bluuebunny/crossref_metadata_2025 huggingface dataset:
Global, Low-Amplitude Cortical State Predicts Response Outcomes in a Selective Detection Task in Mice
Authors: Marrero Krista , Aruljothi Krithiga , Zareian Behzad , Gao Chengchun , Zhang Zhaoran , Zagha Edward
Published: September 2021

Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield Ca2+ imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices. We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity predicted response versus no response outcomes and faster reaction times. The activity predictive of trial outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions. Using principal component analysis, we demonstrate that response trials are associated with a distinct and less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor encoding. These findings support low amplitude and low variability as an optimal prestimulus cortical state for stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.
From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder
Authors: Liu Dong-Yu , Ju Xuan , Gao Yuan , Han Jin-Fang , Li Zhe , Hu Xi-Wen , Tan Zhong-Lin , Northoff Georg , Song Xue Mei
Published: September 2021

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.
Fine Particulate Air Pollution, Early Life Stress, and Their Interactive Effects on Adolescent Structural Brain Development: A Longitudinal Tensor-Based Morphometry Study
Authors: Miller Jonas G , Dennis Emily L , Heft-Neal Sam , Jo Booil , Gotlib Ian H
Published: September 2021

Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9–13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white matter regions. Fewer effects of PM2.5 were observed for adolescents who had experienced more severe ELS, although occasionally they were in the opposite direction. This pattern of results suggests that for many brain regions, moderate to severe ELS largely constrains the effects of PM2.5 on structural development. Further theory and research is needed on the joint effects of ELS and air pollution on the brain.
Layer-specific pyramidal neuron properties underlie diverse anterior cingulate cortical motor and limbic networks
Authors: Medalla Maria , Chang Wayne , Ibañez Sara , Guillamon-Vivancos Teresa , Nittmann Mathias , Kapitonava Anastasia , Busch Silas E , Moore Tara L , Rosene Douglas L , Luebke Jennifer I
Published: September 2021

The laminar cellular and circuit mechanisms by which the anterior cingulate cortex (ACC) exerts flexible control of motor and affective information for goal-directed behavior have not been elucidated. Using multimodal tract-tracing, in vitro patch-clamp recording and computational approaches in rhesus monkeys (M. mulatta), we provide evidence that specialized motor and affective network dynamics can be conferred by layer-specific biophysical and structural properties of ACC pyramidal neurons targeting two key downstream structures —the dorsal premotor cortex (PMd) and the amygdala (AMY). AMY-targeting neurons exhibited significant laminar differences, with L5 more excitable (higher input resistance and action potential firing rates) than L3 neurons. Between-pathway differences were found within L5, with AMY-targeting neurons exhibiting greater excitability, apical dendritic complexity, spine densities, and diversity of inhibitory inputs than PMd-targeting neurons. Simulations using a pyramidal-interneuron network model predict that these layer- and pathway-specific single-cell differences contribute to distinct network oscillatory dynamics. L5 AMY-targeting networks are more tuned to slow oscillations well-suited for affective and contextual processing timescales, while PMd-targeting networks showed strong beta/gamma synchrony implicated in rapid sensorimotor processing. These findings are fundamental to our broad understanding of how layer-specific cellular and circuit properties can drive diverse laminar activity found in flexible behavior.
Resting State Alpha Electroencephalographic Rhythms Are Affected by Sex in Cognitively Unimpaired Seniors and Patients with Alzheimer’s Disease and Amnesic Mild Cognitive Impairment: A Retrospective and Exploratory Study
Authors: Babiloni Claudio , Noce Giuseppe , Ferri Raffaele , Lizio Roberta , Lopez Susanna , Lorenzo Ivan , Tucci Federico , Soricelli Andrea , Zurrón Montserrat , Díaz Fernando , Nobili Flavio , Arnaldi Dario , Famà Francesco , Buttinelli Carla , Giubilei Franco , Cipollini Virginia , Marizzoni Moira , Güntekin Bahar , Yıldırım Ebru , Hanoğlu Lutfu , Yener Görsev , Gündüz Duygu Hünerli , Onorati Paolo , Stocchi Fabrizio , Vacca Laura , Maestú Fernando , Frisoni Giovanni B , Del Percio Claudio
Published: September 2021

