bluuebunny/crossref_metadata_2025 huggingface dataset:
Vessel-specific plaque features on coronary computed tomography angiography among patients of varying atherosclerotic cardiovascular disease risk
Authors: Bax A Maxim , Yoon Yeonyee E , Gianni Umberto , van Rosendael Alexander R , Lu Yao , Ma Xiaoyue , Goebel Benjamin P , Tantawy Sara W , Andreini Daniele , Budoff Matthew J , Cademartiri Filippo , Chinnaiyan Kavitha , Choi Jung Hyun , Conte Edoardo , de Araújo Gonçalves Pedro , Gottlieb Ilan , Hadamitzky Martin , Leipsic Jonathon A , Maffei Erica , Pontone Gianluca , Shin Sanghoon , Kim Yong Jin , Lee Byoung Kwon , Chun Eun Ju , Sung Ji Min , Lee Sang Eun , Berman Daniel S , Narula Jagat , Lin Fay Y , Chang Hyuk Jae , Shaw Leslee J ,   for the PARADIGM investigators
Published: February 2022

Aims

The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque extent and composition, has not been examined. To evaluate differences in quantified plaque characteristics (using CCTA) between the three major coronary arteries [left anterior descending (LAD), right coronary (RCA), and left circumflex (LCx)] among subgroups of patients with varying ASCVD risk.

Methods and results

Patients were included from a prospective, international registry of consecutive patients who underwent CCTA for evaluation of coronary artery disease. ASCVD risk groups were <7.5% (low), 7.5–20% (intermediate), and ≥20% (high). Among the ASCVD risk groups, the three coronary arteries were compared regarding quantified plaque volume and composition. Whole-heart plaque quantification was performed in 1340 patients (age 60 ± 9 years, 58% men). Across low, intermediate, and high ASCVD risk patients, the volume of plaque increased proportionally but was least in the LCx (7.4, 9.0, and 25.3 mm3, respectively) as compared with the RCA (19.3, 32.6, and 67.0 mm3, respectively, all P ≤ 0.006) and LAD (39.9, 60.8, and 93.3 mm3, respectively, all P < 0.001). In each ASCVD risk group, the composition of plaque in the LCx exhibited the least necrotic core and fibrofatty plaque (P < 0.05 vs. LAD and RCA).

Conclusion

Among patients with varying risk of ASCVD, plaque in the LCx is decidedly less and is comprised of less non-calcified plaque supporting prior evidence of the lower rates of acute coronary events in this vessel.
Pool-GWAS on reproductive dormancy in Drosophila simulans suggests a polygenic architecture
Authors: Lirakis Manolis , Nolte Viola , Schlötterer Christian
Published: February 2022

The genetic basis of adaptation to different environments has been of long-standing interest to evolutionary biologists. Dormancy is a well-studied adaptation to facilitate overwintering. In Drosophila melanogaster, a moderate number of genes with large effects have been described, which suggests a simple genetic basis of dormancy. On the other hand, genome-wide scans for dormancy suggest a polygenic architecture in insects. In D. melanogaster, the analysis of the genetic architecture of dormancy is complicated by the presence of cosmopolitan inversions. Here, we performed a genome-wide scan to characterize the genetic basis of this ecologically extremely important trait in the sibling species of D. melanogaster, D. simulans that lacks cosmopolitan inversions. We performed Pool-GWAS in a South African D. simulans population for dormancy incidence at 2 temperature regimes (10 and 12°C, LD 10:14). We identified several genes with SNPs that showed a significant association with dormancy (P-value < 1e-13), but the overall modest response suggests that dormancy is a polygenic trait with many loci of small effect. Our results shed light on controversies on reproductive dormancy in Drosophila and have important implications for the characterization of the genetic basis of this trait.
A chromosomal-level reference genome of the widely utilized Coccidioides posadasii laboratory strain “Silveira”
Authors: de Melo Teixeira Marcus , Stajich Jason E , Sahl Jason W , Thompson George R , Brem Rachel B , Dubin Claire A , Blackmon Austin V , Mead Heather L , Keim Paul , Barker Bridget M
Published: February 2022

Coccidioidomycosis is a common fungal disease that is endemic to arid and semi-arid regions of both American continents. Coccidioides immitis and Coccidioides posadasii are the etiological agents of the disease, also known as Valley Fever. For several decades, the C. posadasii strain Silveira has been used widely in vaccine studies, is the source strain for production of diagnostic antigens, and is a widely used experimental strain for functional studies. In 2009, the genome was sequenced using Sanger sequencing technology, and a draft assembly and annotation were made available. In this study, the genome of the Silveira strain was sequenced using single molecule real-time sequencing PacBio technology, assembled into chromosomal-level contigs, genotyped, and the genome was reannotated using sophisticated and curated in silico tools. This high-quality genome sequencing effort has improved our understanding of chromosomal structure, gene set annotation, and lays the groundwork for identification of structural variants (e.g. transversions, translocations, and copy number variants), assessment of gene gain and loss, and comparison of transposable elements in future phylogenetic and population genomics studies.
Effects of harvest date and growth stage on triticale forages in the southwest USA: kinetics of in vitro disappearance of fiber and dry matter
Authors: Coblentz Wayne K , Ottman Michael J
Published: February 2022

