bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association Between Adverse Childhood Experiences and Late-Life Cognition: A Systematic Review of Cross-Sectional and Case-Control Studies
Authors: Patel Priya , Oremus Mark
Published: March 2022

Background and Objectives

Adverse childhood experiences (ACEs) are a recognized risk factor for unfavorable health outcomes. No prior systematic review has explored the association between ACEs and cognition in late life, a critical period for cognitive fluctuation. The objective of this review is to address the following research question: What is the association between ACEs and late-life cognition?

Research Design and Methods

Articles were obtained from PubMed, PsycINFO, and Scopus. The last search was performed in May 2021. Eligible articles examined the association between exposure to at least 1 ACE and the outcome of late-life cognition, measured either by cognitive testing or the presence/absence of a neurocognitive disorder. Data were synthesized narratively using the synthesis without meta-analysis guidelines, and the risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) and Adapted NOS.

Results

Twenty articles representing 18 unique studies were included in the narrative synthesis. Associations with lower late-life cognition were reported for: childhood maternal death, parental divorce, physical neglect, emotional neglect, physical abuse, and combinations of ACEs. However, most results were statistically nonsignificant, and many were unlikely to be clinically important.

Discussion and Implications

We found an association between ACEs and late-life cognition. However, the direction and magnitude of association varied between and within types of ACEs and measures of cognitive function. Most included articles had a moderate risk of bias. This review is the first attempt to synthesize the literature on this topic and it outlines the next steps to improve the evidence base in the area.
The Kauffman Skein Algebra of the Torus
Authors: Morton Hugh , Pokorny Alex , Samuelson Peter
Published: March 2022

We give a presentation of the Kauffman (BMW) skein algebra of the torus. This algebra is the “type $BCD$” analogue of the Homflypt skein algebra of torus, which was computed in earlier work of the 1st and 3rd authors [17]. This suggests the existence of a “type $BCD$” version of the Hall algebra of an elliptic curve [4]. In the appendix, we show this presentation is compatible with the Frohman–Gelca description of the Kauffman bracket (Temperley–Lieb) skein algebra of the torus [12].
Well-Posedness for the Dispersive Hunter–Saxton Equation
Authors: Ai Albert , Avadanei Ovidiu-Neculai
Published: March 2022

This article represents a 1st step toward understanding the well-posedness of the dispersive Hunter–Saxton equation, which arises in the study of nematic liquid crystals. Although the equation has formal similarities with the KdV equation, the lack of $L^2$ control gives it a quasilinear character. Further, the lack of spatial decay obstructs access to dispersive tools, including local smoothing estimates. Here, we give the 1st proof of local and global well-posedness for the Cauchy problem. Secondly, we improve our well-posedness results with respect to the low regularity of the initial data. The key techniques we use include constructing modified energies to realize a normal form analysis in our quasilinear setting, and frequency envelopes to prove continuous dependence with respect to the initial data.
Rules for Mediated Romance: A Digital Exploration of How Couples Negotiate Expectations
Authors: Foster Campbell Jamie
Published: March 2022

Framed by expectancy violation theory, this study used joint interviews to explore why couples create communication rules for their technology use and what happens if the expectation is violated. Participants’ (n = 36) narratives were analyzed through four coding cycles: in vivo, initial, value, and focused coding. Interviews with romantic couples resulted in three themes: rules are performative, rules reduce conflict, and rules guide modality weaving. During an expectation violation, findings revealed that the magnitude of the violation is first determined by the violator defending their behavior. Then, based on the appraisal process, the couple reframes the rule to better work for their future interactions. Key findings conclude that rules are not rigid; they are fluid and develop naturally over time. This research adds to the literature about how mediated communication transforms the dynamics of romantic relationships as couples explicitly and implicitly create communication rules to help maintain their partnership.
Physics of star-formation history and the luminosity function of galaxies therefrom
Authors: Fukugita Masataka , Kawasaki Masahiro
Published: March 2022

We show that the star-formation history, the reionization history and the present luminosity function of galaxies are reproduced in a simple gravitational collapse model within the ΛCDM regime to an almost quantitative accuracy when the physical conditions, the Jeans criterion and the cooling process are taken into account. Taking a reasonable set of model parameters, the reionization takes place sharply at about redshift 1 + z ≃ 7.5, and the resulting luminosity function turns off at $L\simeq 10^{10.7}\, {\rm L}_\odot$, showing the consistency between the star-formation history and the reionization of the Universe. The model gives the total amount of stars Ωstar = 0.004 in units of the critical density, compared with the observational value of 0.0044 with a recycling factor of 1.6. In order to account for the observed star-formation rate and the present luminosity function, the star-formation efficiency is not halo-mass-independent but has a maximum at the halo mass $\simeq 10^{12}\, {\rm M}_\odot$ and is suppressed for both lower- and higher-mass haloes.
Using peculiar velocity surveys to constrain neutrino masses
Authors: Whitford Abbé M , Howlett Cullan , Davis Tamara M
Published: March 2022

