bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the surrogacy of multiple vaccine-induced immune response biomarkers in HIV vaccine trials
Authors: Dasgupta Sayan , Huang Ying
Published: September 2019

Identifying biomarkers as surrogates for clinical endpoints in randomized vaccine trials is useful for reducing study duration and costs, relieving participants of unnecessary discomfort, and understanding vaccine-effect mechanism. In this article, we use risk models with multiple vaccine-induced immune response biomarkers to measure the causal association between a vaccine’s effects on these biomarkers and that on the clinical endpoint. In this setup, our main objective is to combine and select markers with high surrogacy from a list of many candidate markers, allowing us to get a more parsimonious model which can potentially increase the predictive quality of the true markers. To address the missing “potential” biomarker value if a subject receives placebo, we utilize the baseline immunogenicity predictor design augmented with a “closeout placebo vaccination” group. We then impute the missing potential marker values and conduct marker selection through a stepwise resampling and imputation method called stability selection. We test our proposed strategy under relevant simulation settings and on (partially simulated) biomarker data from a HIV vaccine trial (RV144).
Contrasting evolutionary processes drive morphological and genetic differentiation in a subtropical fir (Abies, Pinaceae) species complex
Authors: Cruz-Nicolás Jorge , Giles-Pérez Gustavo , González-Linares Eréndira , Múgica-Gallart Julia , Lira-Noriega Andrés , Gernandt David S , Eguiarte Luis E , Jaramillo-Correa Juan P
Published: September 2019

Interacting stochastic and selective forces drive population and species divergence. Such interaction may generate contrasting clines between genetic and phenotypic factors, which can be related to either geographical or environmental variation depending on the predominant evolutionary force (which in its turn is partly determined by population size). Here, we investigated whether the morphological and genetic differentiation across a species complex in Abies in central Mexico fits isolation by distance (IBD) or isolation-by-adaptation (IBA) frameworks. This complex includes two species (A. religiosa and A. flinckii) with discernible morphological and environmental differences and dissimilar range sizes. After comparing variation at nuclear SSR loci and diagnostic morphological traits of needles with the climate variables contributing to ecological differentiation, we found that the widely distributed A. religiosa has more genetic diversity and is morphologically more heterogeneous than the geographically restricted A. flinckii. Morphological differentiation at three physiologically important traits (needle thickness, number of stomata rows and location of the resin duct) is significantly correlated with geography in A. flinckii (indicative of IBD), but is significantly associated with climate variation in A. religiosa (suggesting IBA). In agreement with quantitative genetics theory, PST (phenotypic differentiation)-G’ST (genetic differentiation) comparisons indicate contrasting contributions of putatively adaptive (A. religiosa) and stochastic (A. flinckii) factors to the morphological differentiation of species related to their population size. The integration of such quantitative genetic/evolutionary aspects may reinforce species descriptions and help in disentangling resilient taxonomic discordance.
Prepared for a journey into wounded communities – and into the self
Authors: van der Watt Phia
Published: October 2019

Community development workers inevitably engage with communal wounding, inflicted over generations by systemic oppression and deprivation. By ignoring this complexity and focussing on surface-level activities, we can unconsciously inflict new wounds. Or, we can consciously engage with the wounds and facilitate healing. The latter implies a complex process, because a journey into the heart of community implies that the workers look into the mirror of their own lived experiences and thereby becomes a journey into the self. Careful preparation of the workers is thus critical. The complexity of in-depth work with communities receives limited recognition in the literature; with the result that there is gap in research on the deliberate and systematic preparation of workers for such work. The aim of the article is to identify critical aspects of such preparation. A family support programme in South Africa was used as case study. The article suggests the healing journey of the workers (‘start-with-self’) as the basis of the approach. Increased self-knowledge is used to guide content and facilitation and protect workers from projecting unconscious issues onto participants’ processes, conflating the different journeys and compounding the fear-to-risk. The benefits of reflection/mirroring, metaphors, integrating the insider/outsider roles and ‘healing questions’ are discussed. The mentor plays a critical role. The article concludes that communal wounds cannot be allowed to fester; instead it is possible and critical to prepare workers to engage with integrity with intergenerational wounding, thereby limiting the unconscious inflicting of new wounds to the community and the worker.
Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview
Authors: MacLennan Calman A , Aguilar Anastazia Older , Steele A Duncan
Published: September 2019