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14–30 Hz) and gamma (30–40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aβ42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.
Cellular Substrates of Functional Network Integration and Memory in Temporal Lobe Epilepsy
Authors: Douw Linda , Nissen Ida A , Fitzsimmons Sophie M D D , Santos Fernando A N , Hillebrand Arjan , van Straaten Elisabeth C W , Stam Cornelis J , De Witt Hamer Philip C , Baayen Johannes C , Klein Martin , Reijneveld Jaap C , Heyer Djai B , Verhoog Matthijs B , Wilbers René , Hunt Sarah , Mansvelder Huibert D , Geurts Jeroen J G , de Kock Christiaan P J , Goriounova Natalia A
Published: September 2021

Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of drug-resistant TLE patients (n = 31), who underwent pseudo resting-state functional magnetic resonance imaging (fMRI), resting-state magnetoencephalography (MEG) and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses. Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As could be hypothesized, greater network centrality related to better memory performance. Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. We conclude that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients. These findings connect previously separate scales of investigation, increasing translational insight into focal pathology and large-scale network disturbances in TLE.
Suppression of Unattended Features Is Independent of Task Relevance
Authors: Gundlach Christopher , Forschack Norman , Müller Matthias M
Published: September 2021

Feature-based attention serves the separation of relevant from irrelevant features. While global amplification of attended features is coherently described as a key mechanism for feature-based attention, nature and constituting factors of neural suppressive interactions are far less clear. One aspect of global amplification is its flexible modulation by the task relevance of the to-be-attended stimulus. We examined whether suppression is similarly modulated by their respective task relevance or is mandatory for all unattended features. For this purpose, participants saw a display of randomly moving dots with 3 distinct colors and were asked to report brief events of coherent motion for a cued color. Of the 2 unattended colored clouds, one contained distracting motion events while the other was irrelevant and without such motion events throughout the experiment. We used electroencephalography-derived steady-state visual-evoked potentials to investigate early visual processing of the attended, unattended, and irrelevant color under sustained feature-based attention. The analysis revealed a biphasic process with an early amplification of the to-be-attended color followed by suppression of the to-be-ignored color relative to a pre-cue baseline. Importantly, the neural dynamics for the unattended and always irrelevant color were comparable. Suppression is thus a mandatory mechanism affecting all unattended stimuli irrespective of their task relevance.
Phase-Based Cortical Synchrony Is Affected by Prematurity
Authors: Yrjölä Pauliina , Stjerna Susanna , Palva J Matias , Vanhatalo Sampsa , Tokariev Anton
Published: September 2021

Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates many higher neurocognitive functions, which are often affected by prematurity, a globally prominent neurodevelopmental risk factor. Here, we used electroencephalography to examine brain-wide cortical PPC networks at term-equivalent age, comparing human infants after early prematurity to a cohort of healthy controls. We found that prematurity affected these networks in a sleep state-specific manner, and the differences between groups were also frequency-selective, involving brain-wide connections. The strength of synchronization in these networks was predictive of clinical outcomes in the preterm infants. These findings show that prematurity affects PPC networks in a clinically significant manner, suggesting early functional biomarkers of later neurodevelopmental compromise that may be used in clinical or translational studies after early neonatal adversity.
Developmental Sex Differences in Negative Emotion Decision-Making Dynamics: Computational Evidence and Amygdala-Prefrontal Pathways
Authors: Xu Jiahua , Hao Lei , Chen Menglu , He Ying , Jiang Min , Tian Ting , Wang Hui , Wang Yanpei , Wang Daoyang , Han Zhuo Rachel , Tan Shuping , Men Weiwei , Gao Jiahong , He Yong , Tao Sha , Dong Qi , Qin Shaozheng
Published: September 2021

Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA–MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA–insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children’s emotion and related functions.
Motor Learning Promotes the Coupling between Fast Spindles and Slow Oscillations Locally over the Contralateral Motor Network
Authors: Solano Agustín , Riquelme Luis A , Perez-Chada Daniel , Della-Maggiore Valeria
Published: September 2021

Recent studies from us and others suggest that traditionally declarative structures mediate some aspects of the encoding and consolidation of procedural memories. This evidence points to the existence of converging physiological pathways across memory systems. Here, we examined whether the coupling between slow oscillations (SO) and spindles, a mechanism well established in the consolidation of declarative memories, is relevant for the stabilization of human motor memories. To this aim, we conducted an electroencephalography study in which we quantified various parameters of these oscillations during a night of sleep that took place immediately after learning a visuomotor adaptation (VMA) task. We found that VMA increased the overall density of fast (≥12 Hz), but not slow (<12 Hz), spindles during nonrapid eye movement sleep, stage 3 (NREM3). This modulation occurred rather locally over the hemisphere contralateral to the trained hand. Although adaptation learning did not affect the density of SOs, it substantially enhanced the number of fast spindles locked to the active phase of SOs. The fact that only coupled spindles predicted overnight memory retention points to the relevance of this association in motor memory consolidation. Our work provides evidence in favor of a common mechanism at the basis of the stabilization of declarative and motor memories.
Precise Topology of Adjacent Domain-General and Sensory-Biased Regions in the Human Brain
Authors: Assem Moataz , Shashidhara Sneha , Glasser Matthew F , Duncan John
Published: September 2021

