bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter Clinical Investigation of a New Active Osseointegrated Steady-State Implant System
Authors: Mylanus Emmanuel A. M. , Hua Håkan , Wigren Stina , Arndt Susan , Skarzynski Piotr Henryk , Telian Steven A. , Briggs Robert J. S.
Published: August 2020

Objective:

A new active transcutaneous bone conduction hearing implant system that uses piezoelectric technology has been developed: an active osseointegrated steady-state implant system (OSI). This was the first clinical investigation undertaken to demonstrate clinical performance, safety, and benefit of the new implant system.

Study Design and Setting:

A multicenter prospective within-subject clinical investigation was conducted.

Patients:

Fifty-one adult subjects with mixed and conductive hearing loss (MHL/CHL, n = 37) and single-sided sensorineural deafness (SSD, n = 14) were included.

Main Outcome Measure:

Audiological evaluations included audiometric thresholds, speech recognition in noise, and quiet. Hearing and health-related patient-reported outcomes (PROs; health utilities index [HUI], abbreviated profile of hearing aid benefit [APHAB], and speech, spatial of qualities of hearing scale [SSQ]), daily use, surgical and safety parameters were collected.

Results:

Intra- and postoperative complications were few. One implant was removed before activation due to post-surgical infection. Compared with the preoperative softband tests, a significant improvement in speech recognition-in-noise was observed in the MHL/CHL group (–7.3 dB,p ≤ 0.0001) and the SSD group (–8.1 dB,p = 0.0008). In quiet, word recognition improved in the MHL/CHL group, most markedly at lower intensity input of 50 dB SPL (26.7%,p ≤ 0.0001). The results of all PROs showed a significant improvement with the new device compared with preoperative softband in the MHL/CHL group. In the SSD group significant improvements were observed in the APHAB and SSQ questionnaires.

Discussion:

The results confirmed the clinical safety, performance, and benefit of this new treatment modality for subjects with CHL, MHL, and SSD.
The Feasibility of Magnetic Resonance Imaging Without General Anesthesia Using the “Bundle and Scan” Technique for Infants With Sensorineural Hearing Loss
Authors: Grose Elysia , Pigeon Marie , Abdeen Nishard , Belanger Melissa , Schramm David , Vaccani Jean-Philippe
Published: August 2020

Objective:

The purpose of this study is to determine the feasibility of magnetic resonance imaging (MRI) without general anesthesia (GA) for infants being evaluated for sensorineural hearing loss (SNHL) using the bundle and scan technique.

Study Design:

Retrospective study.

Setting:

Pediatric tertiary care hospital.

Patients:

All infants who underwent MRI using the bundle and scan technique as part of the diagnostic workup for unilateral or bilateral SNHL between June 2016 to April 2019 were included.

Main Outcome Measure:

The primary outcome was the proportion of clinically useful images produced.

Results:

We reviewed 21 bundle and scan MRI examinations in infants being evaluated for SNHL. Patients had a median age of 10 (range: 6–25) weeks at the time of MRI. Motion artifact was noted in 38% (8/21) of cases. Eighty-six percent (18/21) of the magnetic resonance images produced using the bundle and scan technique were of diagnostic quality and/or sufficient for surgical planning for cochlear implantation. Repeat imaging with GA was required for three cases (14%) as the initial images were not clinically useful. All patients requiring GA had unilateral SNHL. All patients with bilateral SNHL successfully underwent MRI without GA using the bundle and scan technique.

Conclusion:

The results of our study demonstrate that it is feasible to perform MRI using the bundle and scan technique in the majority of young infants being evaluated for SNHL. This has the potential to help determine cochlear implant candidacy earlier, reduce exposure to GA, and reduce healthcare costs.
Implementation of a Learning Collaborative Model Increases Chlamydia Screening at 37 Family Planning Clinics: Lessons Learned From 3 Cohorts
Authors: Quimby Katherine DeAngelis , Kawatu Jennifer Ewing , Saul Katie Martocci , Schamus Lisa Anne
Published: August 2020

Background

Chlamydia is the most commonly reported notifiable condition in the United States. Chlamydia disproportionately impacts young women and women of color. Annual screening of sexually active women 24 years and younger is recommended.

Methods

Between 2016 and 2019, we facilitated 3 learning collaboratives to increase chlamydia screening at a combined 37 family planning clinics funded by the Planned Parenthood Federation of America, the Office of Population Affairs in the Department of Health and Human Services, and the New York State Department of Health. We applied a consistent learning collaborative approach across the 3 cohorts. Participating clinics sought to improve the proportion of clients screened for chlamydia each month, implemented a standard set of recommended practices, attended virtual learning sessions, reported updates on quality improvement efforts and chlamydia screening data monthly, and provided qualitative feedback in an online final assessment.

