bluuebunny/crossref_metadata_2025 huggingface dataset:
Ernest Gaines
Authors: Babb Valerie
Published: June 2019

With the publication of The Autobiography of Miss Jane Pittman in 1971, Ernest J. Gaines (b. 15 January 1933) was acknowledged as a major American writer. This landmark novel, which was subsequently made into a television movie starring Cicely Tyson, came at a time when all manner of American discourse was re-evaluating the nation’s practices of African American enslavement. The fictional autobiography of a young girl living in slavery whose personal voice relates the events of Emancipation, Joe Louis defeating Max Schmeling, Jackie Robinson integrating baseball, and the birth of the Civil Rights movement became a microcosm of American history. The intertwining of history with individual stories is a hallmark of Gaines’s writing style. His texts are set in the fictional Bayonne, a reimagining of his Louisiana parish, Pointe Coupée, and all contain characters whose cadences render the traditions and stories of the region, a landscape of bayous, decaying plantations, and tenant farms. Gaines may have been popularly “discovered” with Miss Jane, but he wrote two previous novels, Catherine Carmier (1964) and Of Love and Dust (1967), and numerous short stories, five of which were collected in Bloodline (1968). All mine the reservoir of Louisiana’s culture and exemplify narrative techniques that replicate in writing the oral storytelling intrinsic to his native area. Coming from a long line of storytellers or “liars,” and wanting to incorporate their rural Southern worldview and way of telling in his fiction, he imbricates written form with a mosaic of folk materials. A flawless ear for language developed while listening to storytellers as he sat on his Aunt Augusteen’s porch gives his prose a unique rhythm, while research into the marginalized—the recollections of former slaves, the voices of the incarcerated—gives his themes timeless resonances. Gaines’s long career has seen the advent of many literary movements. He lived in San Francisco during that city’s literary renaissance, and wrote during the social upheavals of the Black Arts period, but through it all kept close to his aesthetic vision. His fiction is filled with political nuances and historic moments from enslavement to contemporary civil rights, but all are rendered in intimate terms through characters, each in his or her own way, facing deterministic factors stemming from race and social class. Gaines has a modernist impulse to make it new, and transforms conventions of prose literature, but change is always in service to embracing a social past that is not really past. Though his writing is deeply rooted in the complex hybrid histories of black and white Americans, Cajuns, and Creoles living in a single fictional parish, it is conversant with perpetual questions of humanity and social justice.
Maternal Effects
Authors: Uller Tobias
Published: June 2019

A maternal effect can be considered a causal effect of the parent phenotype on the phenotype of its offspring. Maternal effects contribute fundamentally to organismal life cycles. Maternal effects also contribute to phenotypic variation, to fitness differences between individuals, and to heredity. They are therefore important to many fields of evolutionary biology, which has generated a large and heterogeneous body of literature. One of the earliest (and still most important) motivations to study maternal effects in ecology and evolution is that they influence how populations respond to environmental change. Traits that are affected by maternal effects can exhibit different evolutionary dynamics compared to traits that are not influenced by parents. Maternal effects can also make population size fluctuate over time and contribute to range expansion. Many studies of reproductive investment and parental care are effectively studies of maternal effects, even if the term was not widely used in this context before the 1990s. While traits of parents and offspring can be expected to be co-adapted, the evolution of maternal effects is complicated by the fact that parents and offspring can have different fitness optima: a phenomenon known as “parent-offspring conflict.” Maternal effects are also widely studied in the context of phenotypic plasticity. The parent can act as a cue that enables offspring to adjust their phenotype to match local conditions, a phenomenon often referred to as “adaptive transgenerational plasticity.” Transfer of information between generations is one way to think of inheritance, and the evolution of non-genetic inheritance is one of the more recent additions to the growing literature on maternal effects and evolution. To handle this diversity of perspectives, the sections below are divided into main research themes.
Switching Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) to TDF/FTC/Rilpivirine vs Continuing TDF/FTC/EFV in HIV-Infected Patients With Virological Suppression: A Randomized Controlled Trial
Authors: Wiriyatanakorn Sirichai , Sungkanuparph Somnuek
Published: June 2019

A randomized controlled noninferiority trial was conducted in HIV-infected patients receiving tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) with virological suppression in a resource-limited setting. Switching to TDF/FTC/rilpivirine was noninferior to continuing TDF/FTC/EFV in terms of maintaining compete viral suppression at 24 weeks and provided better lipid profiles and fewer central nervous system adverse effects.
Subversive Humanitarianism: Rethinking Refugee Solidarity through Grass-Roots Initiatives
Authors: Vandevoordt Robin
Published: June 2019