In recent years, controlled human infection models (CHIMs) have become available for a range of infectious agents and have proved invaluable for understanding the disease process, pathogenesis, and mechanisms of immunity. CHIM studies have also contributed significantly to advancing development of a number of vaccines by providing an indication of vaccine efficacy. The Shigella CHIM has been established in 3 sites in the United States, and it is likely that the CHIM will play an important regulatory role for advancing the range of Shigella vaccine candidates that are currently in development. This supplement describes the harmonization of best practices across sites, with a view to maximizing the contribution that CHIM studies can make to Shigella vaccine development.
Scrub Typhus and the Misconception of Doxycycline Resistance
Authors: Wangrangsimakul Tri , Phuklia Weerawat , Newton Paul N , Richards Allen L , Day Nicholas P J
Published: September 2019

Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific region with more than a billion people at risk. Treatment with antibiotics such as doxycycline or chloramphenicol is effective for the majority of patients. In the 1990s, reports from northern Thailand raised a troubling observation; some scrub typhus patients responded poorly to doxycycline, which investigators attributed to doxycycline resistance. Despite the controversial nature of these reports, independent verification was neglected, with subsequent studies speculating on the role of doxycycline resistance in contributing to failure of treatment or prophylaxis. In this review, we have outlined the evidence for drug-resistant Orientia tsutsugamushi, assessed the evidence for doxycycline resistance, and highlight more recent findings unsupportive of doxycycline resistance. We conclude that doxycycline resistance is a misconception, with treatment outcome likely to be determined by other bacterial, host, and pharmacological factors.
Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy
Authors: Uil Melissa , Hau Chi M , Ahdi Mohamed , Mills James D , Kers Jesper , Saleem Moin A , Florquin Sandrine , Gerdes Victor E A , Nieuwland Rienk , Roelofs Joris J T H
Published: September 2019

Background

Diabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer.

Methods

In this study, we aimed to characterize the cellular origin and miRNA content of EVs in plasma samples of type 2 diabetes patients at various stages of DN. Type 2 diabetes patients were classified in three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. The concentration and cellular origin of plasma EVs were measured by flow cytometry. A total of 752 EV miRNAs were profiled in 18 subjects and differentially expressed miRNAs were validated.

Results

Diabetic patients with microalbuminuria and/or macroalbuminuria showed elevated concentrations of total EVs and EVs from endothelial cells, platelets, leucocytes and erythrocytes compared with diabetic controls. miR-99a-5p was upregulated in macroalbuminuric patients compared with normoalbuminuric and microalbuminuric patients. Transfection of miR-99a-5p in cultured human podocytes downregulated mammalian target of rapamycin (mTOR) protein expression and downregulated the podocyte injury marker vimentin.

Conclusions

Type 2 diabetes patients with microalbuminuria and macroalbuminuria display differential EV profiles. miR-99a-5p expression is elevated in EVs from macroalbuminuria and mTOR is its validated mRNA target.
Precipitation of de novo atrial fibrillation during Shockwave Intravascular Lithotripsy® after pacing capture during the treatment of proximal right coronary artery disease: a case report
Authors: Curtis Elizabeth , Khan Ali , El-Jack Seif , Glenie Tim
Published: September 2019

Background

Shockwave Intravascular Lithotripsy® has been recently translated to the treatment of coronary artery disease with a long history of use for ureteric stones where it has been observed to have caused cardiac arrhythmias. The risk of arrhythmia with the use of this method in coronary artery disease is currently unknown.

Case summary

A 72-year-old man undergoing planned percutaneous intervention to a heavily calcified proximal right coronary artery (RCA) lesion using S-IVL developed pacing capture from the device and subsequently new atrial fibrillation (AF) during the procedure. The technique resulted in successful treatment of the coronary lesion and he spontaneously reverted within an hour of the procedure before discharge.

Discussion

We postulate the pulsed energy delivered to break apart the calcium has the capacity to cause depolarization, and therefore, affect cardiac rhythm as seen in treatment of renal stones in the past before the introduction of routine electrocardiogram (ECG) gating. In this case, the proximity of the RCA to the right atrium caused short circuiting and development of AF in a susceptible patient. Both the pacing implications and the risk of arrhythmia needs to be investigated further and the potential for ECG gating of the pulsed energy to mitigate this effect needs to be explored to enhance the safety of this technique.
Exploring the midline soft tissue surface changes from 12 to 15 years of age in three distinct country population cohorts
Authors: Richmond Stephen , Zhurov Alexei I , Ali Azrul Bin Mohd , Pirttiniemi Pertti , Heikkinen Tuomo , Harila Virpi , Silinevica Signe , Jakobsone Gundega , Urtane Ilga
Published: September 2019

Introduction

Several studies have highlighted differences in the facial features in a White European population. Genetics appear to have a major influence on normal facial variation, and environmental factors are likely to have minor influences on face shape directly or through epigenetic mechanisms.

Aim

The aim of this longitudinal cohort study is to determine the rate of change in midline facial landmarks in three distinct homogenous population groups (Finnish, Latvian, and Welsh) from 12.8 to 15.3 years of age. This age range covers the pubertal growth period for the majority of boys and girls.

