, Random Forest, and Infinite Latent Feature Selection were applied across six binary tasks in three different frequency bands) were evaluated in this study on two state-of-the-art features, i.e. bandpower and common spatial pattern (CSP). Main results. All four methods provided a statistically significant increase in CA compared to a baseline method using all gradiometer sensors, i.e. 204 channels with band-power features from alpha (8–12 Hz), beta (13–30 Hz), or broadband (α + β) (8–30 Hz). It is also observed that the alpha frequency band performed better than the beta and broadband frequency bands. The performance of the beta band gave the lowest CA compared with the other two bands. Channel selection improved accuracy irrespective of feature types. Moreover, all the methods reduced the NoC significantly, from 204 to a range of 1–25, using bandpower as a feature and from 15 to 105 for CSP. The optimal channel number also varied not only in each session but also for each participant. Reducing the NoC will help to decrease the computational cost and maintain numerical stability in cases of low trial numbers. Significance. The study showed significant improvement in performance of MEG-BCI with channel selection irrespective of feature type and hence can be successfully applied for BCI applications.
3D Printing of large-scale and highly porous biodegradable tissue engineering scaffolds from poly(trimethylene-carbonate) using two-photon-polymerization
Authors: Weisgrab Gregor , Guillaume Olivier , Guo Zhengchao , Heimel Patrick , Slezak Paul , Poot André , Grijpma Dirk , Ovsianikov Aleksandr
Published: September 2020

The introduction of two-photon polymerization (2PP) to the field of tissue engineering and regenerative medicine (TERM) has led to great expectations for the production of scaffolds with an unprecedented degree of complexity and tailorable architecture. Unfortunately, resolution and size are usually mutually exclusive when using 2PP, resulting in a lack of highly-detailed scaffolds with a relevant size for clinical application. Through the combination of using a highly reactive photopolymer and optimizing key printing parameters, we propose for the first time a biodegradable and biocompatible poly(trimethylene-carbonate) (PTMC)-based scaffold of large size (18 × 18 × 0.9 mm) with a volume of 292 mm3 produced using 2PP. This increase in size results in a significant volumetric increase by almost an order of magnitude compared to previously available large-scale structures (Stichel 2010 J. Laser Micro./Nanoeng.
5 209–12). The structure’s detailed design resulted in a highly porous scaffold (96%) with excellent cytocompatibility, supporting the attachment, proliferation and differentiation of human adipose-derived mesenchymal stem cells towards their osteogenic and chondrogenic lineages. This work strongly attests that 2PP is becoming a highly suitable technique for producing large-sized scaffolds with a complex architecture. We show as a proof-of-concept that an arrayed design of repetitive units can be produced, but a further perspective will be to print scaffolds with anisotropic features that are more representative of human tissues.
Direct extrusion of individually encapsulated endothelial and smooth muscle cells mimicking blood vessel structures and vascular native cell alignment
Authors: Bosch-Rué E , Delgado Luis M , Gil F Javier , Perez Roman A
Published: September 2020

Cardiovascular diseases (CVDs) are considered the principal cause of worldwide death, being atherosclerosis the main etiology. Up to now, the predominant treatment for CVDs has been bypass surgery from autologous source. However, due to previous harvest or the type of disease, this is not always an option. For this reason, tissue engineered blood vessels (TEBV) emerged as an alternative graft source for blood vessel replacement. In order to develop a TEBV, it should mimic the architecture of a native blood vessel encapsulating the specific vascular cells in their respective layers with native alignment, and with appropriate mechanical stability. Here, we propose the extrusion of two different cell encapsulating hydrogels, mainly alginate and collagen, and a sacrificial polymer, through a triple coaxial nozzle, which in contact with a crosslinking solution allows the formation of bilayered hollow fibers, mimicking the architecture of native blood vessels. Prior to extrusion, the innermost cell encapsulating hydrogel was loaded with human umbilical vein endothelial cells (HUVECs), whereas the outer hydrogel was loaded with human aortic smooth muscle cells (HASMCs). The size of the TEVB could be controlled by changing the injection speed, presenting homogeneity between the constructs. The obtained structures were robust, allowing its manipulation as well as the perfusion of liquids. Both cell types presented high rates of survival after the extrusion process as well as after 20 d in culture (over 90%). Additionally, a high percentage of HASMC and HUVEC were aligned perpendicular and parallel to the TEBV, respectively, in their own layers, resembling the physiological arrangement foundin vivo. Our approach enables the rapid formation of TEBV-like structures presenting high cell viability and allowing proliferation and natural alignment of vascular cells.
Development of a novel dual reproductive organ on a chip: recapitulating bidirectional endocrine crosstalk between the uterine endometrium and the ovary
Authors: Park Se-Ra , Kim Soo-Rim , Lee Jin Woo , Park Chan Hum , Yu Wook-Joon , Lee Seung-Jin , Chon Seung Joo , Lee Dae Ho , Hong In-Sun
Published: September 2020