Recent functional MRI studies identified sensory-biased regions across much of the association cortices and cerebellum. However, their anatomical relationship to multiple-demand (MD) regions, characterized as domain-general due to their coactivation during multiple cognitive demands, remains unclear. For a better anatomical delineation, we used multimodal MRI techniques of the Human Connectome Project to scan subjects performing visual and auditory versions of a working memory (WM) task. The contrast between hard and easy WM showed strong domain generality, with essentially identical patterns of cortical, subcortical, and cerebellar MD activity for visual and auditory materials. In contrast, modality preferences were shown by contrasting easy WM with baseline; most MD regions showed visual preference while immediately adjacent to cortical MD regions, there were interleaved regions of both visual and auditory preference. The results may exemplify a general motif whereby domain-specific regions feed information into and out of an adjacent, integrative MD core.
Evolution of Fatty Liver Disease and Relationship With Lipoproteins and Clinical Outcomes in Hepatitis B/Human Immunodeficiency Virus Coinfection
Authors: Khalili Mandana , King Wendy C , Kleiner David E , Chung Raymond T , Bhan Atul K , Ghany Marc G , Sulkowski Mark S , Lisker-Melman Mauricio , Jain Mamta K , Janssen Harry L A , Hinerman Amanda S , Sanyal Arun J , Sterling Richard K
Published: September 2021

Background

Fatty liver disease (FLD) and hepatitis B virus (HBV) infection occur commonly in human immunodeficiency virus (HIV). FLD resolution is associated with improvement in lipoproteins in HIV-uninfected patients. We evaluated changes in FLD in an HBV/HIV-coinfected cohort.

Methods

One hundred eight HBV/HIV-coinfected adults with baseline liver biopsies were followed every 24 weeks (median, 166 weeks) and 60 had follow-up biopsies. Baseline FLD categories (none, ≥5% steatosis, steatohepatitis), their change, and relationships with clinical and lipid/lipoprotein parameters were explored using multivariable modeling.

Results

Median age was 50 years, and 93% were male. At baseline 30% had FLD. With control for lipid-lowering medications and body mass index, low-density lipoprotein (LDL) cholesterol (LDL-C), LDL particle concentration (LDL-P), and apolipoprotein B (apoB) decreased and adiponectin increased over time (all P < .05); On follow-up (vs baseline), there was no significant difference in FLD category (P = .85); 60% remained without FLD, 17% had unchanged, 12% worsening, and 12% improved FLD. Baseline low-density lipoproteins (LDL-C, LDL-P, small LDL-P) and apoB appeared highest in those with unchanged FLD status (all P < .05). No associations between changes in FLD across follow-up (worsening/improvement vs unchanged) and lipid/lipoproteins changes were identified.

Conclusions

In this cohort, there was no significant change in FLD prevalence over a relatively short timeframe. Baseline atherogenic lipids appeared highest in those with persistent steatosis or steatohepatitis, suggesting potentially increased cardiovascular risk in this group, but an independent relationship between individual-level change in FLD status and lipid/lipoprotein levels across follow-up was not observed.
Train-the-Trainer as an Effective Approach to Building Global Networks of Experts in Genomic Surveillance of Antimicrobial Resistance (AMR)
Authors: Abrudan Monica , Matimba Alice , Nikolic Dusanka , Hughes Darren , Argimón Silvia , Kekre Mihir , Underwood Anthony , Aanensen David M ,   NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, Abudahab Khalil , Harste Harry , Muddyman Dawn , Taylor Ben , Wheeler Nicole , David Sophia , Donado-Godoy Pilar , Fabian Bernal Johan , Arevalo Alejandra , Fernanda Valencia Maria , Osma Castro Erik C D , Ravikumar K L , Nagaraj Geetha , Shamanna Varun , Govindan Vandana , Prabhu Akshata , Sravani D , Shincy M R , Rose Steffimole , Ravishankar K N , Okeke Iruka N , Oaikhena Anderson O , Afolayan Ayorinde O , Ajiboye Jolaade J , Ewomazino Odih Erkison , Carlos Celia , Lagrada Marietta L , Macaranas Polle Krystle V , Olorosa Agnettah M , Gayeta June M , Herrera Elmer M , Molloy Ali , Stelling John , Vegvari Carolin
Published: September 2021

