bluuebunny/crossref_metadata_2025 huggingface dataset:
A translational study to evaluate genomic markers and concordance with circulating-tumor DNA and circulating tumor cells to predict clinical outcomes in gastrointestinal and pancreatobiliary cancers: Valor trial.
Authors: Doi Ayako , Umemoto Kumiko , Oguri Tomoyo , Takeda Hiroyuki , Horie Yoshiki , Ogura Takashi , Mizukami Takuro , Izawa Naoki , Jung Sungmok , Kim Byung Chul , Sunakawa Yu
Published: January 2021

TPS481

Background: Circulating tumor cells (CTCs) are cells that have shed into the vasculature or lymphatics from a primary tumor and are carried around the body in the blood circulation. The CTCs constitute seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. Circulating-tumor DNA (ctDNA) includes DNA which derives from tumor necrosis or apoptosis; therefore, CTCs may potentially represent more precise tumor status compared to ctDNA. There have been few reports to assess the genomic concordance between ctDNA and CTCs in cancer patients. In addition, genomic analysis of ctDNA would find novel mechanism of resistance to anti-EGFR monoclonal antibody (mAb) in metastatic colorectal cancer (mCRC). RAS mutations in ctDNA are considered to be one of mechanism of resistance to anti-EGFR mAb in RAS wild-type mCRC. However, there is no data regarding CTCs when mCRC patients acquires resistance to anti-EGFR mAb. Methods: This translational study prospectively recruits patients with advanced/metastatic gastrointestinal and pancreatobiliary cancers (esophageal, gastric, pancreatic, biliary tract and colorectal cancers) who receive systemic chemotherapy in first- or second-line and mCRC with RAS wild-type tumors treated with anti-EGFR mAb in any lines, at St. Marianna University School of Medicine Hospital. We accumulate the clinical data regarding patients’ characteristics, treatment, and survival time. The primary objective is to evaluate genomic markers and concordance with ctDNA and CTCs in patients with advanced/metastatic gastrointestinal and pancreatobiliary cancers. Then, this study approaches to assess which biomarkers can predict clinical outcome more accurately. Secondary objectives include evaluating association between genomic status in ctDNA and clinical outcomes; association between genomic status in CTCs and clinical outcomes; comparing genomic change between ctDNA and CTCs in RAS wild-type mCRC patients treated with anti-EGFR mAb. Blood draw of total 10mL is performed for analyses of ctDNA and CTCs at 3 time points, pre-treatment of chemotherapy, 4 weeks after treatment start, and disease progression. Blood of 5mL is processed with CTCs enrichment using the CD-PRIME system (Clinomics Inc.) and remaining 5mL is used for the plasma preparation. Genomic alterations are measured using the customized cancer panel which allows the detection of mutations in 51 actionable genes. This study will enroll 70 patients with willing to undergo blood draws. Accrual is starting in May 2019. Clinical trial information: UMIN000036681.
Local translation in perisynaptic and perivascular astrocytic processes – a means to ensure astrocyte molecular and functional polarity?
Authors: Mazaré Noémie , Oudart Marc , Cohen-Salmon Martine
Published: January 2021

Together with the compartmentalization of mRNAs in distal regions of the cytoplasm, local translation constitutes a prominent and evolutionarily conserved mechanism mediating cellular polarization and the regulation of protein delivery in space and time. The translational regulation of gene expression enables a rapid response to stimuli or to a change in the environment, since the use of pre-existing mRNAs can bypass time-consuming nuclear control mechanisms. In the brain, the translation of distally localized mRNAs has been mainly studied in neurons, whose cytoplasmic protrusions may be more than 1000 times longer than the diameter of the cell body. Importantly, alterations in local translation in neurons have been implicated in several neurological diseases. Astrocytes, the most abundant glial cells in the brain, are voluminous, highly ramified cells that project long processes to neurons and brain vessels, and dynamically regulate distal synaptic and vascular functions. Recent research has demonstrated the presence of local translation at these astrocytic interfaces that might regulate the functional compartmentalization of astrocytes. In this Review, we summarize our current knowledge about the localization and local translation of mRNAs in the distal perisynaptic and perivascular processes of astrocytes, and discuss their possible contribution to the molecular and functional polarity of astrocytes.
A Theoretical Procedure Based on Classical Electrostatics and Density Functional Theory for Screening Non-Square-Shaped Mixed-Valence Complexes for Logic Gates in Molecular Quantum-Dot Cellular Automata
Authors: Tokunaga Ken , Odate Fumiya , Asami Daiya , Tahara Keishiro , Sato Mitsunobu
Published: January 2021

