bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediating Effects of Coping Strategies on Quality of Life Following Extremity Injury
Authors: Tonapa Santo Imanuel , Lin Wei-Ting , Kuo Fang-Li , Lee Bih-O
Published: January 2022

Background

Few researches have explored the self-regulation process in patients with extremity injuries. Knowledge about the role of coping in the postinjury self-regulation process remains scarce.

Objectives

We examined the relationships between illness representations, coping, and quality of life (QoL) based on the self-regulation framework, assuming adaptive and maladaptive coping strategies play mediating roles between illness representation and QoL in patients with extremity injuries.

Methods

A cross-sectional survey with a correlational model testing design was used. A sample of 192 patients with extremity injury was recruited before hospital discharge at trauma centers in Indonesia. Validated questionnaires were used to assess patients’ illness representations, coping, and QoL. Hierarchical regressions were carried out, and multiple mediation analyses were used to identify the mediating role of coping.

Results

Patients with extremity injuries who harbored negative illness representations were less focused on using adaptive coping strategies, were more focused on using maladaptive coping strategies, and tended to experience reduced QoL. The mediating effects of coping, which manifested as parallel mediations of adaptive and maladaptive coping strategies, could significantly explain the QoL variance.

Discussion

In postinjury self-regulation, coping has a parallel mediating role that can facilitate the effect of illness representations and directly influence postinjury QoL. Enhancing adaptive coping strategies, reducing maladaptive coping techniques, and reframing negative illness representations during the early recovery phase could improve postinjury QoL. Early screening and preventive efforts using psychologically driven interventions may help redirect patients’ focus toward adaptive coping strategies and reframe their illness representations before they transition back into the community.
Brief Report: Patients' Experiences and Opinions After Desimplification of Their Single-Tablet Regimens for the Treatment of HIV Infection: A Survey in a Multicentre Cohort
Authors: Suárez-García Inés , Ruiz-Algueró Marta , Alejos Belén , García-Yubero Cristina , Belza Mª José , Espacio Ramón , Hernández Juanse , Muñoz Sánchez Josefa , Garaialde Ainhoa , Alonso Socas María del Mar , Alcaraz Antonia , Pierola Ruiz de Galarreta Beatriz , Martínez Madrid Onofre Juan , Gutiérrez Cuéllar Isabel , Gómez-Ayerbe Cristina , Olalla Julián , Jarrín Inma ,   on behalf of the Cohort of the Spanish HIV/AIDS Research Network (CoRIS)
Published: January 2022

Objectives:

The aims of this study were to describe patients' experiences after single-tablet regimen (STR) desimplification and its impact on self-reported treatment adherence and quality of life.

Methods:

We performed a survey among all patients from the multicenter cohort of the Spanish HIV/AIDS Network who had desimplified the STRs dolutegravir/abacavir/lamivudine (DGT/ABC/3TC) or rilpivirine/tenofovir disoproxil fumarate/emtricitabine to their separate components (DTG + generic ABC/3TC or RPV + generic TDF/FTC) between December 2016 and November 2018.

Results:

Among 216 patients who fulfilled inclusion criteria, 138 (63.9%) completed the questionnaire. Most of the patients (78.3%) knew what generic drugs are, only 8.7% believed that treatment with 2 pills is less effective than treatment with an STR, and 67.4% agreed that it is reasonable to take 2 pills instead of 1 for HIV treatment to decrease costs for the health care system. After desimplification, 13.0% of the patients stated they had more secondary effects, 8.0% had forgotten one or more doses more frequently than before, and 10.9% had sometimes forgotten to take 1 pill, but not the other. A proportion of 30.4% reported not being happy to take more pills a day, and 10.1% experienced a worse quality of life after the treatment desimplification.

Conclusions:

After STR desimplification, most of the patients had a fair knowledge about generic antiretrovirals, and they agreed to desimplify their STR to decrease costs. Although almost a third of the respondents were not happy to take 2 pills a day, only a minority reported worse adherence or quality of life.
International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers
Authors: Broman Kristy K. , Hughes Tasha M. , Bredbeck Brooke C. , Sun James , Kirichenko Dennis , Carr Michael J. , Sharma Avinash , Bartlett Edmund K. , Nijhuis Amanda A.G. , Thompson John F. , Hieken Tina J. , Kottschade Lisa , Downs Jennifer , Gyorki David E. , Stahlie Emma , van Akkooi Alexander , Ollila David W. , O’shea Kristin , Song Yun , Karakousis Giorgos , Moncrieff Marc , Nobes Jenny , Vetto John , Han Dale , Hotz Meghan , Farma Jeffrey M. , Deneve Jeremiah L. , Fleming Martin D. , Perez Matthew , Baecher Kirsten , Lowe Michael , Bagge Roger Olofsson , Mattsson Jan , Lee Ann Y. , Berman Russell S. , Chai Harvey , Kroon Hidde M. , Teras Juri , Teras Roland M. , Farrow Norma E. , Beasley Georgia M. , Hui Jane Yuet Ching , Been Lukas , Kruijff Schelto , Sinco Brandy , Sarnaik Amod A. , Sondak Vernon K. , Zager Jonathan S. , Dossett Lesly A. ,   for the International High Risk Melanoma Consortium
Published: January 2022

Objective:

The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary Background Data:

Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

Methods:

We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics.