Results

Median screening rates increased by 11%, 22%, and 24% in the 3 collaboratives (P values of <0.01, 0.05, and 0.02, respectively). Increases were sustained after the collaboratives ended though the changes did not reach statistical significance. At least 75% of clinics increased screening rates in each collaborative. Clinics reported that adopting normalizing and opt-out language when counseling clients about screening was both feasible and effective, as was reducing missed opportunities for screening.

Conclusions

Learning collaboratives consistently resulted in improvement across 3 cohorts and shed light on barriers and facilitators to screening in family planning settings. Public health practitioners are encouraged to draw on our results and lessons learned to promote screening.
Prescription History Before Opioid Overdose Death: PDMP Data and Responsible Prescribing
Authors: Shreffler Jacob , Shaw Isaac , Berrones Adam , Huecker Martin
Published: August 2020

Introduction:

As the opioid epidemic continues, state legislatures and clinicians increasingly utilize Prescription Drug Monitoring Programs (PDMPs). These programs record dates prescribed and filled for all controlled substances, attempting to identify high-risk prescribing. The aims of this study were to (i) examine data from individuals who died of accidental opioid overdose and (ii) compare differences between those with prescriptions documented in Kentucky's PDMP with individuals without recorded prescriptions.

Methods:

This was a retrospective, observational cohort study conducted in Jefferson County, Kentucky. We reviewed records for all opioid overdose death subjects from 2017 and 2018, cross-referencing with prescriptions in Kentucky's PDMP (Kentucky All Schedule Prescription Electronic Reporting System [KASPER]) back to 2014. We performed χ2 analyses for categorical variable comparisons and a separate univariate analysis for age.

Results:

Of the 575 individuals who died of accidental opioid overdose in Jefferson County during the study period, 379 (65.9%) had prescriptions documented in KASPER. Individuals had a high prevalence of fentanyl on postmortem toxicology. Only one individual had postmortem toxicology positive for buprenorphine, a medication for opioid use disorder (MOUD). Several subjects experienced what we termed see-saw MOUD prescribing (prescriptions alternating between MOUD and other controlled substances including full agonists), and multiple prescriptions were apparently written and/or filled for deceased subjects.

Conclusions:

Review of PDMP data in deceased patients can prevent unnecessary opioid prescribing and optimize clinical practice. Buprenorphine may have a protective effect in opioid dependence, but access must be consistent. Providers should be aware of see-saw MOUD prescribing and understand the effects on patient care. In response to the prescriptions filled for deceased individuals, legislators could enact a policy such as Void All Prescriptions or VAP alerts to cancel all prescriptions for individuals who have died, reducing drug diversion. It is vital that providers routinely use PDMP data along with counseling and other treatment strategies to optimize patient care.
Concordance of Data on Children's Unmet Health Care Needs Between 2 National Surveys
Authors: White Jessiya , Morris Hannah , Cortright Lindsay , Buckman Cierra , Tumin Dmitry , Jamison Shaundreal
Published: August 2020

Objective:

We used public data from 2 national surveys to determine how survey mode and questionnaire wording potentially impact estimated prevalence and predictors of children's unmet health care needs.

Methods:

Data from 2016-2017 were obtained for the National Health Interview Survey (NHIS), where interviewers ask caregivers about each type of unmet health care need in person, and the National Survey of Children's Health (NSCH), a self-administered questionnaire asking a general question about any unmet health care needs, with subparts about specific types of unmet needs. Weighted proportions and multivariable logistic regression were used to analyze each data set.

Results:

The weighted proportion of any unmet health care needs was significantly higher in the NHIS (7.5%; 95% confidence interval [CI], 7.0-8.1; N = 17 723) than in the NSCH (3.3%; 95% CI, 2.9-3.7; N = 65 766). When analyzing specific unmet needs, unmet need for dental care was significantly higher according to the NHIS (4.2% vs 1.9% in the NSCH), as was unmet need for vision care (1.7% vs 0.8%). Conversely, estimates of unmet need for medical care were comparable between the surveys (1.4% and 1.0%). On multivariable analysis, predictors of unmet health care needs, such as being uninsured, had effect sizes of similar magnitude in both surveys.

Conclusion:

The NHIS design, asking about each type of unmet need in person, may have been more conducive to identifying the full range of unmet health care needs among children. However, our results did not indicate that this was a source of bias in multivariable regression analysis.
Assessing the Retail Environments of Licensed and Unlicensed Cannabis Dispensaries: Adapting the Marijuana Retail Surveillance Tool to Inform Cannabis Regulation in Los Angeles County
Authors: Nicholas Will , Washburn Faith , Lee Grace , Loprieno Daniele , Greenwell Lisa , Berg Carla
Published: August 2020

Context:

After statewide legalization of recreational cannabis in California, the Los Angeles (LA) County Board of Supervisors requested a health equity impact assessment to inform its decisions on whether and how to regulate cannabis dispensaries in unincorporated areas of LA County.

Objective:

As part of this assessment, the LA County Department of Public Health compared the retail environments of licensed and unlicensed cannabis dispensaries in different parts of the county, using the Marijuana Retail Surveillance Tool (MRST), a validated instrument piloted in Colorado and Washington.