Understanding the requisite geometry of molecules and peripheral components is an essential step in endowing molecules with logical functions in quantum-dot cellular automata. To respond to the real problem of structural distortion from the ideal square cell configuration, a practical procedure is presented that simplifies the molecular shapes for device design with features that combine aspects of classical electrostatics and density functional theory calculations. By applying this method to a library of biferrocenium dimers with a three-input junction, it was demonstrated in theory that a covalently bonded parallelogram dimer responds precisely to six different patterns of nanoscale electric fields and works correctly as a device cell in both AND and OR logic gates. The counterintuitive usefulness of the non-square-shape is rationalized by four ferrocene-based orbital orientations and a functional group arrangement, equalizing the disadvantageous energy asymmetry between the states 0 and 1. The present procedure was applied to quasi-square tetrametallic Ru complexes and it was found that these complexes do not work as logic gates. This procedure expands the range of existing candidate molecules from squares to parallelograms and facilitates screening for implementation.
New Idea for Narrowing an Energy Gap by Selective Perturbation of One Frontier Molecular Orbital
Authors: Tanaka Kazuo , Chujo Yoshiki
Published: January 2021

In this manuscript, we will illustrate a new idea for narrowing energy gaps between frontier molecular orbitals (FMOs) by selectively perturbing the levels of highest occupied molecular orbitals (HOMOs) and/or lowest unoccupied molecular orbitals (LUMOs). Initially, the basic concept of the isolated FMOs is explained by employing pentaazaphenalene (5AP) derivatives. It was found that electronic structures of the isolated LUMO of 5AP can be preserved even when incorporated into polymer chains if the connecting points are separated from the isolated LUMO. The mechanism and their unique electronic properties are summarized. Next, conversely, isolated HOMO and LUMO can be perturbed by conjugation effects independently. On the basis of this fact, near infrared (NIR)-absorbing molecules can be obtained by selectively elevating HOMO and lowering LUMO energy levels. We also mention strategies for enhancing luminescent properties of 5AP derivatives. Finally, we demonstrate that the isolated LUMO can be found in commodity luminescent dyes, such as boron dipyrromethene (BODIPY). By selectively lowering the LUMO energy level through the aza-substitution at the skeletal carbon where the isolated LUMO is distributed, NIR-emissive polymers can be obtained. Versatility of the isolated FMOs for obtaining optoelectronic organic materials is explained in this review.
High-resolution structure of eukaryotic Fibrillarin interacting with Nop56 amino-terminal domain
Authors: Höfler Simone , Lukat Peer , Blankenfeldt Wulf , Carlomagno Teresa
Published: January 2021

Ribosomal RNA (rRNA) carries extensive 2′-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet-uncharacterized function. 2′-O-methylation occurs both in archaea and eukaryotes and is accomplished by the Box C/D RNP enzyme in an RNA-guided manner. Extensive and partially conflicting structural information exists for the archaeal enzyme, while no structural data is available for the eukaryotic enzyme. The yeast Box C/D RNP consists of a guide RNA, the RNA-primary binding protein Snu13, the two scaffold proteins Nop56 and Nop58, and the enzymatic module Nop1. Here we present the high-resolution structure of the eukaryotic Box C/D methyltransferase Nop1 from Saccharomyces cerevisiae bound to the amino-terminal domain of Nop56. We discuss similarities and differences between the interaction modes of the two proteins in archaea and eukaryotes and demonstrate that eukaryotic Nop56 recruits the methyltransferase to the Box C/D RNP through a protein–protein interface that differs substantially from the archaeal orthologs. This study represents a first achievement in understanding the evolution of the structure and function of these proteins from archaea to eukaryotes.
Hellenic Republic: Voluntary National Review on the implementation of the 2030 Agenda for sustainable development, High-level Political Forum on sustainable development, July 2018
Authors: Trantas Nikos
Published: January 2021

no abstract
The social impact of the ‘Social solidarity income’ in Greece: A qualitative interpretation
Authors: Sakellaropoulos Theodoros , Lalioti Varvara , Kourachanis Nikos
Published: January 2021

The present article sheds light on the implementation of the ‘Social Solidarity Income’ (SSI) in Greece, an example of a guaranteed minimum income (GMI). Drawing on the findings of 40 semi-structured interviews carried out in five selected municipalities, the article focuses on the ‘social impact’ of the SSI. More specifically, it investigates two inter-related themes: a) the social situation of beneficiaries and the survival strategies they used before and after receiving the SSI; and b) aspects of the SSI that should be improved at the implementation stage. It is argued that, despite certain positive elements of the SSI, such as the monetary allowance, which is a key component of the SSI and assists beneficiaries in covering their basic needs, the impact of the SSI on the lives of individuals is relatively small and a large proportion of the beneficiaries continue to rely on the survival strategies they used before implementation of the SSI
Using patient experience measures to evaluate the quality of medical and nursing care in the newly established PHC units (TOMYs), in Greece
Authors: Konstantakopoulou Olympia , Kaitelidou Daphne , Galanis Petros , Siskou Olga , Economou Charalambos
Published: January 2021