Results:

Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients.

Conclusions:

There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
Who was wearing a mask in 2021? Update on gender-, age-, and location-related differences during the COVID-19 pandemic
Authors: Haischer Michael H. , Beilfuss Rachel N. , Hart Meggie Rose , Opielinski Lauren , Schmit Emma , Wrucke David , Zhao Helena , Uhrich Toni D. , Hunter Sandra K.
Published: January 2022

Previous observational work from 2020 demonstrated gender-, age-, and location-related differences in mask-wearing behavior, despite the efficacy and public health messaging that emphasized face coverings in combatting the spread of COVID-19. In 2021, COVID-19 vaccinations and a corresponding change in public health policy became new considerations in deciding personal protective behaviors. To provide an update on mask wearers and resistors approximately one year after our initial study, we observed shoppers (n = 6,118) entering retail stores using the same experimental methodology. Approximately 26% of individuals wore a mask. Mask wearing has decreased across demographic groups compared to 2020. Aligning with previous findings, females were ∼1.5x more likely to be observed wearing a mask than males, and the odds of observing a shopper wearing a mask in a suburban or urban area was far greater than at rural stores (∼5.7x and ∼3.3x, respectively). Gender and location are confirmed to be significant and stable factors that impact mask-wearing behavior in the United States during the COVID-19 pandemic. The impact of age on mask wearing was heavily reduced compared to 2020, potentially due to the availability of COVID-19 vaccines and change in mask guidance for vaccinated individuals.
Predicting the Degree of Distracted Driving Based on fNIRS Functional Connectivity: A Pilot Study
Authors: Ogihara Takahiko , Tanioka Kensuke , Hiroyasu Tomoyuki , Hiwa Satoru
Published: January 2022

Distracted driving is one of the main causes of traffic accidents. By predicting the attentional state of drivers, it is possible to prevent distractions and promote safe driving. In this study, we developed a model that could predict the degree of distracted driving based on brain activity. Changes in oxyhemoglobin concentrations were measured in drivers while driving a real car using functional near-infrared spectroscopy (fNIRS). A regression model was constructed for each participant using functional connectivity as an explanatory variable and break reaction time to random beeps while driving as an objective variable. As a result, we were able to construct a prediction model for 11 of the 12 participants. Furthermore, the regression model with the highest prediction accuracy for each participant was analyzed to gain a better understanding of the neural basis of distracted driving. The 11 models were classified into five clusters by hierarchical clustering based on their functional connectivity edges used in each cluster. The results showed that the combinations of the dorsal attention network (DAN)-sensory motor network (SMN) and DAN-ventral attention network (VAN) connections were common in all clusters and that these networks were essential to predict the degree of distraction in complex multitask driving. They also confirmed the existence of multiple types of prediction models with different within- and between-network connectivity patterns. These results indicate that it is possible to predict the degree of distracted driving based on the brain activity of the driver during actual driving. These results are expected to contribute to the development of safe driving systems and elucidation of the neural basis of distracted driving.
Analysis of Fatality Impact and Seroprevalence Surveys in a Community Sustaining a SARS-CoV-2 Superspreading Event
Authors: Richter Enrico , Liebl Dominik , Schulte Bianca , Lehmann Nils , Fuhrmann Christine , Jöckel Karl-Heinz , Ioannidis John P.A. , Streeck Hendrik
Published: January 2022

There is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 months of the pandemic in the community had a positive test for SARS-CoV-2. Six out of 18 SARS-CoV-2+ deaths had non-COVID-19 related causes of death (COD). Individuals with confirmed infection and COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p=0.029). Duration between first confirmed infection and death was negatively associated to COVID-19 being COD (p=0.04). Repeated seroprevalence essays on an original sample of 587 individuals in three visits showed modest increases in seroprevalence over time, and substantial seroreversion (30% [27/90] (95% CI: [20.5%; 39.5%])). IFR estimates accordingly varied depending on COVID-19 death attribution and seroprevalence caveats. Careful ascertainment and audit of COVID-19 deaths are important in understanding the impact of the pandemic.
Using quantitative magnetic resonance imaging to track cerebral alterations in multiple sclerosis brain: a longitudinal study
Authors: Vandeleene Nora , Guillemin Camille , Dauby Solène , Requier Florence , Charonitis Maëlle , Chylinski Daphne , Balteau Evelyne , Maquet Pierre , Lommers Emilie , Phillips Christophe
Published: January 2022

