bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Departments' Role in Addressing Social Determinants of Health in Collaboration With Multisector Community Partnerships
Authors: Emery Kyle J. , Durocher Becky , Arena Laura C. , Glasgow LaShawn , Bayer Erin M. , Plescia Marcus , Holtgrave Peter L. , Hacker Karen
Published: November 2022

Multisector community partnerships (MCPs) are key component of the public health strategy for addressing social determinants of health (SDOH) and promoting health equity. Governmental public health agencies are often members or leaders of MCPs, but few studies have examined the role of health departments in supporting MCPs' SDOH initiatives. We engaged 42 established MCPs in a rapid retrospective evaluation to better understand how MCPs' SDOH initiatives contribute to community changes that promote healthy living and improved health outcomes. As part of this work, we gained insights into how health departments support MCPs' SDOH initiatives, as well as opportunities for enhanced collaboration. Results indicate that health departments can support MCPs' SDOH initiatives through the provision of funding and technical assistance, data sharing, and connecting community organizations with shared missions, for example. Findings can be used to inform the development of funding opportunities and technical assistance for MCPs and health department partners.
Coherence of character and temperament drives personality change toward well being in person-centered therapy
Authors: Garcia Danilo , Cloninger Kevin M. , Cloninger C. Robert
Published: November 2022

Purpose of review

People and communities around the world face many crises, including increasing burdens from disease, psychopathology, burn-out, social distrust, and acts of hate and terrorism. Personality disorder is arguably both a root cause and a consequence of these problems, creating a vicious cycle of suffering caused by fears, immoderate desires, and social distrust that are inconsistent with rational goals and prosocial values. Fortunately, recent advances in understanding the biopsychosocial basis and dynamics of development in personality and its disorders offer insights to address these problems in effective person-centered ways.

Recent findings

Fundamental advances have been made recently in the understanding of the psychobiology and sociology of personality in relationship to health, and in basic mechanisms of personality change as a complex process of learning and memory. Promotion of self-awareness and intentional self-control releases a strong tendency for people to seek coherence of their emotions and habits with what gives their life meaning and value.

People have a strong drive to cultivate personalities in which their emotions and habits are reliably in accord with reasonable goals and prosocial values. Person-centered therapeutics provide practical ways to promote a virtuous cycle of increasing well being for individuals and their communities and habitats.
Meiotic drive adaptive testes enlargement during early development in the stalk-eyed fly
Authors: Bradshaw Sasha L. , Meade Lara , Tarlton-Weatherall Jessica , Pomiankowski Andrew
Published: November 2022

The sex ratio (SR) X-linked meiotic drive system in stalk-eyed flies destroys Y-bearing sperm. Unlike other SR systems, drive males do not suffer fertility loss. They have greatly enlarged testes which compensate for gamete killing. We predicted that enlarged testes arise from extended development with resources re-allocated from the accessory glands, as these tend to be smaller in drive males. To test this, we tracked the growth of the testes and accessory glands of wild-type and drive males over 5–6 weeks post-eclosion before males attained sexual maturity. Neither of the original predictions is supported by these data. Instead, we found that the drive male testes were enlarged at eclosion, reflecting a greater allocation of resources to the testes during pupation. Testes grow at a higher rate during early adult development in drive males, but there was no evidence that this retards the growth of the accessory glands. Further experiments are proposed to investigate whether smaller accessory glands only arise in drive males post-copulation or when flies are subjected to nutritional stress. Our experimental findings support the idea that enlarged testes in drive males arise as an adaptive allocation of resources to traits that enhance male reproductive success.
Widespread convergent evolution of alpha-neurotoxin resistance in African mammals
Authors: Drabeck Danielle H. , Holt Jennifer , McGaugh Suzanne E.
Published: November 2022

Convergent evolution is central to the study of adaptation and has been used to understand both the limits of evolution and the diverse patterns and processes which result in adaptive change. Resistance to snake venom alpha-neurotoxins (
α
NTXs) is a case of widespread convergence having evolved several times in snakes, lizards and mammals. Despite extreme toxicity of
α
NTXs, substitutions in its target, the nicotinic acetylcholine receptor (nAChR), prevent
α
NTX binding and render species resistant. Recently, the published meerkat (Herpestidae) genome revealed that meerkats have the same substitutions in nAChR as the venom-resistant Egyptian mongoose (Herpestidae), suggesting that venom-resistant nAChRs may be ancestral to Herpestids. Like the mongoose, many other species of feliform carnivores prey on venomous snakes, though their venom resistance has never been explored. To evaluate the prevalence and ancestry of
α
NTX resistance in mammals, we generate a dataset of mammalian nAChR using museum specimens and public datasets. We find five instances of convergent evolution within feliform carnivores, and an additional eight instances across all mammals sampled. Tests of selection show that these substitutions are evolving under positive selection. Repeated convergence suggests that this adaptation played an important role in the evolution of mammalian physiology and potentially venom evolution.
Hidden species diversity in an iconic living fossil vertebrate
Authors: Brownstein Chase D. , Kim Daemin , Orr Oliver D. , Hogue Gabriela M. , Tracy Bryn H. , Pugh M. Worth , Singer Randal , Myles-McBurney Chelsea , Mollish Jon Michael , Simmons Jeffrey W. , David Solomon R. , Watkins-Colwell Gregory , Hoffman Eva A. , Near Thomas J.
Published: November 2022