Methods

A cohort of children aged 12 were monitored for facial growth in three countries [Finland (n = 60), Latvia (n = 107), and Wales (n = 96)]. Three-dimensional facial surface images were acquired (using either laser or photogrammetric methods) at regular intervals (6–12 months) for 4 years. Ethical approval was granted in each country. Nine midline landmarks were identified and the relative spatial positions of these surface landmarks were measured relative to the mid-endocanthion (men) over a 4-year period.

Results

This study reports the children who attended 95 per cent of all scanning sessions (Finland 48 out of 60; Latvia 104 out of 107; Wales 50 out of 96). Considerable facial variation is seen for all countries and sexes. There are clear patterns of growth that show different magnitudes at different age groups for the different country groups, sexes, and facial parameters. The greatest single yearly growth rate (5.4 mm) was seen for Welsh males for men–pogonion distance at 13.6 years of age. Males exhibit greater rates of growth compared to females. These variations in magnitude and timings are likely to be influenced by genetic ancestry as a result of population migration.

Conclusion

The midline points are a simple and valid method to assess the relative spatial positions of facial surface landmarks. This study confirms previous reports on the subtle differences in facial shapes and sizes of male and female children in different populations and also highlights the magnitudes and timings of growth for various midline landmark distances to the men point.
Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial
Authors: Hermida Ramón C , Crespo Juan J , Domínguez-Sardiña Manuel , Otero Alfonso , Moyá Ana , Ríos María T , Sineiro Elvira , Castiñeira María C , Callejas Pedro A , Pousa Lorenzo , Salgado José L , Durán Carmen , Sánchez Juan J , Fernández José R , Mojón Artemio , Ayala Diana E ,   for the Hygia Project Investigators
Published: October 2019

Aims

The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.

Methods and results

In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio—adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event—of the primary CVD outcome [0.55 (95% CI 0.50–0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34–0.56)], myocardial infarction [0.66 (0.52–0.84)], coronary revascularization [0.60 (0.47–0.75)], heart failure [0.58 (0.49–0.70)], and stroke [0.51 (0.41–0.63)].

Conclusion

Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

Trial registration

ClinicalTrials.gov, number NCT00741585.
Vitamin D deficiency in a population of migrant children: an Italian retrospective cross-sectional multicentric study
Authors: Ceccarelli Manuela , Chiappini Elena , Arancio Rosangela , Zaffaroni Mauro , La Placa Simona , D’Andrea Marianna , de Waure Chiara , Da Riol Rosalia Maria , Valentini Piero ,   on the behalf of National Working Group for the Migrant Children of the Italian Society of Pediatrics (NWGMC-ISP)
Published: September 2019

Background

Vitamin D is a hot topic in the scientific community. Its deficiency and the implications for the children’s health became increasingly discussed during the last 20 years. The main aim of this retrospective study was to determinate the prevalence of vitamin D metabolism disorders in a population of adopted children and their risk factors.

Methods

We gathered data from 2140 children observed in five different National Working Group for the Migrant Children of the Italian Society of Pediatrics centers, variously located in Italy. Serum 25-hydroxy (OH)-D concentration was used to determine every child’s vitamin D status, defined as severely deficient (serum 25-OH-D < 10 ng/ml), moderately deficient (serum 25-OH-D {≥10 ng/ml U < 20 ng/ml}), mildly deficient (serum 25-OH-D {≥20 ng/ml U < 30 ng/ml}) and normal (serum 25-OH-D ≥ 30 ng/ml).

Results

Mean value of serum 25-OH-D was 22.7 ng/ml (SD ± 12.1). Vitamin D status was deemed as normal in 483 (22.6%) children, mildly deficient in 718 (33.6%) children, moderately deficient in 730 (34.1%) children and severely deficient in 209 (9.8%) children.

Conclusions

A very high percentage of migrant children is affected by hypovitaminosis D, with a strong association with age, geographic origin, season of blood sample collection and time spent in Italy after the arrival. This finding highlights the need for corrective measures. However, these measures cannot be applied without increasing the access of migrant populations to healthcare services.
Nutritional requirements for Lactobacillus vini growth in sugarcane derivative substrate of ethanol fermentation
Authors: da Silva Paula Katharina Nogueira , Mendonça Allyson Andrade , de Miranda Andre Ribas , Calazans Tiago Luiz Santana , de Souza Rafael Barros , de Morais Marcos Antonio
Published: September 2019