Quantitative MRI quantifies tissue microstructural properties and supports the characterization of cerebral tissue damages. With an MPM protocol, 4 parameter maps are constructed: MTsat, PD, R1 and R2*, reflecting tissue physical properties associated with iron and myelin contents. Thus, qMRI is a good candidate for in vivo monitoring of cerebral damage and repair mechanisms related to MS. Here, we used qMRI to investigate the longitudinal microstructural changes in MS brain.

Seventeen MS patients (age 25-65, 11 RRMS) were scanned on a 3T MRI, in two sessions separated with a median of 30 months, and the parameters evolution was evaluated within several tissue classes: NAWM, NACGM and NADGM, as well as focal WM lesions. An individual annual rate of change for each qMRI parameter was computed, and its correlation to clinical status was evaluated. For WM plaques, three areas were defined, and a GLMM tested the effect of area, time points, and their interaction on each median qMRI parameter value.

Patients with a better clinical evolution, i.e., clinically stable or improving state, showed positive annual rate of change in MTsat and R2* within NAWM and NACGM, suggesting repair mechanisms in terms of increased myelin content and/or axonal density as well as edema/inflammation resorption. When examining WM lesions, qMRI parameters within surrounding NAWM showed microstructural modifications, even before any focal lesion is visible on conventional FLAIR MRI.

The results illustrate the benefit of multiple qMRI data in monitoring subtle changes within normal appearing brain tissues and plaque dynamics in relation with tissue repair or disease progression.

Key points

Patients with a better clinical evolution showed microstructural improvement in term of MTsat and R2* increase in their normal appearing tissue, suggesting repair mechanisms.

Using qMRI allows to detect modifications in tissue microstructure in normal appearing tissues surrounding lesions several months before they are visible on conventional MRI.
Comparison of total and neutralizing SARS-CoV-2 spike antibodies against omicron and other variants in paired samples after two or three doses of mRNA vaccine
Authors: Debes Amanda K. , Xiao Shaoming , Egbert Emily R. , Caturegli Patrizio , Sitaras Ioannis , Pekosz Andrew , Milstone Aaron M.
Published: January 2022

Recognizing that anti-SARS-CoV-2 antibody levels wane over time following the 2-dose SARS-CoV-2 mRNA series, the FDA approved a booster dose for people greater than 12 years old. Limited data exist on whether a booster dose of the mRNA vaccine results in greater antibody protection than the primary series. We examined total and neutralizing antibodies to the spike protein of SARS-CoV-2, and neutralizing antibodies against Washington-1 (WA-1) and variants of concern (VOC) including Beta, Delta and Omicron in a longitudinal cohort. Healthcare workers (HWs) were included in the analysis if serum was collected 1) within 14-44 days post-dose2 of an mRNA SARS-CoV-2 vaccine (Timepoint 1, TP1), or 2) at least 8 months post-dose2 (Timepoint 2, TP2), or 3) within 14-44 days following mRNA booster (Timepoint 3, TP3). HWs with prior covid-positive PCR were excluded. We found that there is little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested has been lost by 8-months post two-dose vaccination series. However, the mRNA booster series eliminates the immune escape observed by the omicron variant with the two-dose series. Neutralizing titers were significantly higher for all variants post-boost compared to the titers post two-dose series. The longitudinal nature of our cohort facilitated the analysis of paired samples pre and post boost, showing a greater than 15-fold increase in neutralization against omicron post-boost in these paired samples. An mRNA booster dose provides greater quantity and quality of antibodies compared to a two-dose regimen and is critical to provide any protection against the omicron variant.
Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes
Authors: Wendt Frank R , Pathak Gita A , Polimanti Renato
Published: January 2022

Background

Tandem repeats (TRs) are a major source of variation in the human genome under-investigated by large-scale genetic studies. When present in coding regions, TRs may have large effects on protein structure and function contributing to health and disease.

Methods

In a family-based design of 39 European ancestry trios from the UK Biobank (UKB), the GangSTR and MonSTR methods were used to identify de novo TRs in whole-exome sequences. TRs were annotated for association with gene expression and gene set enrichment. The loci harboring de novo TRs were investigated in a phenome-wide association study in up to 148,607 unrelated UKB participants of European descent. Linear and logistic regression included age, sex, sex×age, age2, sex×age2, and ten within-ancestry principal components as covariates. TR loci were fine-mapped to identify likely causal associations.