Ancient, species-poor lineages persistently occur across the Tree of life. These lineages are likely to contain unrecognized species diversity masked by the low rates of morphological evolution that characterize living fossils. Halecomorphi is a lineage of ray-finned fishes that diverged from its closest relatives before 200 Ma and is represented by only one living species in eastern North America, the bowfin,
Amia calva
Linnaeus. Here, we use double digest restriction-site-associated DNA sequencing and morphology to illuminate recent speciation in bowfins. Our results support the delimitation of a second living species of
Amia
, with the timing of diversification dating to the Plio-Pleistocene. This delimitation expands the species diversity of an ancient lineage that is integral to studies of vertebrate genomics and development, yet is facing growing conservation threats driven by the caviar fishery.
Biological adaptations for cultural transmission?
Authors: Scott-Phillips Thom
Published: November 2022

According to several interlinked and influential lines of argument, human minds have been shaped by natural selection so as to include biological adaptations with the evolved, naturally selected function to facilitate the transmission of cultural knowledge. This ‘cultural minds’ hypothesis has proved highly influential, and if it is correct it is a major step forward in understanding how and why humans have survived and prospered in a hugely diverse range of ecologies. It can be contrasted with a ‘social minds’ hypothesis, according to which cultural transmission occurs as an outcome, but not the biologically evolved function, of social cognition the domain of which is relatively small-group interaction. Here, I critique the cultural minds hypothesis and I argue that the data favour the social minds perspective. Cultural phenomena can clearly emerge and persist over time without cognitive adaptations for cultural transmission. Overtly intentional communication plays an especially pivotal role.
Large-scale FRET simulations reveal the control parameters of phycobilisome light-harvesting complexes
Authors: Dodson Emma Joy , Werren Nicholas , Paltiel Yossi , Gauger Erik M. , Keren Nir
Published: November 2022

Phycobilisomes (PBS) are massive structures that absorb and transfer light energy to photochemical reaction centres. Among the range of light harvesting systems, PBS are considered to be excellent solutions for absorption cross-sections but relatively inefficient energy transferring systems. This is due to the combination of a large number of chromophores with intermediate coupling distances. Nevertheless, PBS systems persisted from the origin of oxygenic photosynthesis to present-day cyanobacteria and red algae, organisms that account for approximately half of the primary productivity in the ocean. In this study, we modelled energy transfer through subsets of PBS structures, using a comprehensive dynamic Hamiltonian model. Our approach was applied, initially, to pairs of phycobilin hexamers and then extended to short rods. By manipulating the distances and angles between the structures, we could probe the dynamics of exciton transfer. These simulations suggest that the PBS chromophore network enhances energy distribution over the entire PBS structure—both horizontally and vertically to the rod axis. Furthermore, energy transfer was found to be relatively immune to the effects of distances or rotations, within the range of intermediate coupling distances. Therefore, we suggest that the PBS provides unique advantages and flexibility to aquatic photosynthesis.
Evolutionary dynamics of sustainable blockchains
Authors: Alberto Javarone Marco , Di Antonio Gabriele , Valerio Vinci Gianni , Pietronero Luciano , Gola Carlo
Published: November 2022

The energy sustainability of blockchains, whose consensus protocol rests on the Proof-of-Work, nourishes a heated debate. The underlying issue lies in a highly energy-consuming process, defined as mining, required to validate crypto-asset transactions. Mining is the process of solving a cryptographic puzzle, incentivized by the possibility of gaining a reward. The higher the number of users performing mining, i.e. miners, the higher the overall electricity consumption of a blockchain. For that reason, mining constitutes a negative environmental externality. Here, we study whether miners’ interests can meet the collective need to curb energy consumption. To this end, we introduce the Crypto-Asset Game, namely a model based on the framework of Evolutionary Game Theory devised for studying the dynamics of a population whose agents can play as crypto-asset users or as miners. The proposed model, studied via numerical simulations, reveals a rich spectrum of possible steady states. Interestingly, by setting the miners’ reward in the function of the population size, agents reach a strategy profile that optimizes global energy consumption. To conclude, can a Proof-of-Work-based blockchain become energetically sustainable? Our results suggest that blockchain protocol parameters could have a relevant role in the global energy consumption of this technology.
An Optimized Circular Polymerase Extension Reaction-based Method for Functional Analysis of SARS-CoV-2
Authors: Liu GuanQun , Gack Michaela U.
Published: November 2022