Across Europe, hundreds of thousands of volunteers have brought food, clothes, medicines, and numerous others forms of support to newly arrived refugees. While humanitarian action has always been subversive, I argue that the recent wave of civil actions has pushed its subversive effects one step further. Whereas more modest forms of humanitarian action tend to misrecognise recipients’ social and political subjectivities, their more subversive counterparts can be better understood as enacting a particularistic form of solidarity that emphasises precisely those subjectivities. To explore the potential for political innovation in these civil initiatives, I argue that it can be useful to do so through the lens of “subversive humanitarianism”. More concretely, I suggest the following seven dimensions with which the subversive character of any humanitarian action can be compared across time and space: acts of civil disobedience; the reconstitution of social subjects; contending symbolic spaces; the creation of social spaces and personal bonds; assuming equality; putting minds into motion; and the transformation of individuals’ life-worlds. I support the argument by drawing upon the recent wave of empirical studies on civil initiatives across the continent as well as my own ethnographic data on the Brussels-based Plateforme Citoyenne de Soutien aux Réfugiés.
Feminisms
Authors: Watz Anna
Published: June 2019

This chapter reviews a selection of books published in 2018 relevant to feminist critical and cultural theory. The chapter is divided into three sections: 1. Introduction; 2. Feminist Pasts, which reviews Victoria Margree’s Neglected or Misunderstood: The Radical Feminism of Shulamith Firestone, Celia Marshik and Allison Pease’s Modernism, Sex, and Gender, and Ania Loomba’s Revolutionary Desires: Women, Communism, and Feminism in India; 3. Feminist Presents, which reviews Orienting Feminism: Media, Activism and Cultural Representation, edited by Catherine Dale and Rosemary Overell, and Emma Young’s Contemporary Feminism and Women’s Short Stories.
Sharing the Story of the Cardiac Rehab Patient Experience
Authors: Ellis Jordan M. , Freeman John Taylor , Midgette Emily P. , Sanghvi Anup P. , Sarathy Brinda , Johnson Colin G. , Greenway Stacey B. , Whited Matthew C.
Published: June 2019

Purpose:

To provide a prototypical patient narrative of the cardiac rehabilitation (CR) experience for providers and prospective patients using narrative analysis.

Methods:

Qualitative interviews with 17 CR patients from a previous study regarding their experiences, reasons, and motivations related to engagement in CR were analyzed using narrative inquiry. Interviews were previously analyzed and coded for recurring themes, and these themes were implemented in an exploratory narrative inquiry to craft a CR patient “story.” A hypothetical composite character representing the varied experiences of CR patients interviewed was developed, and a patient story was constructed that reflected on an initial cardiac event, time during rehabilitation, difficult experiences, social interactions, and personal values and accomplishments.

Results:

The CR patient narrative is presented for use in CR recruitment and programming materials, and in provider education.

Conclusion:

The narrative analysis comprehensively provides patients with an amalgam of patient experiences and can be used by providers to gain an understanding of CR patient experiences. Further research is needed to determine whether use of the resulting narrative analysis within the referral process and/or programming could increase participation and engagement.
PERSISTENT LOCULATED SUBRETINAL FLUID AFTER RHEGMATOGENOUS RETINAL DETACHMENT SURGERY
Authors: Mimouni Michael , Jaouni Tareq , Ben-Yair Mor , Almus Shiran , Derman Laura , Ehrenberg Scott , Almeida Diego , Barak Yoreh , Zayit-Soudry Shiri , Averbukh Edward
Published: June 2019

Purpose:

To identify factors associated with persistent subretinal fluid (SRF) after small-gauge pars plana vitrectomy for primary rhegmatogenous retinal detachment.

Methods:

This retrospective study included patients from 2 tertiary centers who underwent pars plana vitrectomy for repair of rhegmatogenous retinal detachment between 2013 and 2016. Preoperative and intraoperative parameters were examined for association with development of SRF.

Results:

Overall, 153 eyes of 153 patients, mean age of 55.2 ± 17.9 years were included. Persistent SRF occurred in 15.0% (n = 23) and was associated with high myopia (65.22 vs. 26.15%, P < 0.001), macula-involving retinal detachment (91.30 vs. 66.15%, P = 0.02), phakic lens status (86.96 vs. 66.15%, P = 0.04), and younger age (47.8 ± 18.7 vs. 56.5 ± 17.5, P = 0.04) while drainage retinotomy was protective (13.04 vs. 34.11%, P = 0.04). In multivariate analysis, high myopia (P = 0.009) and macula-involving retinal detachment (P = 0.004) were associated with SRF, while drainage retinotomy was protective (P = 0.03). Persistent SRF was associated with outer retinal band irregularity (30.4 vs. 9.3%, P = 0.005). There were no significant differences in terms of change in best-corrected visual acuity from presentation (P = 0.70), or final best-corrected visual acuity (P = 0.54).