Primary Health Care (PHC) is an integral part of both a country’s health system and of the overall social and economic development of the community. In Greece, in an effort to improve the provision of the PHC services on a national level, the Ministry of Health established the first Local Health Units (TOMYs) in December 2017. These new PHC units aimed to contribute to the provision of quality primary care services to citizens, while at the same time favoring the health system by improving the health of the population and helping to reduce health costs. Within this context, it is important for patients/PHC services’ recipients to be able to evaluate their experiences, as accumulated during their visits at these new health PHC structures. The aim of this paper was to evaluate the quality of medical and nursing care in the newly established PHC units (TOMYs) in Greece, using patient experience measures.
Έκθεση έρευνας για το προφίλ των κοινωνικών επιχειρήσεων στο ελληνικό τµήµα της διασυνοριακής περιοχής Ελλάδας - Βουλγαρίας
Authors: Κώστας Αντώνιος
Published: January 2021

no abstract
The fiscal effect of the recalculation of main old-age pensions stemming from L. 4387/2016
Authors: Symeonidis Georgios
Published: January 2021

L.4387/2016 introduced the recalculation of existent pensions based on a new type of formula and replacement. The difference between the amounts paid to pensioners at that time and the amounts calculated based on the new law, quoted as personal difference, was later legislated to be either cut, if it was positive, or paid in the long run, if it was negative. This coincided with legislation that froze pension indexation for the years up to 2022. Even though the pension indexation freeze is still valid, the pension reductions initially planned for 2019 were avoided. The pension increases, where applicable, were paid as planned, again in 2019. The extensive workload demanded to make the recalculation and the fiscal gap in contributions in the Greek pension system creates space for possible future application. In this view, this paper focuses on the fiscal effect of the reduction of the personal difference in combination with the freeze in pension indexation.
Κωνσταντίνος Ρόντος, Νικόλαος Ναγόπουλος, Νικόλαος Πανάγος Το προσφυγικό-μεταναστευτικό ζήτημα στη Λέσβο και η τοπική κοινωνία: Στάσεις και συμπεριφορές Εκδόσεις ΤΖΙΟΛΑ, Αθήνα, 2017
Authors: Συρμαλή Μαρία- Ελένη
Published: January 2021

no abstract
Spyros Sakellaropoulos The Cypriot Social Formation (1191–2004): From the Establishment to the Partition, Athens: Topos, 2017
Authors: Christofis Nicos
Published: January 2021

no abstract
Minimally invasive (flapless) crown lengthening by erbium:YAG laser in aesthetic zone
Authors: Capodiferro Saverio , Tempesta Angela , Limongelli Luisa , Barile Giuseppe , Di Venere Daniela , Corsalini Massimo
Published: January 2021

Crown lengthening is a surgical procedure aimed at exposure of a larger tooth surface by gingivectomy alone or with cortical bone remodelling for aesthetic purposes in the anterior zone of the maxilla or for reconstruction of teeth affected by subgingival caries. We report two cases of crown lengthening in the anterior maxilla for aesthetic purposes by gingival and bone re-contouring performed by erbium-doped yttrium aluminium garnet (erbium:YAG) laser. As highlighted in this report, the erbium:YAG laser-assisted crown lengthening is less invasive and also leads to faster clinical outcomes in contrast to the conventional surgical technique by scalpel incision, flap elevation and osteoplastic.
Uma Análise Crítica Sobre Amor e Cuidado em Binswanger e Heidegger
Authors: Feijoo Ana Maria Lopez Calvo de , Accetta Marcello Furst de Freitas , Protasio Myriam Moreira , Costa Paulo Victor Rodrigues da , Silva Victor Portavales
Published: January 2021

