bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycoproteomics of NOTCH1 EGF repeat fragments overexpressed with different glycosyltransferases in HEK293T cells reveals insights into O-GlcNAcylation of NOTCH1
Authors: Tsukamoto Yohei , Ogawa Mitsutaka , Yogi Kentarou , Tashima Yuko , Takeuchi Hideyuki , Okajima Tetsuya
Published: March 2022

O-GlcNAc modification of Notch receptors regulates Notch ligand interactions in a manner distinct from other forms of O-glycans on epidermal growth factor (EGF)-like repeats of Notch receptors. Although many proteins, besides Notch receptors, are expected to be O-GlcNAcylated by EGF domain-specific O-GlcNAc transferase (EOGT), only a small number of proteins have been reported to be modified in vivo, and elongated O-GlcNAc glycans have not been extensively explored. To extend our view of the specificity and variety of the glycan modification, we conducted a comprehensive analysis of O-GlcNAc glycans on NOTCH1 in mammals. Mass spectrometric analysis of NOTCH1 fragments expressed in HEK293T cells revealed that several EGF domains with putative O-GlcNAcylation sites were hardly modified with O-GlcNAc. Although amino acid residues before the modification site are preferentially occupied with aromatic residues, Phe and Tyr are preferable to Trp for the apparent modification with O-GlcNAc. Furthermore, a minor form of fucosylated O-GlcNAc glycans was detected in a subset of EGF domains. Fucosylation of O-GlcNAc glycans was enhanced by FUT1, FUT2, or FUT9 expression. The FUT9-dependent Lewis X epitope was confirmed by immunoblotting using an anti-Lewis X antibody. As expected from the similarity in the extended structures between O-Fuc and O-GlcNAc glycans, the Lexis X antigen was detected on NOTCH1 fragments co-expressed with L-Fringe, which mediates elongation of O-Fuc glycans. Our results refined the putative consensus sequence for the EOGT-dependent O-GlcNAc modification in mammals and revealed the structural diversity of functional Notch O-glycans.
Foregone healthcare during the COVID-19 pandemic: early survey estimates from 39 low- and middle-income countries
Authors: Kakietek Jakub Jan , Eberwein Julia Dayton , Stacey Nicholas , Newhouse David , Yoshida Nobuo
Published: March 2022

In addition to the direct health effects of the Coronavirus disease (COVID-19) pandemic, the pandemic has increased the risks of foregone non-COVID-19 healthcare. Likely, these risks are greatest in low- and middle-income countries (LMICs), where health systems are less resilient and economies more fragile. However, there are no published studies on the prevalence of foregone healthcare in LMICs during the pandemic. We used pooled data from phone surveys conducted between April and August 2020, covering 73 638 households in 39 LMICs. We estimated the prevalence of foregone care and the relative importance of various reported reasons for foregoing care, disaggregated by country income group and region. In the sample, 18.8% (95% CI 17.8–19.8%) of households reported not being able to access healthcare when needed. Financial barriers were the most-commonly self-reported reason for foregoing care, cited by 31.4% (28.6–34.3%) of households. More households in wealthier countries reported foregoing care for reasons related to COVID-19 [27.2% (22.5–31.8%) in upper-middle-income countries compared to 8.0% (4.7–11.3%) in low-income countries]; more households in poorer countries reported foregoing care due to financial reasons [65.6% (59.9–71.2%)] compared to 17.4% (13.1–21.6%) in upper-middle-income countries. A substantial proportion of households in LMICs had to forgo healthcare in the early months of the pandemic. While in richer countries this was largely due to fear of contracting COVID-19 or lockdowns, in poorer countries foregone care was due to financial constraints.
The Scaling of Olfaction: Moths have Relatively More Olfactory Surface Area than Mammals
Authors: Mohebbi Nina , Schulz Andrew , Spencer Thomas L , Pos Kelsie , Mandel Andrew , Casas Jérôme , Hu David L
Published: March 2022

Synopsis

Body size affects nearly every aspect of locomotion and sensing, but little is known of its influence on olfaction. One reason for this missing link is that olfaction differs fundamentally from vision and hearing in that molecules are advected by fluid before depositing on olfactory sensors. This critical role of fluid flow in olfaction leads to complexities and trade-offs. For example, a greater density of hairs and sensory neurons may lead to greater collection, but can also lead to reduced flow through hairs and additional weight and drag due to a larger olfactory organ. In this study, we report the surface area and sensory neuron density in olfactory organs of 95 species of moths and mammals. We find that approximately 12–14% of an olfactory system’s surface area is devoted to chemosensors. Furthermore, total olfactory surface area and olfactory sensing surface area scale with body mass to the 0.49 and 0.38 powers, respectively, indicating that moths have a higher proportion of olfactory surface area than mammals. The density of olfactory neurons appears to be near the limit, at 10,000 to 100,000 neurons per square mm across both insects and mammals. This study demonstrates the need for future work detailing how the scaling of olfaction and other senses vary across taxa.
High-risk landscapes of Japanese encephalitis virus outbreaks in India converge on wetlands, rain-fed agriculture, wild Ardeidae, and domestic pigs and chickens
Authors: Walsh Michael G , Pattanaik Amrita , Vyas Navya , Saxena Deepak , Webb Cameron , Sawleshwarkar Shailendra , Mukhopadhyay Chiranjay
Published: March 2022

Background

Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne virus that causes a significant burden of disease across Asia, particularly in India, with high mortality in children. JEV circulates in wild ardeid birds and domestic pig reservoirs, both of which generate sufficiently high viraemias to infect vector mosquitoes, which can then subsequently infect humans. The landscapes of these hosts, particularly in the context of anthropogenic ecotones and resulting wildlife–livestock interfaces, are poorly understood and thus significant knowledge gaps in the epidemiology of JEV persist. This study sought to investigate the landscape epidemiology of JEV outbreaks in India over the period 2010–2020 to determine the influence of shared wetland and rain-fed agricultural landscapes and animal hosts on outbreak risk.