Conclusion:

Eyes with preoperative high myopia and macular involvement, and those in which a drainage retinotomy was not performed, were more likely to develop persistent SRF.
Brain mechanisms of social touch-induced analgesia in females
Authors: López-Solà Marina , Geuter Stephan , Koban Leonie , Coan James A. , Wager Tor D.
Published: June 2019

Supportive touch has remarkable benefits in childbirth and during painful medical procedures. But does social touch influence pain neurophysiology, ie, the brain processes linked to nociception and primary pain experience? What other brain processes beyond primary pain systems mediate their analgesic effects? In this study, women (N = 30) experienced thermal pain while holding their romantic partner's hand or an inert device. Social touch reduced pain and attenuated functional magnetic resonance imaging activity in the Neurologic Pain Signature (NPS)—a multivariate brain pattern sensitive and specific to somatic pain—and increased connectivity between the NPS and both somatosensory and “default mode” regions. Brain correlates of touch-induced analgesia included reduced pain-related activation in (1) regions targeted by primary nociceptive afferents (eg, posterior insula, and anterior cingulate cortex); and (b) regions associated with affective value (orbitofrontal cortex), meaning (ventromedial prefrontal cortex [PFC]), and attentional regulation (dorsolateral PFC). Activation reductions during handholding (vs holding a rubber device) significantly mediated reductions in pain intensity and unpleasantness; greater pain reductions during handholding correlated with greater increases in emotional comfort, which correlated with higher perceived relationship quality and (a trend toward) greater perceived closeness with the romantic partner. The strongest mediators of analgesia were activity reductions in a brain circuit traditionally associated with stress and defensive behavior in mammals, including ventromedial and dorsomedial PFC, rostral anterior cingulate cortex, amygdala/hippocampus, hypothalamus, and periaqueductal gray matter. Social touch affects core brain processes that contribute to pain and pain-related affective distress in females, and should be considered alongside other treatments in medical and caregiving contexts.
The rostromedial tegmental nucleus: a key modulator of pain and opioid analgesia
Authors: Taylor Norman E. , Long Hu , Pei JunZhu , Kukutla Phanidhar , Phero Anthony , Hadaegh Farnaz , Abdelnabi Ahmed , Solt Ken , Brenner Gary J.
Published: June 2019

A recently defined structure, the rostromedial tegmental nucleus (RMTg; aka tail of the ventral tegmental area [VTA]), has been proposed as an inhibitory control center for dopaminergic activity of the VTA. This region is composed of GABAergic cells that send afferent projections to the ventral midbrain and synapse onto dopaminergic cells in the VTA and substantia nigra. These cells exhibit µ-opioid receptor immunoreactivity, and in vivo, ex vivo, and optogenetic/electrophysiological approaches demonstrate that morphine excites dopamine neurons by targeting receptors on GABAergic neurons localized in the RMTg. This suggests that the RMTg may be a key modulator of opioid effects and a major brake regulating VTA dopamine systems. However, no study has directly manipulated RMTg GABAergic neurons in vivo and assessed the effect on nociception or opioid analgesia. In this study, multiplexing of GABAergic neurons in the RMTg was achieved using stimulatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and inhibitory kappa-opioid receptor DREADDs (KORD). Our data show that locally infused RMTg morphine or selective RMTg GABAergic neuron inhibition produces 87% of the maximal antinociceptive effect of systemic morphine, and RMTg GABAergic neurons modulate dopamine release in the nucleus accumbens. In addition, chemoactivation of VTA dopamine neurons significantly reduced pain behaviors both in resting and facilitated pain states and reduced by 75% the dose of systemic morphine required to produce maximal antinociception. These results provide compelling evidence that RMTg GABAergic neurons are involved in processing of nociceptive information and are important mediators of opioid analgesia.
Immunohistochemistry Critical Assay Performance Controls (ICAPC) Reduce Interobserver Variability in the Interpretation of BRAFV600E Immunohistochemistry
Authors: Gale Nadia S. , Kalloger Steve E. , Cai Ellen , Abozina Alisa , Derakhshan Fatameh , Hickey Tyler , Liu Ariel , Ongaro Deidre , Wolber Robert , Schaeffer David F.
Published: June 2019

The utility of prognostic and predictive immunohistochemistry biomarkers in the context of cancer is plagued by inconsistent interpretation of results which can lead to poor rates of adoption or inappropriate use of novel therapeutic strategies. To monitor immunohistochemistry assay performance, a new on-slide control motif, Immunohistochemistry Critical Assay Performance Controls (ICAPC) was developed. We hypothesized that the use of these controls by the diagnosing pathologist to interpret BRAFV600E would result in reduced interobserver and intraobserver interpretation errors. A cross-sectional, sequentially obtained sample of surgical pathology cases stained for BRAFV600E was assembled from a single hospital in Vancouver, British Columbia. Half of the cases had normal on-slide controls and the remainder with ICAPC. Results from 6 independent and blinded readers were compared with each other and to the gold-standard pathologic diagnosis with the goal of demonstrating superior interrater agreement with ICAPC relative to standard on-slide controls. Cohen’s κ was used to compute pair-wise reader agreements, whereas Fleiss’ κ was used to compare to the gold standard. The implementation of ICAPC resulted in statistically significant improvements in the interobserver agreement of BRAF mutation status ascertained by BRAFV600E immunohistochemistry. Half of the readers demonstrated significant improvements in agreement with the gold-standard diagnosis with the addition of ICAPC. Across all readers, the mean increase in κ was 0.14 with a 95% confidence interval of 0.01-0.28 (P=0.04). This study demonstrates that the addition of ICAPC serves to significantly reduce interobserver variability in the assessment of BRAFV600E immunohistochemistry. As such, we recommend that this approach should be used as part of a comprehensive quality management strategy in the setting of histopathology.
Establishing Dosing Recommendations for Efavirenz in HIV/TB-Coinfected Children Younger Than 3 Years
Authors: Bwakura Dangarembizi Mutsa , Samson Pearl , Capparelli Edmund V. , Moore Carolyn Bolton , Jean-Philippe Patrick , Spector Stephen A. , Chakhtoura Nahida , Benns Alex , Zimmer Bonnie , Purdue Lynette , Jackson Chivon , Wallis Carole , Libous Jennifer L. , Chadwick Ellen G. ,   for the IMPAACT P1070 Study Team
Published: June 2019