Lactobacillus vini is a bacterial contaminant found in industrial environments of winemaking and fuel-ethanol fermentation. However, there has been no standard analysis of its physiology that can pinpoint its adaptive traits to these kinds of environments. In view of this lack of information, the aim of this study is to determine the nutritional factors that lead to the growth of L. vini in the industrial plants of fuel-ethanol. First of all, the limited growth of this bacterium was studied in the industrial substrate, which was improved by nutritional supplementation with amino acids, and its homofermentative status was confirmed. Metabolite analysis showed that citrate is a growth factor of paramount importance for this bacterium in industrial processes through pyruvate metabolization, and increases ATP production and biomass formation. Furthermore,e acetate uptake, either from the medium or generated from citrate metabolism, was assimilated for biomass production. Hence, a metabolic model was designed to describe the role of citrate and acetate in the growth of L. vini that could be tested on other lactobacilli.
Endoscopic stricturotomy in the treatment of anastomotic strictures in inflammatory bowel disease (IBD) and non-IBD patients
Authors: Zhang Long-Juan , Lan Nan , Wu Xian-Rui , Shen Bo
Published: September 2019

Backgrounds

Endoscopic stricturotomy (ESt) has been shown to be effective in treating inflammatory bowel disease (IBD)-associated anastomotic strictures. However, the outcome of ESt in benign, non-IBD conditions has not been described. The aim of this study was to evaluate the outcome of ESt in the management of IBD and non-IBD-associated strictures.

Methods

Data of all consecutive IBD and non-IBD patients with benign anastomotic strictures treated with ESt from 2009 to 2016 were extracted. The primary outcomes were surgery-free survival and procedure-related complications.

Results

A total of 49 IBD and 15 non-IBD patients were included in this study. The IBD group included 25 patients with Crohn’s disease and 24 with ulcerative colitis and ileal pouches. Underlying diseases in the non-IBD group included colorectal cancer (n = 7), diverticulitis (n = 5), large bowel prolapse (n = 2), and constipation (n = 1). Immediate technical success was achieved in all patients in both groups. Bleeding complications occurred on five occasions (4.7% per procedure) in the IBD group, while no complication occurred in the non-IBD group (P = 0.20). Stricture improvement on follow-up endoscopy was found in 10 (20.4%) and 5 (33.3%) patients in the IBD and non-IBD groups, respectively (P = 0.32). Six (12.2%) patients in the IBD group and four (26.7%) patients in the non-IBD group eventually required stricture-related surgery (P = 0.23). IBD patients appeared to have a higher tendency for maintaining surgery-free after the procedure than non-IBD patients (P = 0.08).

Conclusions

Endoscopic stricturotomy was shown to have comparable outcomes, though non-IBD patients seem to have a higher need for subsequent surgery but a lower complication rate than IBD patients.
Mapping lithological boundaries in mines with array seismology and in situ acoustic emission monitoring
Authors: Pisconti Angelo , Plenkers Katrin , Philipp Joachim , Thomas Christine
Published: October 2019

Knowledge of the position of lithological boundaries is key information for a realistic interpretation of geological settings. Especially in the mining environment, the exact knowledge of geometrical boundaries and characteristics of rock structures has a great impact for both economic decisions and safety awareness. For this purpose, we investigate the P-coda of high frequency acoustic emission (AE) events (picoseismicity) and test the application of array seismology techniques, usually used to study the Earth's deep interior, on a much smaller scale in a mining environment. In total 52 events were used, all of them recorded in the Asse II salt mine in Lower Saxony (Germany) using a network of 16 piezoelectric sensors. Many of these events show a pulse-like arrival in the late P-coda, suggesting the presence of a well-defined structure which scatters seismic energy. To explore the directional information of the signals in the seismograms we use the sliding-window slowness-backazimuth analysis, performed on the waveform envelope of the entire recording. Strong direct P-wave arrivals are clearly visible with observed slowness and backazimuth as expected for a homogenous medium. This implies straight ray paths from event to sensors indicating that the medium between the events and the sensors is homogeneous for wavelengths larger than about 60 cm. In the late P-coda we observe out-of-plane arrivals from southeast and, assuming single P-to-P scattering, we find that the scatterers responsible for these observations are clustered in space defining a sharp reflector corresponding to a known lithological boundary located at the southern flank of the salt dome. In agreement with the established geological model we observe no other dominant reflections in the analysed waveforms that would indicate previously unknown lithological boundaries. This study shows that array seismology can be applied to AEs in mines to gain more information on structures and heterogeneities located in the vicinity of the monitored rock volume. In micro-acoustically monitored mines, this technique could be a valuable addition to increase hazard awareness and mining efficiency at little or no extra costs.
Crustal structure variations in south-central Mexico from receiver functions
Authors: Rodríguez-Domínguez Miguel , Pérez-Campos Xyoli , Montealegre-Cázares Conrado , Clayton Robert W , Cabral-Cano Enrique
Published: October 2019