Methods

Using surveillance data from India’s National Centre for Disease Control Integrated Disease Surveillance Programme, JEV outbreaks were modelled as an inhomogeneous Poisson point process and externally validated against independently sourced data.

Results

Outbreak risk was strongly associated with the habitat suitability of ardeid birds, both pig and chicken density, and the shared landscapes between fragmented rain-fed agriculture and both river and freshwater marsh wetlands.

Conclusion

The results from this work provide the most complete understanding of the landscape epidemiology of JEV in India to date and suggest important One Health priorities for control and prevention across fragmented terrain comprising a wildlife–livestock interface that favours spillover to humans.
Estimation in tensor Ising models
Authors: Mukherjee Somabha , Son Jaesung , Bhattacharya Bhaswar B
Published: March 2022

The $p$-tensor Ising model is a one-parameter discrete exponential family for modeling dependent binary data, where the sufficient statistic is a multi-linear form of degree $p \geqslant 2$. This is a natural generalization of the matrix Ising model that provides a convenient mathematical framework for capturing, not just pairwise, but higher-order dependencies in complex relational data. In this paper, we consider the problem of estimating the natural parameter of the $p$-tensor Ising model given a single sample from the distribution on $N$ nodes. Our estimate is based on the maximum pseudolikelihood (MPL) method, which provides a computationally efficient algorithm for estimating the parameter that avoids computing the intractable partition function. We derive general conditions under which the MPL estimate is $\sqrt N$-consistent, that is, it converges to the true parameter at rate $1/\sqrt N$. Our conditions are robust enough to handle a variety of commonly used tensor Ising models, including spin glass models with random interactions and models where the rate of estimation undergoes a phase transition. In particular, this includes results on $\sqrt N$-consistency of the MPL estimate in the well-known $p$-spin Sherrington–Kirkpatrick model, spin systems on general $p$-uniform hypergraphs and Ising models on the hypergraph stochastic block model (HSBM). In fact, for the HSBM we pin down the exact location of the phase transition threshold, which is determined by the positivity of a certain mean-field variational problem, such that above this threshold the MPL estimate is $\sqrt N$-consistent, whereas below the threshold no estimator is consistent. Finally, we derive the precise fluctuations of the MPL estimate in the special case of the $p$-tensor Curie–Weiss model, which is the Ising model on the complete $p$-uniform hypergraph. An interesting consequence of our results is that the MPL estimate in the Curie–Weiss model saturates the Cramer–Rao lower bound at all points above the estimation threshold, that is, the MPL estimate incurs no loss in asymptotic statistical efficiency in the estimability regime, even though it is obtained by minimizing only an approximation of the true likelihood function for computational tractability.
The Singular Support of the Ising Model
Authors: Andrews George E , van Ekeren Jethro , Heluani Reimundo
Published: March 2022

We prove a new quasiparticle sum expression for the character of the Ising model vertex algebra, related to the Jackson–Slater $q$-series identity of Rogers–Ramanujan type and to Nahm sums for the matrix $\left (\begin {smallmatrix}8&3\\3&2 \end {smallmatrix}\right ) $. We find, as consequences, an explicit monomial basis for the Ising model and a description of its singular support. We find that the ideal sheaf of the latter, defining it as a subscheme of the arc space of its associated scheme, is finitely generated as a differential ideal. We prove three new $q$-series identities of the Rogers–Ramanujan–Slater type associated with the three irreducible modules of the Virasoro Lie algebra of central charge $1/2$. We give a combinatorial interpretation to the identity associated with the vacuum module.
Do Invasive and Naturalized Aphid Pest Populations Respond Differently to Climatic and Landscape Factors?
Authors: Adhikari Subodh , Seamon Erich , Wu Ying , Sadeghi Seyed E , Eigenbrode Sanford D
Published: March 2022

Ongoing environmental change affects pest populations, migration, and propensity to damage crops, but the responses to climatic drivers could vary among newly invasive and already naturalized closely related species. To compare these responses of a newly invasive aphid, Metopolophium festucae cerealium (Stroyan), with its naturalized congeneric [M. dirhodum (Walker)] and confamilial [Sitobian avenae (Fab.)], we conducted annual surveys over four years across a total of 141 winter wheat fields in the inland Pacific Northwest, USA. Key climatic factors (cumulative precipitation for each calendar year to sampling date, cumulative degree days), landscape factors (proportion of wheat and landscape diversity within the sample year), and Julian day were calculated for each sampling event, and aphid abundance by species, total aphid abundance, overall species richness, diversity, and aphid community composition were assessed. Metopolophium f. cerealium, the second most abundant species, was positively associated with precipitation, suggesting a projected increase in precipitation in winter and spring in the region could favor its establishment and expansion. Although M. dirhodum and S. avenae linearly (positively) associated with temperature, M. f. cerealium did not, indicating that continued warming may be detrimental to the species. Despite the weak impacts of landscape factors, our study indicated that more wheat generally facilitates cereal aphid abundance. Metopolophium f. cerealium abundance tended to be higher in earlier (May/early June vs. late June/July) samples when wheat crop could be vulnerable to aphid feeding. This study suggests that the new presence of M. f. cerealium has important pest management implications in the region.
Measuring PROMIS® Emotional Distress in Early Childhood
Authors: Sherlock Phillip , Blackwell Courtney K , Kallen Michael A , Lai Jin-Shei , Cella David , Krogh-Jespersen Sheila , Luby Joan L , Buss Kristin A , Burns James , Wakschlag Lauren S
Published: March 2022