Reverse genetics systems have been crucial for studying specific viral genes and their relevance in the virus lifecycle, and become important tools for the rational attenuation of viruses and thereby for vaccine design. Recent rapid progress has been made in the establishment of reverse genetics systems for functional analysis of SARS-CoV-2, a coronavirus that causes the ongoing COVID-19 pandemic that has resulted in detrimental public health and economic burden. Among the different reverse genetics approaches, CPER (circular polymerase extension reaction) has become one of the leading methodologies to generate recombinant SARS-CoV-2 infectious clones due to its accuracy, efficiency, and flexibility. Here, we report an optimized CPER methodology which, through the use of a modified linker plasmid and by performing DNA nick ligation and direct transfection of permissive cells, overcomes certain intrinsic limitations of the ‘traditional’ CPER approaches for SARS-CoV-2, allowing for efficient virus rescue. This optimized CPER system may facilitate research studies to assess the contribution of SARS-CoV-2 genes and individual motifs or residues to virus replication, pathogenesis and immune escape, and may also be adapted to other viruses.
Gambling Disorder: Simultaneous Measurement of Screening Scales in Multiple Regions of Japan
Authors: Noda Tatsuya , Kido Moritoshi , Ito Chieko
Published: November 2022

Background and Objectives

Gambling disorder is defined as persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress in DSM-5 diagnostic criteria. According to the DSM-5, the past-year prevalence rate of gambling disorder is about 0.2%-0.3% in the general population, and the lifetime prevalence is about 0.4%-1.0%. Japan currently has no casinos, but three integrated resorts (IRs), including casinos, are scheduled to open in the late 2020s. In abroad, there have been studies on the effect of casinos on the prevalence of gambling in a region, but similar empirical studies do not exist in Japan. There are a lot of surveys being conducted in many areas, but the different screening tests used make it difficult to compare the results. However, comparisons between screening tests are less common. The first objective of this study is to measure the prevalence of gambling disorder in areas where IRs are planned to open and control areas. The second objective is to identify relationships among screening tests and examine differences between measures by administering multiple screening tests for gambling disorder to the same subjects.

Materials and methods

This survey was a self-administered, online survey of 2000 people in Japan, ranging in age from 20 to 69 conducted in 2021. We administered 4 gambling disorder screening tests (SOGS, PGSI, LieBet Screen,DSM-5). Experience rates for each of 8 gambles were measured. Percentage above cut-off score (PAC) was calculated and compared by gender and region for 4 tests.

Results

Among the eight gambling activities, the lottery had the largest experience rate at 58.5%, PACHINKO was second at 42.2%, and there were no major regional disparities. In each of the 4 screening tests, PAC was greater in males, and regional differences were found in SOGS and DSM-5. The distribution of PAC for different cut-off scores for each test is illustrated in a “dango chart” for comparison.

Discussion

This study indicates PACs for 4 gambling disorder screening tests in planned and non-IR areas, and this will be a baseline survey to measure the impact of opening an IR. Although our results will contain some biases likely due to methodological factors, by continuing to use the same measurement method, our research project will be able to reach its ultimate goal of observing changes in the applicable rate before and after the opening of the IR. In addition, this study administered several gambling disorder screening tests to the same subjects in the same region and illustrated them in a chart format named the dango chart. This visualized the changes in the applicable person rate when the cut-off scores of the screening tests were changed (within-test comparisons) and the differences in the distribution of the applicable person rate across tests (between-test comparisons). We think that the dango chart is a useful presentation method for comparing several different tests.
Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline
Authors: Wood Madeline E. , Xiong Lisa Y. , Wong Yuen Yan , Buckley Rachel F. , Swardfager Walter , Masellis Mario , Lim Andrew S. P. , Nichols Emma , Joie Renaud La , Casaletto Kaitlin B. , Kumar Raj G. , Dams-O’Connor Kristen , Palta Priya , George Kristen M. , Satizabal Claudia L. , Barnes Lisa L. , Schneider Julie A. , Binet Alexa Pichette , Villeneuve Sylvia , Pa Judy , Brickman Adam M. , Black Sandra E. , Rabin Jennifer S. ,   the ADNI and Prevent-AD Research Groups
Published: November 2022

INTRODUCTION

We examined whether sex modifies the association betweenAPOEε2and cognitive decline across two independent samples.

METHODS

We used observational data from non-Hispanic White (NHW) and non-Hispanic Black (NHB) cognitively unimpaired adults. Linear mixed models examined interactive associations ofAPOEgenotype (ε2or ε4carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.

RESULTS

In both Sample 1 (N=9,766) and Sample 2 (N=915), sex modified the association betweenAPOEε2and cognitive decline in NHW participants. Specifically, relative toAPOEε3/ε3, APOEε2protected against cognitive decline in men but not women. AmongAPOEε2carriers, men had slower decline than women. AmongAPOEε3/ε3carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations ofAPOEε2 with cognitive decline in NHB participants (N=2,010).

