bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood–brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans
Authors: Mora Pierre , Hollier Pierre-Louis , Guimbal Sarah , Abelanet Alice , Diop Aïssata , Cornuault Lauriane , Couffinhal Thierry , Horng Sam , Gadeau Alain-Pierre , Renault Marie-Ange , Chapouly Candice
Published: November 2020

Inflammation of the central nervous system (CNS) induces endothelial blood–brain barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only during neuroinflammation but also when BBB integrity is compromised in the resting state. Previous studies found that astrocyte-derived Sonic hedgehog (SHH) stabilizes the BBB during CNS inflammatory disease, while endothelial-derived desert hedgehog (DHH) is expressed at the BBB under resting conditions. Here, we investigated the effects of endothelial Dhh on the integrity of the BBB and Glia Limitans. We first characterized DHH expression within endothelial cells at the BBB, then demonstrated that DHH is down-regulated during experimental autoimmune encephalomyelitis (EAE). Using a mouse model in which endothelial Dhh is inducibly deleted, we found that endothelial Dhh both opens the BBB via the modulation of forkhead box O1 (FoxO1) transcriptional activity and induces a tight junctional barrier at the Glia Limitans. We confirmed the relevance of this glial barrier system in human multiple sclerosis active lesions. These results provide evidence for the novel concept of “chronic neuroinflammatory tolerance” in which BBB opening in the resting state is sufficient to stimulate a protective barrier at the Glia Limitans that limits the severity of subsequent neuroinflammatory disease. In summary, genetic disruption of the BBB generates endothelial signals that drive the formation under resting conditions of a secondary barrier at the Glia Limitans with protective effects against subsequent CNS inflammation. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology.
Rules warp feature encoding in decision-making circuits
Authors: Ebitz R. Becket , Tu Jiaxin Cindy , Hayden Benjamin Y.
Published: November 2020

We have the capacity to follow arbitrary stimulus–response rules, meaning simple policies that guide our behavior. Rule identity is broadly encoded across decision-making circuits, but there are less data on how rules shape the computations that lead to choices. One idea is that rules could simplify these computations. When we follow a rule, there is no need to encode or compute information that is irrelevant to the current rule, which could reduce the metabolic or energetic demands of decision-making. However, it is not clear if the brain can actually take advantage of this computational simplicity. To test this idea, we recorded from neurons in 3 regions linked to decision-making, the orbitofrontal cortex (OFC), ventral striatum (VS), and dorsal striatum (DS), while macaques performed a rule-based decision-making task. Rule-based decisions were identified via modeling rules as the latent causes of decisions. This left us with a set of physically identical choices that maximized reward and information, but could not be explained by simple stimulus–response rules. Contrasting rule-based choices with these residual choices revealed that following rules (1) decreased the energetic cost of decision-making; and (2) expanded rule-relevant coding dimensions and compressed rule-irrelevant ones. Together, these results suggest that we use rules, in part, because they reduce the costs of decision-making through a distributed representational warping in decision-making circuits.
A multi-scale cortical wiring space links cellular architecture and functional dynamics in the human brain
Authors: Paquola Casey , Seidlitz Jakob , Benkarim Oualid , Royer Jessica , Klimes Petr , Bethlehem Richard A. I. , Larivière Sara , Vos de Wael Reinder , Rodríguez-Cruces Raul , Hall Jeffery A. , Frauscher Birgit , Smallwood Jonathan , Bernhardt Boris C.
Published: November 2020

The vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here, we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico–cortical wiring established by postmortem anatomical studies and capitalises on cutting-edge in vivo neuroimaging and machine learning. The new model expands the currently prevailing diffusion magnetic resonance imaging (MRI) tractography approach by incorporation of additional features of cortical microstructure and cortico–cortical proximity. Studying several datasets and different parcellation schemes, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior–posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics based on resting-state functional magnetic resonance imaging (rs-fMRI) and human intracranial electroencephalography (EEG) coherence. Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals.
The role of sensory uncertainty in simple contour integration
Authors: Zhou Yanli , Acerbi Luigi , Ma Wei Ji
Published: November 2020