Conventional 2D or even 3D in vitro culture models for human reproductive organs cannot properly recapitulate the bidirectional endocrine crosstalk between the uterine endometrium and the ovary. This crosstalk is essential for maintaining the various physiological features and functions of each tissue. Moreover, most in vitro models for the female reproductive tract also fail to mimic its multicellular structure. We therefore developed a novel ‘dual reproductive organ on a chip’ that reflects the bidirectional endocrine cross-talk and the complex multicellular structures by integrating various cellular components of both the human uterine endometrium and the ovary with several biodegradable natural polymers. Indeed, the bidirectional endocrine crosstalk between these two tissues is achieved through media sharing between channels, and it can markedly improve the viability of loaded cells within each chamber of the chip platform. In addition, we also identified a reliable reproductive toxicity marker, SERPINB2, which is significantly increased in response to various toxic exposures in both endometrial and ovarian follicular cells. Based on these findings, we next established a SERPINB2 luciferase reporter system that was specifically designed for detecting and quantifying the toxicity of certain substances. By introducing this SERPINB2 luciferase reporter system into the loaded cells within the chip platform, we ultimately developed an effective ‘dual reproductive organ-on-chip’ that was successfully used to predict the reproductive toxicity of various hazardous materials.
Financial performance and reimbursement of pharmacist-led chronic care management
Authors: Martin Randy , Tram Kathlynn , Le Lan , Simmons Crystal
Published: September 2020

Purpose

The purpose of this study was to evaluate the financial performance and reimbursement of chronic care management (CCM) provided by clinical pharmacists in a primary care setting using Current Procedural Terminology codes that were added to the Medicare Physician Fee Schedule in 2017.

Methods

A retrospective study assessing financial performance of pharmacist-led CCM was conducted for the 12-month period from May 1, 2018, through April 30, 2019, at an academic multiclinic medical practice. Pharmacist-led CCM encounters included a combination of telephone and in-clinic visits. Return on investment, a ratio of net income to financial investment, was the primary outcome. Secondary outcomes included the number of CCM encounters, time spent by pharmacists delivering CCM (ie, “time-on-task”), and third-party claim reimbursement.

Result

Sixty-five patients were enrolled in CCM during the 12-month study period. Pharmacists provided 236 CCM encounters, including 31 enrollment visits and 102 hours of clinical time-on-task. Gross revenue for CCM during the 12-month period was $7,433.91, and expenses totaled $6,430.36, resulting in a 15.6% return on investment. Out of 158 CCM claims, 131 (83%) were paid and 27 (17%) were unpaid or remained in adjudication at study completion.

Conclusion

Pharmacist-led CCM resulted in a modest positive return on investment compared to other reimbursable pharmacy services. Practitioners should evaluate opportunities to synergize CCM with other fee-for-service and quality-based reimbursement programs.
Dux facilitates post-implantation development, but is not essential for zygotic genome activation†
Authors: Bosnakovski Darko , Gearhart Micah D , Ho Choi Si , Kyba Michael
Published: September 2020

Double homeobox genes are unique to eutherian mammals. It has been proposed that the DUXC clade of the double homeobox gene family, which is present in multicopy long tandem arrays, plays an essential role in zygotic genome activation (ZGA). We generated a deletion of the tandem array encoding the DUXC gene of mouse, Double homeobox (Dux), and found it surprisingly to be homozygous viable and fertile. We characterize the embryonic development and ZGA profile of knockout (KO) embryos, finding that zygotic genome activation still occurs, with only modest alterations in 2-cell embryo gene expression, no defect in in vivo preimplantation development, but an increased likelihood of post-implantation developmental failure, leading to correspondingly smaller litter sizes in the KO strain. While all known 2-cell specific Dux target genes are still expressed in the KO, a subset is expressed at lower levels. These include numerous genes involved in methylation, blastocyst development, and trophectoderm/placental development. We propose that rather than driving ZGA, which is a process common throughout the animal kingdom, DUXC genes facilitate a process unique to eutherian mammals, namely the post-implantation development enabled by an invasive placenta.
Pleiotropic role of prokineticin 1 in the porcine endometrium during pregnancy establishment and embryo implantation †
Authors: Goryszewska Ewelina , Kaczynski Piotr , Baryla Monika , Waclawik Agnieszka
Published: September 2020