DISCUSSION

In NHW adults,APOEε2may selectively protect men against cognitive decline.
Unappreciated Subcontinental Admixture in Europeans and European Americans: Implications for Genetic Epidemiology Studies
Authors: Gouveia Mateus H. , Bentley Amy R. , Tarazona-Santos Eduardo , Bustamante Carlos D. , Adeyemo Adebowale A. , Rotimi Charles N. , Shriner Daniel
Published: November 2022

European-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrated individual-level genome-wide data from~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generated a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European-Americans are admixed at subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant inLCT(rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association betweenLCTand body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
NanoPack2: Population scale evaluation of long-read sequencing data
Authors: De Coster Wouter , Rademakers Rosa
Published: November 2022

Increases in the cohort size in long-read sequencing projects necessitate more efficient software for quality assessment and processing of sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. Here we describe novel tools for summarizing experiments, filtering datasets and visualizing phased alignments results, as well as updates to the NanoPack software suite.

Availability and implementation

Cramino, chopper, and phasius are written in Rust and available as executable binaries without requiring installation or managing dependencies. NanoPlot and NanoComp are written in Python3. Links to the separate tools and their documentation can be found athttps://github.com/wdecoster/nanopack. All tools are compatible with Linux, Mac OS, and the MS Windows 10 Subsystem for Linux and are released under the MIT license. The repositories include test data, and the tools are continuously tested using GitHub Actions.

Contact

wouter.decoster@uantwerpen.vib.be
Bimodal stimulation for the reduction of tinnitus using vibration on the skin
Authors: Perrotta Michael V. , Kohler Izzy , Eagleman David M.
Published: November 2022

Tinnitus (ringing in the ears) affects 1 in 10 adults in the United States, often with damaging psychological consequences. Currently, there exists no cure for most forms of tinnitus. Recently, bimodal stimulation – the pairing of sounds with haptic stimulation – has shown efficacy in reducing the symptoms of tinnitus. Previous bimodal stimulation approaches have used electrical shocks on the tongue, a technique that requires daily in-person sessions at an audiologist’s office. We here show that excellent results can be achieved wearing a wristband with multiple vibratory motors. Tones are played and the wristband correspondingly vibrates the wrist of the user at different spatial locations depending on the frequency of the tone. We compared the experimental group with a control group who listened to the tones but did not wear the wristband. The tone frequencies were centered on each user’s tinnitus frequency and the tones were randomized both in frequency and duration. 45 participants with Tinnitus Functional Index (TFI) scores of 25 and above were tested. Results show a significantly greater reduction in TFI scores for the experimental group compared to the control. Importantly, with higher baseline severity we find larger differences between the experimental and control groups, revealing greater symptom improvement for those with severe tinnitus. The therapeutic approach of combining sounds with spatially- and temporally-correlated vibrations on the wrist is found to be a simple, time-efficient, and effective procedure to lessen the symptoms of tinnitus.
Zebrafish embryos are more efficient and robust than zebrafish larvae in evaluating human norovirus infectivity
Authors: Tan Malcolm Turk Hsern , Gong Zhiyuan , Li Dan
Published: November 2022

This study reports an essential improvement of the method for replication of human norovirus (hNoV) with the use of zebrafish (Danio rerio) embryos. With three globally prevalent hNoV genotypes and P-types GII.2[P16], GII.4[P16], and GII.17[P31], we demonstrated that this tool had high efficiency and robustness, and enabled continuous virus passaging. This tool is versatile in being applied in hNoV related research. In pathogenesis study, the zebrafish embryo generated hNoVs showed clear binding patterns to human histo-blood group antigens (HBGAs) in human saliva by a simple saliva-binding reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In disinfection study, it was shown that a dose of 6 mJ/cm2UV254was able induce > 2-log reduction in hNoV infectivity for all three hNoV strains tested, suggesting that hNoVs were more UV susceptible than multiple enteric viruses and commonly used hNoV surrogates as tested before.

IMPORTANCE

HNoVs are a leading cause of gastroenteritis outbreaks worldwide. The zebrafish embryo tool as developed in this study serves as an efficient way to generate viruses with high titers and clean background and a straightforward platform to evaluate hNoV inactivation efficacies. It is expected that this tool will not only benefit epidemiological research of hNoV but also be used to generate hNoV inactivation parameters which are highly needed by the water treatment and food industry.
Age-related differences in colon and rectal cancer survival: An analysis of United States SEER-18 data
Authors: Pilleron Sophie , Withrow Diana , Nicholson Brian D , Morris Eva JA
Published: November 2022

Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine to what extent stage, tumour site, or histology could contribute to these differences, we estimated 1-year relative survival (RS) age stratified by these factors. Colon and rectal cancer cases diagnosed between 2012 and 2016 and followed up until 2017 were retrieved from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8% [95% Confidence Interval: 87.5-88.2] in the 50–64-year-old age group to 62.3% [61.3-63.3] in the 85–99-year-old age group and for rectal cancer ranged from 92.3% [91.8-82.7] to 65.0% [62.3-67.5]. With respect to stage, absolute differences in RS between 50–64-year-old and 75–84-year-old in RS increased with increasing stage (from 6 [5-7] %-points in localized disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (>28%-points). With respect to topography, age-related differences in survival were smallest for those in right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without topography further specified (25 [21-29] %-points). While age-related differences in survival varied by histology and tumour site, the overall age-related differences in survival could not be explained by differences in distribution of these factors by age, consistent with a hypothesis that stage at diagnosis or treatment are more likely drivers. Incorporating data on geriatric conditions such as frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.
Characterizing the interactions between influenza and respiratory syncytial viruses and their implications for epidemic control
Authors: Kramer Sarah C. , Pirikahu Sarah , Casalegno Jean-Sébastien , Domenech de Cellès Matthieu
Published: November 2022