Perceptual organization is the process of grouping scene elements into whole entities. A classic example is contour integration, in which separate line segments are perceived as continuous contours. Uncertainty in such grouping arises from scene ambiguity and sensory noise. Some classic Gestalt principles of contour integration, and more broadly, of perceptual organization, have been re-framed in terms of Bayesian inference, whereby the observer computes the probability that the whole entity is present. Previous studies that proposed a Bayesian interpretation of perceptual organization, however, have ignored sensory uncertainty, despite the fact that accounting for the current level of perceptual uncertainty is one of the main signatures of Bayesian decision making. Crucially, trial-by-trial manipulation of sensory uncertainty is a key test to whether humans perform near-optimal Bayesian inference in contour integration, as opposed to using some manifestly non-Bayesian heuristic. We distinguish between these hypotheses in a simplified form of contour integration, namely judging whether two line segments separated by an occluder are collinear. We manipulate sensory uncertainty by varying retinal eccentricity. A Bayes-optimal observer would take the level of sensory uncertainty into account—in a very specific way—in deciding whether a measured offset between the line segments is due to non-collinearity or to sensory noise. We find that people deviate slightly but systematically from Bayesian optimality, while still performing “probabilistic computation” in the sense that they take into account sensory uncertainty via a heuristic rule. Our work contributes to an understanding of the role of sensory uncertainty in higher-order perception.
Precise determination of input-output mapping for multimodal gene circuits using data from transient transfection
Authors: Stelzer Christoph , Benenson Yaakov
Published: November 2020

The mapping of molecular inputs to their molecular outputs (input/output, I/O mapping) is an important characteristic of gene circuits, both natural and synthetic. Experimental determination of such mappings for synthetic circuits is best performed using stably integrated genetic constructs. In mammalian cells, stable integration of complex circuits is a time-consuming process that hampers rapid characterization of multiple circuit variants. On the other hand, transient transfection is quick. However, it is an extremely noisy process and it is unclear whether the obtained data have any relevance to the input/output mapping of a circuit obtained in the case of a stable integration. Here we describe a data processing workflow, Peakfinder algorithm for flow cytometry data (PFAFF), that allows extracting precise input/output mapping from single-cell protein expression data gathered by flow cytometry after a transient transfection. The workflow builds on the numerically-proven observation that the multivariate modes of input and output expression of multi-channel flow cytometry datasets, pre-binned by the expression level of an independent transfection reporter gene, harbor cells with circuit gene copy numbers distributions that depend deterministically on the properties of a bin. We validate our method by simulating flow cytometry data for seven multi-node circuit architectures, including a complex bi-modal circuit, under stable integration and transient transfection scenarios. The workflow applied to the simulated transient transfection data results in similar conclusions to those reached with simulated stable integration data. This indicates that the input/output mapping derived from transient transfection data using our method is an excellent approximation of the ground truth. Thus, the method allows to determine input/output mapping of complex gene network using noisy transient transfection data.
Phenotypes to remember: Evolutionary developmental memory capacity and robustness
Authors: Szilágyi András , Szabó Péter , Santos Mauro , Szathmáry Eörs
Published: November 2020

There is increased awareness of the possibility of developmental memories resulting from evolutionary learning. Genetic regulatory and neural networks can be modelled by analogous formalism raising the important question of productive analogies in principles, processes and performance. We investigate the formation and persistence of various developmental memories of past phenotypes asking how the number of remembered past phenotypes scales with network size, to what extent memories stored form by Hebbian-like rules, and how robust these developmental “devo-engrams” are against networks perturbations (graceful degradation). The analogy between neural and genetic regulatory networks is not superficial in that it allows knowledge transfer between fields that used to be developed separately from each other. Known examples of spectacular phenotypic radiations could partly be accounted for in such terms.
Pre-existing resistance in the latent reservoir can compromise VRC01 therapy during chronic HIV-1 infection
Authors: Saha Ananya , Dixit Narendra M.
Published: November 2020

Passive immunization with broadly neutralizing antibodies (bNAbs) of HIV-1 appears a promising strategy for eliciting long-term HIV-1 remission. When administered concomitantly with the cessation of antiretroviral therapy (ART) to patients with established viremic control, bNAb therapy is expected to prolong remission. Surprisingly, in clinical trials on chronic HIV-1 patients, the bNAb VRC01 failed to prolong remission substantially. Identifying the cause of this failure is important for improving VRC01-based therapies and unraveling potential vulnerabilities of other bNAbs. In the trials, viremia resurged rapidly in most patients despite suppressive VRC01 concentrations in circulation, suggesting that VRC01 resistance was the likely cause of failure. ART swiftly halts viral replication, precluding the development of resistance during ART. If resistance were to emerge post ART, virological breakthrough would have taken longer than without VRC01 therapy. We hypothesized therefore that VRC01-resistant strains must have been formed before ART initiation, survived ART in latently infected cells, and been activated during VRC01 therapy, causing treatment failure. Current assays preclude testing this hypothesis experimentally. We developed a mathematical model based on the hypothesis and challenged it with available clinical data. The model integrated within-host HIV-1 evolution, stochastic latency reactivation, and viral dynamics with multiple-dose VRC01 pharmacokinetics. The model predicted that single but not higher VRC01-resistant mutants would pre-exist in the latent reservoir. We constructed a virtual patient population that parsimoniously recapitulated inter-patient variations. Model predictions with this population quantitatively captured data of VRC01 failure from clinical trials, presenting strong evidence supporting the hypothesis. We attributed VRC01 failure to single-mutant VRC01-resistant proviruses in the latent reservoir triggering viral recrudescence, particularly when VRC01 was at trough levels. Pre-existing resistant proviruses in the latent reservoir may similarly compromise other bNAbs. Our study provides a framework for designing bNAb-based therapeutic protocols that would avert such failure and maximize HIV-1 remission.
Modelling pathogen spread in a healthcare network: Indirect patient movements
Authors: Piotrowska Monika J. , Sakowski Konrad , Karch André , Tahir Hannan , Horn Johannes , Kretzschmar Mirjam E. , Mikolajczyk Rafael T.
Published: November 2020