Advanced genomics and sequencing technologies are increasingly becoming critical for global health applications such as pathogen and antimicrobial resistance (AMR) surveillance. Limited resources challenge capacity development in low- and middle-income countries (LMICs), with few countries having genomics facilities and adequately trained staff. Training research and public health experts who are directly involved in the establishment of such facilities offers an effective, but limited, solution to a growing need. Instead, training them to impart their knowledge and skills to others provides a sustainable model for scaling up the much needed capacity and capability for genomic sequencing and analysis locally with global impact. We designed and developed a Train-the-Trainer course integrating pedagogical aspects with genomic and bioinformatics activities. The course was delivered to 18 participants from 12 countries in Africa, Asia, and Latin America. A combination of teaching strategies culminating in a group project created a foundation for continued development at home institutions. Upon follow-up after 6 months, at least 40% of trainees had initiated training programs and collaborations to build capacity at local, national, and regional level. This work provides a framework for implementing a training and capacity building program for the application of genomics tools and resources in AMR surveillance.
Histopathology Is Key to Interpreting Multiplex Molecular Test Results From Postmortem Minimally Invasive Tissue Samples
Authors: Ritter Jana M , Seixas Josilene N , Walong Edwin , Dawa Jeanette , Onyango Clayton , Pimenta Fabiana C , da Gloria Carvalho Maria , Silva-Flannery Luciana , Jenkinson Tiffany , Howard Katie , Bhatnagar Julu , Diaz Maureen , Winchell Jonas M , Zaki Sherif R , Chaves Sandra S , Martines Roosecelis B
Published: September 2021

Background

Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms.

Methods

MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results.

Results

MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present.

Conclusions

TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS.
Burden of Serious Bacterial Infections and Multidrug-Resistant Organisms in an Adult Population of Nepal: A Comparative Analysis of Minimally Invasive Tissue Sampling Informed Mortality Surveillance of Community and Hospital Deaths
Authors: Bhattarai Suraj , Sharma Binita Koirala , Subedi Nuwadatta , Ranabhat Sunita , Baral Madan Prasad
Published: September 2021

Background

Bacterial diseases are the leading cause of mortality globally, and due to haphazard use of antibiotics, antimicrobial resistance has become an emerging threat.

Methods

This cross-sectional observational study utilized a minimally invasive tissue sampling procedure to determine the cause of death among an adult population. Bacterial cultures (blood, cerebrospinal fluid, lung tissue) and antibiotic susceptibility were evaluated, and the results were compared between community and hospital deaths.

Results

Of 100 deceased persons studied, 76 (76%) deaths occurred in the community and 24 (24%) in the hospital. At least 1 bacterial agent was cultured from 86 (86%) cases; of these, 74 (86%) had a bacterial disease attributed as the primary cause of death, with pneumonia (35, 47.3%), sepsis (33, 44.6%), and meningitis (3, 4.1%) most common. Of 154 bacterial isolates (76.6% from the community and 23.4% from the hospital) detected from 86 culture-positive cases, 26 (16.8%) were multidrug-resistant (MDR). Klebsiella species were the most common (13 of 26) MDR organisms. The odds of getting an MDR Klebsiella infection was 6-fold higher among hospital deaths compared with community deaths (95% confidence interval [CI], 1.37–26.40; P = .017) and almost 23-fold higher (CI, 2.45–213.54; P = .006) among cases with prior antibiotic use compared to those without.

Conclusions

High incidence of serious bacterial infections causing death of adults in the community, with most MDR organisms isolated from hospitalized cases, calls for robust surveillance mechanisms and infection prevention activities at the community level and evidence-driven antibiotic stewardship in healthcare settings.
Out of balance? Revisiting the nexus of income inequality, household debt and current account imbalances after the Great Recession
Authors: Ascione Fabio , Schnetzer Matthias
Published: September 2021

Rising current account imbalances around the globe preceded the Great Recession in the late 2000s. These imbalances narrowed significantly during the crisis mainly due to a negative demand shock and plummeting imports in deficit countries. While income inequality and household debt played a pivotal role in current account imbalances prior to the crisis, it is unclear whether these relations still hold when including the post-crisis era. We estimate current account determinants using a panel of 31 OECD countries over 45 years and include measures for functional and personal income distribution as well as household debt. We find a sustained relation between income inequality and current accounts when including the post-crisis period, while the link to household debt diminishes, indicating a change in the debt regime in a number of countries.
Clinical Evaluation of Plasma Separation Cards as a Tool to Collect, Store, and Test Blood Samples for Hepatitis B and C Serological Markers
Authors: Colucci Giuseppe , Renteria Sara Uceda , Ceriotti Ferruccio , Lampertico Pietro
Published: September 2021

Background

The plasma separation card (PSC) is a new device for collecting finger-pricking–derived small amount of blood in a solid support that is stable at room temperature and can be archived, mailed, and processed at a later time. This tool can facilitate screening at risk populations located in rural areas without local health care infrastructures. We evaluated the performance of PSC in the collection and preparation of blood samples for the determination of hepatitis B and C serological markers.