Design:

Two waves of observational surveys were conducted, one comparing licensed and unlicensed dispensaries within and near unincorporated areas of LA County and another comparing licensed dispensaries across LA County in areas with varying levels of health advantage according to a neighborhood index measuring social determinants of health.

Main Outcome Measures:

Dispensaries were compared on measures of product types, promotional activities, security measures, regulatory compliance, and neighborhood context.

Results:

Unlicensed dispensaries were more likely than licensed dispensaries to sell products in packaging designed to be attractive to children (71.8% vs 10.8%, P < .001) and in non–child-resistant packaging (98.9% vs 15.6%, P < .001) and were more likely allow on-site consumption (60.9% vs 0%, P < .001). Licensed dispensaries showed high compliance with regulations, regardless of whether they were in areas of high or low health advantage.

Conclusions:

The study points to the importance of efforts to eliminate illicit businesses as part of an overall strategy for regulating cannabis. It also demonstrates that the MRST is a flexible tool for regulatory surveillance and for continuing to study the relationships between cannabis retail environments and potential risks to public health.
Trends and Rural-Urban Differences in Participation in Diabetes Self-management Education Among Adults in North Carolina: 2012-2017
Authors: Luo Huabin , Bell Ronny A. , Winterbauer Nancy L. , Xu Lei , Zeng Xiaoming , Wu Qiang , Rafferty Ann P. , Watson Angie M.
Published: August 2020

Purpose:

This study aimed to report recent trends in self-reported diabetes self-management education (DSME) participation rates among adults in North Carolina and to compare these rates between rural and urban residents.

Methods:

Data for this analysis were obtained from the NC Behavioral Risk Factor Surveillance System (BRFSS) for the years 2012, 2013, 2015, and 2017, when the survey included the diabetes module. Respondents were classified as having participated in DSME if they answered “Yes” to the question, “Have you ever taken a course or class in how to manage your diabetes yourself?” We used the Rural Urban Continuum Code to classify urban and rural residence. The study sample included 4368 adults 18 years or older with self-reported diabetes. We assessed the changes in DSME participation from 2012 to 2017. We used multiple logistic regression modeling to assess the association between rural residence and DSME participation. All analyses were conducted in Stata 14 and accounted for the survey design of the BRFSS. Statistical significance was set at P < .01.

Results:

Overall, the DSME participation rates decreased slightly in the study period, from 55.8% in 2012 to 55.6% in 2013 to 56.5% in 2015 to 52.1% in 2017. By rural-urban residence, the rates were 52.3% versus 57.8% in 2012, 54.0% versus 56.5% in 2013, 48.8% versus 62.0% in 2015, and 46.7% versus 56.1% in 2017. The multiple logistic regression model results showed that rural residents were less likely to have participated in DSME (adjusted odds ratio = 0.78; 95% confidence interval, 0.64-0.94) than urban residents. Adults with higher income and education levels were also more likely to have participated in DSME (P < .01).

Conclusions:

The recent BRFSS data showed that the DSME participation rate declined slightly in North Carolina. There were persistent rural-urban disparities in DSME participation, with rural residents showing lower rates, and the gaps seemed to be widening.

Implications for Policy or Practice:

Continuous efforts are needed to bring more American Diabetes Association/American Association of Diabetes Educators programs to rural communities and assist persons with diabetes to participate in DSME training to reduce the burden of diabetes. Furthermore, those in rural areas may need additional support.
Best Practices and Theoretical Foundations for Simulation Instruction Using Rapid-Cycle Deliberate Practice
Authors: Perretta Julianne S. , Duval-Arnould Jordan , Poling Shannon , Sullivan Nancy , Jeffers Justin M. , Farrow Lynne , Shilkofski Nicole A. , Brown Kristen M. , Hunt Elizabeth A.
Published: August 2020

Summary Statement

Rapid-cycle deliberate practice (RCDP) is a learner-centered simulation instructional strategy that identifies performance gaps and targets feedback to improve individual or team deficiencies. Learners have multiple opportunities to practice observational, deductive, decision-making, psychomotor, and crisis resource management skills. As its implementation grows, simulationists need to have a shared mental model of RCDP to build high-quality RCDP-based initiatives. To compare and make general inferences from RCDP data, each training needs to follow a similar structure. This article seeks to describe the fundamentals of RCDP, including essential components and potential variants. We also summarize the current published evidence regarding RCDP's effectiveness. This article serves to create a shared understanding of RCDP, provide clear definitions and classifications for RCDP research, and provide options for future RCDP investigation.
Fasting Ghrelin and Postprandial GLP-1 Levels in Patients With Morbid Obesity and Medical Comorbidities After Sleeve Gastrectomy and One-anastomosis Gastric Bypass: A Randomized Clinical Trial
Authors: Roushdy Ahmed , Abdel-Razik Mohamed A. , Emile Sameh H. , Farid Mohamed , Elbanna Hosam G. , Khafagy Wael , Elshobaky Ayman
Published: August 2020

Background:

Sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are among the commonly performed bariatric procedures. This randomized study aimed to compare SG and OAGB in terms of weight loss, improvement in comorbidities, and change in serum ghrelin and glucagon-like peptide-1 (GLP-1) levels.