Pathogen-pathogen interactions represent a critical but little-understood feature of infectious disease dynamics. In particular, experimental evidence suggests that influenza virus and respiratory syncytial virus (RSV) compete with each other, such that infection with one confers temporary protection against the other. However, such interactions are challenging to study using common epidemiologic methods. Here, we use a mathematical modeling approach, in conjunction with detailed surveillance data from Hong Kong and Canada, to infer the strength and duration of the interaction between influenza and RSV. Based on our estimates, we further utilize our model to evaluate the potential conflicting effects of live attenuated influenza vaccines (LAIV) on RSV burden. We find evidence of a moderate to strong, negative, bidirectional interaction, such that infection with either virus yields 40-100% protection against infection with the other for one to five months. Assuming that LAIV reduces RSV susceptibility in a similar manner, we predict that the impact of such a vaccine at the population level would likely depend greatly on underlying viral circulation patterns. More broadly, we highlight the utility of mathematical models as a tool to characterize pathogen-pathogen interactions.
A Functional Sensor-to-Segment Orientation Method to Reduce the Effects of Varied Sensor Placement: Implications for IMU Best Practices
Authors: Mihy Julien A. , Wagatsuma Mayumi , Cain Stephen M. , Hafer Jocelyn F.
Published: November 2022

To collect reliable data, it is important to determine how inertial measurement unit (IMU) sensor placement affects measurements of segment motion and to establish best practices for sensor placement and orientation procedures. We aimed to determine the extent to which a functional orientation method minimizes the effect of variations in sensor placement on IMU-derived segment excursions. Twenty healthy adults walked overground in a lab. Three IMUs were placed per segment on the pelvis, thigh, shank, and foot. Differences in estimated segment angular excursions between sensor placements were compared between an assumed sensor-to-segment orientation and two versions of a walking-based functional sensor-to-segment orientation. For time series data, differences in angular excursion between sensor placements were reduced from 60% of the gait cycle (assumed orientation) to 44% of the gait cycle (functional orientation) for the pelvis; from 31% (assumed) to 28% (functional) of the gait cycle for the thigh; and from 84% (assumed) to 0% (functional) of the gait cycle for the shank. Mean angular excursion RMSDs between sensor placements were <5° for most comparisons for the functionally oriented data. Functional orientation did not minimize inter-sensor placement effects when one sensor was located on a region with high soft tissue artifact (e.g., anterior thigh). Functional orientation reduced inter-sensor differences in segment excursion for the shank and foot and between-subject variance in inter-sensor differences for all segments. Functional orientation minimizes the effect of variations in IMU sensor placement, but care should be taken to select sensor placements that minimize soft-tissue artifact.
Selective whole-genome sequencing ofPlasmodiumparasites directly from blood samples by Nanopore adaptive sampling
Authors: De Meulenaere Katlijn , Cuypers Wim L. , Rosanas-Urgell Anna , Laukens Kris , Cuypers Bart
Published: November 2022

Background

Whole-genome sequencing (WGS) is becoming an increasingly popular tool to study the population genetics and drug resistance ofPlasmodiumspp. However, the predominance of human DNA in a malaria patient blood sample requires time-consuming lab procedures to filter out human DNA or enrichPlasmodiumDNA. Here, we investigated the potential of adaptive sampling to enrich forPlasmodiumDNA while sequencing unenriched patient blood samples on a minION device.

Results

To compare adaptive sampling versus regular sequencing, a dilution series consisting of 0% up to 100%P. falciparumDNA in human DNA was sequenced. Half of the flowcell channels were run in adaptive sampling mode, enriching for theP. falciparumreference genome, resulting in a 3.2 fold enrichment ofP. falciparumbases on average. Samples with a lower concentration of parasite DNA had a higher enrichment potential. We confirmed these findings by sequencing twoP. falciparumpatient blood samples with common levels of parasitaemia (0.1% and 0.2%). The estimated enrichment was 3.9 and 5.8, which was sufficient to cover at least 97% of theP. falciparumreference genome at a median depth of 20 (highest parasitaemia) or 5 (lowest parasitaemia). A comparison of 38 drug resistance variants (WHO) obtained via adaptive sequencing or Sanger sequencing showed a high concordance between the two methods, suggesting that the obtained sequencing data is of sufficient quality to address common clinical research questions for patients with parasitaemias of 0.1% and higher.