Inter-hospital patient transfers (direct transfers) between healthcare facilities have been shown to contribute to the spread of pathogens in a healthcare network. However, the impact of indirect transfers (patients re-admitted from the community to the same or different hospital) is not well studied. This work aims to study the contribution of indirect transfers to the spread of pathogens in a healthcare network. To address this aim, a hybrid network–deterministic model to simulate the spread of multiresistant pathogens in a healthcare system was developed for the region of Lower Saxony (Germany). The model accounts for both, direct and indirect transfers of patients. Intra-hospital pathogen transmission is governed by a SIS model expressed by a system of ordinary differential equations. Our results show that the proposed model reproduces the basic properties of healthcare-associated pathogen spread. They also show the importance of indirect transfers: restricting the pathogen spread to direct transfers only leads to 4.2% system wide prevalence. However, adding indirect transfers leads to an increase in the overall prevalence by a factor of 4 (18%). In addition, we demonstrated that the final prevalence in the individual healthcare facilities depends on average length of stay in a way described by a non-linear concave function. Moreover, we demonstrate that the network parameters of the model may be derived from administrative admission/discharge records. In particular, they are sufficient to obtain inter-hospital transfer probabilities, and to express the patients’ transfers as a Markov process. Using the proposed model, we show that indirect transfers of patients are equally or even more important as direct transfers for the spread of pathogens in a healthcare network.
Mosquito genomes are frequently invaded by transposable elements through horizontal transfer
Authors: Melo Elverson Soares de , Wallau Gabriel Luz
Published: November 2020

Transposable elements (TEs) are mobile genetic elements that parasitize basically all eukaryotic species genomes. Due to their complexity, an in-depth TE characterization is only available for a handful of model organisms. In the present study, we performed ade novoand homology-based characterization of TEs in the genomes of 24 mosquito species and investigated their mode of inheritance. More than 40% of the genome ofAedes aegypti,Aedes albopictus, andCulex quinquefasciatusis composed of TEs, while it varied substantially amongAnophelesspecies (0.13%–19.55%). Class I TEs are the most abundant among mosquitoes and at least 24 TE superfamilies were found. Interestingly, TEs have been extensively exchanged by horizontal transfer (172 TE families of 16 different superfamilies) among mosquitoes in the last 30 million years. Horizontally transferred TEs represents around 7% of the genome inAedesspecies and a small fraction inAnophelesgenomes. Most of these horizontally transferred TEs are from the three ubiquitous LTR superfamilies: Gypsy, Bel-Pao and Copia. Searching more than 32,000 genomes, we also uncovered transfers between mosquitoes and two different Phyla—Cnidaria and Nematoda—and two subphyla—Chelicerata and Crustacea, identifying a vector, the wormWuchereria bancrofti, that enabled the horizontal spread of a Tc1-mariner element among variousAnophelesspecies. These data also allowed us to reconstruct the horizontal transfer network of this TE involving more than 40 species. In summary, our results suggest that TEs are frequently exchanged by horizontal transfers among mosquitoes, influencing mosquito's genome size and variability.
Involvement of glycogen metabolism in circadian control of UV resistance in cyanobacteria
Authors: Kawasaki Koji , Iwasaki Hideo
Published: November 2020