Mexico has a complex geological history that is typified by the distinctive terranes that are found in the south-central region. Crustal thickness variations often correlate with geological terranes that have been altered by several processes in the past, for example aerial or subduction erosion, underplating volcanic material or rifting but few geophysical studies have locally imaged the entire continental crust in Mexico. In this paper, the thickness of three layers of the crust in south-central Mexico is determined. To do this, we use P- and S-wave receiver functions (RF) from 159 seismological broad-band stations. Thanks to its adaptive nature, we use an empirical mode decomposition (EMD) algorithm to reconstruct the RFs into intrinsic mode functions (IMF) in order to enhance the pulses related to internal discontinuities within the crust. To inspect possible lateral variations, the RFs are grouped into quadrants of 90°, and their amplitudes are mapped into the thickness assuming a three-layer model. Using this approach, we identify a shallow sedimentary layer with a thickness in the range of 1–4 km. The upper-crust was estimated to be of a few kilometers (<10 km) thick near the Pacific coast, and thicker, approximately 15 km in central Oaxaca and under the Trans-Mexican Volcanic Belt (TMVB). Close to the Pacific coast, we infer a thin crust of approximately 16 ± 0.9 km, while in central Oaxaca and beneath the TMVB, we observe a thicker crust ranging between 30 and 50 km ± 2.0 km. We observe a crustal thinning, of approximately 6 km, from central Oaxaca (37 ± 1.9 km) towards the Gulf of Mexico, under the Veracruz Basin, where we estimate a crustal thickness of 31.6 ± 1.9 km. The boundary between the upper and lower crust in comparison with the surface of the Moho do not show significant variations other than the depth difference. We observe small crustal variations across the different terranes on the study area, with the thinnest crust located at the Pacific coast and Gulf of Mexico coast. The thickest crust is estimated to be in central Oaxaca and beneath the TMVB.
Delivering on the European Pillar of Social Rights: The New Directive on Transparent and Predictable Working Conditions in the European Union
Authors: Bednarowicz Bartłomiej
Published: October 2019

Chapter II of the European Pillar of Social Rights envisages fair working conditions that are further spelled out in two principles on secure and adaptable employment (Principle 5) and information about employment conditions and protection in dismissals (Principle 7). In order to deliver on this framework, in December 2017 the European Commission presented an ambitious and far-reaching proposal for a Directive on transparent and predictable working conditions in the European Union that would repeal Directive 91/533/EC on an employer’s obligation to inform employees of the conditions applicable to the contract or employment relationship. The proposal, after a series of uneasy negotiations in the Parliament and the Council, and with substantial modifications, was subsequently adopted in June 2019. Against this background, the main aim of this note is to analyse the new Directive (EU) 2019/1152. This piece focuses firstly on the Directive’s nuanced hybrid personal ambit of application. Secondly, it examines its material scope of application and sheds some light on the new set of rights and entitlements available to workers, including novel enforcement mechanisms. Finally, the note provides a critical assessment of the Directive with the aim of unveiling its potential to boost workers’ rights in the European Union, in particular those engaged in non-standard forms of employment, who are especially prone to experiencing precarious working conditions, such as on-demand and platform workers.
Whose Autonomy is it Anyway? Freedom of Contract, the Right to Work and the General Principles of EU Law
Authors: O’Connor Niall
Published: September 2019

Just how significant is the freedom of contract found in Article 16 of the EU Charter of Fundamental Rights for the regulation of the employment relationship? For the first half of its existence, few could have foreseen that Article 16 would soon be at the centre of debates surrounding the place of business freedoms within EU employment law. This has changed in the wake of a number of controversial decisions in which the Court of Justice of the EU relied on Article 16 to undermine the effectiveness of employee-protective legislation. The article begins by setting out the nature of freedom of contract in EU law and its effects in the employment context. This is followed by a consideration of the relationship between the general principles and the Charter. Critical Legal Studies is relied on to show that existing arguments as to the use of Article 16 as a radical tool in the employment context have been both exaggerated and underplayed. Finally, potential counterweights to freedom of contract are examined, notably the right to work as both a general principle and Charter right.
Advances in the Development of Therapeutics for Cytomegalovirus Infections
Authors: Acosta Edward , Bowlin Terry , Brooks Jennifer , Chiang Lillian , Hussein Islam , Kimberlin David , Kauvar Lawrence M , Leavitt Randi , Prichard Mark , Whitley Richard
Published: September 2019