Objective

Create and validate developmentally sensitive parent-report measures of emotional distress for children ages 1–5 years that conceptually align with the Patient-Reported Outcome Measurement Information System (PROMIS®) pediatric measures.

Methods

Initial items were generated based on expert and parent input regarding core components of emotional distress in early childhood and review of theoretical and empirical work in this domain. Items were psychometrically tested using data from two waves of panel surveys. Item response theory (IRT) was applied to develop item calibration parameters (Wave 1), and scores were centered on a general U.S. population sample (Wave 2). Final PROMIS early childhood (EC) instruments were compared with existing measures of related constructs to establish construct validity.

Results

Experts and parents confirmed the content validity of the existing PROMIS Pediatric emotional distress domains (i.e., anger, anxiety, and depressive symptoms) as developmentally salient for young children. Existing items were adapted and expanded for early childhood by employing best practices from developmental measurement science. Item banks as well as 4- and 8-item short forms, free from differential item functioning across sex and age, were constructed for the three domains based on rigorous IRT analyses. Correlations with subscales from previously validated measures provided further evidence of construct validity.

Conclusions

The PROMIS EC Anger/Irritability, Anxiety, and Depressive Symptoms measures demonstrated good reliability and initial evidence of validity for use in early childhood. This is an important contribution to advancing brief, efficient measurement of emotional distress in young children, closing a developmental gap in PROMIS pediatric emotional distress assessment.
A knotty problem: phytobezoar and small bowel occlusion as a complication of a gastro-jejunal catheter for continuous Duodopa infusion: a case report
Authors: Ivanov Todor , Perlot Ingrid , Stoca Laura Romero , Deleuze Catherine , Rasmont Celine , Lemaitre Jean
Published: March 2022

We report a case of small bowel occlusion due to the formation of a bezoar around a knot at the distal end a gastro-jejunal catheter used for continuous levodopa/carbidopa intestinal gel (LCIG) in a patient with advanced Parkinson’s disease. The patient presented with a history of abdominal pain and vomiting starting 24 h before admission and frequent failure of his LCIG device for the past week. Small bowel occlusion along with a knot formation on the distal catheter was confirmed by contrast enhanced CT scan. After failure of endoscopic extraction, the patient was taken to theater. The presence of a knot and a bezoar was confirmed and extraction proceeded via transverse enterotomy without the need for bowel resection. Despite inhalation pneumonia and prolonged ileus, the patient recovered fully. LCIG treatment was reinstated a month later through new gastro-jejunal catheter. This case highlights a severe and surprising complication of LCIG treatment.
Encoding, transmission, decoding, and specificity of calcium signals in plants
Authors: Allan Claudia , Morris Richard J , Meisrimler Claudia-Nicole
Published: March 2022

Calcium acts as a signal and transmits information in all eukaryotes. Encoding machinery consisting of calcium channels, stores, buffers, and pumps can generate a variety of calcium transients in response to external stimuli, thus shaping the calcium signature. Mechanisms for the transmission of calcium signals have been described, and a large repertoire of calcium binding proteins exist that can decode calcium signatures into specific responses. Whilst straightforward as a concept, mysteries remain as to exactly how such information processing is biochemically implemented. Novel developments in imaging technology and genetically encoded sensors (such as calcium indicators), in particular for multi-signal detection, are delivering exciting new insights into intra- and intercellular calcium signaling. Here, we review recent advances in characterizing the encoding, transmission, and decoding mechanisms, with a focus on long-distance calcium signaling. We present technological advances and computational frameworks for studying the specificity of calcium signaling, highlight current gaps in our understanding and propose techniques and approaches for unravelling the underlying mechanisms.
The evolution of the corona in MAXI J1535−571 through type-C quasi-periodic oscillations with Insight-HXMT
Authors: Zhang Yuexin , Méndez Mariano , García Federico , Zhang Shuang-Nan , Karpouzas Konstantinos , Altamirano Diego , Belloni Tomaso M , Qu Jinlu , Zhang Shu , Tao Lian , Zhang Liang , Huang Yue , Kong Lingda , Ma Ruican , Yu Wei , Rawat Divya , Bellavita Candela
Published: March 2022