The presence of massive neutrinos in the early Universe is expected to have influenced the observed distribution of galaxies and their observed motions. In this work, we explore whether measurements of galaxy peculiar velocities could allow us to improve upon neutrino mass constraints from galaxy redshift surveys alone. Using Fisher matrix forecasts, we show that the galaxy peculiar motions do contain information on the sum of the masses of neutrinos ∑mν, and that this information can be used to improve upon constraints that may be obtained from low-redshift galaxy surveys (z < 0.5) combined with Planck measurements of the cosmic microwave background. Compared to the full constraining power offered by Planck and higher redshift DESI data, we find that the benefit of including peculiar velocities only marginally improves neutrino mass constraints. However, when one does not include information from Planck, our results show that the inclusion of peculiar velocity measurements can substantially improve upon the constraints from redshift surveys alone, and that in some cases the addition of further data from high-density peculiar velocity surveys is more successful at overcoming the sample variance than adding further data from redshifts only. We demonstrate that it may be possible to achieve upper bounds of ∑mν ≈ 0.14 eV (68 per cent confidence limit), from upcoming spectroscopic galaxy surveys alone, as long as the peculiar velocity data is available, an improvement of ∼14 per cent over redshift surveys alone, but not as strong as when CMB data are included.
Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study
Authors: Hamano Takayuki , Imaizumi Takahiro , Hasegawa Takeshi , Fujii Naohiko , Komaba Hirotaka , Ando Masahiko , Nangaku Masaomi , Nitta Kosaku , Hirakata Hideki , Isaka Yoshitaka , Wada Takashi , Maruyama Shoichi , Fukagawa Masafumi
Published: March 2022

Background

The Kidney Disease: Improving Global Outcomes guidelines advocate the cause–glomerular filtration rate (GFR)–albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction.

Methods

We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B).

Results

In analysis A, adding biopsy-proven diagnoses to the GFR–albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine–Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11–15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09–13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02–8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05–17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24–0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39–0.97)].

Conclusions

The CGA classification is of greater value in predicting outcomes than the GA classification.
A note on the unemployment volatility puzzle
Authors: Kokonas Nikolaos
Published: March 2022

This paper features an economy with frictional labour markets, Nash bargaining, cyclical opportunity cost of employment and demand-determined output. I show that the model generates big responses of unemployment to productivity movements. The key insight is that strongly countercyclical markups amplify the impact of aggregate shocks on the fundamental surplus, and as a consequence, on labour market outcomes. This answers the critique of Chodorow-Reich and Karabarbounis that the cyclicality of the opportunity cost poses a challenge to the solution of the unemployment volatility puzzle.
Pivotal roles of ELONGATED HYPOCOTYL5 in regulation of plant development and fruit metabolism in tomato
Authors: Zhang Chunli , Wu Yujie , Liu Xiaorui , Zhang Jiayi , Li Xin , Lin Li , Yin Ruohe
Published: March 2022

The transcription factor ELONGATED HYPOCOTYL5 (HY5) plays critical roles in plant photomorphogenesis. Previous studies on HY5 have mainly focused on the seedling stage in Arabidopsis (Arabidopsis thaliana), and its functions in other plant species have not been well characterized, particularly at adult stages of development. In this report, we investigated the functions of tomato (Solanum lycopersicum) HY5 (SlHY5) from seedlings to adult plants with a focus on fruits. Genome-edited slhy5 mutants exhibited typical compromised photomorphogenesis in response to various light conditions. The slhy5 mutants showed reduced primary root length and secondary root number, which is associated with altered auxin signaling. SlHY5 promoted chlorophyll biosynthesis from seedling to adult stages. Notably, the promotive role of SlHY5 on chlorophyll accumulation was more pronounced on the illuminated side of green fruits than on their shaded side. Consistent with this light-dependent effect, we determined that SlHY5 protein is stabilized by light. Transcriptome and metabolome analyses in fruits revealed that SlHY5 has major functions in the regulation of metabolism, including the biosynthesis of phenylpropanoids and steroidal glycoalkaloids. These data demonstrate that SlHY5 performs both shared and distinct functions in relation to its Arabidopsis counterpart. The manipulation of SlHY5 represents a powerful tool to influence the two vital agricultural traits of seedling fitness and fruit quality in tomato.
Predicting Treatment Response with Sensory Phenotyping in Post-Traumatic Neuropathic Pain
Authors: Gewandter Jennifer S , Sohn Michael B , De Guzman Rachel , Frazer Maria E , Chiodo Valerie , Sharma Sonia , Geha Paul , Markman John D
Published: March 2022

Objective

Currently available treatments for neuropathic pain are only modestly efficacious when assessed in randomized clinical trials and work for only some patients in the clinic. Induced-pain or gain-of-function phenotypes have been shown to predict response to analgesics (vs placebos) in patients with neuropathic pain. However, the predictive value of these phenotypes has never been studied in post-traumatic neuropathic pain.