Results

There were 427 mutated TRs with a trend towards expansions versus contractions (χ2=5.46, df=1, P=0.019). These TRs were enriched for targets of the tumor suppressor microRNA-184 (21.1-fold, P=4.30×10−5). There were 123 TR-phenotype associations with posterior probabilities>0.95. These were related to body structure, cognition, and cardiovascular, metabolic, psychiatric, and respiratory outcomes. The most significant was between NCOA6-[GT]N and “ease of skin tanning” (beta=0.069, se=0.003, P=1.51×10−155). There were several loci with large likely causal effects on tissue microstructure, including the association of FAN1-[TG]N with carotid intima-media thickness (mean thickness: beta=5.22, se=1.08, P=1.22×10−6; maximum thickness: beta=6.44, se=1.32, P=1.12×10−6.

Conclusions

Combined with the TR de novo mutational background characterized herein, TR-phenotype associations contribute clear and testable hypotheses of dose-dependent TR implications linking genetic variation and protein structure with health and disease outcomes.
mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in patients with antibody deficiency syndromes
Authors: Zimmerman Ofer , Altman Doss Alexa Michelle , Kaplonek Paulina , VanBlargan Laura A. , Liang Chieh-Yu , Chen Rita E. , Monroy Jennifer Marie , Wedner H. James , Kulczycki Anthony , Mantia Tarisa L. , O’Shaughnessy Caitlin C. , Davis-Adams Hannah G. , Bertera Harry L. , Adams Lucas J. , Raju Saravanan , Zhao Fang R. , Rigell Christopher J. , Biason Dy Tiffany , Kau Andrew L. , Ren Zhen , Turner Jackson , O’Halloran Jane A. , Presti Rachel M. , Fremont Daved H , Kendall Peggy L. , Ellebedy Ali H. , Alter Galit , Diamond Michael S.
Published: January 2022

Patients with primary antibody deficiency syndromes (PAD) have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed PAD patients after SARS-CoV-2 vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, FcγR binding, and neutralizing activities. Immunoglobulin replacement products had low anti-spike and receptor binding domain (RBD) titers and neutralizing activity. In COVID-19-naive PAD patients, anti-spike and RBD titers increased after mRNA vaccination but decreased to pre-immunization levels by 90 days. Patients vaccinated after SARS-CoV-2 infection developed higher responses comparable to healthy donors. Most vaccinated PAD patients had serum neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this was improved by boosting. Thus, currently used immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of PAD patients with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.
On health effects of resveratrol in wine. A bibliometric view based on papers having achieved a high citation impact within the scientific discourse
Authors: Haunschild Robin , Marx Werner
Published: January 2022

We analyzed 3344 publications that are concerned with the health-related effects of resveratrol that occurs in wine and grapes. We found that the publication activity increased until 2010 and decreased slightly afterwards. The most frequent author keywords were classified into six groups: (1) beverages-related keywords, (2) compounds-related keywords, (3) diseases-related keywords, (4) effects-related keywords, (5) mechanisms-related keywords, and (6) broader keywords. By means of reference publication year spectroscopy, we analyzed and discussed the most frequently cited references (i.e., key papers) within the publication set. A rather large portion of the key papers takes a positive attitude and reports about health effects of resveratrol, although limited data in humans preclude drawing unambiguous conclusions on the health-related benefits of resveratrol. From our analysis, we could not identify specific publications that provide a distinct change of direction of the ongoing scientific discourse. Moderate red wine consumption seems to have the potential of being health promoting, whereas excessive alcohol consumption can induce liver cirrhosis and cancer.
Interventions designed to improve vaccination uptake: Scoping review of systematic reviews and meta-analyses - (version 1)
Authors: Heneghan CJ , Plüddemann A , Spencer EA , Brassey J , Rosca EC , Onakpoya IJ , Evans DH , Conly JM , Jefferson T
Published: January 2022

Background

Resources to ensure high vaccination uptake differ widely across countries, but the best use of these precious resources is unclear. To better meet immunization programmes’ a pressing need to understand what works, particularly in low-resource settings, the World Health Organization commissioned a scoping view.