The development of therapeutics for cytomegalovirus (CMV) infections, while progressing, has not matched the pace of new treatments of human immunodeficiency virus (HIV) infections; nevertheless, recent developments in the treatment of CMV infections have resulted in improved human health and perhaps will encourage the development of new therapeutic approaches. First, the deployment of ganciclovir and valganciclovir for both the prevention and treatment of CMV infections and disease in transplant recipients has been further improved with the licensure of the efficacious and less toxic letermovir. Regardless, late-onset CMV disease, specifically pneumonia, remains problematic. Second, the treatment of congenital CMV infections with valganciclovir has beneficially improved both hearing and neurologic outcomes, both fundamental advances for these children. In these pediatric studies, viral load was decreased but not eliminated. Thus, an important lesson learned from studies in both populations is the need for new antiviral agents and the necessity for combination therapies as has been shown to be beneficial in the treatment of HIV infections, among others. The development of monoclonal antibodies, sirtuins, and cyclopropovir may provide new treatment options.
Isolation and Molecular Characterization of Tick-Borne Relapsing Fever Borrelia Infecting Ornithodoros (Pavlovskyella) verrucosus Ticks Collected in Ukraine
Authors: Filatov Serhii , Krishnavajhala Aparna , Armstrong Brittany A , Kneubehl Alexander R , Nieto Nathan C , Pérez De León Adalberto A , Lopez Job E
Published: September 2019

Background

Tick-borne relapsing fever (TBRF) is a neglected zoonotic bacterial disease known to occur on 5 continents. We report a laboratory-acquired case of TBRF caused by Borrelia caucasica, which is endemic in Ukraine and transmitted by Ornithodoros verrucosus ticks.

Methods

We isolated spirochetes and characterized them by partially sequencing the 16s ribosomal ribonucleic acid (rrs), flagellin (flaB), and deoxyribonucleic acid gyrase (gyrB) genes and conducting a phylogenetic analysis.

Results

These analyses revealed a close relationship of Ukrainian spirochetes with the Asian TBRF species, Borrelia persica. The taxonomic and nomenclature problems related to insufficient knowledge on the spirochetes and their vectors in the region are discussed.

Conclusions

Although these findings enhance our understanding of species identities for TBRF Borrelia in Eurasia, further work is required to address the neglected status of TBRF in this part of the world. Public health practitioners should consider TBRF and include the disease into differential diagnosis of febrile illnesses with unknown etiology.
Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members
Authors: Park Young Hyun , Chungu Kelly , Lee Su Bin , Woo Seung Je , Cho Ho Yeon , Lee Hong Jo , Rengaraj Deivendran , Lee Ji-Ho , Song Chang-Seon , Lim Jeong Mook , Han Jae Yong
Published: October 2019

Background

Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear.

Methods

In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family.

Results

We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B.

Conclusions

Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.
Uncovering the relationship between food-related discussion on Twitter and neighborhood characteristics
Authors: Vydiswaran V G Vinod , Romero Daniel M , Zhao Xinyan , Yu Deahan , Gomez-Lopez Iris , Lu Jin Xiu , Iott Bradley E , Baylin Ana , Jansen Erica C , Clarke Philippa , Berrocal Veronica J , Goodspeed Robert , Veinot Tiffany C
Published: September 2019

Objective

Initiatives to reduce neighborhood-based health disparities require access to meaningful, timely, and local information regarding health behavior and its determinants. We examined the validity of Twitter as a source of information for neighborhood-level analysis of dietary choices and attitudes.

Materials and Methods

We analyzed the “healthiness” quotient and sentiment in food-related tweets at the census tract level, and associated them with neighborhood characteristics and health outcomes. We analyzed keywords driving the differences in food healthiness between the most and least-affluent tracts, and qualitatively analyzed contents of a random sample of tweets.

Results

Significant, albeit weak, correlations existed between healthiness and sentiment in food-related tweets and tract-level measures of affluence, disadvantage, race, age, U.S. density, and mortality from conditions associated with obesity. Analyses of keywords driving the differences in food healthiness revealed foods high in saturated fat (eg, pizza, bacon, fries) were mentioned more frequently in less-affluent tracts. Food-related discussion referred to activities (eating, drinking, cooking), locations where food was consumed, and positive (affection, cravings, enjoyment) and negative attitudes (dislike, personal struggles, complaints).

Discussion

Tweet-based healthiness scores largely correlated with offline phenomena in the expected directions. Social media offer less resource-intensive data collection methods than traditional surveys do. Twitter may assist in informing local health programs that focus on drivers of food consumption and could inform interventions focused on attitudes and the food environment.

Conclusions

Twitter provided weak but significant signals concerning food-related behavior and attitudes at the neighborhood level, suggesting its potential usefulness for informing local health disparity reduction efforts.
Emotion sharing in remote patient monitoring of patients with chronic kidney disease
Authors: Huang Robin , Liu Na , Nicdao Mary Ann , Mikaheal Mary , Baldacchino Tanya , Albeos Annabelle , Petoumenos Kathy , Sud Kamal , Kim Jinman
Published: October 2019

Objective

To investigate the relationship between emotion sharing and technically troubled dialysis (TTD) in a remote patient monitoring (RPM) setting.