Type-C quasi-periodic oscillations (QPOs) in black hole X-ray transients can appear when the source is in the low-hard and hard-intermediate states. The spectral-timing evolution of the type-C QPO in MAXI J1535−571 has been recently studied with Insight-HXMT. Here, we fit simultaneously the time-averaged energy spectrum, using a relativistic reflection model, and the fractional rms and phase-lag spectra of the type-C QPOs, using a recently developed time-dependent Comptonization model when the source was in the intermediate state. For the first time, we show that the time-dependent Comptonization model can successfully explain the X-ray data up to 100 keV. We find that in the hard-intermediate state the frequency of the type-C QPO decreases from 2.6 to 2.1 Hz, then increases to 3.3 Hz, and finally increases to ∼9 Hz. Simultaneously with this, the evolution of corona size and the feedback fraction (the fraction of photons up-scattered in the corona that return to the disc) indicates the change of the morphology of the corona. Compared with contemporaneous radio observations, this evolution suggests a possible connection between the corona and the jet when the system is in the hard-intermediate state and about to transit into the soft-intermediate state.
Rec8 Cohesin-mediated Axis-loop chromatin architecture is required for meiotic recombination
Authors: Sakuno Takeshi , Tashiro Sanki , Tanizawa Hideki , Iwasaki Osamu , Ding Da-Qiao , Haraguchi Tokuko , Noma Ken-ichi , Hiraoka Yasushi
Published: March 2022

During meiotic prophase, cohesin-dependent axial structures are formed in the synaptonemal complex (SC). However, the functional correlation between these structures and cohesion remains elusive. Here, we examined the formation of cohesin-dependent axial structures in the fission yeast Schizosaccharomyces pombe. This organism forms atypical SCs composed of linear elements (LinEs) resembling the lateral elements of SC but lacking the transverse filaments. Hi-C analysis using a highly synchronous population of meiotic S. pombe cells revealed that the axis-loop chromatin structure formed in meiotic prophase was dependent on the Rec8 cohesin complex. In contrast, the Rec8-mediated formation of the axis-loop structure occurred in cells lacking components of LinEs. To dissect the functions of Rec8, we identified a rec8-F204S mutant that lost the ability to assemble the axis-loop structure without losing cohesion of sister chromatids. This mutant showed defects in the formation of the axis-loop structure and LinE assembly and thus exhibited reduced meiotic recombination. Collectively, our results demonstrate that the Rec8-dependent axis-loop structure provides a structural platform essential for LinE assembly, facilitating meiotic recombination of homologous chromosomes, independently of its role in sister chromatid cohesion.
Stitchr: stitching coding TCR nucleotide sequences from V/J/CDR3 information
Authors: Heather James M , Spindler Matthew J , Alonso Marta Herrero , Shui Yifang Ivana , Millar David G , Johnson David S , Cobbold Mark , Hata Aaron N
Published: March 2022

The study and manipulation of T cell receptors (TCRs) is central to multiple fields across basic and translational immunology research. Produced by V(D)J recombination, TCRs are often only recorded in the literature and data repositories as a combination of their V and J gene symbols, plus their hypervariable CDR3 amino acid sequence. However, numerous applications require full-length coding nucleotide sequences. Here we present Stitchr, a software tool developed to specifically address this limitation. Given minimal V/J/CDR3 information, Stitchr produces complete coding sequences representing a fully spliced TCR cDNA. Due to its modular design, Stitchr can be used for TCR engineering using either published germline or novel/modified variable and constant region sequences. Sequences produced by Stitchr were validated by synthesizing and transducing TCR sequences into Jurkat cells, recapitulating the expected antigen specificity of the parental TCR. Using a companion script, Thimble, we demonstrate that Stitchr can process a million TCRs in under ten minutes using a standard desktop personal computer. By systematizing the production and modification of TCR sequences, we propose that Stitchr will increase the speed, repeatability, and reproducibility of TCR research. Stitchr is available on GitHub.
EXT1 and NCAM1-associated membranous lupus nephritis in a cohort of patients undergoing repeat kidney biopsies
Authors: Miller Paul P , Caza Tiffany , Larsen Christopher P , Charu Vivek
Published: March 2022

Background

Exostosin 1/2 (EXT1/2) and neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) may represent distinct disease phenotypes with prognostic significance.

Methods

We searched our archives for patients with systemic lupus erythematous (SLE) and at least two kidney biopsies demonstrating MLN. Each biopsy was stained for EXT1 and NCAM1 and scored as positive or negative. Histopathologic and clinical data were reviewed.

Results

We identified 31 patients with a clinical diagnosis of SLE and at least two kidney biopsies with MLN. A total of 28 patients (90%) showed concordant staining for EXT1 and NCAM1 in both biopsies; 8 patients (26%) were EXT1 positive and NCAM1 negative, 18 patients (58%) were EXT1 negative and NCAM1 negative and 2 patients (7%) were EXT1 negative and NCAM1 positive. A total of three patients (10%) had discordant EXT1 staining between their first and last biopsies; two patients (7%) were EXT1 positive in their first biopsy and EXT1 negative in the last biopsy and one patient (3%) was EXT1 negative in his first biopsy and EXT1 positive in the last biopsy. Compared with the EXT1-negative cohort at the time of the first biopsy, the EXT1-positive cohort had a higher average estimated glomerular filtration rate (eGFR; 141 versus 108 mL/min/1.73 m2; P = 0.04), lower average percent global glomerulosclerosis (0.5 versus 12%; P = 0.05), lower average interstitial fibrosis and tubular atrophy (2.5 versus 11.7%; P = 0.06) and lower average total National Institutes of Health (NH) chronicity scores (0.75 versus 2.33; P = 0.05). On long-term follow-up, the rate of change in eGFR did not significantly differ between the two groups (P = 0.24). One EXT1-positive patient (12.5%) developed stage 4 chronic kidney disease (CKD) or end-stage kidney disease (ESKD) compared with four patients (20%) in the EXT-negative group and two of the three EXT1-discordant patients (P = 0.38).