Most organisms harbor circadian clocks as endogenous timing systems in order to adapt to daily environmental changes, such as exposure to ultraviolet (UV) light. It has been hypothesized that the circadian clock evolved to prevent UV-sensitive activities, such as DNA replication and cell division, during the daytime. Indeed, circadian control of UV resistance has been reported in several eukaryotic organisms, from algae to higher organisms, although the underlying mechanisms remain unknown. Here, we demonstrate that the unicellular cyanobacterium Synechococcus elongatus PCC 7942 exhibits a circadian rhythm in resistance to UV-C and UV-B light, which is higher during subjective dawn and lower during subjective dusk. Nullification of the clock gene cluster kaiABC or the DNA-photolyase phr abolished rhythmicity with constitutively lower resistance to UV-C light, and amino acid substitutions of KaiC altered the period lengths of the UV-C resistance rhythm. In order to elucidate the molecular mechanism underlying the circadian regulation of UV-C resistance, transposon insertion mutants that alter UV-C resistance were isolated. Mutations to the master circadian output mediator genes sasA and rpaA and the glycogen degradation enzyme gene glgP abolished circadian rhythms of UV-C resistance with constitutively high UV-C resistance. Combining these results with further experiments using ATP synthesis inhibitor and strains with modified metabolic pathways, we showed that UV-C resistance is weakened by directing more metabolic flux from the glycogen degradation to catabolic pathway such as oxidative pentose phosphate pathway and glycolysis. We suggest glycogen-related metabolism in the dark affects circadian control in UV sensitivity, while the light masks this effect through the photolyase function.
The economic burden of dengue fever in the Kingdom of Saudi Arabia
Authors: Akbar Naeema A. , Assiri Abdullah M. , Shabouni Omima I. , Alwafi Osama M. , Al-Raddadi Rajaa , H. Alzahrani Mohamad , Azhar Esam I. , Amir Ashraf , Aljiffri Abdullah M. , Althaqafi Abdulhakeem O.
Published: November 2020

Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013–2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity.
An elimination method for isolated meshes in a road network considering stroke edge feature
Authors: Li Chengming , Wu Wei , Wu Pengda , Yin Jie , Guo Peipei
Published: November 2020

The road network is the skeletal element of topographic maps at different scales. In general, urban roads are connected by road segments, thus forming a series of road meshes. Mesh elimination is a key step in evaluating the importance of roads during the road network data management and a prerequisite to the implementation of continuous multiscale spatial representation of road networks. The existing mesh-based method is an advanced road elimination method whereby meshes with the largest density are sequentially selected and road segments with the least importance in each mesh are eliminated. However, the road connectivity and integrity may be destroyed in specific areas by this method because some eliminated road segments could be located in the middle of road strokes. Therefore, this paper proposed an elimination method for isolated meshes in a road network considering stroke edge feature. First, small meshes were identified by using mesh density thresholds, which can be obtained by the sample data statistical algorithm. Thereafter, the small meshes related to the edge segments of road strokes were taken out and defined as stroke edge meshes, and the remaining small meshes were defined as stroke non-edge meshes. Second, by computing the mesh density of all stroke edge meshes, the mesh with the largest density was selected as the starting mesh, and the least important edge segment in the mesh was eliminated. The difference between the existing mesh-based method and the proposed method is that the starting mesh is a stroke edge mesh, not any given small mesh, and the eliminated segment is just only one of edge segments of strokes not chosen from among all segments. Third, mesh elimination was implemented by iteratively processing the stroke edge meshes with the largest mesh density until all of them were eliminated and their mesh density exceeded the threshold. The stroke non-edge meshes were directly preserved. Finally, a 1:10,000 topographic road map of an area in Jiangsu Province of China was used for validation. The experimental results show that for all stroke non-edge meshes and 23% of the stroke edge meshes, compared to the mesh-based method, the road stroke connectivity and integrity of road strokes were better preserved by the proposed method, and the remaining 77% of the elimination results for the stroke edge meshes were the same under the two methods.
Feasibility of using surgical implantation methods for acoustically tagging alewife (Alosa pseudoharengus) with V5 acoustic transmitters
Authors: Tsitrin Elizabetha , McLean Montana F. , Gibson A. Jamie F. , Hardie David C. , Stokesbury Michael J. W.
Published: November 2020

Anadromous alewives (Alosa pseudoharengus) are abundant in the Canadian Maritimes, where they support lucrative commercial fisheries. Little is known about their coastal movement, and their potential to interact with anthropogenic structures. Acoustic telemetry can provide detailed information on the spatiotemporal distribution and survival of fishes in coastal areas, using information transmitted from tagged fishes and recorded by moored receivers. However, few acoustic telemetry studies have been performed on clupeids as they are extremely sensitive to handling, and are often compromised by surgical tag implantation. This research assesses the feasibility of a surgical tagging protocol using novel High Residency acoustic tags in alewives, and establishes a baseline of short-term tagging effects. Alewives from the Gaspereau River population were tagged between 2018 (n = 29) and 2019 (n = 96) with non-transmitting models of Vemco/Innovasea V5 HR tags. Tagging effects were evaluated based on recovery rate, reflex impairment, and necropsy-based health assessments. Alewives responded well to tagging, with low mortality (3%) and no observed instances of tag shedding 72 hours post-surgery. The use of sutures to close the incision site had no effect on recovery times. Water temperature and spawning condition had the greatest effect on the behavioural response of fish to tagging. Our findings suggest that, with proper handling and smaller acoustic tags, telemetry studies on alewives are feasible.
Computer-based inhibitory control training in children with Attention-Deficit/Hyperactivity Disorder (ADHD): Evidence for behavioral and neural impact
Authors: Meyer Kristin N. , Santillana Rosario , Miller Brian , Clapp Wes , Way Marcus , Bridgman-Goines Katrina , Sheridan Margaret A.
Published: November 2020