Recently, there has been interest in including triticale (X Triticosecale Wittmack) within forage programs in the southwest USA. Our objectives were to evaluate in vitro disappearance kinetics of neutral detergent fiber (NDF) and dry matter (DM) for cultivars identified during 2019 as positively or negatively deviant from typical cultivars, based specifically on regressions of 48-h in vitro disappearance of NDF on growth stage (GRST). All NDF analyses included the use of heat-stable α-amylase and sodium sulfite, as well as correction for residual ash (asNDFom). Seven triticale cultivars were established on December 18, 2019 at the University of Arizona Maricopa Agricultural Center, located near Maricopa, AZ. Forage plots were arranged in a randomized complete block design with three complete blocks (replications), and then harvested on seven dates the following late-winter and spring (February 26, March 17, April 1, April 14, April 28, May 12, and May 26). Based on a linear model, GRST was highly variable among cultivars on March 17 (44 ± 10.6), April 1 (57 ± 12.1), April 14 (67 ± 8.9), and April 28 (79 ± 7.2) compared with other harvest dates (SD ≤ 1.7). For concentrations of asNDFom, all cultivars exhibited linear (P ≤ 0.042) and quadratic (P < 0.001) polynomial contrasts in response to harvest date, and all cultivars except Merlin Max (P ≥ 0.063) exhibited at least one additional cubic or quartic effect (P ≤ 0.015). A contributing factor to the unique response by Merlin Max was the numerically greater maximum canopy height (145 ± 9.8 cm) compared with the mean of all cultivars (107 ± 17.7 cm), which also was associated with greater percentages of stem, as well as reduced percentages of DM partitioned within the grain head. Regressions of asNDFom disappearance after 30- or 48-h incubations on GRST indicated this was an effective independent variable (R2 ≥ 0.927), and responses were most often linear in nature. Generally, relationships for DM disappearance were quadratic, ostensibly due to the complicating effect of grain fill, but GRST was again an effective predictor variable with R2 statistics ≥ 0.852 for 12 of 14 combinations of cultivar and incubation time. Predicted percentages of digestible DM attributed to asNDFom disappearance were ≥50.3% through the fully flowered stage of growth, but digestible contributions from nonfiber components following the onset of grain fill profoundly affected overall DM digestibility among cultivars harvested at later GRST.
Ensuring Respect by Partners: Revisiting the Debate on Common Article 1
Authors: Wiesener Cornelius , Kjeldgaard-Pedersen Astrid
Published: February 2022

According to the International Committee of the Red Cross (ICRC), the duty to ‘ensure respect’ in Common Article 1 of the Geneva Conventions includes an external dimension: States have to ensure that other states respect their obligations under the Conventions, and arguably under international humanitarian law as a whole. This potentially has far-reaching consequences for states engaging in military operations together with partners, and the ICRC interpretation has been met with explicit pushback from a number of states as well as scholars. The present article seeks to revisit the debate on the extent of the obligation following from Common Article 1 in the context of partnered operations. We begin by providing a detailed outline of the ICRC view on the duty to ‘ensure respect by others’, as well as the reactions from states and scholarly contributions. Against this background, we examine—by carefully applying the customary rules on treaty interpretation enshrined in the Vienna Convention of the Law of Treaties—whether the duty to ensure respect has an external dimension judged by the ordinary meaning and intentions of the drafters, subsequent practice (both in relation to the ICRC and in other contexts) and judicial pronouncements. Having concluded that doctrinal legal analysis does indeed support an external dimension of Common Article 1, we then explore whether this duty to ensure respect by others applies to states regardless of the nature of the armed conflict and their own involvement in it. Finally, we analyse the exact content of the obligations arising from the duty to ensure respect by others under Common Article 1.
The Judicial Function of Investment Tribunals: Taking Foundational Assumptions Seriously
Authors: Zhang Yanwen
Published: February 2022