Conclusions

We performed the largest retrospective repeat-biopsy study to evaluate EXT1 and NCAM1 autoantigens in MLN. Our data demonstrate that EXT1 positivity is associated with better kidney function at the time of diagnosis and raises the possibility that EXT1 status may change throughout the disease course of MLN.
The harmful effects of partisan polarization on health
Authors: Fraser Timothy , Aldrich Daniel P , Panagopoulos Costas , Hummel David , Kim Daniel
Published: March 2022

Partisan polarization significantly drives stress and anxiety among Americans, and recent aggregate-level studies suggest polarization may be shaping their health. This individual-level study uses a new representative dataset of 2,752 US residents surveyed between December 2019 and January 2020, some US residents report more days of poor physical and mental health per month than others. Using negative binomial models, zero inflated models, and visualizations, we find evidence that polarization is linked to declines in physical health: the more distant an individual feels politically from the average voter in their state, the worse health outcomes he or she reports. By uncovering the individual-level political correlates of health, this study aims to encourage further study and attention to the broader consequences of political polarization on American communities.
Continuous genomic diversification of long polynucleotide fragments drives the emergence of new SARS-CoV-2 variants of concern
Authors: Murugadoss Karthik , Niesen Michiel J M , Raghunathan Bharathwaj , Lenehan Patrick J , Ghosh Pritha , Feener Tyler , Anand Praveen , Simsek Safak , Suratekar Rohit , Hughes Travis K , Soundararajan Venky
Published: March 2022

Highly transmissible or immuno-evasive SARS-CoV-2 variants have intermittently emerged, resulting in repeated COVID-19 surges. With over 6 million SARS-CoV-2 genomes sequenced, there is unprecedented data to decipher the evolution of fitter SARS-CoV-2 variants. Much attention has been directed to studying the functional importance of specific mutations in the Spike protein, but there is limited knowledge of genomic signatures shared by dominant variants. Here, we introduce a method to quantify the genome-wide distinctiveness of polynucleotide fragments (3- to 240-mers) that constitute SARS-CoV-2 sequences. Compared to standard phylogenetic metrics and mutational load, the new metric provides improved separation between Variants of Concern (VOCs; Reference = 89, IQR: 65–108; Alpha = 166, IQR: 149–181; Beta 131, IQR: 114–149; Gamma = 164, IQR: 150–178; Delta = 235, IQR: 217–255; and Omicron = 459, IQR: 395–521). Omicron's high genomic distinctiveness may confer an advantage over prior VOCs and the recently emerged and highly mutated B.1.640.2 (IHU) lineage. Evaluation of 883 lineages highlights that genomic distinctiveness has increased over time (R2 = 0.37) and that VOCs score significantly higher than contemporary non-VOC lineages, with Omicron among the most distinctive lineages observed. This study demonstrates the value of characterizing SARS-CoV-2 variants by genome-wide polynucleotide distinctiveness and emphasizes the need to go beyond a narrow set of mutations at known sites on the Spike protein. The consistently higher distinctiveness of each emerging VOC compared to prior VOCs suggests that monitoring of genomic distinctiveness would facilitate rapid assessment of viral fitness.
Cognitive processing of a common stimulus synchronizes brains, hearts, and eyes
Authors: Madsen Jens , Parra Lucas C
Published: March 2022

Neural, physiological, and behavioral signals synchronize between human subjects in a variety of settings. Multiple hypotheses have been proposed to explain this interpersonal synchrony, but there is no clarity under which conditions it arises, for which signals, or whether there is a common underlying mechanism. We hypothesized that cognitive processing of a shared stimulus is the source of synchrony between subjects, measured here as intersubject correlation (ISC). To test this, we presented informative videos to participants in an attentive and distracted condition and subsequently measured information recall. ISC was observed for electro-encephalography, gaze position, pupil size, and heart rate, but not respiration and head movements. The strength of correlation was co-modulated in the different signals, changed with attentional state, and predicted subsequent recall of information presented in the videos. There was robust within-subject coupling between brain, heart, and eyes, but not respiration or head movements. The results suggest that ISC is the result of effective cognitive processing, and thus emerges only for those signals that exhibit a robust brain–body connection. While physiological and behavioral fluctuations may be driven by multiple features of the stimulus, correlation with other individuals is co-modulated by the level of attentional engagement with the stimulus.
Research calls, competition for funding and inefficiency
Authors: Osório António , Bornmann Lutz
Published: March 2022

Research groups spend time and resources in the process of applying for funding. This issue raises important questions regarding inefficiency and whether the currently used funding mechanisms are adequate. This article aims to identify ways of reducing the inefficiency and the waste of resources when making research funding calls. We look at four ways of reducing inefficiency. Inefficiency decreases when: (1) the most productive research groups are favoured over the less productive ones, (2) the call is restricted to a small number of research groups actively working on the subject of the call, (3) the funding process is less dependent on the amount of effort spent on fund-seeking activities by the research groups, and (4) the number of research groups competing in the same call is small. However, not all these mechanisms are equally powerful or easy to implement. Our results suggest that (1) reducing the dependence of the funding process on funding activities’ efforts, or (2) reducing the number of research groups by narrowing the subject of the call to groups that are very active in the call’s subject might be particularly effective in reducing inefficiency.
Immigration and Redistribution
Authors: Alesina Alberto , Miano Armando , Stantcheva Stefanie
Published: March 2022