Conclusions

Our results demonstrate that adaptive Nanopore sequencing has the potential to replace more time-consumingPlasmodium-enrichment protocols and sequence directly from patient blood, given further improvements in cost-efficiency.
A novel and simple heat-based method eliminates the highly detrimental effect of xylene deparaffinization on acid-fast stains
Authors: Marinho Pedro F. , Vieira Soraia L. , Carvalho Tânia G. , Peleteiro Maria C. , Hanscheid Thomas
Published: November 2022

Objectives

Histopathology is an important method for the diagnosis of extrapulmonary tuberculosis, yet tissue sections are often negative for mycobacteria after acid-fast-staining (AFS). This study investigated the mechanism of AFS and the detrimental effect of histological processing, in particular xylene deparaffinization, on AFS staining and mycobacterial detection.

Methods

The target of the fluorescent Auramine O (AuO) AFS was investigated using triple staining with DNA and RNA specific dyes. The effect of xylene deparaffinization on acid-fastness of mycobacteria in cultures or tissue sections was studied using AuO fluorescence as a quantitative marker. The xylene method was compared to a novel, solvent-free projected-hot-air-deparaffinization (PHAD).

Results

Colocalization of AuO with DNA/RNA stains suggests that intracellular nucleic acids are the true target of AFS, producing highly specific patterns. Xylene reduces mycobacterial fluorescence significantly (p<0,0001, moderate effect size:r= 0.33). PHAD yielded significantly higher fluorescence than xylene deparaffinization in tissues (p<0.0001, large effect size:r= 0.85).

Conclusions

AuO can be applied for nucleic-acid-staining of mycobacteria in tissues producing typical beaded patterns. AFS depends crucially on the integrity of the mycobacterial cell-wall, which seems to be damaged by xylene. A solvent-free tissue deparaffinization method has the potential to increase mycobacterial detection significantly.

Key Points

Acid-fast-stains for mycobacterial detection have a notoriously poor yield, due to misconceptions of the underlying staining principle, but mainly because of the possible detrimental effect of xylene.

The yield of acid-fast-stains for mycobacterial detection in histology, including fluorescent stains, can be significantly increased by eliminating solvents (xylene) in the deparaffinization step.

Acid-fast-stains depend on bacterial integrity because they target nucleic acids. A simple hot air deparaffinization is significantly superior to xylene, avoiding damage to the lipid-rich cell wall.
PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer
Authors: Nikolatou Konstantina , Sandilands Emma , Román-Fernández Alvaro , Cumming Erin M. , Freckmann Eva , Lilla Sergio , Buetow Lori , McGarry Lynn , Neilson Matthew , Shaw Robin , Strachan David , Miller Crispin , Huang Danny T. , McNeish Iain A. , Norman James C. , Zanivan Sara , Bryant David M.
Published: November 2022

Dysregulation of the PI3K/AKT pathway is a common occurrence in ovarian carcinomas. Loss of the tumour suppressorPTENin high-grade serous ovarian carcinoma (HGSOC) is associated with a patient subgroup with poor prognosis. The cellular mechanisms of howPTENloss contributes to HGSOC are largely unknown. We utilise long-term time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype ofPTENloss.PTENdeficiency does not affect proliferation but rather induces PI(3,4,5)P3-rich and -dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability uponPTENloss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase-activating protein (GAP) AGAP1 and the ECM receptor β1-integrin (ITGB1) as key ARF6 interactors regulating thePTENloss-associated invasion phenotype. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1-integrin complexes to maintain invasive activity into the ECM. The expression of the ARF6-centred complex in HGSOC patients is inversely associated with outcome, allowing identification of patient groups with improved versus poor outcome. ARF6 may represent a new therapeutic vulnerability inPTEN- depleted HGSOC tumours.
Clustering and temporal organization of sleep spindles underlie motor memory consolidation
Authors: Boutin Arnaud , Gabitov Ella , Pinsard Basile , Boré Arnaud , Carrier Julie , Doyon Julien
Published: November 2022

Sleep benefits motor memory consolidation, which is mediated by sleep spindle activity and associated memory reactivations during non-rapid eye movement (NREM) sleep. However, the particular role of NREM2 and NREM3 sleep spindles and the mechanisms triggering this memory consolidation process remain controversial. Here, simultaneous electroencephalographic and functional magnetic resonance imaging (EEG-fMRI) recordings were collected during night-time sleep following the learning of a motor sequence task. Adopting a time-based clustering approach, we provide evidence that spindles iteratively occur within clustered and temporally organized patterns during both NREM2 and NREM3 sleep. However, the clustering of spindles in trains is related to motor memory consolidation during NREM2 sleep only. Altogether, our findings suggest that spindles’ clustering and rhythmic occurrence during NREM2 sleep may serve as an intrinsic rhythmic sleep mechanism for the timed reactivation and subsequent consolidation of motor memories, through synchronized oscillatory activity within a subcortical-cortical network involved during learning.
Dysregulation of neuroproteasomes by ApoE isoforms drives endogenous Tau aggregation
Authors: Paradise V , Sabu M , Bafia J , Sharif NA , Nguyen C , Konrad-Vicario KD , Dhanraj Mukim R , Wang X , Corjuc BT , Fu J , Maldonado G , Ndubisi J , Strickland M , Figueroa H , Almeida D , Hyman B , Holtzman DM , Nuriel T , Ramachandran KV
Published: November 2022