Patients and Methods:

This was a prospective randomized trial on patients with morbid obesity associated with medical comorbidities who were randomly assigned to 1 of 2 equal groups; group I underwent SG and group II underwent OAGB. Outcome measures were percent of excess weight loss (%EWL), improvement in comorbidities, change in the venous levels of fasting ghrelin and postprandial GLP-1 at 12 months after surgery, in addition to operation time and complications.

Results:

Forty patients (38 female) of a mean age of 33.8 years and mean body mass index of 48.6 kg/m2 were included. Operation time in group II was significantly longer than in group I (86 vs. 52.87 min; P<0.001). There were 6 recorded complications (1 in group I and 5 in group II, P=0.18). The %EWL, %total weight loss, and %excess body mass index loss at 6 and 12 months postoperatively were significantly higher in group II than in group I. Both groups had similar rates of improvement in comorbidities. Group I had significantly lower ghrelin and GLP-1 levels postoperatively at 6 and 12 months, respectively, as compared with group II.

Conclusions:

OAGB was associated with significantly higher EWL than SG. The reduction in fasting ghrelin and postprandial GLP-1 serum levels at 12 months after SG was significantly higher than that after OAGB.
West Nile Virus Neuroinvasive Disease Accelerating Probable Dementia With Lewy Bodies
Authors: Segers Kurt , Van Ranst Alexander , Bostan Alionka , Glibert Gerald , Maillart Evelyne , Clevenbergh Philippe , Dachy Bernard
Published: August 2020

We describe a case of dementia with Lewy bodies immediately following encephalitis due to West Nile virus (WNV). The patient had rapid eye movement–sleep behavior disorder and constipation before the onset of encephalitis, which suggests that he would have ultimately developed dementia with Lewy bodies even without WNV infection. Our case illustrates the interactions between α-synuclein and WNV, as observed in mouse models, wherein synuclein expression augments after WNV infection and protects neurons against the virus.
Utility of Quantitative EEG for Seizure Detection in Adults
Authors: Kaleem Safa , Swisher Christa B.
Published: August 2020

Traditional review of EEG for seizure detection requires time and the expertise of a trained neurophysiologist; therefore, it is time- and resource-intensive. Quantitative EEG (qEEG) encompasses a variety of methods to make EEG review more efficient and allows for nonexpert review. Literature supports that qEEG is commonly used by neurophysiologists and nonexperts in clinical practice. In this review, the different types of qEEG trends and spectrograms used for seizure detection in adults, from basic concepts to clinical applications, are discussed. The merits and drawbacks of the most common qEEG trends are detailed. The authors detail the retrospective literature on qEEG sensitivity, specificity, and false alarm rate as interpreted by experts and nonexperts alike. Finally, the authors discuss the future of qEEG as a useful screening tool and speculate on the trajectory of future investigations in the field.
Functional redundancy in natural pico-phytoplankton communities depends on temperature and biogeography
Authors: Zhong Duyi , Listmann Luisa , Santelia Maria-Elisabetta , Schaum C-Elisa
Published: August 2020

Biodiversity affects ecosystem function, and how this relationship will change in a warming world is a major and well-examined question in ecology. Yet, it remains understudied for pico-phytoplankton communities, which contribute to carbon cycles and aquatic food webs year-round. Observational studies show a link between phytoplankton community diversity and ecosystem stability, but there is only scarce causal or empirical evidence. Here, we sampled phytoplankton communities from two geographically related regions with distinct thermal and biological properties in the Southern Baltic Sea and carried out a series of dilution/regrowth experiments across three assay temperatures. This allowed us to investigate the effects of loss of rare taxa and establish causal links in natural communities between species richness and several ecologically relevant traits (e.g. size, biomass production, and oxygen production), depending on sampling location and assay temperature. We found that the samples' biogeographical origin determined whether and how functional redundancy changed as a function of temperature for all traits under investigation. Samples obtained from the slightly warmer and more thermally variable regions showed overall high functional redundancy. Samples from the slightly cooler, less variable, stations showed little functional redundancy, i.e. function decreased when species were lost from the community. The differences between regions were more pronounced at elevated assay temperatures. Our results imply that the importance of rare species and the amount of species required to maintain ecosystem function even under short-term warming may differ drastically even within geographically closely related regions of the same ecosystem.
Identification of a queen pheromone mediating the rearing of adult sexuals in the pharaoh ant
Monomorium pharaonis
Authors: Oliveira Ricardo Caliari , Warson Jonas , Sillam-Dussès David , Herrera-Malaver Beatriz , Verstrepen Kevin , Millar Jocelyn G. , Wenseleers Tom
Published: August 2020