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychological disorder of childhood. Medication and cognitive behavioral therapy are effective treatments for many children; however, adherence to medication and therapy regimens is low. Thus, identifying effective adjunct treatments is imperative. Previous studies exploring computerized training programs as supplementary treatments have targeted working memory or attention. However, many lines of research suggest inhibitory control (IC) plays a central role in ADHD pathophysiology, which makes IC a potential intervention target. In this randomized control trial (NCT03363568), we target IC using a modified stop-signal task (SST) training designed by NeuroScouting, LLC in 40 children with ADHD, aged 8 to 11 years. Children were randomly assigned to adaptive treatment (n = 20) or non-adaptive control (n = 20) with identical stimuli and task goals. Children trained at home for at least 5 days a week (about 15m/day) for 4-weeks. Relative to the control group, the treatment group showed decreased relative theta power in resting EEG and trending improvements in parent ratings of attention (i.e. decreases in inattentive behaviors). Both groups showed improved SST performance. There was not evidence for treatment effects on hyperactivity or teacher ratings of symptoms. Results suggest training IC alone has potential to positively impact symptoms of ADHD and provide evidence for neural underpinnings of this impact (change in theta power; change in N200 latency). This shows promising initial results for the use of computerized training of IC in children with ADHD as a potential adjunct treatment option for children with ADHD.
Genetic diversity and population structure in the endangered tree Hopea hainanensis (Dipterocarpaceae) on Hainan Island, China
Authors: Wang Chen , Ma Xiang , Ren Mingxun , Tang Liang
Published: November 2020

Hopea hainanensisMerrill & Chun (Dipterocarpaceae) is an endangered tree species restricted to Hainan Island, China and a small part of Northern Vietnam. On Hainan Island, it is an important indicator species for tropical forests. However, because of its highly valued timber,H.hainanensishas suffered from overexploitation, leading to a sharp population decline. To facilitate the conservation of this species, genetic diversity and population structure were assessed using 12 SSR markers for 10 populations sampled across Hainan Island. Compared to non-threatenedHopeaspecies,H.hainanensisexhibited reduced overall genetic diversity and increased population differentiation (AMOVA:FST= 0.23). Bayesian model-based clustering and principal coordinate analysis consistently assignedH.hainanensisindividuals into three genetic groups, which were found to be widespread and overlapping geographically. A Mantel test found no correlation between genetic and geographical distances (r= 0.040,p= 0.418). The observed genetic structure suggests that long-distance gene flow occurred amongH.hainanensispopulations prior to habitat fragmentation. A recent population bottleneck was revealed, which may cause rapid loss of genetic diversity and increased differentiation across populations. Based on these findings, appropriate strategies for the long-term conservation of the endangered speciesH.hainanensisare proposed.
Development and validation of medication assessment tools to evaluate prescribing adherence to evidence-based guidelines for secondary prevention of coronary heart disease in post-acute coronary syndromes patients in Kuwait
Authors: Al-Taweel Dalal , Awad Abdelmoneim
Published: November 2020