Background:

CYP2B6 516 genotype-directed dosing improves efavirenz (EFV) exposures in HIV-infected children younger than 36 months, but such data are lacking in those with tuberculosis (TB) coinfection.

Methods:

Phase I, 24-week safety and pharmacokinetic (PK) study of EFV in HIV-infected children aged 3 to <36 months, with or without TB. CYP2B6 516 genotype classified children into extensive metabolizers (516 TT/GT) and poor metabolizers [(PMs), 516 TT]. EFV doses were 25%–33% higher in children with HIV/TB coinfection targeting EFV area under the curve (AUC) 35–180 μg × h/mL, with individual dose adjustment as necessary. Safety and virologic evaluations were performed every 4–8 weeks.

Results:

Fourteen children from 2 African countries and India with HIV/TB enrolled, with 11 aged 3 to <24 months and 3 aged 24–36 months, 12 extensive metabolizers and 2 PMs. Median (Q1, Q3) EFV AUC was 92.87 (40.95, 160.81) μg × h/mL in 8/9 evaluable children aged 3 to <24 months and 319.05 (172.56, 360.48) μg × h/mL in children aged 24–36 months. AUC targets were met in 6/8 and 2/5 of the younger and older age groups, respectively. EFV clearance was reduced in PM's and older children. Pharmacokinetic modeling predicted adequate EFV concentrations if children younger than 24 months received TB-uninfected dosing. All 9 completing 24 weeks achieved viral suppression. Five/14 discontinued treatment early: 1 neutropenia, 3 nonadherence, and 1 with excessive EFV AUC.

Conclusions:

Genotype-directed dosing safely achieved therapeutic EFV concentrations and virologic suppression in HIV/TB-coinfected children younger than 24 months, but further study is needed to confirm appropriate dosing in those aged 24–36 months. This approach is most important for young children and currently a critical unmet need in TB-endemic countries.
Nocturnal torpor by superb fairy-wrens: a key mechanism for reducing winter daily energy expenditure
Authors: Romano Alex B. , Hunt Anthony , Welbergen Justin A. , Turbill Christopher
Published: June 2019

Many passerine birds are small and require a high mass-specific rate of resting energy expenditure, especially in the cold. The energetics of thermoregulation is, therefore, an important aspect of their ecology, yet few studies have quantified thermoregulatory patterns in wild passerines. We used miniature telemetry to record the skin temperature (
T
skin
) of free-living superb fairy-wrens (
Malurus cyaneus
, 8.6 g;
n
= 6 birds over
N
= 7–22 days) and determine the importance of controlled reductions in body temperature during resting to their winter energy budgets. Fairy-wrens routinely exhibited large daily fluctuations in
T
skin
between maxima of 41.9 ± 0.6°C and minima of 30.4 ± 0.7°C, with overall individual minima of 27.4 ± 1.1°C (maximum daily range: 14.7 ± 0.9°C). These results provide strong evidence of nocturnal torpor in this small passerine, which we calculated to provide a 42% reduction in resting metabolic rate at a
T
a
of 5°C compared to active-phase
T
skin
. A capacity for energy-saving torpor has important consequences for understanding the behaviour and life-history ecology of superb fairy-wrens. Moreover, our novel field data suggest that torpor could be more widespread and important than previously thought within passerines, the most diverse order of birds.
Hyperthyroidism in the personalized medicine era: the rise of mathematical optimization
Authors: Meng Fanwen , Li Enlin , Yen Paul Michael , Leow Melvin Khee Shing
Published: June 2019

Thyroid over-activity or hyperthyroidism constitutes a significant morbidity afflicting the world. The current medical practice of dose titration of anti-thyroid drug (ATD) treatment for hyperthyroidism is relatively archaic, being based on arbitrary and time-consuming trending of thyroid function that requires multiple clinic monitoring visits before an optimal dose is found. This prompts a re-examination into more deterministic and efficient treatment approaches in the present personalized medicine era. Our research project seeks to develop a personalized medicine model that facilitates optimal drug dosing via the titration regimen. We analysed 49 patients' data consisting of drug dosage, time period and serum free thyroxine (FT4). Ordinary differential equation modelling was applied to describe the dynamic behaviour of FT4 concentration. With each patient's data, an optimization model was developed to determine parameters of synthesis rate, decay rate and IC
50
. We derived the closed-form time- and dose-dependent solution which allowed explicit estimates of personalized predicted FT4. Our equation system involving time, drug dosage and FT4 can be solved for any variable provided the values of the other two are known. Compared against actual FT4 data within a tolerance, we demonstrated the feasibility of predicting the FT4 subsequent to any prescribed dose of ATD with favourable accuracy using the initial three to five patient-visits' data respectively. This proposed mathematical model may assist clinicians in rapid determination of optimal ATD doses within allowable prescription limits to achieve any desired FT4 within a specified treatment period to accelerate the attainment of euthyroid targets.
The influence of drug solubility and sampling frequency on metformin and glibenclamide release from double-layered particles: experimental analysis and mathematical modelling
Authors: Shams T. , Brako F. , Huo S. , Harker A. H. , Edirisinghe U. , Edirisinghe M.
Published: June 2019