The proliferation of international courts and tribunals has given rise to debates about the judicial function beyond dispute settlement. These debates provide a broader context to study investment tribunals, especially when various conceptions of their judicial function are articulated in the ongoing reform process at United Nations Commission on International Trade Law Working Group III on investor–state dispute settlement. The current reform debate is largely driven by problems and issues that emerged in the contemporary practice of investment arbitration. However, the original balance that the founders of the system intended to strike receives much less attention. This paper focuses on the founders’ original assumptions about the judicial function of investment tribunals. It addresses the drafting process of selected key institutional features of investment arbitration established by the Convention on the Settlement of Investment Disputes between States and Nationals of Other States. The key claim is that the drafters’ conception of the judicial function was consciously narrow, without carrying major assumptions about public functions. This original view is in marked contrast with certain broader conceptions developed in subsequent arbitral practice. The rationales underpinning the original institutional design choices can also inform the ongoing institutional reform where similar tensions and issues re-emerge.
Power (im)balances in ‘conversation triads’ within qualitative research projects in the field of (forced) migration: Chances and challenges in conversations between interpreter, (forced) migrant and researcher
Authors: Tempes Jana , Rumpel Andrea
Published: February 2022

Qualitative research in the field of (forced) migration is confronted with language diversity in conversations. The integration of interpreters within these conversations changes the setting profoundly. While methodological reflections on the relationship between researcher and (forced) migrant have already led to new research methods that are sensitive to the (re)production of power (im)balances, the role of interpreters in this process is still surprisingly underexposed. This article captures qualitative research with interpreters as parts of the ‘conversation triad’ and links this approach to postcolonial theories. Considering processes of Othering we attain a better understanding of the possible roles of each participant within the conversation and how background knowledge comes into play. These methodological reflections enable us to consider the (re-)production of power (im)balances in such a conversation setting. The authors describe the chances and challenges in conversations between interpreter, (forced) migrant and researcher and thus make the involvement of interpreters visible.
Non-radial instabilities in collapsing galaxies: an analytically solvable model
Authors: Vietri Mario
Published: February 2022

This study examines the stability of a family of simplified, collisionless models of galaxy collapse, to fluid-like perturbations that leave the radial density profile unaltered, but distort the galaxy’s shape. The unperturbed models have constant density, and exhibit fully non-linear oscillations around an equilibrium radius in physical space. The equations that determine the time-development of perturbations in the linear regime are derived, and are shown to be of the Mathieu type; they are solved in the special case of the quadrupole mode. The ranges of values of the usual parameter 2T/|W| for which instability exists, leading inevitably to triaxial solutions, are determined. It is shown that, for 2T/|W|<0.1541, the initial configurations are unstable and the growth time of the instability is sufficiently short to lead to flattened final configurations. It is suggested that all of these results apply to realistic models of galaxy collapse.
The mass function of galaxies based on correlated velocity structure
Authors: Henriksen R N , Lachièze-Rey M
Published: February 2022

This paper introduces a new approach to the calculation of the galactic mass multiplicity function based on the probability of correlated velocity structures existing on a given spatial scale. The correlations are supposed to have developed during a protogalactic era of virialized structures, before which time the density evolution had already become non-linear. We determine the density index empirically in this paper, although it may eventually be related to a spectrum of initial fluctuations. The subsequent non-linear dynamics are dealt with explicitly using a continuum model with tidal interactions simulated by an effective shear viscosity. Our predictions for the (unnormalized) mass function and for the large-scale velocity correlations between galaxies are deduced relatively directly from the ‘cosmic von Karman-Howarth’ equation implicit in our basic model. Our predictions are in good agreement with existing data. The first part of our paper offers a summary and a critique of alternative methods.
Altered cortical structure network in children with obstructive sleep apnea
Authors: Lee Min-Hee , Sin Sanghun , Lee Seonjoo , Park Hyunbin , Wagshul Mark E , Zimmerman Molly E , Arens Raanan
Published: February 2022

Study Objectives

Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects.

Methods

We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ± 1.66 years, male 19) and 50 children with OSA (age 15.32 ± 1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups.

Results

We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls.

Conclusions

Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders.
Getting to “No”: The scope of protectors’ powers to consent
Authors: Hubbard Mark
Published: February 2022

When can a protector properly refuse to consent to the exercise of a power by a trustee? Three recent decisions have given different answers to this question of fundamental importance. Those advising settlors, trustees, beneficiaries and, of course, protectors need to have an informed view on this critical issue. This article examines the issue in depth, analyses the new law and gives practical guidance.
Impact of COVID-19 on Nursing Students
Authors: Joseph Rachel A. , Turner Tracey , Lee Chansoon , Akers Shanna W. , Whorley Elizabeth , Goodrich Cindy
Published: February 2022