The division of labour between reproductive queens and mostly sterile workers is among the defining characteristics of social insects. Queen-produced chemical signals advertising her presence and fertility status, i.e. queen pheromones, are normally used to assert the queen's reproductive dominance in the colony. Most queen pheromones identified to date are chemicals that stop the daughter workers from reproducing. Nevertheless, it has long been suggested that queen pheromones could also regulate reproduction in different ways. In some multiple-queen ants with obligately sterile workers, for example—such as fire ants and pharaoh ants—queen pheromones are thought to regulate reproduction by inhibiting the rearing of new sexuals. Here, we identify the first such queen pheromone in the pharaoh ant
Monomorium pharaonis
and demonstrate its mode of action via bioassays with the pure biosynthesized compound. In particular, we show that the monocyclic diterpene neocembrene, which in different
Monomorium
species is produced solely by fertile, egg-laying queens, strongly inhibits the rearing of new sexuals (queens and males) and also exerts a weakly attractive ‘queen retinue’ effect on the workers. This is the first time that a queen pheromone with such a dual function has been identified in a social insect species with obligately sterile workers.
‘We must send you a sample’—a Persian–European dialogue: insights into late nineteenth-century ceramic technology based on chemical analysis of tiles from the Ettehadieh house complex, Tehran, Iran
Authors: Matin Moujan , Gholamnejad Mohammad , Abkenar Ali Nemati
Published: August 2020

This paper focuses on the production technology of late nineteenth-century tiles from the Ettehadieh House Complex in Tehran, Iran. It makes use of the opportunity to provide for the first time the results of chemical and microstructural analyses of late nineteenth-century tiles selected directly from context and with known provenance. The paper integrates the results of chemical study of the Ettehadieh tiles with other available technological information on nineteenth-century Persian tiles, including chemical analyses of signed tiles and samples of pigments, as well as the study of the treatise of a certain Persian potter, ‘Ali Mohammad Isfahani, to suggest processes of materials procurement and manufacture. These processes are used as evidence to discuss trade and technological interactions between Iran and Europe in the nineteenth century.
A self-assembled cylindrical platform for Plk4-induced centriole biogenesis
Authors: Lee Kyung S. , Park Jung-Eun , Il Ahn Jong , Wei Zhuang , Zhang Liang
Published: August 2020

The centrosome, a unique membraneless multiprotein organelle, plays a pivotal role in various cellular processes that are critical for promoting cell proliferation. Faulty assembly or organization of the centrosome results in abnormal cell division, which leads to various human disorders including cancer, microcephaly and ciliopathy. Recent studies have provided new insights into the stepwise self-assembly of two pericentriolar scaffold proteins, Cep63 and Cep152, into a near-micrometre-scale higher-order structure whose architectural properties could be crucial for proper execution of its biological function. The construction of the scaffold architecture appears to be centrally required for tight control of a Ser/Thr kinase called Plk4, a key regulator of centriole duplication, which occurs precisely once per cell cycle. In this review, we will discuss a new paradigm for understanding how pericentrosomal scaffolds are self-organized into a new functional entity and how, on the resulting structural platform, Plk4 undergoes physico-chemical conversion to trigger centriole biogenesis.
Ribosomal proteins: mutant phenotypes by the numbers and associated gene expression changes
Authors: Polymenis Michael
Published: August 2020

Ribosomal proteins are highly conserved, many universally so among organisms. All ribosomal proteins are structural parts of the same molecular machine, the ribosome. However, when ribosomal proteins are mutated individually, they often lead to distinct and intriguing phenotypes, including specific human pathologies. This review is an attempt to collect and analyse all the reported phenotypes of each ribosomal protein mutant in several eukaryotes (
Saccharomyces cerevisiae
,
Caenorhabditis elegans
,
Drosophila melanogaster
,
Danio rerio
,
Mus musculus
,
Homo sapiens
). These phenotypes were processed with unbiased computational approaches to reveal associations between different phenotypes and the contributions of individual ribosomal protein genes. An overview of gene expression changes in ribosomal protein mutants, with emphasis on ribosome profiling studies, is also presented. The available data point to patterns that may account for most of the observed phenotypes. The information presented here may also inform future studies about the molecular basis of the phenotypes that arise from mutations in ribosomal proteins.
The dynamics of trait variance in multi-species communities
Authors: Nordbotten Jan Martin , Bokma Folmer , Hermansen Jo Skeie , Stenseth Nils Chr.
Published: August 2020