Methods

Mixed-effects models for repeated measures were used to evaluate the efficacy of pregabalin vs placebo in subgroups with induced-pain phenotypes (i.e., hyperalgesia or allodynia) in data from a recent, multinational randomized clinical trial (N = 539) that identified phenotypic subgroups through the use of a structured clinical exam.

Results

The difference in mean pain score between the active and placebo groups (i.e., delta) after 15 weeks of treatment for the subgroup with hyperalgesia was –0.76 (P = 0.001), compared with 0.19 (P = 0.47) for the subgroup that did not have hyperalgesia. The treatment-by-phenotype interaction, which tests whether subgroups have statistically different treatment responses, was significant (P = 0.0067). The delta for the subgroup with allodynia was –0.31 (P = 0.22), compared with –0.30 (P = 0.22) for the subgroup that did not have allodynia (treatment-by-phenotype interaction P = 0.98).

Conclusions

These data suggest that hyperalgesia, but not allodynia, predicts response to pregabalin in patients with chronic post-traumatic neuropathic pain. This study extends the growing data supporting the utility of induced-pain phenotypes to predict response to analgesics in post-traumatic neuropathic pain. Sensory phenotyping in large, multisite trials through the use of a structured clinical exam has the potential to accelerate the development of new analgesics and improve the generalizability of clinical trial results.
The Modifying of Functional Connectivity Induced by Peripheral Nerve Field Stimulation using Electroacupuncture for Migraine: A Prospective Clinical Study
Authors: Ishiyama Sumire , Shibata Yasushi , Ayuzawa Satoshi , Matsushita Akira , Matsumura Akira , Ishikawa Eiichi
Published: March 2022

Objective

We examined the functional connectivity (FC) in patients with migraine compared with healthy subjects before and after C2 peripheral nerve field stimulation with electroacupuncture (EA-C2-PNfS) to evaluate the effect of EA-C2-PNfS and elucidate the mechanism of migraine.

Methods

Twenty-six patients with migraine and 24 healthy controls were recruited. All patients underwent resting state functional magnetic resonance imaging before and after 3 months of EA-C2-PNfS. We evaluated a numerical rating scale, the Headache Impact Test, and the Self-Rating Depression Scale, which assesses depression. Healthy controls underwent magnetic resonance imaging twice at a 3-month interval without acupuncture. An analysis of FC in the region of interest in the pain matrix was performed.

Results

Twenty patients with migraine and 23 healthy controls (mean ± standard deviation: 44.9 ± 12.9 years of age) were included. Three patients had migraine with aura (55.0 ± 18.0 years of age), 11 patients had migraine without aura (MWoA) (45.6 ± 14.6 years of age), and six patients had chronic migraine (40.8 ± 13.9 years of age). The clinical assessments significantly improved after EA-C2-PNfS in the MWoA group only. In FC analysis, the MWoA group showed a significant decrease after EA-C2-PNfS in FC between the right hypothalamus and left insula. Right hypothalamus–related FC was lower before acupuncture in the chronic migraine group than in the MWoA group.

Conclusion

After EA-C2-PNfS for MWoA, significant changes in FC were observed at the hypothalamus and insula. Our results indicate that EA-C2-PNfS could improve migraine headache by modifying pain-related FC.
Omicron Spread in Vaccinated Jurisdictions: a Statistical Study
Authors: Dolgikh Serge
Published: March 2022