Materials and Methods

A custom software system was developed for home hemodialysis patients to use in an RPM setting, with focus on emoticon sharing and sentiment analysis of patients’ text data. We analyzed the outcome of emoticon and sentiment against TTD. Logistic regression was used to assess the relationship between patients’ emotions (emoticon and sentiment) and TTD.

Results

Usage data were collected from January 1, 2015 to June 1, 2018 from 156 patients that actively used the app system, with a total of 31 159 dialysis sessions recorded. Overall, 122 patients (78%) made use of the emoticon feature while 146 patients (94%) wrote at least 1 or more session notes for sentiment analysis. In total, 4087 (13%) sessions were classified as TTD. In the multivariate model, when compared to sessions with self-reported very happy emoticons, those with sad emoticons showed significantly higher associations to TTD (aOR 4.97; 95% CI 4.13–5.99; P = < .001). Similarly, negative sentiments also revealed significant associations to TTD (aOR 1.56; 95% CI 1.22–2; P = .003) when compared to positive sentiments.

Discussion

The distribution of emoticons varied greatly when compared to sentiment analysis outcomes due to the differences in the design features. The emoticon feature was generally easier to understand and quicker to input while the sentiment analysis required patients to manually input their personal thoughts.

Conclusion

Patients on home hemodialysis actively expressed their emotions during RPM. Negative emotions were found to have significant associations with TTD. The use of emoticons and sentimental analysis may be used as a predictive indicator for prolonged TTD.
The Greenconsumption Effect: How Using Green Products Improves Consumption Experience
Authors: Tezer Ali , Bodur H Onur
Published: September 2019

In many situations, consumers use green products without a deliberate choice to use or purchase the product. This research explores how using a green product (e.g., a pair of headphones made from recycled materials) influences the enjoyment of the accompanying consumption experience (e.g., listening to music), even if consumers have not deliberately chosen or purchased the product. Five experiments in actual consumption settings revealed that using a green (vs. conventional) product enhances the enjoyment of the accompanying consumption experience, referred to as the greenconsumption effect. Merely using a green product makes consumers perceive an increase in the extent to which they are valued as individuals by society, which leads to warm glow feelings, and consequently enhances the enjoyment of the accompanying consumption experience. When consumers experience low social worth, the positive effect of using green products on the accompanying consumption experience is amplified. The greenconsumption effect disappears when the negative environmental impact of the green product attribute is low. From a managerial standpoint, the current research identifies instances where brands can benefit from going green and encourages marketers, especially service providers, to promote green products that are instrumental in consumption experiences.
Grand Corruption and the International Criminal Court in the ‘Venezuela Situation’
Authors: Roht-Arriaza Naomi , Martínez Santiago
Published: October 2019

Venezuela’s ongoing crisis has resulted in the first-ever joint request from states parties to the International Criminal Court (ICC) to open a preliminary examination. The evidence presented until now of crimes against humanity focuses on attacks on political opposition and demonstrators. We contend that the situation in Venezuela is not fully comprehensible, and the referral falls short, without the use of the lens of grand corruption. We describe what we mean by ‘grand corruption’, how it has corroded Venezuela, and why grand corruption and the atrocities are connected. We explain how every step of the preliminary examination process is better understood if a corruption-infused analysis is brought to bear upon it. We then turn to some caveats and limiting considerations. Finally, we draw some implications for other, increasingly common, situations where grave violations of international criminal law take place because of, and are maintained by, systems of kleptocracy.
BDI logic applied to a dialogical interpretation of human–machine cooperative dialogues
Authors: Sierra Pablo
Published: October 2019

We first define a language for the dialogical logic and the models that the language generates. This language is thought to capture the structure of the dialogues captured by Lekta—a software framework oriented to the design and implementation of natural language processing-related applications—and its users. These dialogues are defined as cooperative dialogues in which the dialogical logic perspective of a dialogue seen as a competition is shifted into a perspective in which both agents cooperate towards a common goal. Later we define a BDI temporal logic based on a modal framework that we will use to study the beliefs, desires and intentions of both agents based on the model generated by the dialogical logic.
Effects of Aqueous Extracts from Amazon Plants on Plutella xylostella (Lepidoptera: Plutellidae) and Brevicoryne brassicae (Homoptera: Aphididae) in Laboratory, Semifield, and field trials
Authors: Cerda Hugo , Carpio Carlos , Ledezma-Carrizalez A Carolina , Sánchez Jessica , Ramos Luis , Muñoz-Shugulí Cristina , Andino Marco , Chiurato Matteo
Published: September 2019