In this paper, we establish the explicit connection between deterministic trait-based population-level models (in the form of partial differential equations) and species-level models (in the form of ordinary differential equations), in the context of eco-evolutionary systems. In particular, by starting from a population-level model of density distributions in trait space, we derive what amounts to an extension of the typical models at the species level known from adaptive dynamics literature, to account not only for abundance and mean trait values, but also explicitly for trait variances. Thus, we arrive at an explicitly polymorphic model at the species level. The derivations make precise the relationship between the parameters in the two classes of models and allow us to distinguish between notions of fitness on the population and species levels. Through a formal stability analysis, we see that exponential growth of an eigenvalue in the trait covariance matrix corresponds to a breakdown of the underlying assumptions of the species-level model. In biological terms, this may be interpreted as a speciation event: that is, we obtain an explicit notion of the blow-up of the variance of (possibly a linear combination of) traits as a precursor to speciation. Moreover, since evolutionary volatility of the mean trait value is proportional to trait variance, this provides a notion that species at the cusp of speciation are also the most adaptive. We illustrate these concepts and considerations using a numerical simulation.
Characterization of platinum(II) complexes exhibiting inhibitory activity against the 20S proteasome
Authors: Kiwada Tatsuto , Katakasu Hiromu , Okumura Serina , Odani Akira
Published: August 2020

Proteasome inhibitors are useful for biochemical research and clinical treatment. In our previous study, we reported that the 4N-coordinated platinum complexes with anthracenyl ring and heterocycle exhibited proteasome-inhibitory activity. In the present study, the structure–activity relationships and characterization of these complexes were determined for the elucidation of the role of aromatic ligands. Lineweaver–Burk analysis revealed that the chemical structure of heterocycles affects the binding mode of platinum complexes. Platinum complexes with anthracenyl ring and pyridine showed competitive inhibition, although platinum complexes with anthracenyl ring and phenanthroline showed non-competitive inhibition. The structure–activity relationships demonstrated that anthracenyl moiety plays a crucial role in proteasome-inhibitory activity. The platinum complexes with naphthyl or phenyl rings exhibited lower inhibitory activities than the platinum complex with anthracenyl ring. The reactivity with N-acetylcysteine varied according to the chemical structure of complexes.
Route selection in non-Euclidean virtual environments
Authors: Muryy Alexander , Glennerster Andrew
Published: August 2020

The way people choose routes through unfamiliar environments provides clues about the underlying representation they use. One way to test the nature of observers’ representation is to manipulate the structure of the scene as they move through it and measure which aspects of performance are significantly affected and which are not. We recorded the routes that participants took in virtual mazes to reach previously-viewed targets. The mazes were either physically realizable or impossible (the latter contained ‘wormholes’ that altered the layout of the scene without any visible change at that moment). We found that participants could usually find the shortest route between remembered objects even in physically impossible environments, despite the gross failures in pointing that an earlier study showed are evident in the physically impossible environment. In the physically impossible conditions, the choice made at a junction was influenced to a greater extent by whether that choice had, in the past, led to the discovery of a target (compared to a shortest-distance prediction). In the physically realizable mazes, on the other hand, junction choices were determined more by the shortest distance to the target. This pattern of results is compatible with the idea of a graph-like representation of space that can include information about previous success or failure for traversing each edge and also information about the distance between nodes. Our results suggest that complexity of the maze may dictate which of these is more important in influencing navigational choices.
The association of household food insecurity and HIV infection with common mental disorders among newly diagnosed tuberculosis patients in Botswana
Authors: Wang Qiao , Dima Mbatshi , Ho-Foster Ari , Molebatsi Keneilwe , Modongo Chawangwa , Zetola Nicola M. , Shin Sanghyuk S.
Published: August 2020

Objective

To determine the association between food insecurity and HIV-infection with depression and anxiety among new tuberculosis patients.

Design

Our cross-sectional study assessed depression, anxiety, and food insecurity with Patient Health Questionnaire (PHQ9), Zung Anxiety Self-Assessment Scale (ZUNG), and Household Food Insecurity Access Scale, respectively. Poisson regression models with robust variance were used to examine correlates of depression (PHQ9 ≥ 10) and anxiety (ZUNG ≥ 36)

Setting

Gaborone, Botswana.

Participants

Patients who were newly diagnosed with tuberculosis.

Results

Between January and December 2019, we enrolled 180 TB patients from primary health clinics in Botswana. Overall, 99 (55.0%) were HIV-positive, 47 (26.1%),85 (47.2%), and 69 (38.5%) indicated depression, anxiety, and moderate to severe food insecurity, respectively. After adjusting for potential confounders, food insecurity was associated with a higher prevalence of depression (adjusted prevalence ratio [aPR] =2.30; 95% confidence interval [CI] = 1.40, 3.78) and anxiety (aPR = 1.41; 95% CI = 1.05, 1.91). Prevalence of depression and anxiety were similar between HIV-infected and -uninfected participants. Estimates remained comparable when restricted to HIV-infected participants.

Conclusions

Mental disorders may be affected by food insecurity among new tuberculosis patients, regardless of HIV status.
Impact of COVID-19 on Primary Care Mental Health Services: A Descriptive, Cross-Sectional Timeseries of Electronic Healthcare Records
Authors: Bauer-Staeb Clarissa , Davis Alice , Smith Theresa , Wilsher Wendy , Betts David , Eldridge Chris , Griffith Emma , Faraway Julian , Button Katherine
Published: August 2020

Introduction

There are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare. Ultimately, this could potentially lead to unmet needs of individuals requiring mental health support.