A correlation hypothesis between the level of vaccination and the rate of spread of the new Covid-19 variant is investigated based on the case and vaccination data from European and North American jurisdictions available in the public domain at the time point of past the crest of the Omicron wave in most jurisdictions. Statistical variables describing the rate of the spread based on observed new case statistics defined and discussed. An unexpected moderate positive correlation between the rate of the variant spread measured by two related parameters and vaccination level based on the dataset in the study is reported. While negative correlation was not statistically excluded, the analysis of the data in the study statistically excluded moderate to strong negative correlation. The results of this work, if confirmed by further independent studies can have implications for development of policies aimed at controlling future course of the Covid-19 pandemic.
Good recovery of immunization stress-related responses presenting as cluster of stroke-like events following CoronaVac and ChAdOx1 vaccinations
Authors: Apiwattanakul Metha , Suanprasert Narupat , Rojana-Udomsart Arada , Termglinchan Thanes , Sinthuwong Chaichana , Tantirittisak Tasanee , Hanchaiphiboolkul Suchat , Angchaisuksiri Pantep , Srimahachota Suphot , Wongsawat Jurai , Stiudomkajorn Somjit , Kiertiburanakul Sasisopin , Techasaensiri Chonnamet , Laisuan Wannada , Manosuthi Weerawat , Doungngern Pawinee , Jaroenkunathum Wereyarmarst , Jivapaisarnpong Teeranart , Panjangampatthan Apinya , Chimmanee Jirapa , Chokephaibulkit Kulkanya
Published: March 2022

Background

Immunization stress-related responses presenting as stroke-like symptoms may develop following COVID-19 vaccination. This study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination.

Methods

We conducted a retrospective study of the secondary data of reported adverse events following COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score (i.e., defining the degree of severity/dependence, with higher scores indicating greater disability). The affected side was evaluated for associations with the injection site.

Results

In total, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28–42) years in patients receiving CoronaVac and 46 (33.5–60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16–960) min and 30 (8.8–750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (53.8%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 90% of those receiving ChAdOx1 recovered well (modified Rankin scores ≤2, indicating slight or no disability).

Conclusions

Immunization stress-related responses presenting as stroke-like symptoms can develop following COVID-19 vaccination. Symptoms that are more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.
Selection of appropriate reference genes for normalization of qRT-PCR based gene expression analysis in SARS-CoV-2, and Covid-associated Mucormycosis infection
Authors: Kumar Sunil , Ahmad Ayaan , Kushwaha Namrata , Negi Sheetal , Gautam Kamini , Singh Anup , Tiwari Pawan , Garg Rakesh , Agarwal Richa , Mohan Anant , Trikha Anjan , Thakar Alok , Saini Vikram
Published: March 2022

Selection of reference genes in quantitative PCR is critical to determine accurate and reliable mRNA expression. Despite this knowledge, not a single study has investigated the expression stability of housekeeping genes to determine their suitability to act as reference gene in SARS-CoV-2 or Covid19 associated mucormycosis (CAM) infections. Herein, we address these gaps by investigating the expression stability of nine most commonly used housekeeping genes including TBP, CypA, B2M, 18S, PGC-1α, GUSB, HPRT-1, β-ACTIN and GAPDH in the patients of varying severity (asymptomatic, mild, moderate and severe). We observed significant differences in the expression of candidate genes across the disease spectrum. Next, using various statistical algorithms (delta Ct, Normfinder, Bestkeeper, RefFinder and GeNorm), we observed that CypA demonstrated the most consistent expression across the patients of varying severity and emerged as the most suitable gene in Covid19, and CAM infections. Incidentally, the most commonly used reference gene GAPDH showed maximum variations and found to be the least suitable. Lastly, comparative evaluation of expression of NRF2 is performed following normalization with GAPDH and CypA to highlight the relevance of an appropriate reference gene. Our results reinforce the idea of a selection of housekeeping genes only after validation especially during infections.
How can instructions and feedback with external focus be shaped to enhance motor learning in children? A systematic review
Authors: van der Veer Ingrid P.A. , Verbecque Evi , Rameckers Eugene A.A. , Bastiaenen Caroline H.G. , Klingels Katrijn
Published: March 2022

Aim

This systematic review investigates the effectiveness of instructions and feedback with external focus applied with reduced frequency, self-controlled timing and/or in visual or auditory form, on the performance of functional gross motor tasks in children aged 2 to 18 with typical or atypical development.

Methods

Four databases (PubMed, Web of Science, Scopus, Embase) were systematically searched (last updated May 31st 2021). Inclusion criteria were: 1. children aged 2 to 18 years old; 2. Instructions/feedback with external focus applied with reduced frequency, self-controlled timing, and/or visual or auditory form as intervention, to learn functional gross motor tasks; 3. Instructions/feedback with external focus applied with continuous frequency, instructor-controlled timing, and/or verbal form as control; 4. performance measure as outcome; 5. (randomized) controlled studies. Article selection and risk of bias assessment (with the Cochrane risk of bias tools) was conducted by two reviewers independently. Due to heterogeneity in study characteristics and incompleteness of the reported data, a best-evidence synthesis was performed.