The COVID-19 pandemic rapidly transformed nursing education, creating multiple stressors for students. The researchers in this study examined how undergraduate and graduate nursing students at a faith-based university perceived the impact of COVID-19. A multiple linear regression model explored the effect of 17 variables on the Impact of Events Scale-Revised (IES-R) scores. Anxiety level, quality of sleep, and perceived health demonstrated a statistically significant influence on IES-R scores; 27% of students had IES-R scores above 33, indicating high risk for posttraumatic stress disorder. Strategies to help address student stress and anxiety are discussed.
Superior Long-term Appearance of Strip Craniectomy Compared with Cranial Vault Reconstruction in Metopic Craniosynostosis
Authors: Badiee Ryan K. , Popowitz Emma , Mark Ian T. , Alcon Andre , Hwang Joan , Rorison Eve , Auguste Kurtis I. , Hoffman William Y. , Sun Peter P. , Pomerantz Jason H.
Published: February 2022

Background:

Strip craniectomy with orthotic helmet therapy (SCOT) is an increasingly supported treatment for metopic craniosynostosis, although the long-term efficacy of deformity correction remains poorly defined. We compared the longterm outcomes of SCOT versus open cranial vault reconstruction (OCVR).

Methods:

Patients who underwent OCVR or SCOT for isolated metopic synostosis with at least 3 years of follow-up were identified at our institution. Anthropometric measurements were used to assess baseline severity and postoperative skull morphology. Independent laypersons and craniofacial surgeons rated the appearance of each patient’s 3D photographs, compared to normal controls.

Results:

Thirty-five patients were included (15 SCOT and 20 OCVR), with similar follow-up between groups (SCOT 7.9 ± 3.2 years, OCVR 9.2 ± 4.1 years). Baseline severity and postoperative anthropometric measurements were equivalent. Independent adolescent raters reported that the forehead, eye, and overall appearance of SCOT patients was better than OCVR patients (P < 0.05, all comparisons). Craniofacial surgeons assigned Whitaker class I to a greater proportion of SCOT patients with moderate-to-severe synostosis (72.2 ± 5.6%) compared with OCVR patients with the same severity (33.3 ± 9.2%, P = 0.02). Parents of children who underwent SCOT reported equivalent satisfaction with the results of surgery (100% versus 95%, P > 0.99), and were no more likely to report bullying (7% versus 15%, P = 0.82).

Conclusions:

SCOT was associated with superior long-term appearance and perioperative outcomes compared with OCVR. These findings suggest that SCOT should be the treatment of choice for patients with a timely diagnosis of metopic craniosynostosis.
Prevalence of US Adults With Cardiovascular Disease Reporting Barriers to Clinician Office Visits
Authors: Platz Katherine , Zelle Heather , Howie-Esquivel Jill
Published: February 2022

Purpose:

Despite known health benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), only a quarter of eligible patients attend. Among CR barriers are physical (eg, walking) and in-person attendance limitations. The purpose of this study was to determine the prevalence of difficulty walking and dependence on another person to attend medical appointments among people with and without CVD using national survey data.

Methods:

We compared the prevalence of difficulty walking and difficulty attending medical appointments alone among adults with and without CVD using national survey data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2015-2019. We used logistic regression and Rao-Scott χ2 analysis while controlling for several social determinants of health as covariates.

Results:

Of 2 212 973 respondents, 200 087 (9.04%) had CVD. The odds of individuals with CVD experiencing either difficulty walking or difficulty attending medical appointments alone were >3 times greater than the odds for individuals without CVD. In all adults with CVD, 42% reported difficulty walking and 20% reported dependence on another person to attend medical appointments. In all adults with CVD, 46% reported difficulty with one or both difficulties compared with 14% of adults without CVD.

Conclusions:

We estimate that 11.9 million Americans with self-reported CVD have difficulty walking, or are dependent on another person to attend medical appointments, or both. Alternative models of CR that adapt to these limitations are needed to increase attendance of CR so that all adults with CVD can improve their health outcomes.
Surgeons' perspectives on intraoperative gray area surgical complications of cataract surgery
Authors: Khan Asher , Murphy David A. , Kloek Carolyn E. , Dvorak Justin D. , Woreta Fasika A. , Riaz Kamran M.
Published: February 2022

Purpose:

To explore surgeons' perspectives and practice patterns in gray area surgical complications (GASCs) within cataract surgery.

Setting:

Tertiary care academic referral center.

Design:

Retrospective observational cross-sectional study.

Methods:

An anonymous, online survey consisting of 11 potential intraoperative GASC scenarios was developed and distributed to practicing and resident ophthalmologists in the U.S. Demographic data such as gender, experience, and practice settings were recorded. Using a Likert scale, respondents scaled their perception of likelihood that a GASC could lead to postoperative complications and their obligation toward patient disclosure and documentation in the operative report. Respondents also scaled their likelihood of agreement with a series of statements inserted to assess baseline anxiety levels and inherent perspectives regarding disclosure.