Cardiovascular diseases are estimated to cause 46% of all mortalities in Kuwait. The aim of evidence-based clinical practice has led to an increased interest in the design of medication assessment tools (MATs) to identify deviations from evidence-based practice, and eventually provide the basis of consistent standardized prescribing. This study was designed to develop and validate MATs using quality standards extracted from international guidelines to evaluate prescribing practices in secondary prevention of coronary heart disease in patients with post-acute coronary syndrome (STEMI or NSTEACS]. International guidelines were reviewed to develop two MATs (MATSTEMI and MATNSTEACS). Face and content validity of the developed tools was performed with three MAT experts and thirteen cardiologists. Two quantitative approaches were used to determine content validity: (i) Content Validity Ratio (CVR) and the average of CVR values; and (ii) Content validity index at item level (I-CVI) and scale-level of the tool (S-CVI/Ave) with the average approach. Criteria with a CVR<0.54 and I-CVI <70% were eliminated. Ultimately, feasibility testing of both MATs was performed on 66 patients’ records as a pilot study. The initial developed MATSTEMI and MATNSTEACS consisted of eighteen and twelve medication-related criteria, respectively. Face validity resulted in dividing each MAT into five dimensions. In the MATSTEMI, three criteria had CVR values < 0.54 and I-CVIs < 70%. Two criteria were eliminated and one was retained. This resulted in sixteen criteria with average CVR 0.85 and S-CVI/Ave 92.3%. In the MATNSTEACS, one criterion was eliminated. This resulted in eleven criteria with average CVR 0.93 and S-CVI/Ave 96.5%. The overall adherence scores to the MATSTEMI and MATNSTEACS were 64.1% (95% CI: 57.8–69.9%) and 62.0% (95% CI: 53.4–69.9%), respectively. It was judged as intermediate adherence for both MATs. MATSTEMI and MATNSTEACS were developed and validated to be utilized for optimizing medication therapy management and improving therapeutic interventions.
Growth change in Polish women: Reduction of the secular trends?
Authors: Łopuszańska-Dawid Monika , Szklarska Alicja
Published: November 2020

The aim of the study was to analyse changes in the average height of adult Polish women born in 1931–2001 in the aspect of dynamically changing economic and socio-economic conditions of the living environment. An ethnically homogeneous group of 6,028 adult women from large Polish cities, born in 1931–2001, living between 1931 and 2020, were examined using the same research methods and research equipment. All women were divided into eight birth cohorts. The Kruskal-Wallis test and multiple regression analyses were used. Root Mean Square Standardized Effect (RMSSE), critical value of the test, and test power were calculated. The average height of women born during 70 years of the study increased by 9.63 cm, from 158.22 cm (SD = 5.57 cm) to 167.85 cm (SD = 6.91 cm) (H = 1084.84, p<0.001). The intensity of the intergenerational trend in subsequent cohorts of years of birth varied strongly between decades, averaging 1.34 cm/decade. The body height in women increased significantly up to the height of those born between 1970 and 1979 and then the trend weakened noticeably, although it remained positive. The observed secular trend confirms positive changes in the standard of living of Polish women between 1931 and 2020. Improving living conditions allow people to fully achieve their genetically determined growth potential.
Examining trends in substance use disorder capacity and service delivery by Health Resources and Services Administration-funded health centers: A time series regression analysis
Authors: Pourat Nadereh , O’Masta Brenna , Chen Xiao , Lu Connie , Zhou Weihao , Daniel Marlon , Hoang Hank , Sripipatana Alek
Published: November 2020

Background

The opioid epidemic and subsequent mortality is a national concern in the U.S. The burden of this problem is disproportionately high among low-income and uninsured populations who are more likely to experience unmet need for substance use services. We assessed the impact of two Health Resources and Services Administration (HRSA) substance use disorder (SUD) service capacity grants on SUD staffing and service use in HRSA -funded health centers (HCs).

Methods and findings

We conducted cross-sectional analyses of the Uniform Data System (UDS) from 2010 to 2017 to assess HC (n = 1,341) trends in capacity measured by supply of SUD and medication-assisted treatment (MAT) providers, utilization of SUD and MAT services, and panel size and visit ratio measured by the number of patients seen and visits delivered by SUD and MAT providers. We merged mortality and national survey data to incorporate SUD mortality and SUD treatment services availability, respectively. From 2010 to 2015, 20% of HC organizations had any SUD staff, had an average of one full-time equivalent SUD employee, and did not report an increase in SUD patients or SUD services. SUD capacity grew significantly in 2016 (43%) and 2017 (22%). MAT capacity growth was measured only in 2016 and 2017 and grew by 29% between those years. Receipt of both supplementary grants increased the probability of any SUD capacity by 35% (95% CI: 26%, 44%) and service use, but decreased the probability of SUD visit ratio by 680 visits (95% CI: -1,013, -347), compared to not receiving grants.