Acquisition of endometrial receptivity for embryo implantation is one of the crucial processes during pregnancy and is induced mainly by progesterone and enhanced by conceptus signals. Prokineticin 1 (PROK1) is characterized as a secretory protein with diverse functions in various tissues, including the reproductive tract. PROK1, with its receptor PROKR1, are up-regulated in the porcine endometrium during implantation and in women’s receptive endometrium and decidua. However, the function of PROK1 in embryo-maternal communication has still not been fully elucidated. Hence, we hypothesize that PROK1 is involved in endometrial receptivity development and implantation in pigs. In this study, using the porcine in vivo model of intrauterine infusions of estradiol-17β (E2) and prostaglandin E2 (PGE2), we revealed that these hormones elevated endometrial expression of PROK1 and PROKR1 mRNA, respectively. Moreover, E2, acting synergistically with PGE2, increased PROKR1 protein expression. We also evidenced that PROK1–PROKR1 signaling induced expression of following genes and/or proteins CCN2, CDH13, FGF2, NFATC2, ANGPT1, ANGPT2, CDH1, MUC4, SPP1, IFNG, IL6, LIF, LIFR, TNF, TGFB3, and FGF9, as well as phosphorylation of PTK2 and secretion of IL6 and IL11 by endometrial explants in vitro. Ingenuity pathway analysis revealed that functions associated with the PROK1-regulated genes/proteins include cell-to-cell contact, cell attachment, migration and viability, differentiation of epithelial tissue, leukocyte migration, inflammatory response, angiogenesis, and vasculogenesis. Summarizing, our study suggests that PROK1 acts pleiotropically as an embryonic signal mediator that regulates endometrial receptivity by increasing the expression of the genes and proteins involved in implantation and pregnancy establishment in pigs.
Kindergarten for Free?! Empirical Evidence on the Utilization of Income Tax Deductions for Child Care Expenses
Authors: Calahorrano Lena , Stöwhase Sven
Published: September 2020

In most developed countries there exist ample possibilities for individuals to minimize their personal income tax burden by means of tax deductions. The associated revenue losses for the government have been estimated for a variety of tax deductions. However, relatively little is known about the share of eligible taxpayers who actually use these deductions, and, more specifically, about what determines utilization. The present paper tries to shed some light on this question in the context of the tax deductibility of expenses for child care in Germany. Using survey data on actual child care expenses and official tax-return data on deductions for child-care expenses, we derive utilization rates. We also analyze the determinants of utilization among those who filed a tax-return, using a subsample of the tax-return data. Our estimation results show that (potential) tax breaks from utilization are significantly positively correlated with the probability of utilization. Other kinds of deductions are also highly significant, suggesting that knowledge of tax statutes as well as opportunity costs matter. Moreover, we simulate the effects of a policy reform that enhances the generosity of deductions on the utilization rate. Such a reform would substantially increase utilization. Our results indicate that responses in utilization are more important than potential responses in labor supply. (JEL codes: D14, H24, H43).
Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial
Authors: Luckraz Heyman , Giri Ramesh , Wrigley Benjamin , Nagarajan Kumaresan , Senanayake Eshan , Sharman Emma , Beare Lawrence , Nevill Alan
Published: September 2020

OBJECTIVES

Our goal was to investigate the efficacy of balanced forced diuresis in reducing the rate of acute kidney injury (AKI) in cardiac surgical patients requiring cardiopulmonary bypass (CPB), using the RenalGuard® (RG) system.

METHODS

Patients at risk of developing AKI (history of diabetes and/or anaemia; estimated glomerular filtration rate 20–60 ml/min/1.73 m2; anticipated CPB time >120 min; log EuroSCORE > 5) were randomized to the RG system group (n = 110) or managed according to current practice (control = 110). The primary end point was the development of AKI within the first 3 postoperative days as defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria.

RESULTS

There were no significant differences in preoperative and intraoperative characteristics between the 2 groups. Postoperative AKI rates were significantly lower in the RG system group compared to the control group [10% (11/110) vs 20.9% (23/110); P = 0.025]. This effect persisted even after controlling for a number of potential confounders (odds ratio 2.82, 95% confidence interval 1.20–6.60; P = 0.017) when assessed by binary logistic regression analysis. The mean volumes of urine produced during surgery and within the first 24 h postoperatively were significantly higher in the RG system group (P < 0.001). There were no significant differences in the incidence of blood transfusions, atrial fibrillation and infections and in the median duration of intensive care unit stays between the groups. The number needed to treat with the RG system to prevent AKI was 9 patients (95% confidence interval 6.0–19.2).