Results

Thirteen studies of low methodological quality were included, investigating effectiveness of reduced frequencies (n = 8), self-controlled timing (n = 5) and visual form (n = 1) on motor performance of inexperienced typically (n = 348) and atypically (n = 195) developing children, for acquisition, retention and/or transfer. For accuracy, conflicting or no evidence was found for most comparisons, at most time points. However, there was moderate evidence that self-controlled feedback was most effective for retention, and limited evidence that visual analogy was most effective for retention and transfer. To improve quality of movement, there was limited evidence that continuous frequency was most effective for retention and transfer.

Conclusion

More methodologically sound studies are needed to draw conclusions about the preferred frequency, timing or form. However, we cautiously advise considering self-controlled feedback, visual instructions, and continuous frequency.

Registration

Prospero CRD42021225723
Survey of nationwide public perceptions regarding acceptance of wastewater used for community health monitoring in the United States
Authors: LaJoie A. Scott , Holm Rochelle H. , Anderson Lauren B. , Ness Heather D. , Smith Ted
Published: March 2022

During the coronavirus disease 2019 (COVID-19) pandemic researchers looked for evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in feces dissolved in wastewater samples to assess levels of infection across communities. This activity is known colloquially as sewer monitoring and called wastewater-based epidemiology in academic settings. When used for public health surveillance in the United States, wastewater monitoring is not regulated, although general ethical principles have been described. Prior to this study, no nationwide data existed regarding the public’s perceptions of wastewater being used for community health monitoring. Using an online survey distributed to a representative sample of adults in the Unites States (N=3,083), we investigated the public’s perceptions regarding what is monitored, where monitoring occurs, and privacy concerns related to wastewater monitoring as a public health surveillance tool. Further, the Privacy Attitudes Questionnaire assessed respondents’ general privacy boundaries. The results suggest that respondents supported using wastewater for health monitoring, but within some bounds. Participants were most likely to support or strongly support monitoring for disease (95%), environmental toxins (94%), and terroristic threats (90%, e.g., anthrax). Two-thirds of respondents endorsed no prohibition to locations being monitored while the most common category of location respondents wanted to be prohibited from monitoring was personal residencies. Additionally, the findings suggest that those younger in age and living in an urban area were more supportive of wastewater monitoring, compared to older, suburban dwellers.
Patient-reported respiratory outcome measures in the recovery of adults hospitalised with COVID-19: A systematic review and meta-analysis
Authors: Middleton Sophie , Chalitsios Christos , McKeever Tricia. M. , Jenkins Alex R. , Bolton Charlotte. E.
Published: March 2022

Background

Acute COVID-19 clinical symptoms have been clearly documented, but long-term functional and symptomatic recovery from COVID -19 is less well described.

Methods

A systematic review and meta-analysis were conducted to describe patient-reported outcome measures (PROMs) in adults at least 8 weeks post hospital discharge for COVID-19. Comprehensive database searches in accordance with the PRISMA statement were carried out up till 31/05/2021. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method.

Results

From 49 studies, across 14 countries with between 2-12 months follow up, the most common persisting symptom reported was fatigue with meta-analysis finding 36.6% (95 % CI 27.6 to 46.6, n=14) reporting it at 2-4 months, decreasing slightly to 32.5% still reporting it at >4 months (95% CI 22.6 to 44.2, n=15). This was followed by dyspnoea. Modified MRC score (mMRC) ≥1 was reported in 48% (95% CI 30 to 37, n=5) at 2-4months reducing to 32% (95% CI 22 to 43, n=7) at 4 months. Quality of life (QOL) as assessed by the EQ-5D-5L VAS remained reduced at >4 months (73.6 95% CI 68.1 to 79.1, n=6). Hospitalisation with COVID-19 also resulted in persisting sick leave, change in scope of work, and continued use of primary and secondary healthcare.

Conclusion

The symptomatic and functional impact of COVID-19 continues to be felt by patients months after discharge from hospital. This widespread morbidity points towards a multi-disciplinary approach to aid functional recovery.
Phenotypic variability and Gastrointestinal Manifestations/Interventions for growth in Ogden syndrome (also known as NAA10-related Syndrome)
Authors: Sandomirsky Katherine , Marchi Elaine , Gavin Maureen , Amble Karen , Lyon Gholson J.
Published: March 2022