Conclusions

The significant growth in HC specialized SUD capacity is likely due to supplemental SUD-specific HRSA grants and may vary by structure of grants. Expanding SUD capacity in HCs is an important step in increasing SUD access for low income and uninsured populations broadly and for patients of these organizations.
Valuing disaster risk reduction neighborhood interventions in informal settlements of Latin American and the Caribbean
Authors: Arrieta Alejandro , Sarmiento Juan Pablo , Chabba Meenakshi , Chen Weiwei
Published: November 2020

This study assesses the dollar benefit of a neighborhood approach intervention on disaster risk reduction in small-sized, densely populated, and hazard-prone informal settlements across Latin American and Caribbean countries. We use a life satisfaction approach that assigns a dollar value to gains in wellbeing associated with the neighborhood approach intervention. Our primary data was a survey to a sample of 349 beneficiaries from small towns in Haiti, Guatemala, and Jamaica, and in major cities’ surrounded areas of Peru, Colombia, and Honduras. Out of 14 interventions, we found that community empowerment, physical works in public spaces and urban gardens/food approaches produced a gain of USD1,038 to USD1,241 to individual beneficiaries. Our study suggests a large benefit associated with the neighborhood approach intervention. It also shows that the life satisfaction approach is a promising method for the valuation of non-market and public goods, especially for countries where data on hazards and risks is not available to help monetize risk reductions.
Less amputations for diabetic foot ulcer from 2008 to 2014, hospital management improved but substantial progress is still possible: A French nationwide study
Authors: Amadou Coralie , Denis Pierre , Cosker Kristel , Fagot-Campagna Anne
Published: November 2020

Objective

To assess the improvement in the management of diabetes and its complications based on the evolution of hospitalisation rates for diabetic foot ulcer (DFU) and lower extremity amputation (LEA) in individuals with diabetes in France.

Methods

Data were provided by the French national health insurance general scheme from 2008 to 2014. Hospitalisations for DFU and LEA were extracted from the SNIIRAM/SNDS French medical and administrative database.

Results

In 2014, 22,347 hospitalisations for DFU and 8,342 hospitalisations for LEA in patients with diabetes were recorded. Between 2008 and 2014, the standardised rate of hospitalisation for DFU raised from 508 to 701/100,000 patients with diabetes. In the same period, the standardised rate of LEA decreased from 301 to 262/100,000 patients with diabetes. The level of amputation tended to become more distal. The proportion of men (69% versus 73%) and the frequency of revascularization procedures (39% versus 46%) increased. In 2013, the one-year mortality rate was 23% after hospitalisation for DFU and 26% after hospitalisation for LEA.

Conclusions

For the first time in France, the incidence of a serious complication of diabetes, i.e. amputations, has decreased in relation with a marked improvement in hospital management.
The strength of association between psychological factors and clinical outcome in tendinopathy: A systematic review
Authors: Stubbs Carl , Mc Auliffe Sean , Mallows Adrian , O’sullivan Kieran , Haines Terence , Malliaras Peter
Published: November 2020

Objective

Tendinopathy is often a disabling, and persistent musculoskeletal disorder. Psychological factors appear to play a role in the perpetuation of symptoms and influence recovery in musculoskeletal pain. To date, the impact of psychological factors on clinical outcome in tendinopathy remains unclear. Therefore, the purpose of this systematic review was to investigate the strength of association between psychological factors and clinical outcome in tendinopathy.

Methods

A systematic review of the literature and qualitative synthesis of published trials was conducted. Electronic searches of ovid MEDLINE, ovid EMBASE, PsychINFO, CINAHL and Cochrane Library was undertaken from their inception to June 2020. Eligibility criteria included RCT’s and studies of observational design incorporating measurements of psychological factors and pain, disability and physical functional outcomes in people with tendinopathy. Risk of Bias was assessed by two authors using a modified version of the Newcastle Ottawa Scale. High or low certainty evidence was examined using the GRADE criteria.

Results

Ten studies of observational design (6-cross sectional and 4 prospective studies), involving a sample of 719 participants with tendinopathy were included. Risk of bias for the included studies ranged from 12/21 to 21/21. Cross-sectional studies of low to very low level of certainty evidence revealed significant weak to moderate strength of association (r = 0.24 to 0.53) between psychological factors and clinical outcomes. Prospective baseline data of very low certainty evidence showed weak strength of association between psychological factors and clinical outcome. However, prospective studies were inconsistent in showing a predictive relationship between baseline psychological factors on long-term outcome. Cross sectional studies report similar strengths of association between psychological factors and clinical outcomes in tendinopathy to those found in other musculoskeletal conditions.