CONCLUSIONS

In patients at risk for AKI who had cardiac surgery with CPB, the RS RG system significantly reduced the incidence of AKI and can be used safely and reproducibly. Larger studies are required to confirm cost benefits.

Clinical trial registration number

NCT02974946
Temperature-sensitive recombinant subtilisin protease variants that efficiently degrade molecular biology enzymes
Authors: Thompson Vanessa C , McGuire Bailey E , Frier Mia S , Legg Max S G , Dyer Tyler W , Gudavicius Geoff , Potter Sheila , Nano Francis E
Published: September 2020

We used error-prone PCR to generate mutations in a subtilisin protease-encoding gene, and screened for recombinants that expressed temperature-sensitive (TS) variants. From the dozens of mutations that we detected in the recombinant genes we found that those mutations that affected aspartate-75 had the most profound effect on temperature stability. We thus focused our analysis on two variants of subtilisin C, the more heat-sensitive variant 24 (V24), with amino acid changes D75G, L234M and Q274P; and variant 25 (V25), with a single amino acid change, D75A. For V24 a two log-fold reduction in activity occurs in under 10 min at 50°C. For V25, a two log-fold reduction occurs at 60°C, a temperature that reduces the activity of the wild type enzyme by about 30%. The V24 variant fully inactivates enzymes commonly used in molecular biology research and in molecular diagnostics, and is stabilized against autolysis with propylene glycol concentrations of 10% or greater. The subtilisin variants are produced by a strain of Bacillus subtilis that lacks expression of its native secreted proteases, and the variants can be isolated from the supernatants using nickel affinity chromatography.
New Environment, New Invaders—Repeated Horizontal Transfer of LINEs to Sea Snakes
Authors: Galbraith James D. , Ludington Alastair J. , Suh Alexander , Sanders Kate L. , Adelson David L.
Published: September 2020

Although numerous studies have found horizontal transposon transfer (HTT) to be widespread across metazoans, few have focused on HTT in marine ecosystems. To investigate potential recent HTTs into marine species, we searched for novel repetitive elements in sea snakes, a group of elapids which transitioned to a marine habitat at most 18 Ma. Our analysis uncovered repeated HTTs into sea snakes following their marine transition. The seven subfamilies of horizontally transferred LINE retrotransposons we identified in the olive sea snake (Aipysurus laevis) are transcribed, and hence are likely still active and expanding across the genome. A search of 600 metazoan genomes found all seven were absent from other amniotes, including terrestrial elapids, with the most similar LINEs present in fish and marine invertebrates. The one exception was a similar LINE found in sea kraits, a lineage of amphibious elapids which independently transitioned to a marine environment 25 Ma. Our finding of repeated horizontal transfer events into marine snakes greatly expands past findings that the marine environment promotes the transfer of transposons. Transposons are drivers of evolution as sources of genomic sequence and hence genomic novelty. We identified 13 candidate genes for HTT-induced adaptive change based on internal or neighboring HTT LINE insertions. One of these, ADCY4, is of particular interest as a part of the KEGG adaptation pathway “Circadian Entrainment.” This provides evidence of the ecological interactions between species influencing evolution of metazoans not only through specific selection pressures, but also by contributing novel genomic material.
10. Children needing services, care, and protection
Authors: Gilmore Stephen , Glennon Lisa
Published: September 2020

This chapter examines the relationship between children, parents, and the state, looking at how the law responds to children needing services, care, and protection. Topics discussed include: Part III of the Children Act 1989; the threshold for compulsory intervention in family life based on the concept of ‘significant harm’; protecting children in an emergency; care and supervision orders; the local authority’s care plan and respective roles of the local authority and court; and discharge of care orders.
A novel two-layer-integrated microfluidic device for high-throughput yeast proteomic dynamics analysis at the single-cell level
Authors: Chen Kaiyue , Rong Nan , Wang Shujing , Luo Chunxiong
Published: September 2020