Results:

389 responses were analyzed. Female surgeons were more likely than male surgeons to disclose GASCs to their patients and experience psychological anxiety regarding patient outcomes. Both early- and late-stage residents were more likely to believe that GASCs could lead to vision-limiting outcomes when compared with attending surgeons. Surgeons at academic centers were more likely than community-based surgeons to disclose GASCs in the operative report and experience psychological anxiety regarding patient outcomes.

Conclusions:

Significant differences based on gender, practice setting, and level of experience exist in disclosure and documentation of intraoperative GASCs. Additional studies are needed to further explore reasons for these differences, as reporting patterns may affect patient satisfaction, medicolegal risks, and postoperative surgeon-experienced anxiety.
The Development and Psychometric Evaluation of the Mid-adult Human Papillomavirus Vaccine Knowledge Scale in the United States
Authors: Garg Ashvita , Wheldon Christopher W. , Galvin Annalynn M. , Moore Jonathan D. , Griner Stacey B. , Thompson Erika L.
Published: February 2022

Background

Previous human papillomavirus (HPV) and HPV vaccine knowledge scales have focused on young adults in the vaccination catch-up age range or parents of vaccine eligible adolescents. Previous scales are not specific to the new guidelines for HPV vaccination in mid-adults. The study aimed to develop and validate a mid-adult HPV vaccine knowledge scale informed by the latest vaccine recommendations.

Methods

Self-reported data were collected using a cross-sectional survey of adults aged 27 to 45 years with no history of HPV vaccination (n = 706). Exploratory and confirmatory factor analyses identified latent constructs in a 13-item mid-adult HPV vaccine knowledge scale. Sociodemographic differences in the HPV vaccine knowledge were also assessed.

Results

The mean of correct responses across all items was 5.9 (SD, 2.8; range, 0–13). Exploratory and confirmatory factor analyses revealed a 3-factor structure best explained the data with a good construct validity and reliability. The first factor contained 6 items about HPV infection, the second factor contained 3 items about HPV prevention through vaccination, and the third factor contained items about HPV vaccination misinformation. Analysis of variance and t test found significant group level differences in knowledge among sex, race, educational level, annual income, health insurance, and marital status.

Conclusions

Our study supports the use of a knowledge scale for US mid-adults to assess HPV and HPV vaccination knowledge because the patient requires some baseline knowledge of this recommendation to discuss the vaccine with their health care provider. The mid-adult HPV vaccine knowledge scale can measure basic HPV knowledge important to informed decision making.
Lord Wolfson of Marylebone. 11 November 1927—20 May 2010
Authors: Ramsbottom Paul
Published: February 2022

Leonard Wolfson (Lord Wolfson of Marylebone) was a businessman and philanthropist. His family's wealth was made in the retail trade, and, with his father, he helped to turn Great Universal Stores into one the largest retail conglomerates in Europe. In 1955, alongside his father and mother, he created the Foundation that bears his family name. The Wolfson Foundation's activities and grant-making have been focused on research and education—and, not least, the advancement of science and medicine.
Pinisolibacter aquiterrae sp. nov., a novel aromatic hydrocarbon-degrading bacterium isolated from benzene-, and xylene-degrading enrichment cultures, and emended description of the genus Pinisolibacter
Authors: Bedics Anna , Banerjee Sinchan , Bóka Károly , Tóth Erika , Benedek Tibor , Kriszt Balázs , Táncsics András
Published: February 2022

Two Gram-reaction-negative strains, designated as B13T and MA2-2, were isolated from two different aromatic hydrocarbon-degrading enrichment cultures and characterized using a polyphasic approach to determine their taxonomic position. The two strains had identical 16S rRNA gene sequences and were most closely related to

Pinisolibacter ravus

E9T (97.36 %) and

Siculibacillus lacustris

SA-279T (96.33 %). Cells were facultatively aerobic rods and motile with a single polar flagellum. The strains were able to degrade ethylbenzene as sole source of carbon and energy. The assembled genome of strain B13T had a total length of 4.91 Mb and the DNA G+C content was 68.8 mol%. The predominant fatty acids (>5 % of the total) of strains B13T and MA2-2 were C18 : 1
 ω7c/C18 : 1
 ω6c, C16 : 1
 ω7c/C16 : 1
 ω6c and C16 : 0. The major ubiquinone of strain B13T was Q10, while the major polar lipids were phosphatidyl-N-methylethanolamine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and a phospholipid. Based on phenotypic characteristics and phylogenetic data, it is concluded that strains B13T and MA2-2 are members of the genus

Pinisolibacter

and represent a novel species for which the name Pinisolibacter aquiterrae sp. nov. is proposed. The type strain of the species is strain B13T (=LMG 32346T=NCAIM B.02665T).
Effects of a single-dose methylphenidate challenge on resting-state functional connectivity in stimulant-treatment naive children and adults with ADHD
Authors: Kaiser Antonia , Broeder Caroline , Cohen Jessica , Douw Linda , Reneman Liesbeth , Schrantee Anouk
Published: February 2022