Neuroproteasomes are a subset of 20S proteasomes that are localized to the neuronal plasma membrane and degrade newly synthesized proteins. To date, the molecular composition of neuroproteasomes is undefined, and moreover, whether neuroproteasomes can influence protein aggregation with relevance to neurodegenerative disorders remains unexplored. Using a Cre-dependent conditional knock-in mouse line to endogenously tag the proteasome, we find that neuroproteasomes co-purify with ApoE, the most significant risk factor for late-onset Alzheimer’s Disease (AD). We discover that neuroproteasome membrane localization is differentially modulated by ApoE isoforms (E4<E3<E2)in vitro,in vivo, and in human postmortem samples. We synthesized selective, neuroproteasome-specific inhibitors and discovered that neuroproteasome inhibition induces aggregation of endogenous mouse and human Tau, without the need for seeding or pathogenic mutations. Using hApoE-KI/hTau-KI crosses, we find that ApoE isoforms differentially shift the aggregation threshold for Tau. Neuroproteasome inhibitionin vivois sufficient to induce sarkosyl-insoluble and Thioflavin-S positive endogenous Tau aggregates in only three days, which are completely abrogated by co-application of cycloheximide. Newly synthesized Tau levels increase threefold after neuroproteasome inhibition, leading us to posit that newly synthesized Tau is uniquely susceptible to aggregation due to neuroproteasome dysfunction. Overall, our data define neuroproteasomes as a pivotal proteostasis mechanism underlying the formation of endogenous Tau aggregates, which is directly regulated by the largest genetic risk factor for late-onset Alzheimer’s Disease.
NanoTrans: an integrated computational framework for comprehensive transcriptome analysis with Nanopore direct RNA sequencing
Authors: Yang Ludong , Zhang Xinxin , Wang Fan , Zhang Li , Li Jing , Yue Jia-Xing
Published: November 2022

Nanopore direct RNA sequencing (DRS) provides the direct access to native RNA strands with full-length information, shedding light on rich qualitative and quantitative properties of gene expression profiles. Here with NanoTrans, we present an integrated computational framework that comprehensively covers all major DRS-based application scopes, including isoform clustering and quantification, poly(A) tail length estimation, RNA modification profiling, and fusion gene detection. In addition to its merit in providing such a streamlined one-stop solution, NanoTrans also shines in its workflow-orientated modular design, batch processing capability, all-in-one tabular and graphic report output, as well as automatic installation and configuration supports. Finally, by applying NanoTrans to real DRS datasets of yeast,Arabidopsis, as well as human embryonic kidney and cancer cell lines, we further demonstrated its utility, effectiveness, and efficacy across a wide range of DRS-based application settings.
Single-cell Transcriptomic Analysis of Systemic Autoinflammatory Diseases with Anti-TNFα Therapy
Authors: Hua Yichao , Wu Na , Miao Junke , Shen Min
Published: November 2022

Systemic autoinflammatory diseases (SAIDs) are a group of rare diseases characterized by recurrent or continuous inflammation, typically accompanied by genetic variants. Good responses to anti-TNFα therapy were observed in SAIDs patients. However, the mechanisms underlying the disease flare and the response to TNFα blocking therapy have not been fully elucidated. Here, we use single-cell RNA sequencing technology to describe the transcriptomic profile of PBMCs and PMNs in SAIDs patients both before and after anti-TNFα treatment. We found that interferon responses are involved in the active phase of the disease. After anti-TNFα therapy, we observed remission from clinical symptoms while unexpected elevation of TNFα and IL-1, indicating that these inflammatory cytokines are not positively correlated with disease activity. Trajectory analysis showed that inhibition of macrophage differentiation, rather than reduction of the inflammatory cytokines, as the potential mechanism of anti-TNFα treatment response in SAIDs.
The functional role of oscillatory dynamics in neocortical circuits: a computational perspective
Authors: Effenberger Felix , Carvalho Pedro , Dubinin Igor , Singer Wolf
Published: November 2022

The dynamics of neuronal systems are characterized by hallmark features such as oscillations and synchrony. However, it has remained unclear whether these characteristics are epiphenomena or are exploited for computation. Due to the challenge of specifically interfering with oscillatory network dynamics in neuronal systems, we simulated recurrent networks (RNNs) of damped harmonic oscillators in which oscillatory activity is enforced in each node, a choice well-supported by experimental findings. When trained on standard pattern recognition tasks, these harmonic oscillator networks (HORNs) outperformed non-oscillatory architectures with respect to learning speed, noise tolerance, and parameter efficiency. HORNs also reproduced a substantial number of characteristic features of neuronal systems such as the cerebral cortex and the hippocampus. In trained HORNs, stimulus-induced interference patterns holistically represent the result of comparing sensory evidence with priors stored in recurrent connection weights, and learning-induced weight changes are compatible with Hebbian principles. Implementing additional features characteristic of natural networks, such as heterogeneous oscillation frequencies, inhomogeneous conduction delays, and network modularity, further enhanced HORN performance without requiring additional parameters. Taken together, our model allows us to give plausible a posteriori explanations for features of natural networks whose computational role has remained elusive. We conclude that neuronal systems are likely to exploit the unique dynamics of recurrent oscillators networks whose computational superiority critically depends on the oscillatory patterning of their nodal dynamics. Implementing the proposed computational principles in analog hardware is expected to enable the design of highly energy-efficient and self-adapting devices that could ideally complement existing digital technologies.
Compression supports low-dimensional representations of behavior across neural circuits
Authors: Zhou Dale , Kim Jason Z. , Pines Adam R. , Sydnor Valerie J. , Roalf David R. , Detre John A. , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Dani S.
Published: November 2022