Methods

We conducted a scoping review of interventions designed to increase vaccination uptake, including systematic reviews and meta-analyses of interventional studies. We searched the following electronic databases: MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, Epistemonikos, Google Scholar, LILACs and TRIP database until 01 July 2021 and hand-searched the reference lists of included articles. We included systematic reviews if they summarized studies with quantitative data on the impact on vaccine uptake for any age group. To assess review quality, we used a modified AMSTAR score. To evaluate the quality of the evidence in included reviews, we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

The final analysis set included 107 full-text reviews. Publication of reviews increased markedly over time, from seven reviews in 2010 to 38 reviews filtered in 2021. We conducted quality assessments for 72 reviews (132 outcomes). Based on the AMSTAR criteria, 40 included reviews (56%) received a quality rating of good, while the remaining 32 (44%) were of moderate quality. Only 13 reviews summarized data primarily for low- and middle-income countries (LMIC). The interventions were commonly multi-component, educational or reminder interventions; the description of intervention components was suboptimal and heterogeneous across most reviews. Effect estimates were available for 73 outcomes; in 52 (71%) of these, interventions led to statistically significant higher vaccine uptake compared with controls.

Conclusions

The literature has a large number of relevant systematic reviews on interventions to increase vaccine uptake, with an increased publication rate over time. However, problems with the definitions and the current reporting of vaccine uptake evidence make it difficult to determine what works best in low-resource settings.
A phenome-wide association study identifies effects of copy number variation of VNTRs and multicopy genes on multiple human traits
Authors: Garg Paras , Jadhav Bharati , Lee William , Rodriguez Oscar L. , Martin-Trujillo Alejandro , Sharp Andrew J.
Published: January 2022

The human genome contains tens of thousands of large tandem repeats and hundreds of genes that show common and highly variable copy number changes. Due to their large size and repetitive nature, these Variable Number Tandem Repeats (VNTRs) and multicopy genes are generally recalcitrant to standard genotyping approaches, and as a result this class of variation is poorly characterized. However, several recent studies have demonstrated that copy number variation of VNTRs can modify local gene expression, epigenetics and human traits, indicating that many have a functional role. Here, using read depth from whole genome sequencing to profile copy number, we report results of a phenome-wide association study (PheWAS) of VNTRs and multicopy genes in a discovery cohort of ∼35,000 samples, identifying 32 traits associated with copy number of 38 VNTRs and multicopy genes at 1% FDR. We replicated many of these signals in an independent cohort, and observed that VNTRs showing trait associations were significantly enriched for expression QTLs with nearby genes, providing strong support for our results. Fine-mapping studies indicated that in the majority (∼90%) of cases, the VNTR and multicopy genes we identified represent the causal variants underlying the observed associations. Furthermore, several lie in regions where prior SNV-based GWAS have failed to identify any significant associations with these traits. Our study indicates that copy number of VNTRs and multicopy genes contributes to diverse human traits, and suggests that complex structural variants potentially explain some of the so-called “missing heritability” of SNV-based GWAS.
Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults
Authors: De Angelis Flavio , Zeleznik Oana A. , Wendt Frank R. , Pathak Gita A. , Tylee Daniel S. , De Lillo Antonella , Koller Dora , Cabrera-Mendoza Brenda , Clifford Royce E , Maihofer Adam X. , Nievergelt Caroline M. , Curhan Gary C. , Curhan Sharon G. , Polimanti Renato
Published: January 2022

We conducted a comprehensive genome-wide investigation of hearing loss (HL) in 748,668 adult participants of the UK Biobank, the Nurses’ Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program. We identified 54 risk loci and characterized HL polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically-correlated traits, and gene interactions with HL environmental risk factors. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HL pathogenesis. This was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HL associations. Additionally, the genetically-informed causal inference analysis showed that HL is linked to many physical and mental health outcomes. These results provide many novel insights into the complex biology and epidemiology of HL in adults.
Brain network mechanisms of visual perceptual organization in schizophrenia and bipolar disorder
Authors: Keane Brian P. , Krekelberg Bart , Mill Ravi D. , Silverstein Steven M. , Thompson Judy L. , Serody Megan , Barch Deanna M. , Cole Michael W.
Published: January 2022

Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether similar neural differences arise in bipolar disorder or vary across the schizo-bipolar spectrum. To address these topics, we scanned (fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting-state connections for shape completion. Illusory/fragmented task activation differences (“modulations”) in the dorsal attention network (DAN) could distinguish people with schizophrenia (AUCs>.85) and could trans-diagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except among those with schizophrenia. The secondary visual network was strongly and similarly modulated in each subject group. Task modulations were dispersed over a larger number of networks in patients compared to controls. In summary, abnormal DAN activity emerges during perceptual organization in schizophrenia and may be related to improper attention-related feedback into secondary visual areas. Patients with either disorder may compensate for abnormal perception by relying upon non-visual networks.
Water Insecurity, Water Borrowing, and Psychosocial Stress Among Daasanach Pastoralists in Northern Kenya
Authors: Ford Leslie , Bethancourt Hilary J , Swanson Zane , Nzunza Rosemary , Wutich Amber , Brewis Alexandra , Young Sera , Almeida David , Douglass Matthew , Ndiema Emmanuel K. , Braun David R. , Pontzer Herman , Rosinger Asher Y.
Published: January 2022