O presente artigo tem como objetivo refletir, por meio de um estudo teórico, acerca do existencial cuidado (Sorge) no pensamento de Martin Heidegger e amor (Liebe) em Ludwig Binswanger. O texto retoma os principais aspectos da forma como ambos compreendem a noção de cuidado e amor, desdobrando criticamente o impasse gerado a partir daí. Demonstra-se que o cerne da querela se dá no modo como Binswanger compreende e interpreta o ser-no-mundo (In-der-Welt-sein) heideggeriano, ligando-o à noção de ser-para-além-do-mundo (Über-die-Welt-hinaus-sein). O psiquiatra suíço procede desse modo na medida em que julga ter identificado um limite e uma carência do elemento eternidade no modo como Heidegger desenvolve sua ontologia fundamental. Com tal apontamento, Binswanger elege a tonalidade do amor como fundamento de toda relação, que faz dessa experiência de infinito sua forma de ser. No bojo de tal apontamento se encontra o desenvolvimento da Daseinsanálise como o desdobramento – a princípio psiquiátrico – de uma relação clínica pautada pelo amor como meio do acesso fundamental ao outro e como elemento que promove a cura. O artigo conclui que tal indicação binswangeriana recai sutilmente em elementos instrumentais e produtivistas, uma vez que Binswanger reproduz elementos da técnica justamente lá onde tais elementos deveriam permanecer inoperantes.
A Mediação Fenomenológica-Hermenêutica em Paul Ricoeur: Uma Proposta ao Psicoterapeuta Frente o Imediatismo da Consciência
Authors: Silva Jefferson Da
Published: January 2021

O artigo tem como objeto apresentar a perspectiva fenomenológica-hermenêutica de Paul Ricoeur como um caminho para o psicoterapeuta fenomenológico frente ao risco do imediatismo da consciência que se julga autoevidente. O processo metodológico adotado baseia-se em pesquisa bibliográfica, com o objetivo de compreender os conceitos de fenomenologia, hermenêutica e aplicá-los à psicoterapia. O filósofo Paul Ricoeur partindo da crítica ao idealismo husserliano afirma que a consciência só pode se compreender para além de si mesma, perpassando pelas mediações. É pela crítica ao idealismo que se aproximará a perspectiva ricoeuriana do psicoterapeuta fenomenológico. Para ele, a hermenêutica é uma tarefa que exige esforço e desejo de ser, perpassando as obras da cultura, e, assim, possibilitando que a existência faça sentido. É por esse caminho, partindo da perspectiva ricoeuriana, que o psicoterapeuta também é convidado a sair de si mesmo e mergulhar por entre as obras da cultura, para poder compreender e ajudar seu cliente. É por via da mediação com tais obras que é possível oferecer ao psicoterapeuta uma visão mais ampla do seu cliente.
Delivering a school-based immunisation programme and maintaining uptake in the context of the COVID-19 pandemic
Authors: Henty Neil
Published: January 2021

While school-based immunisation programmes generally show good uptake rates, the current COVID-19 pandemic has an impact on their delivery. Neil Henty looks at some of the new challenges faced by health professionals delivering these programmes and how some teams have adapted to overcome them.
Crohn's and colitis: New research offers insights into caring for young people
Authors: Qualter Pamela , Carter Bernie
Published: January 2021

The unpredictable nature of inflammatory bowel disease symptoms and stigma can affect young people's ability to form close friendships and affect their social interactions. New research shows the importance of addressing the mental health and wellbeing of young people with Crohn's disease and colitis.
#SayTheWords: Supporting grieving children
Authors: Penny Alison
Published: January 2021

Children's Grief Awareness Week is especially poignant this year given the ongoing impact of the Covid-19 pandemic
Partial Glossectomy as an adjunct to Orthodontic Treatment of Anterior Open Bite Associated with Macroglossia: A Case Report
Authors: Mittal Tarun K , Achal Kulraj , Taylor James T , Kindelan Jay D
Published: January 2021

Orthodontic treatment of an anterior open bite is one of the most challenging malocclusions to treat, especially with respect to post-treatment stability. Complete diagnosis and targeted treatment is required for successful post treatment stability. In instances where macroglossia is the primary aetiology, partial glossectomy will greatly improve post treatment stability. The following case report describes a patient with severe anterior open bite and bimaxillary protrusion secondary to macroglossia. Treatment was successfully performed with partial glossectomy and straight wire orthodontics. Post-treatment relapse was minimal.

CPD/Clinical Relevance: This article describes a review of the aetiology of anterior open bite and documents one possible treatment option, when the main aetiology of the malocclusion is of soft tissue origin
Traumatic Iatrogenic Complications Associated with Orthodontic Treatments: A Systematic Review
Authors: Manouchehri Shaadi , Haddad Ali Rezaei , Shakib Kaveh
Published: January 2021

Adverse outcomes of orthodontic treatment have been reported in the literature, yet there are currently no systematic reviews on the subject. We undertook a comprehensive review of the literature using the Medline and Ovid electronic databases, complemented by manual searching. The occurrence of unforeseen iatrogenic traumatic complications due to orthodontic treatment was used as the primary outcome. Traumatic iatrogenic complications associated with orthodontic treatment are infrequent. The most common complication reported is ingestion of orthodontic components. In the majority of the cases, management of the offending agent resulted in complete recovery without further complaint. The exception to this is ocular injury sustained as a result of improper use of or accidental injuries related to orthodontic headgear. These injuries are potentially devastating for the patient.