Methods

Electronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A cross-sectional, descriptive timeseries was conducted using data from 1st January 2019 to 24th May 2020 across five NHS trusts to examine patterns in referrals to services (n = 171,823) and appointments taking place (n = 865,902).

Results

The number of patients accessing mental health services dropped by an average of 55% in the 9 weeks after lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK. As referrals began to increase again, there was a relatively faster increase in referrals from Black, Asian, and ethnic minority groups as well an increase in referrals from more densely populated areas. Despite a reduction in access, service providers adapted to infection control guidance by rapidly shifting to remote delivery of care.

Interpretation

Services were able to rapidly adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced dramatically, potentially placing a future burden on service providers to treat a likely backlog of patients in addition to a possible excess of patients as the long-term consequences of the pandemic become more apparent. Despite the observational nature of the data, which should be noted, the present study can inform the planning of service provision and policy.
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing
Authors: Xu Gang , Qi Furong , Li Hanjie , Yang Qianting , Wang Haiyan , Wang Xin , Liu Xiaoju , Zhao Juanjuan , Liao Xuejiao , Liu Yang , Amit Ido , Liu Lei , Zhang Shuye , Zhang Zheng
Published: August 2020

Understanding the mechanism that leads to immune dysfunction induced by SARS-CoV2 virus is crucial to develop treatment for severe COVID-19. Here, using single cell RNA-seq, we characterized the peripheral blood mononuclear cells (PBMC) from uninfected controls and COVID-19 patients, and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DC) and increased monocytes resembling myeloid-derived suppressor cells (MDSC) which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8+ T cell subsets, compared to health controls. In contrast, the proportions of various activated CD4+ T cell subsets, including Th1, Th2 and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients’ peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4 and CCL5 etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the patients’ lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.
Pulmonary cavitation – an under-recognized late complication of severe COVID-19 lung disease
Authors: Zoumot Zaid , Bonilla Maria-Fernanda , Wahla Ali S. , Shafiq Irfan , Uzbeck Mateen , El-Lababidi Rania M. , Hamed Fadi , Abuzakouk Mohamed , ElKaissi Mahmoud
Published: August 2020

Background

Radiological findings of the novel coronavirus disease 2019 (COVID-19) pulmonary disease have been well documented and range from scattered ground-glass infiltrates in milder cases to confluent ground-glass change, dense consolidation, and crazy paving in the critically ill, however, lung cavitation has not been described in these patients.

Objectives

To assess the incidence of pulmonary cavitation and describe its characteristics and evolution.

Methods

A retrospective review of all patients admitted to our institution with COVID-19 was undertaken and imaging reviewed to identify patients who developed pulmonary cavitation.

Results

Twelve out of 689 (1.7%) patients admitted to our institution with COVID-19 developed pulmonary cavitation, comprising 3.3% (n = 12/359) of those with COVID-19 pneumonia, and 11% (n = 12/110) of those admitted to the intensive care unit. We describe the imaging characteristics of the cavitation and present the clinical, pharmacological, laboratory, and microbiological parameters for these patients. In this cohort six patients have died while another remains critically ill and unlikely to survive.

Conclusion

Cavitary lung disease in patients with severe COVID-19 disease is not uncommon, and is associated with a high level of morbidity and mortality.
An invasive plant species enhances biodiversity in overgrazed pastures but inhibits its recovery in protected areas
Authors: Losapio Gianalberto , De Moraes Consuelo M. , Dirzo Rodolfo , Dutoit Lilian L. , Tscheulin Thomas , Zouros Nikos , Mescher Mark C.
Published: August 2020

Anthropogenic environmental change exposes biological communities to concurrent stressors (e.g., changes in climate and land-use, overexploitation, biotic invasions) that frequently persist over prolonged periods. Predicting and mitigating the consequences of human action on nature therefore requires understanding how exposure to multiple interacting stressors alters biological communities over relevant (e.g., multi-decadal) time periods. Here, we explore the effects of overgrazing and plant species invasion on plant community diversity and ecosystem functioning (productivity), as well as the patterns of recovery of plant communities following cessation of grazing pressure. In a Mediterranean pasture system, we utilized a “natural” experiment involving long-term exclusion of grazers (for 15-25 years in parks) and also conducted short-term grazing-exclusion and invasive species removal experiments. Our results reveal that invasion by a grazing-resistant plant (prickly burnet) has net positive effects on plant diversity under overgrazing conditions but inhibits the recovery of biodiversity once grazing ceases. Furthermore, while the diversity-productivity relationship was found to be positive in pastures, the interactive effects of overgrazing and species invasion appear to disrupt ecosystem functioning and inhibit the recovery of pasture productivity. These findings highlight the potential for prolonged exposure to anthropogenic stressors, such as overgrazing, to cause potentially-irreversible changes in biological communities that, in turn, compromise ecosystem functioning and resilience. In such cases, sustainable ecosystem management may require direct intervention to boost biodiversity resilience against centennial overgrazing.
Wing damage affects flight kinematics but not flower tracking performance in hummingbird hawkmoths
Authors: Kihlström Klara , Aiello Brett , Warrant Eric J. , Sponberg Simon , Stöckl Anna
Published: August 2020