This article quantifies Daasanach water insecurity experiences in Northern Kenya, examines how water insecurity is associated with water borrowing and psychosocial stress, and evaluates if water borrowing mitigates the stress from water insecurity. Of 133 households interviewed in 7 communities, 95% were water insecure and 74.4% borrowed water three or more times in the prior month. Regression analyses demonstrate water borrowing frequency moderates the relationship between water insecurity and psychosocial stress. Only those who rarely or never borrowed water reported greater stress with higher water insecurity. The coping mechanism of water borrowing may help blunt water insecurity-related stress.
Endogenous pancreatic microRNAs differentially target the Delta, Omicron, and Wuhan SARS-CoV-2 genomes to upregulate the Diabetes-associated genes
Authors: Bhavya Bhavya , Pathak Ekta , Mishra Rajeev
Published: January 2022

The SARS-CoV-2 viral genome is mutating and evolving into new variations, including the recently discovered Delta and Omicron. In this study, we used and evaluated our notion of differential targeting of SARS-CoV-2 variant genomes by microRNAs (miRNAs) of the infected human pancreas. We found that even with UTR mutations, the Delta, Omicron, and original Wuhan variations’ genomes would be differentially targeted by the host pancreas cell’s native miRNAs in the same way. The miRNAs show a difference in Minimal Free Energy (MFE) with the different viral variants’ genomes; however, they would still be responsible for the upregulation of the diabetes-associated genes.
Face processing in the infant brain after pandemic lockdown
Authors: Yates Tristan S. , Ellis Cameron T. , Turk-Browne Nicholas B.
Published: January 2022

The role of visual experience in the development of face processing has long been debated. We present a new angle on this question through a serendipitous study that cannot easily be repeated. Infants viewed short blocks of faces during fMRI in a repetition suppression task. The same identity was presented multiple times in half of the blocks (Repeat condition) and different identities were presented once each in the other half (Novel condition). In adults, the fusiform face area (FFA) tends to show greater neural activity for Novel vs. Repeat blocks in such designs, suggesting that it can distinguish same vs. different face identities. As part of an ongoing study, we collected data before the COVID-19 pandemic and after an initial State lockdown was lifted. The resulting sample of 12 infants (9–24 months) divided equally into pre- and post-lockdown groups with matching ages and data quantity/quality. The groups had strikingly different FFA responses: pre-lockdown infants showed repetition suppression (Novel>Repeat), whereas post-lockdown infants showed the opposite (Repeat>Novel), often referred to as repetition enhancement. These findings provide speculative evidence that altered visual experience during the lockdown, or other correlated environmental changes, may have affected face processing in the infant brain.
An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age
Authors: Kragness S. , Clark Z. , Mullin A. , Guidry J. , Earls L.R.
Published: January 2022

Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity –Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo-A, a well-studied regulator of adult plasticity. Pants interaction with Nogo-A augments its influence over postsynaptic AMPA receptor clustering, thus gating plasticity at adult synapses. This work shows that neural micropeptides can act as architectural modules that increase the functional diversity of the known proteome.
Probabilistic forward replay of anticipated stimulus sequences in human primary visual cortex and hippocampus
Authors: Ekman Matthias , Gennari Giulia , de Lange Floris P.
Published: January 2022

The ability to recognize and predict future spatiotemporal sequences is vital for perception. It has been proposed that the brain makes ‘intelligent guesses’ about future inputs by forward replaying these events. However, it is unknown whether and how this mechanism incorporates the probabilistic structure that is inherent to naturalistic environments. Here we tested forward replay in human V1 and hippocampus using a probabilistic cueing paradigm. Participants were exposed to two visual moving dot sequences (A and B) that shared the same starting point. Each stimulus sequence was paired with either a high or a low tone that predicted which sequence would follow with 80% cue validity (probabilistic context) or 50% cue validity (random context). We found that after exposure, the auditory cue together with the starting point triggered simultaneous forward replay of both the likely (A) and the less likely (B) stimulus sequence. Crucially, forward replay preserved the probabilistic relationship of the environment, such that the likely sequence was associated with greater anticipatory V1 activity compared to the less likely stimulus sequence. Analogous to V1, forward replay in hippocampus was also found to preserve the probabilistic cue-sequence relationship. Further, the anterior hippocampus was found to represent the predicted stimulus sequence, irrespective of the input, while the posterior hippocampus revealed a prediction error-like signal that was only observed when predictions were violated. These findings show how mnemonic and sensory areas coordinate predictive representations in probabilistic contexts to improve perceptual processing.
An interdisciplinary outpatient therapy program for children and adolescents with headache - real world data
Authors: Sobe H , Richter M , Berner R , von der Hagen M , Hähner A , Röder I , Koch T , Sabatowski R , Klimova A , Gossrau G
Published: January 2022

Background/ Objective

More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. We investigate the effects of an outpatient interdisciplinary headache program for children, adolescents and their parents.