Conclusion

The overall body of the evidence after applying the GRADE criteria was low to very low certainty evidence, due to risk of bias, imprecision and indirectness found across included studies. Future, high quality longitudinal cohort studies are required to investigate the predictive value of baseline psychological factors on long-term clinical outcome.
Gross appearance of the fetal membrane on the placental surface is associated with histological chorioamnionitis and neonatal respiratory disorders
Authors: Horikoshi Yoshimasa , Yaguchi Chizuko , Furuta-Isomura Naomi , Itoh Toshiya , Kawai Kenta , Oda Tomoaki , Matsumoto Masako , Kohmura-Kobayashi Yukiko , Tamura Naoaki , Uchida Toshiyuki , Kanayama Naohiro , Itoh Hiroaki
Published: November 2020

An opaque fetal membrane based on gross appearance is traditionally indicative of histological chorioamnionitis; however, to the best of our knowledge, there is currently no supportive evidence, and its diagnostic efficiency has not yet been scientifically demonstrated. The present study aimed to provide scientific insights into the traditional concept of an opaque fetal membrane based on gross appearance being an indicator of histological chorioamnionitis. We examined the placental pathology after screening of the placental gross appearance and perinatal complications and did not examine uncomplicated deliveries. We investigated the relationship between the presence of an opaque fetal membrane and histological chorioamnionitis (Cohort 1, 571 placentas) or the outcomes of neonates delivered at term (Cohort 2, 409 placentas) at Hamamatsu University School of Medicine between 2010 and 2017. The judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis (Cohort 1). Its sensitivity and specificity were 66.7 and 89.9%, respectively, while positive and negative predictive values were 86.8 and 73.0%, respectively. The judgment of a positive opaque fetal membrane based on gross appearance significantly correlated with chorioamnionitis-related complications in term newborns after adjustments for confounding factors (OR;1.82 [1.07–3.11], P<0.05) (Cohort 2). A correlation was observed even after adjustments for confounding factors. The present study is the first to demonstrate that the judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis as well as chorioamnionitis-related complications in newborns delivered at term. The present results provide support for the traditionally-described importance of gross inspections for an opaque fetal membrane soon after birth.
Evaluation of plasma anti-GPL-core IgA and IgG for diagnosis of disseminated non-tuberculous mycobacteria infection
Authors: Nithichanon Arnone , Samer Waraporn , Chetchotisakd Ploenchan , Kewcharoenwong Chidchamai , Ato Manabu , Lertmemongkolchai Ganjana
Published: November 2020

Detection of IgA antibody against Mycobacterium avium complex (MAC) glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC pulmonary disease but has yet to be tested in disseminated Non-tuberculous mycobacteria (NTM) infection. In this study, we address the diagnostic efficacies of an anti-GPL-core ELISA kit in disseminated lymphadenopathy patients positive for NTM culture and anti-IFN-γ autoantibodies. The study was conducted in a tertiary referral center in northeastern Thailand and patients with NTM, tuberculosis, melioidosis, and control subjects were enrolled. Plasma immunoglobulin A (IgA) and G (IgG) antibodies against GPL-core were detected in the subjects and the specificity and sensitivity of the assay was assessed. Anti-GPL-core IgA and IgG levels were significantly higher in NTM patients than other groups (p < 0.0001). Diagnostic efficacy for NTM patients using anti-GPL-core IgA cut-off value of 0.352 U/ml showed good sensitivity (91.18%) and intermediate specificity (70.15%). Using a cut-off value of 4.140 AU/ml for anti-GPL-core IgG showed the same sensitivity (91.18%) with increased specificity (89.55%) and an 81.58% positive predictive value. Most patients with moderate levels (4.140–7.955 AU/ml) of anti-GPL-core IgG had rapidly growing mycobacteria (RGM) infection. Taken together, the detection of anti-GPL-core antibodies could provide a novel option for the diagnosis and management of disseminated NTM infected patients.
Robust optimal design of FOPID controller for five bar linkage robot in a Cyber-Physical System: A new simulation-optimization approach
Authors: Parnianifard Amir , Zemouche Ali , Chancharoen Ratchatin , Imran Muhammad Ali , Wuttisittikulkij Lunchakorn
Published: November 2020

This paper aims to further increase the reliability of optimal results by setting the simulation conditions to be as close as possible to the real or actual operation to create a Cyber-Physical System (CPS) view for the installation of the Fractional-Order PID (FOPID) controller. For this purpose, we consider two different sources of variability in such a CPS control model. The first source refers to the changeability of a target of the control model (multiple setpoints) because of environmental noise factors and the second source refers to an anomaly in sensors that is raised in a feedback loop. We develop a new approach to optimize two objective functions under uncertainty including signal energy control and response error control while obtaining the robustness among the source of variability with the lowest computational cost. A new hybrid surrogate-metaheuristic approach is developed using Particle Swarm Optimization (PSO) to update the Gaussian Process (GP) surrogate for a sequential improvement of the robust optimal result. The application of efficient global optimization is extended to estimate surrogate prediction error with less computational cost using a jackknife leave-one-out estimator. This paper examines the challenges of such a robust multi-objective optimization for FOPID control of a five-bar linkage robot manipulator. The results show the applicability and effectiveness of our proposed method in obtaining robustness and reliability in a CPS control system by tackling required computational efforts.