Co-axial electrohydrodynamic atomization was used to prepare core/shell polymethylsilsesquioxane particles for co-delivery of metformin and glibenclamide in a sustained release manner. The drug-loaded microparticles were mostly spherical and uniformly distributed in size, with average diameters between 3 and 5 µm across various batches. FTIR was used to confirm the presence of drugs within the particles while X-ray diffraction studies revealed drugs encapsulated existed predominantly in the amorphous state. Intended as systems that potentially can act as depot formulations for long-term release of antidiabetics, a detailed analysis of drug release from these particles was necessary. Drugs of different solubilities were selected in order to study the effects of drug solubility from a core/shell particle system. Further analyses to determine how conditions such as release into a limited volume of media, sampling rate and partitioning of drug between the core and shell layers influenced drug release were conducted by comparing experimental and mathematically modelled outcomes. It was found that while the solubility of drug may affect release from such systems, rate of removal of drug (sampling frequency) which upsets local equilibrium at the particle/solution interface prompting a rapid release to redress the equilibrium influenced release more.
Infective endocarditis caused by Cardiobacterium valvarum
Authors: Washio Yohei , Sakamoto Shun-ichiro , Saito Ryoichi , Nei Takahito , Morishima Masayo , Shinoyama Akihiro , Tashiro Ayaka , Sugimoto Ryoji
Published: June 2019

We report a case with infective endocarditis (IE) due to

Cardiobacterium valvarum

. The patient was a 57-year-old male, who was referred to our hospital based on suspected IE detected by transthoracic echocardiography at a neighbourhood clinic. Three sets of blood cultures obtained on admission yielded positive results, and revealed rather slender and linear Gram-negative bacilli with a rosette formation that dyed minimally, with a pale white appearance. Although no isolates were identified by conventional methods,

C. valvarum

was ultimately identified by 16 S ribosomal RNA genotyping. HACEK group strains are difficult to identify by conventional methods. Therefore, if Gram-negative bacilli are isolated from IE patients, 16 S ribosomal RNA genotyping will be necessary. Furthermore, IE due to

C. valvarum

is very rare. We thus discuss our case in comparison with previous reports.
Prospective and External Evaluation of a Machine Learning Model to Predict In-Hospital Mortality
Authors: Brajer Nathan , Cozzi Brian , Gao Michael , Nichols Marshall , Revoir Mike , Balu Suresh , Futoma Joseph , Bae Jonathan , Setji Noppon , Hernandez Adrian , Sendak Mark
Published: June 2019

The ability to accurately predict in-hospital mortality for patients at the time of admission could improve clinical and operational decision-making and outcomes. Few machine learning models have been developed to predict in-hospital death that are both broadly applicable to all adult patients across a health system and readily implementable, and, to the best of our knowledge, none have been implemented, evaluated prospectively, or externally validated.

The primary objective of this study was to prospectively and externally validate a machine learning model that predicts in-hospital mortality for all adult patients at the time of hospital admission. Model performance was quantified using the area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). Secondary objectives were to design the model using commonly available EHR data and accessible computational methods.

A total of 75,247 hospital admissions (median [IQR] age 59.5 [29.0] years; male [45.9%]) were included in the study. The in-hospital mortality rates for the training validation, retrospective validations at Hospitals A, B, and C, and prospective validation cohorts, respectively, were 3.0%, 2.7%, 1.8%, 2.1%, and 1.6%. The area under the receiver operating characteristic curves (AUROCs), respectively, were 0.87 (0.83-0.89), 0.85 (0.83-0.87), 0.89 (0.86 – 0.92), 0.84 (0.80-0.89), and 0.86 (0.83-0.90). The area under the precision recall curves (AUPRCs), respectively, were 0.29 (0.25-0.37), 0.17 (0.13-0.22), 0.22 (0.14-0.31), 0.13 (0.08-0.21), and 0.14 (0.09-0.21).

The results demonstrated accurate prediction of in-hospital mortality for adult patients at the time of admission. The data elements, methods, and patient selection make the model implementable at a system-level.
The prevalence of scabies, pyoderma and other communicable dermatoses in the Bijagos Archipelago, Guinea-Bissau
Authors: Marks Michael , Sammut Thomas , Cabral Marito Gomes , da Silva Eunice Teixeira , Goncalves Adriana , Rodrigues Amabelia , Manjuba Cristóvão , Nakutum Jose , Ca Janete , D’Alessandro Umberto , Achan Jane , Logan James , Bailey Robin , Mabey David , Last Anna , Walker Stephen L.
Published: June 2019

Introduction

Skin diseases represent a significant public health problem in most low and middle income settings. Nevertheless, there is a relative paucity of high-quality epidemiological data on the prevalence of these conditions.