Methods

Blood obtained from 334 consecutive patients referred for the detection of hepatitis B surface antigens (HBsAg), hepatitis B surface antibodies (anti-HBs) and hepatitis C antibodies (anti-HCV) was analyzed in parallel using standard (STD) and PSC-based sample collection and preparation procedures. Results obtained from STD or PSC processed samples were compared for their detection rate and correlation.

Results

Using STD, we detected 5 samples positive for HBsAg, 150 for anti-HBs, and 23 for anti-HCV with a rate of concordance with PSC of 100%, 100%, and 91% respectively. The 100% concordance observed for anti-HBs was based on a cutoff of 2.6 IU/L for PSC-derived sample corresponding to the 10 IU/L threshold associated with immunity to hepatitis B. STD and PSC showed a good correlation (R2 = 0.85) in the detection of anti-HBs titers. The 2 anti-HCV PSC negative samples had no detectable viremia.

Conclusions

These data confirm the utility of PSC as a tool to support viral hepatitis screening programs in rural areas lacking local clinical infrastructures and testing facilities.
Association of Plasma Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) with All-Cause and Cause-Specific Mortality in Individuals with Type 2 Diabetes
Authors: Liu Jian-Jun , Pek Sharon L T , Liu Sylvia , Wang Jiexun , Lee Janus , Ang Keven , Shao Yi Ming , Gurung Resham L , Tavintharan Subramaniam , Tang Wern Ee , Sum Chee Fang , Lim Su Chi
Published: September 2021

Background

Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein in the transforming growth factor-beta superfamily. We sought to study whether LRG1 might predict risk for all-cause and cause-specific mortality in individuals with type 2 diabetes.

Methods

2012 outpatients with type 2 diabetes were followed for a median of 7.2 years and 188 death events were identified. Association of LRG1 with risk for mortality was assessed by multivariable Cox regression models.

Results

Participants with a higher concentration of LRG1 had an increased risk for all-cause mortality [HR (95% CI), 1.76 (1.03–3.01), 1.75 (1.03–2.98), and 4.37 (2.72–7.02) for quartiles 2, 3, and 4, respectively, compared to quartile 1]. The association remained significant after adjustment for known cardio-renal risk factors including estimated glomerular filtration rate and albuminuria [adjusted HR 2.76 (1.66–4.59), quartile 4 versus 1]. As a continuous variable, a 1-SD increment in LRG1 was associated with 1.34 (1.14–1.57)-fold adjusted risk for all-cause mortality. High plasma LRG1 was independently associated with mortality attributable to cardiovascular disease, infection, and renal diseases. Adding LRG1 into a clinical variable-based model improved discrimination (c statistics from 0.828 to 0.842, P = 0.006) and reclassification (net reclassification improvement 0.47, 95% CI 0.28–0.67) for prediction of 5-year all-cause mortality.

Conclusion

Plasma LRG1 predicts risk for all-cause mortality and mortality attributable to cardiovascular disease, infection, and renal disease independent of known cardio-renal risk factors. It may be a potential novel biomarker to improve risk stratification in individuals with type 2 diabetes.
Development of a Plasma Biomarker Diagnostic Model Incorporating Ultrasensitive Digital Immunoassay as a Screening Strategy for Alzheimer Disease in a Chinese Population
Authors: Wu Xue , Xiao Zhenxu , Yi Jingwei , Ding Saineng , Gu Hongchen , Wu Wanqing , Luo Jianfeng , Liang Xiaoniu , Zheng Li , Xu Hong , Zhao Qianhua , Ding Ding
Published: September 2021

Background

The ultrasensitive detection of blood-based biomarkers such as amyloid β (Aβ), tau, and neurofilament light (NFL) has drawn much attention in Alzheimer disease (AD) diagnosis. However, few studies have been conducted in the Chinese population. This study aimed to evaluate the ability of plasma biomarker diagnostic models for AD in the Chinese population based on a novel digital immunoassay technology.