Methods

91 patients suffering from frequent headaches were treated in a 15 hour group program. Parents received 7 hours of therapy. At the beginning of the therapy program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were collected. The primary endpoint was reduction in headache frequency, secondary endpoint reduction in PedMidas.

Results

75 children and adolescents (9-18 years, median = 14; 66.7% female) and their parents provided prospective patient reported outcome measures. Patients were diagnosed with any form of migraine or tension type headache or a combination of both. 6 and 12 months after completion of the therapy program patients reported reduced headache frequency (headache days in the last three months median at baseline: 30; T1: 18 days; T2: 13 days). Linear mixed models revealed significant reduction over time (T0/T1 p = 0,002; T0/T2 p = 0,001). In addition, reduced headache disability has been reported 6 and 12 months after therapy (PedMidas median T0= 30, T1=15, T2=7; p<0,001 and p<0,001 respectively).

Conclusions

The interdisciplinary headache therapy program for children and adolescents, reported here, reduces headache frequency and headache related disability significantly in a period of 6-12 month following its completion. Comparative studies of children and adolescents with headaches in general outpatient treatment are needed to further describe the therapeutic gains of the program.
Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations
Authors: Petros Brittany A. , Turcinovic Jacquelyn , Welch Nicole L. , White Laura F. , Kolaczyk Eric D. , Bauer Matthew R. , Cleary Michael , Dobbins Sabrina T. , Doucette-Stamm Lynn , Gore Mitch , Nair Parvathy , Nguyen Tien G. , Rose Scott , Taylor Bradford P. , Tsang Daniel , Wendlandt Erik , Hope Michele , Platt Judy T. , Jacobson Karen R. , Bouton Tara , Yune Seyho , Auclair Jared R. , Landaverde Lena , Klapperich Catherine M. , Hamer Davidson H. , Hanage William P. , MacInnis Bronwyn L. , Sabeti Pardis C. , Connor John H. , Springer Michael
Published: January 2022

The Omicron variant of SARS-CoV-2 is transmissible in vaccinated and unvaccinated populations. Here, we describe the rapid dominance of Omicron following its introduction to three Massachusetts universities with asymptomatic surveillance programs. We find that Omicron was established and reached fixation earlier on these campuses than in Massachusetts or New England as a whole, rapidly outcompeting Delta despite its association with lower viral loads. These findings highlight the transmissibility of Omicron and its propensity to fixate in small populations, as well as the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.
The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomization study
Authors: Taylor Kurt , Wootton Robyn E. , Yang Qian , Oddie Sam , Wright John , Yang Tiffany C , Magnus Maria , Andreassen Ole A. , Borges Maria Carolina , Caputo Massimo , Lawlor Deborah A
Published: January 2022

Background

Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference.

Methods

Three birth cohorts, including 38,662 mother/offspring pairs (N = 319 CHD cases) were included. We used Mendelian randomization (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large scale genome-wide association studies and validated the strength of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) change in GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings.

Results

The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 1.01 (0.90, 1.13)) and lifetime smoking (pooled OR: 0.97 (0.87, 1.08)) were close to the null, though with wide confidence intervals. We observed weak evidence of an increased odds of offspring CHDs with increase in the maternal GRS for alcoholic drinks per week (pooled OR: 1.09 (0.98, 1.22)). Sensitivity analyses yielded similar results.

Conclusions

Our results do not provide robust evidence of an effect of maternal BMI or smoking on offspring CHDs. However, results were imprecise. Our findings, including the potential effect of maternal alcohol intake on offspring CHD need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.
The effect of reactive balance training on falls in daily life: an updated systematic review and meta-analysis
Authors: Devasahayam Augustine Joshua , Farwell Kyle , Lim Bohyung , Morton Abigail , Fleming Natalie , Jagroop David , Aryan Raabeae , Saumur Tyler Mitchell , Mansfield Avril
Published: January 2022

Objective

Reactive balance training is an emerging approach to reduce falls risk in people with balance impairments. The purpose of this study was to determine the effect of reactive balance training on falls in daily life among individuals at increased risk of falls, and to document associated adverse events.

Data sources

Databases searched were Ovid MEDLINE (1946-November 2020), Embase Classic and Embase (1947-November 2020), Cochrane Central Register of Controlled Trials (2014-November 2020), Physiotherapy Evidence Database (PEDro; searched on 9 November 2020).