Dimensionality reduction, a form of compression, can simplify representations of information to increase efficiency and reveal general patterns. Yet, this simplification also forfeits information, thereby reducing representational capacity. Hence, the brain may benefit from generating both compressed and uncompressed activity, and may do so in a heterogeneous manner across diverse neural circuits that represent low-level (sensory) or high-level (cognitive) stimuli. However, precisely how compression and representational capacity differ across the cortex remains unknown. Here we predict different levels of compression across regional circuits by using random walks on networks to model activity flow and to formulate rate-distortion functions, which are the basis of lossy compression. Using a large sample of youth (n= 1, 040), we test predictions in two ways: by measuring the dimensionality of spontaneous activity from sensorimotor to association cortex, and by assessing the representational capacity for 24 behaviors in neural circuits and 20 cognitive variables in recurrent neural networks. Our network theory of compression predicts the dimensionality of activity (t= 12.13,p <0.001) and the representational capacity of biological (r= 0.53,p= 0.016) and artificial (r= 0.61,p <0.001) networks. The model suggests how a basic form of compression is an emergent property of activity flow between distributed circuits that communicate with the rest of the network.
Next generation protein-based materials capture and preserve projectiles from supersonic impacts
Authors: Doolan Jack A. , Alesbrook Luke S. , Baker Karen B. , Brown Ian R. , Williams George T. , Hiscock Jennifer R. , Goult Benjamin T.
Published: November 2022

Extreme energy dissipating materials are essential for a range of applications. The military and police force require ballistic armour to ensure the safety of their personnel, while the aerospace industry requires materials that enable the capture, preservation and study of hypervelocity projectiles. However, current industry standards display at least one inherent limitation. To resolve these limitations we have turned to nature, utilising proteins that have evolved over millennia to enable effective energy dissipation. Specifically, a recombinant form of the mechanosensitive protein talin was incorporated into a monomeric unit and crosslinked, resulting in the production of the first reported example of a talin shock absorbing material (TSAM). When subjected to 1.5 km/s supersonic shots, TSAMs were shown not only to absorb the impact, but to capture/preserve the projectile, making TSAMs the first reported protein material to achieve this.
Antecedents and effects of green supply chain management (GSCM) practices
Authors: Chatzoudes Dimitrios , Chatzoglou Prodromos
Published: November 2022

Purpose

During the previous two decades, “Green Supply Chain Management” (GSCM) has been gaining the attention of researchers and practitioners from various fields (e.g. operations, logistics and supply chain management). Its significance is constantly growing, and various studies are conducted in order to capture its overall organizational contribution. The present study attempts to bring together various organizational aspects that have never been collectively investigated before in the relevant literature. Under that rationale, a robust conceptual framework is developed and empirically tested. This framework includes 17 factors that are classified in three dimensions: (1) drivers of GSCM practices, (2) GSCM practices and (3) firm performance (GSCM outcomes).

Design/methodology/approach

The examination of the proposed conceptual framework was performed using a newly developed structured questionnaire that was distributed to a sample of Greek manufacturing organizations. Supply Chain managers and Chief Executive Officers (CEOs) were used as key respondents, due to their knowledge and experience. After the completion of the three-month research period (last quarter of 2019), 292 useable questionnaires were returned. The empirical data were analyzed using the “Structural Equation Modeling” technique. The study is empirical (based on primary data), explanatory (examines cause and effect relationships), deductive (tests research hypotheses) and quantitative (includes the analysis of quantitative data collected with the use of a structured questionnaire).

Findings

Empirical results point out that internal environmental management, green innovative practices and environmental proactivity are GSCM practices with the most significant impact on firm performance. Moreover, the mediating role of GSCM practices in the relationship between GSCM drivers and firm performance is also highlighted. Finally, it was found that GSCM practices can explain 35% of the variance in firm performance and the drivers of GSCM practices can explain 78% of the variance of these practices.

Originality/value

The proposed three-dimensional conceptual framework of this empirical study and its underlining rationale has rarely been adopted in the relevant literature. Moreover, the study investigates which GSCM practices have an impact on firm performance, thus offering value to practitioners of the field. Also, it is one of the few similar studies that have been conducted on a European country.