Methods

159 patients with AD, 148 patients with amnestic mild cognitive impairment (aMCI), and 121 cognitively normal control participants were recruited from 2 cohorts. The concentrations of plasma Aβ42, Aβ40, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau 181), and NFL were quantified using an ultrasensitive single molecule array (Simoa) platform. Comprehensive and simplified diagnostic models were established based on the plasma biomarker profile and clinical characteristics.

Results

Among all blood biomarkers, p-tau181 had the greatest potential for identifying patients with cognitive impairment. The simplified diagnostic model, which combined plasma p-tau181, Aβ42, and clinical features, achieved 93.3% area under the curve (AUC), 78.6% sensitivity, and 94.2% specificity for distinguishing AD from control participants, indicating a diagnostic ability approaching that of the comprehensive diagnostic model including 5 plasma biomarkers and clinical characteristics (95.1% AUC, 85.5% sensitivity, 94.2% specificity). Moreover, the simplified model reached 95.9% AUC and 94.0% AUC for early- and late-onset AD/control participants, respectively.

Conclusions

We established AD diagnostic models using plasma biomarkers for Chinese participants. These findings suggest the simplified diagnostic model provides an accessible and practical way for large-scale screening in the clinic and community, especially in developing countries.
The Past, Present, and Future of Online Dispute Resolution
Authors: Rabinovich-Einy Orna
Published: September 2021

This article chronicles the evolution of the field of online dispute resolution from its inception in the mid-1990s to its current application in and outside the court system. While originally ODR played a modest role in the limited domain of e-commerce, over the years its application has expanded significantly, as have its form and function: from processes that have sought to replicate online equivalents to ones that reimagine the design of procedures to better fit party needs and to address the justice system’s longstanding problems. The article predicts that the future of ODR lies in increased automation, which includes artificial intelligence and various forms of structured negotiation, and, consequently, a reduced role for human third parties. This will require a rethinking of the ways in which access to justice, procedural justice and substantive justice can be realized. The key for realizing the values and goals of the justice system lies in the careful design and ongoing evaluation of online systems, activities that have themselves been transformed by technology and the availability of big data.
The Star-Structure Connectivity and Star-Substructure Connectivity of Hypercubes and Folded Hypercubes
Authors: Ba Lina , Zhang Heping
Published: September 2021

As a generalization of vertex connectivity, for connected graphs $G$ and $T$, the $T$-structure connectivity $\kappa (G; T)$ (resp. $T$-substructure connectivity $\kappa ^{s}(G; T)$) of $G$ is the minimum cardinality of a set of subgraphs $F$ of $G$ that each is isomorphic to $T$ (resp. to a connected subgraph of $T$) so that $G-F$ is disconnected. For $n$-dimensional hypercube $Q_{n}$, Lin et al. showed $\kappa (Q_{n};K_{1,1})=\kappa ^{s}(Q_{n};K_{1,1})=n-1$ and $\kappa (Q_{n};K_{1,r})=\kappa ^{s}(Q_{n};K_{1,r})=\lceil \frac{n}{2}\rceil $ for $2\leq r\leq 3$ and $n\geq 3$ (Lin, C.-K., Zhang, L.-L., Fan, J.-X. and Wang, D.-J. (2016) Structure connectivity and substructure connectivity of hypercubes. Theor. Comput. Sci., 634, 97–107). Sabir et al. obtained that $\kappa (Q_{n};K_{1,4})=\kappa ^{s}(Q_{n};K_{1,4})= \lceil \frac{n}{2}\rceil $ for $n\geq 6$ and for $n$-dimensional folded hypercube $FQ_{n}$, $\kappa (FQ_{n};K_{1,1})=\kappa ^{s}(FQ_{n};K_{1,1})=n$, $\kappa (FQ_{n};K_{1,r})=\kappa ^{s}(FQ_{n};K_{1,r})= \lceil \frac{n+1}{2}\rceil $ with $2\leq r\leq 3$ and $n\geq 7$ (Sabir, E. and Meng, J.(2018) Structure fault tolerance of hypercubes and folded hypercubes. Theor. Comput. Sci., 711, 44–55). They proposed an open problem of determining $K_{1,r}$-structure connectivity of $Q_n$ and $FQ_n$ for general $r$. In this paper, we obtain that for each integer $r\geq 2$, $\kappa (Q_{n};K_{1,r})$  $=\kappa ^{s}(Q_{n};K_{1,r})$  $=\lceil \frac{n}{2}\rceil $ and $\kappa (FQ_{n};K_{1,r})=\kappa ^{s}(FQ_{n};K_{1,r})= \lceil \frac{n+1}{2}\rceil $ for all integers $n$ larger than $r$ in quare scale. For $4\leq r\leq 6$, we separately confirm the above result holds for $Q_n$ in the remaining cases.
SS6: Online Short-Code RAID-6 Scaling by Optimizing New Disk Location and Data Migration
Authors: Yuan Zhu , You Xindong , Lv Xueqiang , Xie Ping
Published: September 2021

Thanks to excellent reliability, availability, flexibility and scalability, redundant arrays of independent (or inexpensive) disks (RAID) are widely deployed in large-scale data centers. RAID scaling effectively relieves the storage pressure of the data center and increases both the capacity and I/O parallelism of storage systems. To regain load balancing among all disks including old and new, some data usually are migrated from old disks to new disks. Owing to unique parity layouts of erasure codes, traditional scaling approaches may incur high migration overhead on RAID-6 scaling. This paper proposes an efficient approach based Short-Code for RAID-6 scaling. The approach exhibits three salient features: first, SS6 introduces $\tau $ to determine where new disks should be inserted. Second, SS6 minimizes migration overhead by delineating migration areas. Third, SS6 reduces the XOR calculation cost by optimizing parity update. The numerical results and experiment results demonstrate that (i) SS6 reduces the amount of data migration and improves the scaling performance compared with Round-Robin and Semi-RR under offline, (ii) SS6 decreases the total scaling time against Round-Robin and Semi-RR under two real-world I/O workloads (iii) the user average response time of SS6 is better than the other two approaches during scaling and after scaling.
Mean Error Rate Weighted Online Boosting Method
Authors: Honnikoll Nagaraj , Baidari Ishwar
Published: September 2021

Boosting is a generally known technique to convert a group of weak learners into a powerful ensemble. To reach this desired objective successfully, the modules are trained with distinct data samples and the hypotheses are combined in order to achieve an optimal prediction. To make use of boosting technique in online condition is a new approach. It motivates to meet the requirements due to its success in offline conditions. This work presents new online boosting method. We make use of mean error rate of individual base learners to achieve effective weight distribution of the instances to closely match the behavior of OzaBoost. Experimental results show that, in most of the situations, the proposed method achieves better accuracies, outperforming the other state-of-art methods.
Circadian rhythms in ischaemic heart disease: key aspects for preclinical and translational research: position paper of the ESC working group on cellular biology of the heart
Authors: Lecour Sandrine , Du Pré Bastiaan C , Bøtker Hans Erik , Brundel Bianca J J M , Daiber Andreas , Davidson Sean M , Ferdinandy Peter , Girao Henrique , Gollmann-Tepeköylü Can , Gyöngyösi Mariann , Hausenloy Derek J , Madonna Rosalinda , Marber Michael , Perrino Cinzia , Pesce Maurizio , Schulz Rainer , Sluijter Joost P G , Steffens Sabine , Van Linthout Sophie , Young Martin E , Van Laake Linda W
Published: September 2021

Circadian rhythms are internal regulatory processes controlled by molecular clocks present in essentially every mammalian organ that temporally regulate major physiological functions. In the cardiovascular system, the circadian clock governs heart rate, blood pressure, cardiac metabolism, contractility, and coagulation. Recent experimental and clinical studies highlight the possible importance of circadian rhythms in the pathophysiology, outcome, or treatment success of cardiovascular disease, including ischaemic heart disease. Disturbances in circadian rhythms are associated with increased cardiovascular risk and worsen outcome. Therefore, it is important to consider circadian rhythms as a key research parameter to better understand cardiac physiology/pathology, and to improve the chances of translation and efficacy of cardiac therapies, including those for ischaemic heart disease. The aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to highlight key aspects of circadian rhythms to consider for improvement of preclinical and translational studies related to ischaemic heart disease and cardioprotection. Applying these considerations to future studies may increase the potential for better translation of new treatments into successful clinical outcomes.
Deaf Children’s ASL Vocabulary and ASL Syntax Knowledge Supports English Knowledge
Authors: Hoffmeister Robert , Henner Jon , Caldwell-Harris Catherine , Novogrodsky Rama
Published: September 2021

The current study contributes empirical data to our understanding of how knowledge of American Sign Language (ASL) syntax aids reading print English for deaf children who are bilingual and bimodal in ASL and English print. The first analysis, a conceptual replication of Hoffmeister ( 2000), showed that performance on the American Sign Language Assessment Instrument correlated with the Sanford Achievement Test—Reading Comprehension (SAT-RC) and the Rhode Island Test of Language Structures (RITLS, Engen & Engen, 1983). The second analysis was a quantile regression using ASL assessments to predict English print abilities. Different ASL skills were important for English reading comprehension (SAT-RC) versus understanding English syntax (RITLS); the relationship between ASL skills and English print performance also varied for students at different English print ability levels. Strikingly, knowledge of ASL syntax was robustly correlated with knowledge of English syntax at all ability levels. Our findings provide novel and strong evidence for the impact of ASL on the development of English literacy.
A high-quality chromosome-level genome of wild Rosa rugosa
Authors: Zang Fengqi , Ma Yan , Tu Xiaolong , Huang Ping , Wu Qichao , Li Zhimin , Liu Tao , Lin Furong , Pei Surui , Zang Dekui , Zhang Xuemei , Zheng Yongqi , Yu Yunyan
Published: September 2021

Rosa rugosa is an important shrub with economic, ecological, and pharmaceutical value. A high-quality chromosome-scale genome for R. rugosa sequences was assembled using PacBio and Hi-C technologies. The final assembly genome sequences size was about 407.1 Mb, the contig N50 size was 2.85 Mb, and the scaffold N50 size was 56.6 Mb. More than 98% of the assembled genome sequences were anchored to seven pseudochromosomes (402.9 Mb). The genome contained 37,512 protein-coding genes, with 37,016 genes (98.68%) that were functionally annotated, and 206.67 Mb (50.76%) of the assembled sequences are repetitive sequences. Phylogenetic analyses indicated that R. rugosa diverged from Rosa chinensis ∼6.6 million years ago, and no lineage-specific whole-genome duplication event occurred after divergence from R. chinensis. Chromosome synteny analysis demonstrated highly conserved synteny between R. rugosa and R. chinensis, between R. rugosa and Prunus persica as well. Comparative genome and transcriptome analysis revealed genes related to colour, scent, and environment adaptation. The chromosome-level reference genome provides important genomic resources for molecular-assisted breeding and horticultural comparative genomics research.
Spotted Lanternfly (Hemiptera: Fulgoridae) Nymphal Dispersion Patterns and Their Influence on Field Experiments
Authors: Calvin D D , Keller J , Rost J , Walsh B , Biddinger D , Hoover K , Treichler B , Johnson A , Roush R T
Published: September 2021

The spotted lanternfly, Lycorma delicatula (Hemiptera: Fulgoridae) (White, 1845), is an invasive pest in the Mid-Atlantic region of the United States. Understanding this pest’s dispersion patterns is fundamental for development of management and surveillance programs. To address this knowledge gap, we quantified spotted lanternfly nymph dispersion patterns by instar for rural and urban/suburban habitats, and we compared the number of sample units required for sticky traps and in situ visual counts to estimate population densities at several precisions. In addition, we assessed the ability of two experimental designs (completely random and randomized complete block) to detect management practices’ impacts in the field. All instars typically followed an aggregated dispersion pattern. Sample size and time requirements for checking and replacing sticky traps and for conducting in situ counts were similar, but in situ counts do not require purchasing traps, installation time, or delays before treatment, and do not remove insects. Although the cost for using in situ counts is likely less than for sticky traps, early instar spotted lanternfly nymph populations are harder to visually detect than later instars because of their small size, which may negate any cost advantage when treatments are applied early. In general, using a randomized complete block design resulted in higher statistical power than a completely random design, allowing detection of proportional population reductions of 10–20% less with equal replication. Studies aiming to evaluate treatments that reduce spotted lanternfly numbers by less than 60% will require researchers to evaluate the feasibility of using the required large sample sizes.
Women and Late Chartism: Women’s Rights in Mid-Victorian England
Authors: Roberts Matthew
Published: September 2021

This article revisits the relationship between women and Chartism, the British mass movement for democratic rights that dominated popular politics from the late 1830s to the 1850s. It argues that the opportunities for women to participate in the movement were more varied, extensive and enduring than has often been appreciated. Particular attention is paid to late Chartism (1843–52) by documenting in full, for the first time, the number of female Chartist bodies in existence. By presenting new material, based on a combing of the press and the Home Office files, the article moves on to consider the role played by Chartist women in 1848, the year of European revolution when the movement revived. It then builds on the theme of late Chartism by offering a case-study of the Women’s Rights Association (WRA). This body was established in 1851 by a group of Sheffield Chartist women to campaign for votes for women, which, it is argued here, represented the culmination of a women’s rights discourse within early Chartism. The article concludes by comparing the women’s rights discourse in early Chartism and other contemporary feminisms with that deployed by the WRA.