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant-treatment naïve children and adults with ADHD. We obtained resting-state functional MRI from 50 boys (10-12 years of age) and 49 men (23-40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically-developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre-methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate’s effects on connectivity of subcortical regions are age-dependent in stimulant-treatment naïve ADHD patients, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.
A longitudinal CA2/3 to CA1 circuit for initiating context-dependent associative learning
Authors: Chen Hao-Shan , Qiu Shou , Wang Guang-Ling , Yang Rong-Rong , Zhang Na , Wu Jin-Ni , Yang Qi-Xin , Xu Chun
Published: February 2022

Associating environmental context with emotional experience is a vital brain function that requires the activity in both dorsal and ventral hippocampus. While only ventral hippocampus connects with the amygdala, a hub for fear learning, it remains unclear how the two hippocampal areas interact during contextual fear conditioning (CFC). We found that projections from dorsal CA2/CA3 (dCA2/3) to the dorsal part of ventral CA1 (vCA1d) contributed significantly to CFC. Deep-brain Ca2+ imaging revealed a CFC-enhanced difference in neuronal activities evoked by conditioned vs. neutral environmental context in both dCA2/3 and vCA1d areas. Notably, contextual fear retrieval correlated with changes in conditioned context-evoked activity in vCA1d, but not in dCA2/3. Furthermore, slice recordings showed that CFC potentiated dCA2/3-to-vCA1d projection strength, in line with coordinated elevation of monosynaptic excitation and reduction of disynaptic inhibition mediated by somatostatin-expressing interneurons. Thus, vCA1d represents a critical site for initiating emotional association with contextual information from dCA2/3.
The genetics of specific cognitive abilities
Authors: Procopio Francesca , Zhou Quan , Wang Ziye , Gidziela Agnieska , Rimfeld Kaili , Malanchini Margherita , Plomin Robert
Published: February 2022

Most research on individual differences in performance on tests of cognitive ability focuses on general cognitive ability (g), the highest level in the three-level Cattell-Horn-Carroll (CHC) hierarchical model of intelligence. About 50% of the variance of g is due to inherited DNA differences (heritability) which increases across development. Much less is known about the genetics of the middle level of the CHC model, which includes 16 broad factors such as fluid reasoning, processing speed, and quantitative knowledge. We provide a meta-analytic review of 863,041 monozygotic-dizygotic twin comparisons from 80 publications for these middle-level factors, which we refer to as specific cognitive abilities (SCA). Twin comparisons were available for 11 of the 16 CHC domains. The average heritability across all SCA is 55%, similar to the heritability of g. However, there is substantial differential heritability and the SCA do not show the dramatic developmental increase in heritability seen for g. We also investigated SCA independent of g (g-corrected SCA, which we refer to as SCA.g). A surprising finding is that SCA.g remain substantially heritable (53% on average), even though 25% of the variance of SCA that covaries with g has been removed. Our review frames expectations for genomic research that will use polygenic scores to predict SCA and SCA.g. Genome-wide association studies of SCA.g are needed to create polygenic scores that can predict SCA profiles of cognitive abilities and disabilities independent of g. These could be used to foster children’s cognitive strengths and minimise their weaknesses.
TOWARDS A SINGLE PARAMETER FOR THE ASSESSMENT OF EEG OSCILLATIONS
Authors: Tozzi Arturo , Peters James F.
Published: February 2022

The single macroscopic flow on the boundary of a closed curve equals the sum of the countless microscopic flows in the enclosed area. According to the dictates of the Green’s theorem, the counterclockwise movements on the border of a two-dimensional shape must equal all the counterclockwise movements taking place inside the shape. This mathematical approach might be useful to analyse neuroscientific data sets for its potential capability to describe the whole cortical activity in terms of electric flows occurring in peripheral brain areas. Once mapped raw EEG data to coloured ovals in which different colours stand for different amplitudes, the theorem suggests that the sum of the electric amplitudes measured inside every oval equals the amplitudes measured just on the oval’s edge. This means that the collection of the vector fields detected from the scalp can be described by a novel, single parameter summarizing the counterclockwise electric flow detected in the outer electrodes. To evaluate the predictive power of this parameter, in a pilot study we investigated EEG traces from ten young females performing Raven’s intelligence tests of various complexity, from easy tasks (n=5) to increasingly complex tasks (n=5). Despite the seemingly unpredictable behavior of EEG electric amplitudes, the novel parameter proved to be a valuable tool to to discriminate between the two groups and detect hidden, statistically significant differences. We conclude that the application of this promising parameter could be expanded to assess also data sets extracted from neurotechniques other than EEG.
Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease
Authors: Huang Yingyi , Liu Xiang , Wang Hong-Yan , Chen Jian-Yang , Zhang Xianghui , Li Yubang , Lu Yifang , Dong Zhongdian , Liu Kaiqiang , Wang Zhongduo , Wang Qian , Fan Guangyi , Zou Jun , Liu Shanshan , Shao Changwei
Published: February 2022