Current microfluidic methods for studying multicell strains (e.g., m-types) with multienvironments (e.g., n-types) require large numbers of inlets/outlets (m*n), a complicated procedure or expensive machinery. Here, we developed a novel two-layer-integrated method to combine different PDMS microchannel layers with different functions into one chip by a PDMS through-hole array, which improved the design of a PDMS-based microfluidic system. Using this method, we succeeded in converting 2 × m × n inlets/outlets into m + n inlets/outlets and reduced the time cost of loading processing (from m × n to m) of the device for studying multicell strains (e.g., m-types) in varied multitemporal environments (i.e., n-types). Using this device, the dynamic behavior of the cell-stress-response proteins was studied when the glucose concentration decreased from 2% to a series of lower concentrations. Our device could also be widely used in high-throughput studies of various stress responses, and the new concept of a multilayer-integrated fabrication method could greatly improve the design of PDMS-based microfluidic systems.
Assessment of the amino acid profile in Thai patients with type 2 diabetes mellitus using liquid chromatography-mass spectrometry
Authors: Sriboonvorakul Natthida , Pan-Ngum Wirichada , Poovorawan Kittiyod , Winterberg Markus , Tarning Joel , Muangnoicharoen Sant
Published: September 2020

Background

Type 2 diabetes mellitus (T2DM) is a global health problem. Early identification of those at risk is necessary to prevent its onset through lifestyle and pharmacologic interventions. T2DM is characterized by metabolic abnormalities, including protein metabolism. Evaluation of the amino acid profile might be beneficial for early assessment.

Methods

Liquid chromatography-mass spectrometry was performed to separate and quantify plasma amino acids from two groups of Thai individuals, patients with T2DM (n=103) and healthy individuals (n=104). Multivariate analysis was applied to compare free amino acid levels between groups. Subgroup analyses of patients with T2DM were performed to assess the association between amino acid profiles and important T2DM clinical characteristics.

Results

The multivariate analysis showed that glutamic acid was significantly associated with T2DM (OR 1.113, 95% CI 1.006 to 1.231) and results from the subgroup analyses showed that this correlation was significant in all subgroups of patients (p<0.05).

Conclusions

This finding needs to be confirmed in larger groups of patients with T2DM to explore glutamic acid as a biomarker for early prevention in particular at-risk groups. An in-depth understanding of the involvement of glutamic acid in T2DM could enhance our understanding of the disease and potentially provide novel interventions.
Introduction
Authors: Chronis-Tuscano Andrea , O’Brien Kelly , Danko Christina M.
Published: September 2020

The etiology of ADHD lies in the brain, yet the quality of the parenting and family environment can scaffold the child’s development to maximize their functioning, while minimizing impairment and the development of comorbid problems. Given that parents and children exert reciprocal, transactional influences on one another, parent and child mental health must both be targeted in parenting interventions for ADHD. In this introduction, the authors present behavioral and cognitive-behavioral theoretical models that lay the foundation for the skills presented in this therapist guide. In addition, general guidelines for delivering this program in both individual and group formats are presented.
Module 1: Psychoeducation and Theoretical Foundations
Authors: Chronis-Tuscano Andrea , O’Brien Kelly , Danko Christina M.
Published: September 2020

In Module 1, parents learn the theoretical foundations for the program. This is a time to build rapport, learn more about the child’s specific problems, identify treatment goals, and instill hope. Parents learn about two foundational models in Module 1: the ABC model of child behavior and the transactional model of attention-deficit/hyperactivity disorder (ADHD) and families. The difficulties that children with ADHD experience can contribute to parent stress and/or negative reactions to their child. Parents may feel frustrated, stressed, worried, and/or sad about their child’s behavior. Some parents may blame themselves or feel they’re not doing a good job. On the other hand, the degree to which a parent is responsive and sensitive can help or hinder temperamentally at-risk infants and young children in terms of the later development of ADHD-related problems. Teaching parents effective ways to respond to their child can have important implications for the child’s ongoing adjustment.
Module 8: Working Effectively with the Schools
Authors: Chronis-Tuscano Andrea , O’Brien Kelly , Danko Christina M.
Published: September 2020

In Module 8, parents learn the importance of advocating for their children’s educational needs by developing and maintaining a collaborative working relationship with the school. The most effective outcomes come when parent(s) and school collaboratively work together toward the common goal of helping the child succeed. To be the most effective advocate for the child, parents must understand their educational rights. Parents should also be familiar with evidence-based strategies for addressing academic productivity and behavior management in the classroom (e.g., Daily Report Card [DRC]) so that they know what to ask for. Some parents will need support to appropriately assert themselves in this context, refraining from being either too passive or too aggressive. Other parents will need support with keeping organized records of their children’s psychological evaluations, records, and report cards, which is essential as they prepare for school (IEP, 504 Plan) meetings.