Materials/methods

We conducted two cross-sectional population-based skin-surveys of children (6 months to 9 years old) in the Bijagós Archipelago of Guinea-Bissau during the dry season (February-March 2018) and the wet season (June-July 2018). Following a period of training, a nurse performed a standardised examination for communicable dermatoses for each participant. We calculated the prevalence of each skin condition and investigated demographic associations.

Results

1062 children were enrolled in the dry season survey of whom 318 (29.9%) had at least one skin diseases. The most common diagnosis was tinea capitis (154/1062, 14.5% - 95% CI 12.5-16.8%) followed by tinea corporis (84/1062, 7.9% - 95% CI 6.4-9.7%), pyoderma (82/1062, 7.7% - 95% CI 6.2-9.5%) and scabies (56/1062. 5.2% - 95%CI 4.0 – 6.8%). 320 children were enrolled in the wet season survey of whom 121 (37.8%) had at least one skin problem. Tinea capitis remained the most common diagnosis (79/320, 24.7% - 95% CI 20.1 – 29.9%), followed by pyoderma (38/320, 11.9% - 95% CI 8.6-16.1%), tinea corporis (23/320, 7.2% - 95% 4.7 – 10.7%) and scabies (6/320, 1.9% - 95% CI 0.8-4.2%).

Conclusions

Our study, which utilised robust population-based cluster random sampling methodology, demonstrates the substantial disease burden caused by common communicable dermatoses in this setting. Given these findings, there is a need to consider common dermatoses as part of Universal Health Coverage to deliver ‘skin-health for all’.

Author Summary

Skin conditions are very common in many low and middle income settings but there have been relatively few surveys of skin disease conducted using the best epidemiological approaches. We performed two cross-sectional population-based skin-surveys of children in the Bijagós Archipelago, Guinea-Bissau, using gold-standard sampling methodologies. Skin conditions were extremely common and almost 30% of children had at least one common, infectious skin condition in both surveys. Fungal skin and scalp infections were the most common conditions followed by bacterial skin infections. Our survey demonstrates that common, easily treatable skin conditions are responsible for a high burden of disease in this population. Skin-health should be considered a key component of the Universal Health Coverage agenda.
Predicting epileptic seizures using nonnegative matrix factorization
Authors: Stojanović Olivera , Pipa Gordon
Published: June 2019

This paper presents a procedure for the patient-specific prediction of epileptic seizures. To this end, a combination of nonnegative matrix factorization (NMF) and smooth basis functions with robust regression is applied to power spectra of intracranial electroencephalographic (iEEG) signals. The resulting time and frequency components capture the dominant information from power spectra, while removing outliers and noise. This makes it possible to detect structure in preictal states, which is used for classification. Linear support vector machines (SVM) with L1 regularization are used to select and weigh the contributions from different number of not equally informative channels among patients. Due to class imbalance in data, synthetic minority over-sampling technique (SMOTE) is applied. The resulting method yields a computationally and conceptually simple, interpretable model of EEG signals of preictal and interictal states, which shows a good performance for the task of seizure prediction.
18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy
Authors: Nicastro Nicolas , Vazquez Rodriguez Patricia , Malpetti Maura , Bevan-Jones William Richard , Jones P. Simon , Passamonti Luca , Aigbirhio Franklin I. , O’brien John T. , Rowe James B.
Published: June 2019

Introduction

Progressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.

Methods

Twenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.

Results

Widespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).

Conclusion

This cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.
Transfer of Statistical Innovations of the 1990s-2000s in Oncology to the Biomedical Literature
Authors: Vivot Alexandre , Lévy Vincent , Chevret Sylvie
Published: June 2019

Introduction

Innovations in the fields of clinical studies require time to generate and disseminate new knowledge. We aimed to specifically explore lag times between the introduction and widespread use of innovative statistical methods in oncology using the competing risks and phase I model-based clinical trials settings as examples.

Methods

First, we defined a set of closed articles for each setting based on two princeps papers (Gray, Annals of Statistics 1998 for the competing risks setting and O’Quigley et al., Biometrics 1990 for the phase I setting). Secondly, we retrieved from the web of science all citations of the papers included in these sets. Each journal was classified as applied, semi-applied or methodological.

Results

A total of 6,727 citations for the competing risks setting and 2,639 citations for the phase I setting were found. Time to reach 25 citations was 6.2 years for the Gray’s paper and 4.5 years for the Fine and Gray paper, while it ranged from 3.4 years up to at least 20.1 years and not reached for 6 papers from the competing risks setting. The vast majority (91%) of the citing papers for the competing risks setting originated from applied journals. In contrast, less than half (44%) of the citing papers for the phase I setting were published in applied journals.