The integrity of their wings is crucial to the many insect species that spend distinct portions of their life in flight. How insects cope with the consequences of wing damage is therefore a central question when studying how robust flight performance is possible with such fragile chitinous wings. It has been shown in a variety of insect species that the loss in lift-force production resulting from wing damage is generally compensated by an increase in wing beat frequency rather than amplitude. The consequences of wing damage for flight performance, however, are less well understood, and vary considerably between species and behavioural tasks. One hypothesis reconciling the varying results is that wing damage might affect fast flight manoeuvres with high acceleration, but not slower ones. To test this hypothesis, we investigated the effect of wing damage on the manoeuvrability of hummingbird hawkmoths (Macroglossum stellatarum) tracking a motorised flower. This assay allowed us to sample a range of movements at different temporal frequencies, and thus assess whether wing damage affected faster or slower flight manoeuvres. We show that hummingbird hawkmoths compensate for the loss in lift force mainly by increasing wing beat amplitude, yet with a significant contribution of wing beat frequency. We did not observe any effects of wing damage on flight manoeuvrability at either high or low temporal frequencies.
Adaptive evolution at mRNA editing sites in soft-bodied cephalopods
Authors: Moldovan Mikhail A. , Chervontseva Zoe S. , Bazykin Georgii A. , Gelfand Mikhail S.
Published: August 2020

The bulk of variability in mRNA sequence arises due to mutation – change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-translational modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis and with observations onDrosophilaand human editing sites, we show that edited adenines are more frequently substituted with guanine, an informational analogue of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Thus, our study shows that coleoid editing sites may enhance adaptation, which, together with distinct evolutionary features ofDrosophilaand human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.
Rapid and efficientin vivoastrocyte-to-neuron conversion with regional identity and connectivity?
Authors: Wang Lei-Lei , Garcia Carolina Serrano , Zhong Xiaoling , Ma Shuaipeng , Zhang Chun-Li
Published: August 2020

In vivoreprogramming of glia into functional neurons emerges as potential regeneration-based therapeutics for neural injuries or neurological diseases. Recent studies show that AAV-based manipulation of certain factors can rapidly and highly efficiently convert resident glia into functional neurons with brain region-specificity and precise connectivity. Using NEUROD1 as an example, we here show that the presumed astrocytes-converted neurons are essentially endogenous neurons in the adult mouse brain. AAV-mediated co-expression of NEUROD1 and a reporter indeed specifically, rapidly, and efficiently induces numerous reporter-labeled neurons. However, these neurons cannot be traced back to quiescent or reactive astrocytes by using stringent lineage-mapping strategies. Conversely, reporter-labeled neurons cannot be detected when NEUROD1 is strictly expressed in adult brain astrocytes. Through a retrograde labeling approach, our results rather reveal that endogenous neurons are the cell source for NEUROD1-induced reporter-labeled neurons. These results underline the indispensable value of stringent lineage-tracing strategies and beg for cautious interpretation of thein vivoreprogramming phenomena.
Effects of Peripheral Haptic Feedback on Intracortical Brain-Computer Interface Control and Associated Sensory Responses in Motor Cortex
Authors: Deo Darrel R. , Rezaii Paymon , Hochberg Leigh R. , Okamura Allison M. , Shenoy Krishna V. , Henderson Jaimie M.
Published: August 2020

Intracortical brain-computer interfaces (iBCIs) provide people with paralysis a means to control devices with signals decoded from brain activity. Despite recent impressive advances, these devices still cannot approach able-bodied levels of control. To achieve naturalistic control and improved performance of neural prostheses, iBCIs will likely need to include proprioceptive feedback. With the goal of providing proprioceptive feedback via mechanical haptic stimulation, we aim to understand how haptic stimulation affects motor cortical neurons and ultimately, iBCI control. We provided skin shear haptic stimulation as a substitute for proprioception to the back of the neck of a person with tetraplegia. The neck location was determined via assessment of touch sensitivity using a monofilament test kit. The participant was able to correctly report skin shear at the back of the neck in 8 unique directions with 65% accuracy. We found motor cortical units that exhibited sensory responses to shear stimuli, some of which were strongly tuned to the stimuli and well modeled by cosine-shaped functions. We also demonstrated online iBCI cursor control with continuous skin-shear feedback driven by decoded command signals. Cursor control performance increased slightly but significantly when the participant was given haptic feedback, compared to the purely visual feedback condition.