CPD/Clinical Relevance: Orthodontic treatment is carried out routinely and it is important to be aware of the unexpected complications that can occur during treatment and their consequences.
Endogenous Tongue Thrust – Myth?
Authors: Lam Yung , Shelton Andrew , Sandler Jonathan
Published: January 2021

Anterior open bite cases are very challenging to manage due to the high relapse potential associated with this feature of malocclusion. It is helpful if the aetiology is established before embarking on treatment to ensure that the appropriate treatment modalities are carried out. Determining whether the aetiology of an anterior open bite is caused by an ‘endogenous tongue thrust’ is extremely difficult. In particular, differentiating between an adaptive and endogenous tongue thrust can be extremely challenging. The case study presented explores the clinical considerations when diagnosing and treating anterior open bites.

CPD/Clinical Relevance: This report raises the question: is it possible to diagnose an endogenous tongue thrust?
Cementless knee arthroplasty: a review of recent performance
Authors: Asokan Ajay , Plastow Ricci , Kayani Babar , Radhakrishnan Ganan T. , Magan Ahmed A. , Haddad Fares S.
Published: January 2021

Cementless knee arthroplasty has seen a recent resurgence in popularity due to conceptual advantages, including improved osseointegration providing biological fixation, increased surgical efficiency, and reduced systemic complications associated with cement impaction and wear from cement debris. Increasingly younger and higher demand patients are requiring knee arthroplasty, and as such, there is optimism cementless fixation may improve implant survivorship and functional outcomes.

Compared to cemented implants, the National Joint Registry (NJR) currently reports higher revision rates in cementless total knee arthroplasty (TKA), but lower in unicompartmental knee arthroplasty (UKA). However, recent studies are beginning to show excellent outcomes with cementless implants, particularly with UKA which has shown superior performance to cemented varieties. Cementless TKA has yet to show long-term benefit, and currently performs equivalently to cemented in short- to medium-term cohort studies. However, with novel concepts including 3D-printed coatings, robotic-assisted surgery, radiostereometric analysis, and kinematic or functional knee alignment principles, it is hoped they may help improve the outcomes of cementless TKA in the long-term. In addition, though cementless implant costs remain higher due to novel implant coatings, it is speculated cost-effectiveness can be achieved through greater surgical efficiency and potential reduction in revision costs. There is paucity of level one data on long-term outcomes between fixation methods and the cost-effectiveness of modern cementless knee arthroplasty.

This review explores recent literature on cementless knee arthroplasty, with regards to clinical outcomes, implant survivorship, complications, and cost-effectiveness; providing a concise update to assist clinicians on implant choice.

Cite this article: Bone Jt Open 2021;2(1):48–57.
Analysis of sensitivity in quantitative micro-elastography
Authors: Li Jiayue , Hepburn Matt S. , Chin Lixin , Mowla Alireza , Kennedy Brendan F.
Published: January 2021

Quantitative micro-elastography (QME), a variant of compression optical coherence elastography (OCE), is a technique to image tissue elasticity on the microscale. QME has been proposed for a range of applications, most notably tumor margin assessment in breast-conserving surgery. However, QME sensitivity, a key imaging metric, has yet to be systematically analyzed. Consequently, it is difficult to optimize imaging performance and to assess the potential of QME in new application areas. To address this, we present a framework for analyzing sensitivity that incorporates the three main steps in QME image formation: mechanical deformation, its detection using optical coherence tomography (OCT), and signal processing used to estimate elasticity. Firstly, we present an analytical model of QME sensitivity, validated by experimental data, and demonstrate that sub-kPa elasticity sensitivity can be achieved in QME. Using silicone phantoms, we demonstrate that sensitivity is dependent on friction, OCT focus depth, and averaging methods in signal processing. For the first time, we show that whilst lubrication of layer improves accuracy by reducing surface friction, it reduces sensitivity due to the time-dependent effect of lubricant exudation from the layer boundaries resulting in increased friction. Furthermore, we demonstrate how signal processing in QME provides a trade-off between sensitivity and resolution that can be used to optimize imaging performance. We believe that our framework to analyze sensitivity can help to sustain the development of QME and, also, that it can be readily adapted to other OCE techniques.
Burden of disease and productivity impact of Streptococcus suis infection in Thailand
Authors: Rayanakorn Ajaree , Ademi Zanfina , Liew Danny , Lee Learn-Han
Published: January 2021

Background

Streptoccocus suis (S.suis)infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden ofS.suisinfection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease.