Conclusion

Statistical innovations in the competing risks setting have been widely diffused in the medical literature unlike the model-based designs for phase I trials, which are still seldom used 30 years after publication.
Pain Reduction by Inducing Sensory-Motor Adaptation in Complex Regional Pain Syndrome (CRPS PRISMA): Protocol for a Double-blind Randomized Controlled Trial
Authors: Halicka Monika , Vittersø Axel D , Proulx Michael J , Bultitude Janet H
Published: June 2019

Background

Complex Regional Pain Syndrome (CRPS) presents as chronic, continuous pain and sensory, autonomic, and motor abnormalities affecting one or more extremities. People with CRPS can also show changes in their perception of and attention to the affected body part and sensory information in the affected side of space. Prism Adaptation (PA) is a behavioural intervention targeted at reducing attention deficits in post-stroke hemispatial neglect. PA also appears to reduce pain and other CRPS symptoms; however, these therapeutic effects have been demonstrated only in small unblinded studies. This paper describes the protocol for an ongoing double-blind, randomized, sham-controlled clinical trial that will evaluate the efficacy of PA treatment for CRPS. The secondary aims of the study are to examine the relationships between neuropsychological changes (such as spatial attention, space and body representation, and motor spatial performance) and clinical manifestations of CRPS, as well as symptom improvement.

Methods

Forty-two participants with upper-limb CRPS type I will undergo two weeks of twice-daily PA treatment or sham treatment. The primary outcome measures are current pain intensity and CRPS severity score, measured immediately before and after the treatment period. Secondary outcome measures include the results of self-report questionnaires about pain, movement, symptoms interference, and body representation; clinical assessments of sensory, motor, and autonomic functions; and computer-based psychophysical tests of neuropsychological functions. Data are collected in four research visits: four weeks and one day before treatment, and one day and four weeks after the end of treatment. Additional follow-up through postal questionnaires is conducted three and six months post-treatment.

Discussion

It is hypothesised that participants undergoing PA treatment, compared to those receiving sham treatment, will show greater reduction in pain and CRPS severity score, and improvements on other clinical and neuropsychological measures. Also, more pronounced neuropsychological symptoms are predicted to correlate with more severe clinical CRPS symptoms. This study will provide the first randomized double-blind evaluation of the therapeutic effects of PA that could be implemented as a rehabilitation method for CRPS, and will contribute to the understanding of how neuropsychological changes in body representation and attention pertain to the manifestation and treatment of CRPS.
Dimensionality reduction by UMAP to visualize physical and genetic interactions
Authors: Dorrity Michael W. , Saunders Lauren M. , Queitsch Christine , Fields Stanley , Trapnell Cole
Published: June 2019

Dimensionality reduction is often used to visualize complex expression profiling data. Here, we use the Uniform Manifold Approximation and Projection (UMAP) method on published transcript profiles of 1484 single gene deletions of Saccharomyces cerevisiae. Proximity in low-dimensional UMAP space identifies clusters of genes that correspond to protein complexes and pathways, and finds novel protein interactions even within well-characterized complexes. This approach is more sensitive than previous methods and should be broadly useful as additional transcriptome datasets become available for other organisms.
Arabidopsis HY1-Modulated Stomatal Movement: An Integrative Hub Is Functionally Associated with ABI4 in Dehydration-Induced ABA Responsiveness
Authors: Xie Yanjie , Mao Yu , Duan Xingliang , Zhou Heng , Lai Diwen , Zhang Yihua , Shen Wenbiao
Published: June 2019

Heme oxygenase (HO; EC 1.14.99.3) has recently been proposed as a novel component in mediating wide ranges of the plant adaptive signaling processes. However, the physiological significance and molecular basis underlying Arabidopsis (Arabidopsis thaliana) HO1 (HY1) functioning in drought tolerance remained unclear. Here, we report that mutation of HY1 promoted, but overexpression of this gene impaired, Arabidopsis drought tolerance. This was attributed to the abscisic acid (ABA)-hypersensitive or -hyposensitive phenotypes, with the regulation of stomatal closure in particular. However, comparative transcriptomic profile analysis showed that the induction of numerous ABA/stress-dependent genes in dehydrated wild-type plants was differentially impaired in the hy1 mutant. In agreement, ABA-induced ABSCISIC ACID-INSENSITIVE4 (ABI4) transcript accumulation was strengthened in the hy1 mutant. Genetic analysis further identified that the hy1-associated ABA hypersensitivity and drought tolerance were arrested in the abi4 background. Moreover, the promotion of ABA-triggered up-regulation of RbohD abundance and reactive oxygen species (ROS) levels in the hy1 mutant was almost fully blocked by the mutation of ABI4, suggesting that the HY1-ABI4 signaling in the wild type involved in stomatal closure was dependent on the RbohD-derived ROS production. However, hy1-promoted stomatal closure was not affected by a nitric oxide scavenger. Correspondingly, ABA-insensitive behaviors in rbohD stomata were not affected by either the mutation of HY1 or its ectopic expression in the rbohD background, both of which responded significantly to exogenous ROS. These data indicate that HY1 functioned negatively and acted upstream of ABI4 in drought signaling, which was casually dependent on the RbohD-derived ROS in the regulation of stomatal closure.
Cryo-EM structure of Neurospora crassa respiratory complex IV
Authors: Bausewein Thomas , Nussberger Stephan , Kühlbrandt Werner
Published: June 2019