Does immigration change support for redistribution? We design and conduct large-scale surveys and experiments in six countries to investigate how people perceive immigrants and how these perceptions influence their support for redistribution. We find striking misperceptions about the number and characteristics of immigrants. In all countries, respondents greatly overestimate the total number of immigrants, think immigrants are culturally and religiously more distant from them, and economically weaker—less educated, more unemployed, and more reliant on and favoured by government transfers—than they actually are. In the experimental part of our article, we show that simply making respondents think about immigration before asking questions about redistribution makes them support less redistribution, including actual donations to charities. The perception that immigrants are economically weaker and more likely to take advantage of the welfare system is strongly correlated with lower support for redistribution, much more so than the perceived cultural distance or the perceived share of immigrants. These findings are confirmed by further experimental evidence. Information about the true shares and origins of immigrants does not change support for redistribution. An anecdote about a “hard-working” immigrant has somewhat stronger effects but is unable to counteract the negative priming effect of making people think about immigration. Our results further suggest that narratives shape people’s views on immigration more deeply than hard facts.
Hallucinations in Hearing Impairment: How Informed Are Clinicians?
Authors: Marschall Theresa M , van Dijk Pim , Kluk Karolina , Koops Sanne , Linszen Mascha M J , Griffiths Timothy D , Toh Wei Lin , Malicka Alicja N , Kovačić Damir , Mulert Christoph , Sommer Iris E C , Ćurčić-Blake Branislava
Published: March 2022

Background and Hypothesis

Patients with hearing impairment (HI) may experience hearing sounds without external sources, ranging from random meaningless noises (tinnitus) to music and other auditory hallucinations (AHs) with meaningful qualities. To ensure appropriate assessment and management, clinicians need to be aware of these phenomena. However, sensory impairment studies have shown that such clinical awareness is low.

Study Design

An online survey was conducted investigating awareness of AHs among clinicians and their opinions about these hallucinations.

Study Results

In total, 125 clinicians (68.8% audiologists; 18.4% Ear-Nose-Throat [ENT] specialists) across 10 countries participated in the survey. The majority (96.8%) was at least slightly aware of AHs in HI. About 69.6% of participants reported encountering patients with AHs less than once every 6 months in their clinic. Awareness was significantly associated with clinicians’ belief that patients feel anxious about their hallucinations (β = .018, t(118) = 2.47, P < .01), their belief that clinicians should be more aware of these hallucinations (β =.018, t(118) = 2.60, P < .01), and with confidence of clinicians in their skills to assess them (β = .017, t(118) = 2.63, P < .01). Clinicians felt underequipped to treat AHs (Median = 31; U = 1838; PFDRadj < .01).

Conclusions

Awareness of AHs among the surveyed clinicians was high. Yet, the low frequency of encounters with hallucinating patients and their belief in music as the most commonly perceived sound suggest unreported cases. Clinicians in this study expressed a lack of confidence regarding the assessment and treatment of AHs and welcome more information.
Sex-related differences within sleep–wake dynamics, cataplexy, and EEG fast-delta power in a narcolepsy mouse model
Authors: Piilgaard Louise , Rose Laura , Gylling Hviid Camille , Kohlmeier Kristi A , Kornum Birgitte Rahbek
Published: March 2022

Narcolepsy type 1 (NT1) is a sleep–wake disorder caused by selective loss of hypocretin (HCRT, also called orexin) neurons. Although the prevalence of NT1 is equal in men and women, sex differences in NT1 symptomatology have been reported in humans and other species. Yet, most preclinical studies fail to include females, resulting in gender bias within translational drug development. We used hcrt-tTA;TetO DTA mice (NT1 mice) that lose their HCRT neurons upon dietary doxycycline removal to examine in detail the effect of sex on NT1 symptoms and sleep–wake characteristics. We recorded 24-h electroencephalography (EEG), electromyography (EMG), and video in adult male and female NT1 mice for behavioral state quantification. While conducting this study, we recognized another type of behavioral arrest different from cataplexy: shorter lasting and with high δ power. We termed these delta attacks and propose a set of criteria for quantifying these in future research. Our findings show that both sexes exhibit high behavioral state instability, which was markedly higher in females with more behavioral arrests interrupting the wake episodes. Females exhibited increased wake at the expense of sleep during the dark phase, and decreased rapid eye movement (REM) sleep during the 24-h day. During the dark phase, fast-δ (2.5–4 Hz) in non-rapid eye movement (NREM) sleep and θ (6–10 Hz) EEG spectral power in REM sleep were lower in females compared to males. We demonstrate that biologically driven sex-related differences exist in the symptomatology of NT1 mice which calls for including both sexes in future research.
Chemical-Empowered Human Adipose-Derived Stem Cells with Lower Immunogenicity and Enhanced Pro-angiogenic Ability Promote Fast Tissue Regeneration
Authors: Yi Junzhi , Zhang Jiayan , Zhang Qin , Chen Xuri , Qi Rujie , Liang Renjie , Wang Ying , Wang Fei , Zhong Yuliang , Zhang Xianzhu , Chin Grace , Liu Qi , Zhou Wenyan , Liu Hua , Chen Jiansong , Ouyang Hongwei
Published: March 2022