Methods

A decision-analytic Markov model was developed to simulate the impact ofS.suisinfection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected withS.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impactof S.suisinfection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model.

Key results

This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person.

Conclusions

S.suisinfection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.
Integrating human behavior and snake ecology with agent-based models to predict snakebite in high risk landscapes
Authors: Goldstein Eyal , Erinjery Joseph J. , Martin Gerardo , Kasturiratne Anuradhani , Ediriweera Dileepa Senajith , de Silva Hithanadura Janaka , Diggle Peter , Lalloo David Griffith , Murray Kris A. , Iwamura Takuya
Published: January 2021

Snakebite causes more than 1.8 million envenoming cases annually and is a major cause of death in the tropics especially for poor farmers. While both social and ecological factors influence the chance encounter between snakes and people, the spatio-temporal processes underlying snakebites remain poorly explored. Previous research has focused on statistical correlates between snakebites and ecological, sociological, or environmental factors, but the human and snake behavioral patterns that drive the spatio-temporal process have not yet been integrated into a single model. Here we use a bottom-up simulation approach using agent-based modelling (ABM) parameterized with datasets from Sri Lanka, a snakebite hotspot, to characterise the mechanisms of snakebite and identify risk factors. Spatio-temporal dynamics of snakebite risks are examined through the model incorporating six snake species and three farmer types (rice, tea, and rubber). We find that snakebites are mainly climatically driven, but the risks also depend on farmer types due to working schedules as well as species present in landscapes. Snake species are differentiated by both distribution and by habitat preference, and farmers are differentiated by working patterns that are climatically driven, and the combination of these factors leads to unique encounter rates for different landcover types as well as locations. Validation using epidemiological studies demonstrated that our model can explain observed patterns, including temporal patterns of snakebite incidence, and relative contribution of bites by each snake species. Our predictions can be used to generate hypotheses and inform future studies and decision makers. Additionally, our model is transferable to other locations with high snakebite burden as well.
Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study
Authors: Nacher Mathieu , Valdes Audrey , Adenis Antoine , Blaizot Romain , Abboud Philippe , Demar Magalie , Djossou Félix , Epelboin Loïc , Misslin Caroline , Ntab Balthazar , Louvel Dominique , Drak Alsibai Kinan , Couppié Pierre
Published: January 2021

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement.

Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis.

Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01).

Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.
Surgical debulking of podoconiosis nodules and its impact on quality of life in Ethiopia
Authors: Enbiale Wendemagegn , Verdonck Kristien , Gebeyehu Melesse , van Griensven Johan , de Vries Henry J. C.
Published: January 2021

Background

In Ethiopia, severe lymphedema and acute dermato-lymphangio-adenitis (ADLA) of the legs as a consequence of podoconiosis affects approximately 1.5 million people. In some this condition may lead to woody-hard fibrotic nodules, which are resistant to conventional treatment. We present a series of patients who underwent surgical nodulectomy in a resource-limited setting and their outcome.

Methods

In two teaching hospitals, we offered surgical nodulectomies under local anaesthesia to patients with persisting significant fibrotic nodules due to podoconiosis. Excisions after nodulectomy were left to heal by secondary intention with compression bandaging. As outcome, we recorded time to re-epithelialization after surgery, change in number of ADLA episodes, change in quality of life measured with the Dermatology Quality of Live Index (DQLI) questionnaire, and recurrence rate one year after surgery.

Results

37nodulectomy operations were performed on 21 patients. All wounds re-reepithelialised within 21 days (range 17–42). 4 patients developed clinically relevant wound infections. The DLQI values were significantly better six months after surgery than before surgery (P<0.0001). Also the number of ADLA episodes per three months was significantly lower six months after surgery than before surgery (P<0.0001).