Our study of 61 children with Ogden Syndrome, an X-linked disorder due to NAA10 gene mutations, demonstrated a high prevalence of growth failure, with weight and height percentiles often in the failure-to-thrive diagnostic range; although dramatic weight fluctuations and phenotypic variability is evidenced in the growth parameters of this population. Although never previously explored in depth, the gastrointestinal pathology associated with OS includes feeding difficulties in infancy, dysphagia, GERD/silent reflux, vomiting, constipation, diarrhea, bowel incontinence, and presence of eosinophils on esophageal endoscopy, in order from most to least prevalent. Additionally, the gastrointestinal symptom profile for children with this syndrome has been expanded to include eosinophilic esophagitis, cyclic vomiting syndrome, Mallory Weiss tears, abdominal migraine, esophageal dilation, and subglottic stenosis. Although the exact cause of poor growth in OS probands is unclear and the degree of contribution to this problem by GI symptomatology remains uncertain, an analysis including nine G-tube or GJ-tube fed probands demonstrates that G/GJ-tubes are overall efficacious with respect to improvements in weight gain and caregiving. The choice to insert a gastrostomy or gastrojejunal tube to aid with weight gain is often a challenging decision to make for parents, who may alternatively choose to rely on oral feeding, caloric supplementation, calorie tracking, and feeding therapy. In this case, if OS children are not tracking above the FTT range past 1 year of age despite such efforts, they should promptly undergo G-tube placement to avoid prolonged growth failure. If G-tubes are not immediately inducing weight gain after insertion, recommendations include altering formula, increasing caloric input, or exchanging a G-tube for a GJ-tube by means of a minimally invasive procedure. Future directions could include a prospective natural history study investigating whether G/GJ tube insertion affects the cognitive trajectory, rate of reaching developmental milestones, and GI symptomatology of OS children in a positive or negative manner.
Long-term memory in frog-eating bats
Authors: Dixon M. May , Jones Patricia L. , Ryan Michael J. , Carter Gerald G. , Page Rachel A.
Published: March 2022

Long-term memory has clear advantages but also has neurological and behavioral costs1–3. Given these opposing selection pressures, understanding how long memories last can shed light on how memory enhances or constrains animals’ abilities to exploit their niches. Although testing memory retention in wild animals is difficult, it is important because captive conditions do not reflect the complex cognitive demands of wild environments, and long-term captivity changes the brain4 (past studies on nonhuman long-term memory are reviewed in Table S1). Here, we trained wild-caught frog-eating bats (Trachops cirrhosus) to find prey by flying to a novel acoustic cue, released them back into the wild, and then re-captured some of them 1-4 years later. When re-tested, all eight ‘experienced’ bats that previously learned the novel prey sounds flew to those sounds within seconds, whereas 17 naïve bats tested with the same sounds showed weak responses. Experienced bats also showed behavior indicating generalization of memories between novel sounds and rewards over time. The frog-eating bat’s remarkably long memory for novel acoustic cues indicates that an ability to remember rarely encountered prey may be advantageous for this predator, and suggests hitherto unknown cognitive abilities in bats.
A mathematical model of antibiotic resistance gene flow from livestock and spread amongst humans
Authors: Fryer Helen
Published: March 2022

The evolution and spread of antibiotic resistance poses a major threat to human health. The high level of antibiotic use in the rearing of livestock is contributing to the origin and persistence of antibiotic resistance amongst humans. Understanding how resistance genes spread from livestock to humans and investigating the impact of managing antibiotic use in livestock will be important for guiding strategies to reduce the risk to humans. We have developed a mathematical model of the transmission of resistance genes from livestock to humans and their spread amongst the human population. Using this framework we demonstrate that although resistant zoonotic foodborne infections do not contribute significantly to the annual burden of death, they could be a source of resistance amongst other pathogens, including those that exclusively spread between humans. Amongst these pathogens, only livestock-derived resistant strains that are associated with a net fitness cost would be expected to decline in prevalence following control strategies aimed at reducing the impact on humans of antibiotic use in livestock.

Author Summary

Antibiotics are an essential component of human health care. They are also used in the rearing of livestock for human consumption, which contributes to the development of antibiotic resistant pathogens. Although humans are known to be at risk from antibiotic resistance that evolves amongst livestock, the number of human lives that are at stake remains unclear. Furthermore, the number of lives that could be saved through interventions to reduce antibiotic use in livestock has not been evaluated. Here, we have developed a mathematical framework to explore these questions. Using this framework we explicitly demonstrate that there are too many uncertainties to calculate the number of preventable human deaths. Nevertheless, the importance of reserving new and currently effective antibiotics for human use is clear. Once resistance genes that do not have a fitness disadvantage have spread from livestock to humans, it is too late for interventions targeted at livestock to affect their prevalence in humans in the long term.
Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion
Authors: Qin Zhen , Bouteau Aurélie , Herbst Christopher , Igyártó Botond Z.
Published: March 2022

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune responses, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform’s true impact on human health.