Mesenchymal stem cells (MSCs) have been widely used as functional components in tissue engineering. However, the immunogenicity and limited pro-angiogenic efficacy of MSCs greatly limited their pro-regenerative ability in allogenic treatment. Herein, utilizing a chemically defined cocktail in the culture system, including cytokines, small molecules, structural protein, and other essential components, we generated the immunoprivileged and pro-angiogenic cells (IACs) derived from human adipose tissues. Conventional adipose-derived MSCs (cADSCs) were used as a control in all the experiments. IACs show typical MSC properties with enhanced stemness capacity and a robust safety profile. IACs induce a significantly milder immune response of allogenic peripheral blood mononuclear cells in an H3K27me3-HLA axis-dependent manner. IACs, through superior paracrine effects, further promote nitric oxide production, anti-apoptotic ability, and the tube formation of human vein endothelial cells. Embedded in a photo-reactive hydrogel (Gel) termed as GelMA/HA-NB/LAP for tissue engineering treatment, IACs promote faster tissue regeneration in a xenogeneic full-thickness skin defect model, eliciting a milder immune response and enhanced blood vessel formation in IACs-treated defect areas. Together with its excellent pro-regenerative potential and robust safety, our findings suggest that IACs may be a promising candidate for clinically relevant stem cell and tissue engineering therapeutics.
Oxidative Stress-induced Autophagy Compromises Stem Cell Viability
Authors: Prakash Ravi , Fauzia Eram , Siddiqui Abu Junaid , Yadav Santosh Kumar , Kumari Neha , Shams Mohammad Tayyab , Naeem Abdul , Praharaj Prakash P , Khan Mohsin Ali , Bhutia Sujit Kumar , Janowski Miroslaw , Boltze Johannes , Raza Syed Shadab
Published: March 2022

Stem cell therapies have emerged as a promising treatment strategy for various diseases characterized by ischemic injury such as ischemic stroke. Cell survival after transplantation remains a critical issue. We investigated the impact of oxidative stress, being typically present in ischemically challenged tissue, on human dental pulp stem cells (hDPSC) and human mesenchymal stem cells (hMSC). We used oxygen-glucose deprivation (OGD) to induce oxidative stress in hDPSC and hMSC. OGD-induced generation of O2•− or H2O2 enhanced autophagy by inducing the expression of activating molecule in BECN1-regulated autophagy protein 1 (Ambra1) and Beclin1 in both cell types. However, hDPSC and hMSC pre-conditioning using reactive oxygen species (ROS) scavengers significantly repressed the expression of Ambra1 and Beclin1 and inactivated autophagy. O2•− or H2O2 acted upstream of autophagy, and the mechanism was unidirectional. Furthermore, our findings revealed ROS-p38-Erk1/2 involvement. Pre-treatment with selective inhibitors of p38 and Erk1/2 pathways (SB202190 and PD98059) reversed OGD effects on the expression of Ambra1 and Beclin1, suggesting that these pathways induced oxidative stress-mediated autophagy. SIRT3 depletion was found to be associated with increased oxidative stress and activation of p38 and Erk1/2 MAPKs pathways. Global ROS inhibition by NAC or a combination of polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-catalase) further confirmed that O2•− or H2O2 or a combination of both impacts stems cell viability by inducing autophagy. Furthermore, autophagy inhibition by 3-methyladenine (3-MA) significantly improved hDPSC viability. These findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may deduce strategies to minimize therapeutic cell loss under oxidative stress.
Catastrophic Health Expenditures With Pregnancy and Delivery in the United States
Authors: Peterson Jessica A. , Albright Benjamin B. , Moss Haley A. , Bianco Angela
Published: March 2022

OBJECTIVE:

To describe prevalence, trends, and risk factors for catastrophic health expenditures in the year of delivery among birth parents (delivering people).

METHODS:

We conducted a retrospective, cross-sectional study of the Medical Expenditure Panel Survey from 2008–2016. We identified newborn birth parents and a 2:1 nearest-neighbor propensity-matched control cohort of nonpregnant reproductive-aged individuals, then assessed for catastrophic health expenditures (spending greater than 10% of family income) in the delivery year. We applied survey weights to extrapolate to the noninstitutionalized U.S. population and used the adjusted Wald test for significance testing. We compared risk of catastrophic health expenditures between birth parents and the control cohort and described time trends and risk factors for catastrophic spending with subgroup comparisons.

RESULTS:

We analyzed 4,056 birth parents and 7,996 reproductive-aged females without pregnancy in a given year. Birth parents reported higher rates of unemployment (52.6% vs 46.6%, P<.001), and high rates of gaining (22.4%) and losing (25.6%) Medicaid in the delivery year. Birth parents were at higher risk of catastrophic health expenditures (excluding premiums: 9.2% vs 6.8%, odds ratio [OR] 1.95, 95% CI 1.61–2.34; including premiums: 21.3% vs 18.4%, OR 1.53, 95% CI 1.32–1.82). Birth parents living on low incomes had the highest risk of catastrophic health expenditures (18.8% vs 0.7% excluding premiums for 138% or less vs greater than 400% of the federal poverty level, relative risk [RR] 26.9; 29.8% vs 5.9% including premiums, RR 5.1). For birth parents living at low incomes, public insurance was associated with lower risks of catastrophic health expenditures than private insurance, particularly when including premium spending (incomes 138% of the federal poverty level or lower: 18.8% public vs 67.9% private, RR 0.28; incomes 139–250% of the federal poverty level: 6.5% public vs 41.1% private, RR 0.16). The risk of catastrophic spending for birth parents did not change significantly over time from before to after Affordable Care Act implementation.