Conclusion

Nodulectomy in podoconiosis patients leads to a significant improvement in the quality of life with no serious complications, and we recommend this to be a standard procedure in resource-poor settings.
Transmission dynamics and control of COVID-19 in Chile, March-October, 2020
Authors: Tariq Amna , Undurraga Eduardo A. , Laborde Carla Castillo , Vogt-Geisse Katia , Luo Ruiyan , Rothenberg Richard , Chowell Gerardo
Published: January 2021

Since the detection of the first case of COVID-19 in Chile on March 3rd, 2020, a total of 513,188 cases, including ~14,302 deaths have been reported in Chile as of November 2nd, 2020. Here, we estimate the reproduction number throughout the epidemic in Chile and study the effectiveness of control interventions especially the effectiveness of lockdowns by conducting short-term forecasts based on the early transmission dynamics of COVID-19. Chile’s incidence curve displays early sub-exponential growth dynamics with the deceleration of growth parameter,p, estimated at 0.8 (95% CI: 0.7, 0.8) and the reproduction number,R, estimated at 1.8 (95% CI: 1.6, 1.9). Our findings indicate that the control measures at the start of the epidemic significantly slowed down the spread of the virus. However, the relaxation of restrictions and spread of the virus in low-income neighborhoods in May led to a new surge of infections, followed by the reimposition of lockdowns in Greater Santiago and other municipalities. These measures have decelerated the virus spread withRestimated at ~0.96 (95% CI: 0.95, 0.98) as of November 2nd, 2020. The early sub-exponential growth trend (p~0.8) of the COVID-19 epidemic transformed into a linear growth trend (p~0.5) as of July 7th, 2020, after the reimposition of lockdowns. While the broad scale social distancing interventions have slowed the virus spread, the number of new COVID-19 cases continue to accrue, underscoring the need for persistent social distancing and active case detection and isolation efforts to maintain the epidemic under control.
Individual adherence to mass drug administration in neglected tropical disease control: A probability model conditional on past behaviour
Authors: Hardwick Robert J. , Truscott James E. , Oswald William E. , Werkman Marleen , Halliday Katherine E. , Pullan Rachel L. , Anderson Roy M.
Published: January 2021

We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA)—which we refer to as ‘adherence’ and ‘non-adherence’. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs).
Effect of cutting depth during sugarcane (Saccharum spp. hybrid) harvest on root characteristics and yield
Authors: Yang Shao-lin , Zhang Yue-bin , Deng Jun , Li Ru-dan , Fan Xian , Dao Jing-mei , Quan Yi-ji , Hussain Bukhari Syed Asad
Published: January 2021

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21–59% and 41–127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0–2.0mm, and root length and the number of root tips in roots with a diameter of 0–0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle.
Outcome of iron reduction therapy in ex-thalassemics
Authors: Aboobacker Fouzia N. , Dixit Gaurav , Lakshmi Kavitha M. , Korula Anu , Abraham Aby , George Biju , Mathews Vikram , Srivastava Alok
Published: January 2021

There is limited data on iron reduction therapy (IRT) after successful allogeneic haematopoietic stem cell transplantation (aHSCT) for patients with thalassemia major (TM). We present the long term outcome of IRT in 149 patients with TM who underwent aHSCT during January, 2001-December, 2012. The median age was 7 years (range:1–18) and 92 (61.7%) belonged to Pesaro class 3 with a median ferritin at aHSCT of 2480ng/ml (range:866–8921). IRT was reinitiated post-aHSCT at a median of 14 months (range:5–53) post aHSCT with phlebotomy alone in 10 (6.7%) patients or iron chelation alone in 60 (40.3%) patients while 79 (53%) were treated with the combination. Reduction in serum ferritin/month [absolute quantity (ng/ml/month) was as follows: 87 (range:33–195), 130 (range:17–1012) and 147 (range:27.7–1427) in the phlebotomy, chelation and combination therapy groups, respectively (p = 0.038). With a median follow up of 80 months (range:37–182), target ferritin level of <300ng/ml was achieved in 59(40%) while a level <500ng/ml was achieved in 88 patients (59%) in a median duration of 41 months of IRT (range: 3–136). Patients in class III risk category and higher starting serum ferritin levels (>2500ng/ml) were associated with delayed responses to IRT. Our data shows that IRT may be needed for very long periods in ex-thalassaemics to achieve target ferritin levels and should therefore be carefully planned and initiated as soon as possible after aHSCT. A combination of phlebotomy and iron chelators is more effective in reducing iron overload.
Adélie penguins foraging consistency and site fidelity are conditioned by breeding status and environmental conditions
Authors: Michelot Candice , Kato Akiko , Raclot Thierry , Ropert-Coudert Yan
Published: January 2021