Study selection

Randomized controlled trials of reactive balance training were included. The literature search was limited to English language. Records were screened by two investigators separately.

Data extraction

Outcome measures were number of participants who reported falls after training, number of falls reported after training, and the nature, frequency, and severity of adverse events. Authors of included studies were contacted to obtain additional information.

Data synthesis

Twenty-five trials were included, of which 14 reported falls and 19 monitored adverse events. Participants assigned to reactive balance training groups were less likely to fall compared to control groups (fall risk ratio: 0.75, 95% confidence interval=[0.60, 0.92]; p=0.006, I2=37%) and reported fewer falls than control groups (rate ratio: 0.60, 95% confidence interval=[0.42, 0.86]; p=0.005, I2=83%). Prevalence of adverse events was higher in reactive balance training (29%) compared to control groups (19%; p=0.018).

Conclusion

RBT reduces the likelihood of falls in daily life for older adults and people with balance impairments. More adverse events were reported for reactive balance training than control groups.

Impact

Balance training that evokes balance reactions can reduce falls among people at increased risk of falls.
Integrated multi-omics reveals anaplerotic insufficiency in methylmalonyl-CoA mutase deficiency
Authors: Forny Patrick , Bonilla Ximena , Lamparter David , Shao Wenguang , Plessl Tanja , Frei Caroline , Bingisser Anna , Goetze Sandra , van Drogen Audrey , Harshman Keith , Pedrioli Patrick G. A. , Howald Cedric , Poms Martin , Traversi Florian , Cherkaoui Sarah , Morscher Raphael J. , Simmons Luke , Forny Merima , Xenarios Ioannis , Aebersold Ruedi , Zamboni Nicola , Raetsch Gunnar , Dermitzakis Emmanouil , Wollscheid Bernd , Baumgartner Matthias R. , Froese D. Sean
Published: January 2022

Multi-layered omics approaches can help define relationships between genetic factors, biochemical processes and phenotypes thus extending research of inherited diseases beyond identifying their monogenic cause 1. We implemented a multi-layered omics approach for the inherited metabolic disorder methylmalonic aciduria (MMA). We performed whole genome sequencing, transcriptomic sequencing, and mass spectrometry-based proteotyping from matched primary fibroblast samples of 230 individuals (210 affected, 20 controls) and related the molecular data to 105 phenotypic features. Integrative analysis identified a molecular diagnosis for 84% (177/210) of affected individuals, the majority (148) of whom had pathogenic variants in methylmalonyl-CoA mutase (MMUT). Untargeted analysis of all three omics layers revealed dysregulation of the TCA cycle and surrounding metabolic pathways, a finding that was further corroborated by multi-organ metabolomics of a hemizygous Mmut mouse model. Integration of phenotypic disease severity indicated downregulation of oxoglutarate dehydrogenase and upregulation of glutamate dehydrogenase, two proteins involved in glutamine anaplerosis of the TCA cycle. The relevance of disturbances in this pathway was supported by metabolomics and isotope tracing studies which showed decreased glutamine-derived anaplerosis in MMA. We further identified MMUT to physically interact with both, oxoglutarate dehydrogenase complex components and glutamate dehydrogenase providing evidence for a multi-protein metabolon that orchestrates TCA cycle anaplerosis. This study emphasizes the utility of a multi-modal omics approach to investigate metabolic diseases and highlights glutamine anaplerosis as a potential therapeutic intervention point in MMA.

Take home message

Combination of integrative multi-omics technologies with clinical and biochemical features leads to an increased diagnostic rate compared to genome sequencing alone and identifies anaplerotic rewiring as a targetable feature of the rare inborn error of metabolism methylmalonic aciduria.

Graphical abstract
Cueing motor memory reactivation during NREM sleep engenders learning-related changes in precuneus and sensorimotor structures
Authors: Rakowska Martyna , Bagrowska Paulina , Lazari Alberto , Navarrete Miguel , Abdellahi Mahmoud E. A. , Johansen-Berg Heidi , Lewis Penelope A.
Published: January 2022

Memory reactivation during Non-Rapid Eye Movement (NREM) sleep is important for memory consolidation but it remains unclear exactly how such activity promotes the development of a stable memory representation. We used Targeted Memory Reactivation (TMR) in combination with longitudinal structural and functional MRI to track the evolution of a motor memory trace over 20 days. We show that repeated reactivation of motor memory during sleep leads to increased precuneus activation 24 h post-TMR. Interestingly, a decrease in precuneus activity over the next 10 days predicts longer-term cueing benefit. We also find both functional and structural changes in sensorimotor cortex in association with effects of TMR 20 days post-encoding. These findings demonstrate that TMR can engage precuneus in the short-term while also impacting on task-related structure and function over longer timescales.