Authors Summary

We bring experimental evidence that pre-exposure to mRNA-LNPs or its LNP component affects innate and adaptive immune responses. Pre-exposure to mRNA-LNPs led to long-term inhibition of the adaptive immune responses, which the use of adjuvants could overcome. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while Candida albicans decreased. We also detected a general neutropenia in the mRNA-LNP exposed mice. Interestingly, mice pre-exposed to mRNA-LNPs can pass down the acquired immune traits to their offspring. In summary, the mRNA-LNP vaccine platform induces long-term immunological changes that can affect both adaptive immune responses and heterologous protection against infections, some of which can be inherited by the offspring. More studies are needed to understand the mechanisms responsible for these effects and determine this platform’s impact on human health.
Rapid colour changes in a tiny threatened gecko do not impede computer-assisted individual recognition
Authors: Monnet Cindy , Dokhelar Théo , Renet Julien
Published: March 2022

Photo-identification is a non-invasive method used for recognising wild animals with distinctive and stable patterns over time. This method is now widely used for capture-recapture wildlife monitoring. However, in species exhibiting rapid colouration changes, the evolving body patterns can lead to errors in individual recognition. In this study, we assessed the effect of dorsal physiological colour change of the tiny threatened European leaf-toed gecko (Euleptes europaea) on the performance of Wild-ID and Hotspotter, the two most commonly used individual recognition software for wildlife monitoring. We exposed 30 European leaf-toed geckos to several semi-controlled parameters (substrate type, temperature and light from natural diurnal/nocturnal cycles) in order to characterise the extent of variation in dorsal colouration, by standardised reflectance measurements. The colour of the substrate had a significant effect on individual reflectance changes. Body temperature also seemed to significantly affect the reflectance but the experimental conditions did not allow us to clearly distinguish the effect of temperature and light. For each of the 30 geckos, four photographic databases (n= 4*280) were then analysed by both software packages, under two extreme reflectance conditions. Despite the large changes in individual reflectance, Wild-ID and Hotspotter proved to be extremely reliable with a 100% recognition rate. The analysis of similarity scores suggests that Hotspotter is less sensitive to chromatic variation than Wild-ID. We provide here the first evidence that physiological colour change is not a barrier to computer-assisted individual recognition. This study advocates the use of Hotspotter for monitoring populations of European leaf-toed geckos and other saurians that generate significant colouration change over a short time.
The exchange dynamics of biomolecular condensates
Authors: Zhang Yaojun , Pyo Andrew G.T. , Kliegman Ross , Jiang Yoyo , Brangwynne Clifford P. , Stone Howard A. , Wingreen Ned S.
Published: March 2022

A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an “interface resistance”. Here, we first derive an analytical expression for the timescale of condensate material exchange, which clearly conveys the physical factors controlling exchange dynamics. We then utilize sticker-spacer polymer models to show that interface resistance can arise when incident molecules transiently touch the interface without entering the dense phase, i.e., the molecules “bounce” from the interface. Our work provides insight into condensate exchange dynamics, with implications for both natural and synthetic systems.
Distilling complex evolutionary histories with shiftPlot
Authors: Miller Eliot T , Martin Bruce S
Published: March 2022

Phylogenies form the backbone of many modern comparative methods and are integral components of contemporary science communication. Recent years have seen drastic increases in both the size and complexity of phylogenetic data as computational resources and genetic/trait databases expand. Graphical representations of these massive phylogenetic datasets push against the limits of legibility, often veering closer to artwork than scientific figures optimized to communicate results. While attractive scientific illustrations are certainly a laudable goal, researchers may want to opt for simpler representations to communicate results more concisely. Here, we introduce a new R package, shiftPlot, which implements methods for simplifying and plotting phylogenetic comparative data on discrete traits. Specifically, shiftPlot automatically finds and collapses clades exhibiting the same character state, effectively creating smaller phylogenies that may be more legibly rendered on standard page sizes. Further, these visualizations more clearly communicate evolutionary dynamics by emphasizing state shifts over tip states. While there are undoubtedly situations where this graphical approach will not be suitable (e.g., continuous traits), we believe shiftPlot will prove useful for modern researchers faced with the task of communicating the results of complex phylogenetic analyses.
Chlamydia trachomatisinduces the transcriptional activity of host YAP in a Hippo-independent fashion
Authors: Caven Liam T. , Brinkworth Amanda J. , Carabeo Rey T.
Published: March 2022