There is a growing interest in studying consistency and site fidelity of individuals to assess, respectively, how individual behaviour shapes the population response to environmental changes, and to highlight the critical habitats needed by species. In Antarctica, the foraging activity of central place foragers like Adélie penguins (Pygoscelis adeliae) is constrained by the sea-ice cover during the breeding season. We estimated the population-level repeatability in foraging trip parameters and sea-ice conditions encountered by birds across successive trips over several years, and we examined their foraging site fidelity linked to sea-ice concentrations throughout the chick-rearing season. Penguins’ foraging activity was repeatable despite varying annual sea-ice conditions. Birds’ site fidelity is constrained by both sea-ice conditions around the colony that limit movements and resources availability, and also behavioural repeatability of individuals driven by phenological constraints. Adélie penguins favoured sea-ice concentrations between 20–30%, as these facilitate access to open water while opening multiple patches for exploration in restricted areas in case of prey depletion. When the sea-ice concentration became greater than 30%, foraging site fidelity decreased and showed higher variability, while it increased again after 60%. Between two trips, the foraging site fidelity remained high when sea-ice concentration changed by ± 10% but showed greater variability when sea-ice concentrations differed on a larger range. In summary, Adélie penguins specialize their foraging behaviour during chick-rearing according to sea-ice conditions to enhance their reproductive success. The balance between being consistent under favourable environmental conditions vs. being flexible under more challenging conditions may be key to improving foraging efficiency and reproductive success to face fast environmental changes.
Genome-wide association study and pathway analysis identify NTRK2 as a novel candidate gene for litter size in sheep
Authors: Esmaeili-Fard Seyed Mehdi , Gholizadeh Mohsen , Hafezian Seyed Hasan , Abdollahi-Arpanahi Rostam
Published: January 2021

Litter size is one of the most important economic traits in sheep. Identification of gene variants that are associated with the prolificacy rate is an important step in breeding program success and profitability of the farm. So, to identify genetic mechanisms underlying the variation in litter size in Iranian Baluchi sheep, a two-step genome-wide association study (GWAS) was performed. GWAS was conducted using genotype data from 91 Baluchi sheep. Estimated breeding values (EBVs) for litter size calculated for 3848 ewes and then used as the response variable. Besides, a pathway analysis using GO and KEGG databases were applied as a complementary approach. A total of three single nucleotide polymorphisms (SNPs) associated with litter size were identified, one each on OAR2, OAR10, and OAR25. The SNP on OAR2 is located within a novel putative candidate gene, Neurotrophic receptor tyrosine kinase 2. This gene product works as a receptor which is essential for follicular assembly, early follicular growth, and oocyte survival. The SNP on OAR25 is located within RAB4A which is involved in blood vessel formation and proliferation through angiogenesis. The SNP on OAR10 was not associated with any gene in the 1Mb span. Moreover, gene-set analysis using the KEGG database identified several pathways, such as Ovarian steroidogenesis, Steroid hormone biosynthesis, Calcium signaling pathway, and Chemokine signaling. Also, pathway analysis using the GO database revealed several functional terms, such as cellular carbohydrate metabolic, biological adhesion, cell adhesion, cell junction, and cell-cell adherens junction, among others. This is the first study that reports theNTRK2gene affecting litter size in sheep and our study of this gene functions showed that this gene could be a good candidate for further analysis.
Do urban open spaces provide refugia for frogs in urban environments?
Authors: Hutto David , Barrett Kyle
Published: January 2021

Urbanization is among the largest threats to wildlife populations through factors such as fragmentation, isolation, and habitat destruction. Urban open spaces, such as parks and golf courses, have the potential to provide wildlife with suitable habitat within an urbanized matrix. These refugia may be particularly important for amphibians, which represent one of the most endangered and least vagile vertebrate groups on earth. During the spring and summer of 2018, we conducted surveys to determine the presence of anurans at 51 wetland sites within the Piedmont ecoregion of South Carolina. Nearly one-third of these wetlands were located within urban open spaces, one-third in low development areas, and one-third in highly developed areas. Impervious surface and total road length surrounding the wetlands were measured at two scales, a core habitat scale (300 m) and average maximum migration scale (750 m), and we measured several within-wetland habitat variables. Urban Open Space wetlands had levels of surrounding impervious surface similar to High Urbanization wetlands at the larger scale and were intermediate between Low and High Urbanization wetlands at the smaller scale. The total length of road segments occurring within buffers (at both scales) surrounding our study wetlands was higher for Urban Open Space compared to Low and High Urbanization sites. Among the within-wetland variables measured, Low Urbanization sites had higher canopy cover and were more likely to have a terrestrial buffer zone relative to the other categories. Species richness decreased significantly as total road length increased among all wetlands. Wetland category was not a significant driver explaining species richness, but β-diversity was more variable among Urban Open Space wetlands than either Low or High Urbanization wetlands. Urban Open Space wetlands did not appear to increase suitability for anurans relative to High Urbanization wetlands. Urban Open Space wetlands had higher variability in species composition, which was perhaps attributable to the diversity among sites represented in the Urban Open Space category.