In fungi, the mitochondrial respiratory chain complexes (complexes I–IV) are responsible for oxidative phosphorylation, as in higher eukaryotes. Cryo-EM was used to identify a 200 kDa membrane protein from Neurospora crassa in lipid nanodiscs as cytochrome c oxidase (complex IV) and its structure was determined at 5.5 Å resolution. The map closely resembles the cryo-EM structure of complex IV from Saccharomyces cerevisiae. Its ten subunits are conserved in S. cerevisiae and Bos taurus, but other transmembrane subunits are missing. The different structure of the Cox5a subunit is typical for fungal complex IV and may affect the interaction with complex III in a respiratory supercomplex. Additional density was found between the matrix domains of the Cox4 and Cox5a subunits that appears to be specific to N. crassa.
Crystal structure and pseudosymmetry analysis of the triclinic prodrug cloxazolam (Z′ = 4)
Authors: Garraza María Soledad , Gimenez María Emilia , Vega Daniel Roberto , Baggio Ricardo
Published: June 2019

The prodrug cloxazolam [systematic name: 13-chloro-2-(2-chlorophenyl)-3-oxa-6,9-diazatricyclo[8.4.0.02,6]tetradeca-1(10),11,13-trien-8-one], C17H14Cl2N2O2, crystallizes in the triclinic space group P\overline{1}, with four chemically identical independent molecules in the asymmetric unit. However, in order to facilitate the analysis of the striking pseudosymmetry relating the four independent molecules, the structure has been analysed and reported in the nonconventional centred B\overline{1} space-group setting. Pseudosymmetry is an eminently local property, valid only in the realm of the unit-cell boundary and not propagating to the whole crystal structure. It has been analyzed using the MP procedure described in the preceding article [Baggio (2019). Acta Cryst. C75, 837–850]. The molecules consist of a rigid core made up of three rings (five-, six- and seven-membered) and an extra six-membered ring joined to the latter group by a single C—C bond, together with a clamping intramolecular C—H...O interaction preventing free rotation and providing additional rigidity. The four molecules in the asymmetric unit pair into dimers with almost exact twofold pseudosymmetry, further linked into (001) slabs as the building bricks of the structure. Interpenetration of slabs finally leads to a three-dimensional structure of unusual compactness for an organic structure, with a Kitaigorodskii packing index of ca 0.71.
Crystal structure of (S)-3-O-geranylgeranylglyceryl phosphate synthase fromThermoplasma acidophilumin complex with the substratesn-glycerol 1-phosphate
Authors: Nemoto Naoki , Miyazono Ken-ichi , Tanokura Masaru , Yamagishi Akihiko
Published: June 2019

(S)-3-O-Geranylgeranylglyceryl phosphate synthase (GGGPS) catalyzes the initial ether-bond formation betweensn-glycerol 1-phosphate (G1P) and geranylgeranyl pyrophosphate to synthesize (S)-3-O-geranylgeranylglyceryl phosphate in the production of an archaeal cell-membrane lipid molecule. Archaeal GGGPS proteins are divided into two groups (group I and group II). In this study, the crystal structure of the archaeal group II GGGPS fromThermoplasma acidophilum(TaGGGPS) was determined at 2.35 Å resolution. The structure of TaGGGPS showed that it has a TIM-barrel fold, the third helix of which is disordered (α3*), and that it forms a homodimer, although a pre-existing structure of an archaeal group II GGGPS (fromMethanothermobacter thermautotrophicus) showed a hexameric form. The structure of TaGGGPS showed the precise G1P-recognition mechanism of an archaeal group II GGGPS. The structure of TaGGGPS and molecular-dynamics simulation analysis showed fluctuation of the β2–α2, α3* and α5a regions, which is predicted to be important for substrate uptake and/or product release by TaGGGPS.
Structures of the transcriptional regulator BgaR, a lactose sensor
Authors: Newman Janet , Caron Karine , Nebl Tom , Peat Thomas S.
Published: June 2019

The structure of BgaR, a transcriptional regulator of the lactose operon inClostridium perfringens, has been solved by SAD phasing using a mercury derivative. BgaR is an exquisite sensor of lactose, with a binding affinity in the low-micromolar range. This sensor and regulator has been captured bound to lactose and to lactulose as well as in a nominal apo form, and was compared with AraC, another saccharide-binding transcriptional regulator. It is shown that the saccharides bind in the N-terminal region of a jelly-roll fold, but that part of the saccharide is exposed to bulk solvent. This differs from the classical AraC saccharide-binding site, which is mostly sequestered from the bulk solvent. The structures of BgaR bound to lactose and to lactulose highlight how specific and nonspecific interactions lead to a higher binding affinity of BgaR for lactose compared with lactulose. Moreover, solving multiple structures of BgaR in different space groups, both bound to saccharides and unbound, verified that the dimer interface along a C-terminal helix is similar to the dimer interface observed in AraC.