The obligate intracellular pathogenChlamydia trachomatisis the causative agent of the most common bacterial sexually transmitted disease worldwide. While the host response to infection by this pathogen has been well characterized, it remains unclear to what extent host gene expression during infection is the product ofChlamydia-directed modulation of host transcription factors. In this report, we show the transcriptome ofChlamydia-infected epithelial cells exhibits gene expression consistent with activity of YAP, a transcriptional coactivator implicated in cell proliferation, organ morphogenesis, wound healing, and fibrosis. After confirming induction of YAP target genes during infection, we observed increased YAP nuclear translocation inChlamydia-infected epithelial cells. We show that increased YAP activation is aChlamydia-directed process occurring during midcycle infection; critically, this phenotype is sensitive to inhibition of protein synthesis by the pathogen. Infection-mediated YAP activation bypasses YAP inhibition by the Hippo kinase cascade, instead involving YAP tyrosine phospho-activation and the activity of host Src family kinases. Taken together, our results define a mechanism forChlamydia-directed modulation of host gene expression independent of the host inflammatory response to infection, as well as introduce novel therapeutic targets for treatment of this pervasive disease.
Prioritized single-cell proteomics reveals molecular and functional polarization across primary macrophages
Authors: Huffman R Gray , Leduc Andrew , Wichmann Christoph , di Gioia Marco , Borriello Francesco , Specht Harrison , Derks Jason , Khan Saad , Khoury Luke , Emmott Edward , Petelski Aleksandra A. , Perlman David H , Cox Jürgen , Zanoni Ivan , Slavov Nikolai
Published: March 2022

Major aims of single-cell proteomics include increasing the consistency, sensitivity, and depth of protein quantification, especially for proteins and modifications of biological interest. To simultaneously advance all these aims, we developed prioritized Single Cell ProtEomics (pSCoPE). pSCoPE consistently analyzes thousands of prioritized peptides across all single cells (thus increasing data completeness) while analyzing identifiable peptides at full duty-cycle, thus increasing proteome depth. These strategies increased the sensitivity, data completeness, and proteome coverage over 2-fold. The gains enabled quantifying protein variation in untreated and lipopolysaccharide-treated primary macrophages. Within each condition, proteins covaried within functional sets, including phagosome maturation and proton transport. This protein covariation within a treatment condition was similar across the treatment conditions and coupled to phenotypic variability in endocytic activity. pSCoPE also enabled quantifying proteolytic products, suggesting a gradient of cathepsin activities within a treatment condition. pSCoPE is freely available and widely applicable, especially for analyzing proteins of interest without sacrificing proteome coverage. Support for pSCoPE is available at: scp.slavovlab.net/pSCoPE

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High-fidelity dendritic sodium spike generation in human layer 2/3 neocortical pyramidal neurons
Authors: Gooch Helen M. , Bluett Tobias , Perumal Madhusoothanan B. , Vo Hong D. , Fletcher Lee N. , Papacostas Jason , Jeffree Rosalind L. , Wood Martin , Colditz Michael J. , McMillen Jason , Tsahtsarlis Tony , Amato Damian , Campbell Robert , Gillinder Lisa , Williams Stephen R.
Published: March 2022

Dendritic computations have a central role in rodent neocortical circuit function, which are signaled into neuronal output by the initiation and propagation of regenerative dendritic spikes. However, it remains poorly explored whether these mechanisms are operational in the human neocortex. To directly examine the dendritic computational properties of the most numerous class of pyramidal neuron in the human and rat neocortex we made simultaneous electrical recordings from the soma and apical dendrites of layer 2/3 pyramidal neurons maintained in acute brain slices of analogous cortical areas under identical experimental conditions. In both species correlated dendritic excitatory input led to the initiation of sodium channel-mediated dendritic spikes with conserved biophysical properties. Dendritic sodium spikes in human and rat layer 2/3 pyramidal neurons could be generated across a similar wide input range, exhibited a similar frequency range of activation, and forward propagated with high fidelity to drive neuronal output to implement stereotyped computations. Our findings therefore reveal that the dendritic computational properties of human layer 2/3 pyramidal neurons are phylogenetically conserved.
Proteochemometric method for pIC50 prediction of Flaviviridae
Authors: Singh Divye , Mahadik Avani , Surana Shraddha , Arora Pooja
Published: March 2022

Viruses remain an area of concern despite constant development of antiviral drugs and therapies. One of the contributors among others is the flaviviridae family of viruses. Like other spaces, antiviral peptides (AVP) are gaining importance for studying flaviviridae family. Along with antiviral properties of peptides, information about bioactivity takes it even closer to accurate predictions of peptide capabilities. Experimental identification of bioactivity of each potential peptide is an expensive and time consuming task. Computational methods like Proteochemometric modelling (PCM) are promising for prediction of bioactivity based on peptide and target sequence. The additional edge PCM methods bring in is the aspect of considering both peptide and target properties instead of only looking at peptide properties. In this study, we propose prediction of pIC50 for AVP against flaviviridae family target proteins. The target proteins were manually curated from literature. Here we utilize the PCM descriptors as peptide descriptors, target descriptors and cross term descriptors. We observe taking peptide and target information improves the results qualitatively and gives better pIC50 predictions. The R2 and MAPE values are 0.85 and 8.44 % respectively