CONCLUSION:

Pregnancy and delivery are associated with increased risk of catastrophic health expenditures in the delivery year. Medicaid and public coverage were more protective from high out-of-pocket costs than private insurance, particularly among low-income families.
Active surveillance in favorable intermediate risk prostate cancer: outstanding questions and controversies
Authors: Russell J. Ryan , Siddiqui M. Minhaj
Published: March 2022

Purpose of review

Active surveillance has become the preferred management strategy for patients with low risk prostate cancer, but it is unclear if active surveillance can be safely extended to favorable intermediate risk (FIR) prostate cancer patients. Furthermore, defining a favorable intermediate risk prostate cancer population safe for active surveillance remains elusive due to paucity of high-level data in this population. This article serves to review relevant data, particularly the safety of active surveillance in grade group 2 patients, and what tools are available to aid in selecting a favorable subset of intermediate risk patients.

Recent findings

Active surveillance studies with long-term data appear to report worsened survival outcomes in intermediate risk patients when compared to those undergoing definitive treatment, but there exists a subset of intermediate risk patients with nearly equivalent outcomes to low risk patients on active surveillance. Tools such as percentage and total length of Gleason pattern 4, tumor volume, prostate specific antigen density, magnetic resonance imaging, and genomic modifiers may help to select a favorable subset of intermediate risk prostate cancer appropriate for active surveillance.

Active surveillance is a viable strategy in select patients with low volume group grade 2 (GG2) prostate cancer. Prospective and retrospective data in the FIR population appear to be mostly favorable in regards to survival outcomes, but there exists some heterogeneity with respect to long-term outcomes in this patient population.
The Effects of Smartphone Use on Life Satisfaction in Older Adults
Authors: Sagong Hae , Yoon Ju Young
Published: March 2022

As the number of smartphone use by older adults increases, investigating the effects of smartphone use on health outcome become important in healthcare. This study aimed to investigate the effects of smartphone use on life satisfaction and the mediating role of depressive symptoms in older adults. This is a secondary data analysis study using the 2017 Korean Media Panel Survey. A total of 2071 respondents aged 65 years and older were analyzed to examine the effects of mobile phone type (no mobile phone/2G phone/smartphone) on life satisfaction. Among the respondents, data from 680 smartphone owners were analyzed to find the effects of the level of smartphone use on life satisfaction. The 2G mobile phone and smartphone owner groups showed significant positive effects on life satisfaction compared with the no mobile phone group, respectively. The level of smartphone use showed significant positive effects on life satisfaction. Depressive symptoms played a mediating role in both models. Smartphone use showed positive effects on life satisfaction in older adults. Nurses should promote the well-being of older adults and minimize the digital health gap in the future by increasing older adults' smartphone use through multi-level approaches.
Impact of Patient Education via WeChat on Bowel Preparation for Colonoscopy
Authors: Li Peng , He Xueqian , Chen Sufeng
Published: March 2022

Supplemental digital content is available in the text.

The aim of this study was to evaluate the impact of education via WeChat on the quality of bowel preparation in patients undergoing colonoscopy through a meta-analysis of randomized controlled trials. Randomized controlled trials of bowel preparation education provided via WeChat for patients undergoing colonoscopy were screened from databases such as PubMed, Web of Science, Cochrane Library, and Embase. Papers published from the date of database construction to May 1, 2021, were extracted, and a meta-analysis was performed using Review Manager software. A total of four randomized controlled trials were included in the meta-analysis. The results showed that for patients undergoing colonoscopy, education via WeChat significantly improves the quality of bowel preparation for colonoscopy, reduces the insertion time, and increases the adenoma detection rate and the patient's compliance and willingness to repeat bowel preparation. In conclusion, education via WeChat before colonoscopy can significantly improve the quality of bowel preparation.
Development and Effectiveness of a Clinical Decision Support System for Pressure Ulcer Prevention Care Using Machine Learning
Authors: Kim Myoung Soo , Ryu Jung Mi , Choi Byung Kwan
Published: March 2022

This study was conducted to develop and evaluate the effectiveness of a clinical decision support system for pressure ulcer prevention on clinical (performance, visual discrimination ability, and decision-making ability) and cognitive (knowledge and attitude) workflow. After developing a clinical decision support system using machine learning, a quasi-experimental study was used. Data were collected between January and April 2020. Forty-nine RNs who met the inclusion criteria and worked at seven tertiary and five secondary hospitals participated. A clinical decision support system was provided to the intervention group during the same period. Differences in outcome variables between the two groups were analyzed using t tests. The level of pressure ulcer prevention nursing performance and visual differentiation ability of skin pressure and oral mucosa pressure ulcer showed significantly greater improvement in the experimental group compared with the control group, whereas clinical decision making did not differ significantly. A clinical decision support system using machine learning was partially successful in performance of skin pressure ulcer prevention, attitude, and visual differentiation ability for skin and oral mucosa pressure ulcer prevention. These findings indicated that a clinical decision support system using machine learning needs to be implemented for pressure ulcer prevention.