We evaluated the insecticide activities of aqueous extracts of five species of plants from the Ecuadorian Amazon (Deguelia utilis (ACSm.) AMGAZEVEDO (Leguminosae: Papilionoideae), Xanthosoma purpuratum K. Krause (Alismatales: Araceae), Clibadium sp. (Asteracea: Asterales), Witheringia solanacea L'Hér (Solanales: Solanaceae), and Dieffenbachia costata H. Karst. ex Schott (Alismatales: Araceae)) plus Cymbopogon citratus Stapf. (Poales: Poaceae) under laboratory, open-field conditions in Plutella xylostella L. (diamondback moth), and semifield conditions in Brevicoryne brassicae L. Tap water was used as a negative control, and synthetic insecticides were used as positive controls. In a laboratory bioassay, aqueous extracts of D. utilis resulted in P. xylostella larval mortality. In contrast to chlorpyrifos, all botanicals were oviposition deterrents. All extracts except Clibadium sp. decreased leaf consumption by P. xylostella larvae. In semifield experiments, D. utilis, Clibadium sp., D. costata, and X. purpuratum initially controlled the population of B. brassicae, but 7 d after application, all botanicals except the D. utilis lost their ability to control the pest. In field experiments on broccoli crops in both dry and rainy seasons, the extracts did not control the abundance of P. xylostella, where as a mixture of two insecticides (chlorpyrifos + lambda cyhalothrin) did. These results show some incongruences from laboratory to semifield and field conditions, indicating that more studies, including the identification of the chemicals responsible for the biological activity, its stability, and the effects of chemotypes on insecticidal activity, are needed to understand the potential of these plant species as botanical insecticides.
Clinical impact of renal impairment on the safety and efficacy of S-1 plus oxaliplatin in patients with advanced gastric cancer: a single institutional study
Authors: Demachi Ken , Bando Hideaki , Nomura Hisanaga , Shitara Kohei , Yoshino Takayuki , Yamaguchi Masakazu , Kawasaki Toshikatsu
Published: October 2019

Backgrounds

S-1 plus oxaliplatin appears effective in chemo-naïve patients with advanced gastric cancer. However, comprehensive safety and efficacy data for S-1 plus oxaliplatin is limited for patients with impaired renal function.

Methods

We retrospectively extracted data from advanced gastric cancer patients with normal renal function (normal group, CLcr ≥ 60 ml/min), who were treated with standard doses of S-1 (80 mg/m2) plus oxaliplatin (100 mg/m2), and patients with impaired renal function (impaired group, CLcr < 60 ml/min) who were treated with standard or reduced doses of S-1 (60 mg/m2 or 40 mg/m2) plus standard doses of oxaliplatin. Treatment efficacy and safety between the groups were compared.

Results

Data from 100 normal patients and 42 patients with impaired renal function were extracted. Baseline characteristics differed significantly between the two groups, including age (median, 64 vs 72 years, P < 0.0001) and body surface area (median, 1.68 vs 1.51 m2, P < 0.0001). In the impaired group, 66.6% (28/42) started with a reduced dose. Within the impaired group, more patients had a reduced initial S-1 dose when CLcr <50 ml/min (77.3%). The median progression-free and overall survival between the normal and impaired groups was 6.1 vs 5.7 months (P = 0.698) and 16.1 vs 18.5 months (P = 0.638), respectively.

Conclusions

S-1 plus oxaliplatin in advanced gastric cancer patients with impaired renal function appears safe and has demonstrated efficacy given appropriate dose modification.
Modeling Breast Cancer Using CRISPR-Cas9–Mediated Engineering of Human Breast Organoids
Authors: Dekkers Johanna F , Whittle James R , Vaillant François , Chen Huei-Rong , Dawson Caleb , Liu Kevin , Geurts Maarten H , Herold Marco J , Clevers Hans , Lindeman Geoffrey J , Visvader Jane E
Published: September 2019

Breast cancer is characterized by histological and functional heterogeneity, posing a clinical challenge for patient treatment. Emerging evidence suggests that the distinct subtypes reflect the repertoire of genetic alterations and the target cell. However, the precise initiating events that predispose normal epithelium to neoplasia are poorly understood. Here, we demonstrate that breast epithelial organoids can be generated from human reduction mammoplasties (12 out of 12 donors), thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, we exploited clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 for targeted knockout of four breast cancer–associated tumor suppressor genes (P53, PTEN, RB1, NF1) in mammary progenitor cells from six donors. Mutant organoids gained long-term culturing capacity and formed estrogen-receptor positive luminal tumors on transplantation into mice for one out of six P53/PTEN/RB1–mutated and three out of six P53/PTEN/RB1/NF1–mutated lines. These organoids responded to endocrine therapy or chemotherapy, supporting the potential utility of this model to enhance our understanding of the molecular events that culminate in specific subtypes of breast cancer.