Zebrafish have emerged as an attractive animal model for studying nonalcoholic fatty liver disease (NAFLD). However, little is known about the cell types and intercellular interactions in zebrafish liver. Here, we established a liver atlas that consists of 10 cell types using single-cell RNA sequencing. By examining the heterogeneity of hepatocytes and analyzing the expression of NAFLD-associated genes in the specific cluster, we provide a potential target cell model to study NAFLD. Additionally, our analysis identified two distinct resident macrophages with inflammatory and noninflammatory functions and characterized the successive stepwise development of T cell subtypes in the liver. Importantly, we uncovered possible molecular mechanisms and revealed the central regulation of macrophages on target cells of fatty liver by analyzing the cellular interaction between hepatocytes and immune cells. Our data provide valuable information for future research on NAFLD in zebrafish.
NAD homeostasis maintained by NMNAT2 supports vesicular glycolysis and fuels fast axonal transport in distal axons of cortical glutamatergic neurons in mice
Authors: Yang Sen , Niou Zhen-Xian , Enriquez Andrea , LaMar Jacob , Huang Jui-Yen , Ling Karen , Jafar-Nejad Paymaan , Gilley Jonathan , Coleman Michael P. , Tennessen Jason M. , Rangaraju Vidhya , Lu Hui-Chen
Published: February 2022

Background

Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer’s, Parkinson’s and Huntington’s disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose far-projecting axons are vulnerable to neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring proper axonal ATP levels for axonal transport, a critical function of axons.

Methods

We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting NAD hydrolase sterile alpha and TIR motif-containing protein 1 (SARM1) prevented axonal deficits caused by NMNAT2 loss. Our study used a combination of genetic, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos application.

Results

We providein vivoevidence that NMNAT2 in cortical glutamatergic neurons is required for axonal survival. Usingin vivoandin vitrostudies we demonstrate that NMNAT2 protects axons by ensuring the proper NAD-redox potential in distal axons of cortical neurons to support glycolysis on vesicular cargos, thus ensuring “onboard” ATP production fueling axonal transport. Exogenous NAD+supplementation to NMNAT2 KO cortical neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate bothin vitroandin vivothat reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons.

Conclusion

NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.
Automatic identification of intestinal parasites in reptiles using microscopic stool images and convolutional neural networks
Authors: Grijalva Felipe , Núñez Bryan , Núñez Alejandra , Parra Carla , Pérez Noel , Benítez Diego
Published: February 2022

Captive environments trigger the propagation and multiplication of parasites among different reptile species, thus weakening their immune response and causing infections and diseases. Technological advances of convolutional neural networks have opened a new field for detecting and classifying diseases which have shown great potential to overcome the shortcomings of manual detection performed by experts. Therefore, we propose an approach to identify six captive reptiles parasitic agents (Ophionyssus natricis, Blastocystis sp, Oxiurdo egg, Rhytidoides similis, Strongyloides, Taenia) from a microscope stool images dataset. Towards this end, we first use an image segmentation stage to detect the parasite within the image, which combines the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique, the OTSU binarization method, and morphological operations. Then, we carry out a classification stage through Mobilenet CNN under a transfer learning scheme. This method was validated on a stool image dataset containing 3616 images data samples and 26 videos from the six parasites mentioned above. The results obtained indicate that our transfer learning-based approach can learn a helpful representation from the dataset. We obtained an average accuracy of 98.66% across the six parasitic agent classes, which statistically outperformed, at a 95% confidence level, a custom CNN trained from scratch.
SARS-CoV-2 Seroprevalence in three Kenyan Health and Demographic Surveillance Sites, December 2020-May 2021
Authors: Etyang Anthony O. , Adetifa Ifedayo , Omore Richard , Misore Thomas , Ziraba Abdhalah K. , Ng’oda Maurine A. , Gitau Evelyn , Gitonga John , Mugo Daisy , Kutima Bernadette , Karanja Henry , Toroitich Monica , Nyagwange James , Tuju James , Wanjiku Perpetual , Aman Rashid , Amoth Patrick , Mwangangi Mercy , Kasera Kadondi , Ng’ang’a Wangari , Akech Donald , Sigilai Antipa , Karia Boniface , Karani Angela , Voller Shirine , Agoti Charles N. , Ochola-Oyier Lynette I. , Otiende Mark , Bottomley Christian , Nyaguara Amek , Uyoga Sophie , Gallagher Katherine , Kagucia Eunice W. , Onyango Dickens , Tsofa Benjamin , Mwangangi Joseph , Maitha Eric , Barasa Edwine , Bejon Philip , Warimwe George M. , Scott J Anthony G , Agweyu Ambrose
Published: February 2022

Background

Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. We conducted population-based serosurveys at three Health and Demographic Surveillance Systems (HDSSs) to determine the cumulative incidence of infection with SARS-CoV-2.

Methods

We selected random age-stratified population-based samples at HDSSs in Kisumu, Nairobi and Kilifi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. No participant had received a COVID-19 vaccine. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally-validated assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using classical methods and Bayesian modelling to account for the sampling scheme and assay performance.

Results

We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27 (10-78) years and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kisumu, Nairobi and Kilifi, seroprevalences (95% CI) at the beginning of the study were 36.0% (28.2-44.4%), 32.4% (23.1-42.4%), and 14.5% (9.1-21%), and respectively; at the end they were 42.0% (34.7-50.0%), 50.2% (39.7-61.1%), and 24.7% (17.5-32.6%), respectively. Seroprevalence was substantially lower among children (<16 years) than among adults at all three sites (p≤0.001).

Conclusion

By May 2021 in three broadly representative populations of unvaccinated individuals in Kenya, seroprevalence of anti-SARS-CoV-2 IgG was 25-50%. There was wide variation in cumulative incidence by location and age.
Methylation risk scores are associated with a collection of phenotypes within electronic health record systems
Authors: Thompson Mike , Hill Brian L. , Rakocz Nadav , Chiang Jeffrey N. ,   IPH, Sankararaman Sriram , Hofer Ira , Cannesson Maxime , Zaitlen Noah , Halperin Eran
Published: February 2022

Inference of clinical phenotypes is a fundamental task in precision medicine, and has therefore been heavily investigated in recent years in the context of electronic health records (EHR) using a large arsenal of machine learning techniques, as well as in the context of genetics using polygenic risk scores (PRS). In this work, we considered the epigenetic analog of PRS, methylation risk scores (MRS), a linear combination of methylation states. Since methylation states are influenced by both environmental and genetic factors, we hypothesized that MRS would complement PRS and EHR-based machine-learning methods, improving overall prediction accuracy. To evaluate this hypothesis, we performed the largest assessment of methylation risk scores in clinical datasets to be conducted to date. We measured methylation across a large cohort (n=831) of diverse samples in the UCLA Health biobank, for which both genetic and complete EHR data are available. We constructed MRS for 607 phenotypes spanning diagnoses, clinical lab tests, and medication prescriptions. When added to a baseline set of predictive features, MRS significantly improved the imputation of 139 outcomes, whereas the PRS improved only 22 (median improvement for methylation 10.74%, 141.52%, and 15.46% in medications, labs and diagnosis codes, respectively, whereas genotypes only improved the labs at a median increase of 18.42%). We added significant MRS to state-of-the-art EHR imputation methods that leverage the entire set of medical records, and found that including MRS as a medical feature in the algorithm significantly improves EHR imputation in 37% of lab tests examined (median R2 increase 47.6%). Finally, we replicated several MRS in multiple external studies of methylation (minimum p-value of 2.72 × 10−7) and replicated 22 of 30 tested MRS internally in two separate cohorts of different ethnicity. In summary, our work provides a comprehensive evaluation of MRS in comparison to PRS and EHR imputation on the largest dataset consisting of methylation, genotype, and EHR data. Our publicly available results and weights show promise for methylation risk scores as clinical and scientific tools.
Bias amplification of unobserved confounding in pharmacoepidemiological studies using indication-based sampling: there is no free lunch in restricting the sample to those with a particular drug-indication
Authors: Ahlqvist Viktor H. , Madley-Dowd Paul , Ly Amanda , Rast Jessica , Lundberg Michael , Jónsson-Bachmann Egill , Berglind Daniel , Rai Dheeraj , Magnusson Cecilia , Lee Brian K.
Published: February 2022

Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication-based sampling ensures that the exposed and unexposed are exchangeable on the indication - limiting the potential for confounding by indication. However, indication-based sampling has received little scrutiny, despite the hazards of exposure-related covariate control.

Using causal diagrams, simulations, and empirical examples, we demonstrate that indication-based sampling in the presence of unobserved confounding can give rise to bias amplification, a self-inflicted phe-nomenon where one inflates pre-existing bias through inappropriate covariate control. Additionally, we show that indication-based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication (effect-heterogeneity) exist.

We conclude that studies using indication-based sampling should have robust justification - and that it should by no means be considered a “free lunch” to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications.