bluuebunny/crossref_metadata_2025 huggingface dataset:
SABELLARIIDAE JOHNSTON, 1865
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Sabellariidae (known as honeycomb worms or sandcastle worms) build distinctive hard tubes from glued sand or other coarse particles and are commonly seen forming colonies on rocky surfaces in intertidal marine environments (Pl. 9a).
SCALIBREGMATIDAE MALMGREN, 1867
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Scalibregmatidae (sometimes called maggot worms and one group, Travisia are not too fondly, but appropriately, called stink worms) are not routinely encountered, though they can occur in huge numbers in shallow waters in Northern Europe. More often, they occur in muddy sediments at more than 1000 m depth.
TRICHOBRANCHIDAE MALMGREN 1866
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Trichobranchidae have multiple grooved palps (‘tentacles’), often of two kinds, and resemble their close relatives Terebellidae in several ways, though Melinnidae is actually closer to Terebellidae. Historically, they have often been included within the latter taxon.
HETEROSPIO EHLERS, 1875
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Heterospio is a small group with only nine named species and no common name. Usually placed under the redundant names Longosomatidae or Heterospionidae, the systematic position of Heterospio is uncertain, though a relationship with Cirratulida is now apparent.
PARAONIDAE CERRUTI, 1909
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Paraonidae (no common name, but jesting students often call them ‘paranoids’) is a relatively small group in taxonomic terms and, because they tend to be found in deeper waters, there is little known about them.
STERNASPIDAE CARUS, 1863
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Members of Sternaspidae (from the Greek words for breast and shield) are instantly recognizable in their remarkable yellow, reddish, violet, or even black shield that lies ventro-posteriorly, and the posterior veil of branchiae.
PSAMMODRILUS SWEDMARK, 1952
Authors: Rouse Greg W. , Pleijel Fredrik , Ekin Tilic
Published: February 2022

Psammodrilus, meaning ‘sand worm’, is a group of tiny Annelida containing eight named species and several yet to be described. All live among sand grains and can be loosely regarded as interstitial taxa. To date Psammodrilus have all been described from the Northern Hemisphere, with only two records from south of the equator.
Histopathological and Immunohistochemical Characterization of Skin Biopsies From 41 SARS-CoV-2 (+) Patients: Experience in a Mexican Concentration Institute: A Case Series and Literature Review
Authors: Quintero-Bustos Gabriel , Aguilar-Leon Diana , Saeb-Lima Marcela
Published: February 2022

The SARS-CoV-2 pandemic brought countless clinical and pathophysiological questions. Although mucocutaneous infections are the most visible, they are among the least studied. This article provides relevant information to characterize morphologically and immunohistochemically the dermatoses from patients with COVID-19, during the first year of the pandemic. Immunohistochemistry reactions against the spike protein were performed in 48 skin biopsies, and the positive cases were classified according to their histomorphology; at the end, 41 biopsies led us to identify 12 morphological patterns that mimic other skin pathologies, among which pityriasiform patterns predominate. For the literature review, we selected cases of SARS-CoV-2 dermatoses that included complete histopathological information and that were published during the same interval of time; after careful evaluation, 205 biopsies were selected and then classified into 8 groups according to previously published proposals. Dermatoses associated with SARS-CoV-2 are as diverse in their clinical expression as in their histopathology, mimicking entities totally unrelated to COVID-19. Furthermore, some of these groups are characteristically associated with an aggressive course of the disease. Undoubtedly, it is necessary to delve into the possibility that these findings are translatable into prognostic and therapeutic factors.
Postcolonoscopy Complications
Authors: Rodriguez-Silva Jetsen A. , Maykel Justin A.
Published: February 2022

CASE SUMMARY:

A 62-year-old woman presents for her first screening colonoscopy as recommended by her primary care physician after an initial health maintenance examination to establish care. A 1-cm sessile polyp was found in the cecum during the colonoscopy, which was resected using hot snare polypectomy. After appropriate postprocedure recovery, the patient was sent home and presented 12 hours later to the emergency department with severe abdominal pain.
Intravenous to Oral Transition of Amiodarone (IOTA): Effect of Various Durations of Overlap on Atrial Fibrillation Recurrence After Cardiothoracic Surgery
Authors: Lam Jade C. , Stevenson Byron , Lee Yong Gu , Maurer Jennifer , Patanwala Asad E. , Radosevich John J.
Published: February 2022

The use of amiodarone for postoperative atrial fibrillation (AF) is widespread; however, there is a paucity of data on the optimal duration of overlap when transitioning from intravenous (IV) to oral amiodarone. The objective of this study was to evaluate the safety and efficacy of varying durations of overlap when amiodarone IV infusion is transitioned to oral administration in cardiothoracic surgery patients. This retrospective, observational, single-center study included cardiothoracic surgery patients who were initiated on IV amiodarone for supraventricular arrhythmia and subsequently transitioned to oral amiodarone. The primary outcome was AF recurrence within 24 hours after IV amiodarone discontinuation. Safety outcomes include occurrence of bradycardia or hypotension while on amiodarone. A total of 184 patients were included for analysis. AF recurrence occurred in 24.5% of patients (n = 45). No significant association was found between various overlap durations and AF recurrence (odds ratio (OR) 1.00, 95% CI 1.00–1.01, P = 0.9). In addition, no significant association was found between duration of overlap and rates of bradycardia (OR 1.00, 95% confidence interval (CI) 0.99–1.00, P = 0.08) or hypotension (OR 1.00, 95% CI 0.99–1.00, P = 0.21), which occurred in 35.9% and 47.3% of patients, respectively. Our study suggests following conversion to normal sinus rhythm; cardiothoracic surgery patients can effectively and safely be transitioned from IV to oral amiodarone without the need for specific overlap duration or transition strategy.
Repeatability of a Scheimpflug tonometer to measure biomechanical parameters before and after myopic refractive surgery
Authors: Lu Nan-Ji , Hafezi Farhad , Rozema Jos J. , Hillen Mark , Hafezi Nikki , Zhang Jia , Koppen Carina
Published: February 2022

Purpose:

To assess the repeatability of several corneal biomechanical parameters with a Scheimpflug tonometer (Corvis ST) in myopic eyes and eyes that underwent transepithelial photorefractive keratectomy (transPRK), small-incision lenticule extraction (SMILE), or femtosecond laser–assisted in situ keratomileusis (FS-LASIK) surgery.

Setting:

Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Design:

Prospective randomized controlled study.

Methods:

315 eyes from 315 patients (135 myopes, 58 post-transPRK, 52 post-SMILE, and 70 post–FS-LASIK) were included. 3 consecutive scans were performed to evaluate the repeatability of the 40 parameters examined.

Results:

315 eyes were included. In all eyes, the coefficient of variation (CoV) for intraocular pressure (IOP) and biomechanical-corrected IOP (bIOP) ranged from 7.29% to 9.47% and 6.11% to 7.75%, respectively; the CoV of pachymetry was <0.8%. The intraclass correlation coefficient of Corvis Biomechanical Index-Laser Vision Correction (LVC) was 0.680 for post-transPRK, 0.978 for post-SMILE, and 0.911 for post–FS-LASIK. The CoV of Stress–Strain Index (SSI) was 204.93% for post-transPRK, 91.92% for post-SMILE, and 171.72% for post–FS-LASIK. The CoV of the 6 clinically important dynamic corneal response parameters ranged from 2.0% to 7.8% for myopia, 1.8% to 11.1% for post-transPRK, 2.1% to 8.7% for post-SMILE, and 1.8% to 8.8% for post–FS-LASIK.

Conclusions:

Excellent intrameasurement repeatability of IOP, bIOP, and pachymetry was observed in all groups; SSI measurement in post-LVC corneas displayed more variation. Caution is warranted when assessing SSI in post-LVC corneas for the purpose of diagnosing iatrogenic ectasia or evaluating biomechanical remodeling of postoperative refractive corneas.
Intraoperative adjustment of implantable collamer lens vault by lens rotation aided by intraoperative OCT
Authors: Zaldivar Roberto , Zaldivar Roger , Adamek Pablo , Cerviño Alejandro
Published: February 2022

Purpose:

To assess the use of intraoperative optical coherence tomography (OCT) to detect high vault during implantation surgery and guide intraoperative vault adjustment by implantable collamer lens (ICL) rotation.

Setting:

Instituto Zaldivar SA. Mendoza, Argentina.

Design:

Prospective single-arm observational study.

Methods:

25 eyes of 25 consecutive patients showing high intraoperative vault who had undergone ICL rotation from horizontal to vertical or oblique position were evaluated. Central ICL vault was measured both intraoperatively using the microscope-integrated iOCT mounted on a standard surgical microscope (HS Hi-R NEO 900A NIR) and postoperatively using the Casia 2 swept-source OCT at 4 hours, 1 day, and 1 month.

Results:

25 eyes of 25 consecutive patients showing high intraoperative vault who had undergone ICL rotation from horizontal to vertical or oblique position were evaluated. The mean vault value obtained intraoperatively was 1147.88 ± 188.36 μm and changed significantly to 739.76 ± 194.97 μm after lens rotation to either vertical (n = 19, 76% of cases) or oblique (n = 6, 24% of cases) positions (mean difference 408.12 ± 213.57 μm, P < .001). The amount of change due to lens rotation was significantly correlated with white-to-white distance (r = −0.480, P = .015) and vault before rotation (r = −0.564, P = .003). The mean vault values were 758.40 ± 187.10 μm, 729.73 ± 227.86 μm, and 661.88 ± 275.17 μm at 4 hours, 24 hours, and 1 month postsurgery, respectively.

Conclusions:

Intraoperative adjustment of ICL vault by lens rotation using intraoperative OCT was an effective procedure to obtain an optimal vault.
Antivertiginous Effect of Caloric Stimulation for Acute Peripheral Vertigo
Authors: Fukushima Munehisa , Makino Saho , Matsumoto Ken , Okamoto Hidehiko , Akahani Shiro , Imai Takao , Inohara Hidenori
Published: February 2022

Objective:

To clarify therapeutic effect of caloric stimulation for acute peripheral vertigo.

Patients:

Two patients with acute peripheral vertigo accompanied by spontaneous nystagmus.

Interventions:

Therapeutic.

Main Outcomes and Measures:

Changes in the maximum slow phase velocity of spontaneous nystagmus and subjective vertigo.

Results:

Reduction in the maximum slow phase velocity of spontaneous nystagmus and mitigation of subjective vertigo was observed in both patients.

Conclusion:

Caloric stimulation could be one potential option as a suppressant for acute peripheral vertigo.
The neurologic pain signature responds to nonsteroidal anti-inflammatory treatment vs placebo in knee osteoarthritis
Authors: López-Solà Marina , Pujol Jesus , Monfort Jordi , Deus Joan , Blanco-Hinojo Laura , Harrison Ben J. , Wager Tor D.
Published: February 2022

Introduction:

Many drug trials for chronic pain fail because of high placebo response rates in primary endpoints. Neurophysiological measures can help identify pain-linked pathophysiology and treatment mechanisms. They can also help guide early stop/go decisions, particularly if they respond to verum treatment but not placebo. The neurologic pain signature (NPS), an fMRI-based measure that tracks evoked pain in 40 published samples and is insensitive to placebo in healthy adults, provides a potentially useful neurophysiological measure linked to nociceptive pain.

Objectives:

This study aims to validate the NPS in knee osteoarthritis (OA) patients and test the effects of naproxen on this signature.

Methods:

In 2 studies (50 patients, 64.6 years, 75% females), we (1) test the NPS and other control signatures related to negative emotion in knee OA pain patients; (2) test the effect of placebo treatments; and (3) test the effect of naproxen, a routinely prescribed nonsteroidal anti-inflammatory drug in OA.

Results:

The NPS was activated during knee pain in OA (d = 1.51, P < 0.001) and did not respond to placebo (d = 0.12, P = 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d = 0.34, P = 0.03 and pronociceptive NPS component d = 0.38, P = 0.02). Naproxen effects were specific for the NPS and did not appear in other control signatures.

Conclusion:

This study provides preliminary evidence that fMRI-based measures, validated for nociceptive pain, respond to acute OA pain, do not appear sensitive to placebo, and are mild-to-moderately sensitive to naproxen.
An online mental health informed physical activity intervention for emergency service workers and their families: A stepped-wedge trial
Authors: McKeon Grace , Wells Ruth , Steel Zachary , Hadzi-Pavlovic Dusan , Teasdale Scott , Vancampfort Davy , Rosenbaum Simon
Published: February 2022

Objective

Emergency service workers are at risk of experiencing poor mental health due to repeated exposure to potentially traumatic events. Promoting physical activity and diet may help to mitigate some the consequences of emergency work and so this study aimed to evaluate the impact a lifestyle intervention on levels of psychological distress among emergency service workers and their support partners.

Methods

We delivered a 10-week physical activity intervention via a private Facebook group facilitated by exercise physiologists, a dietitian and peer-facilitators. Weekly education modules and telehealth calls were delivered, and participants were provided with a physical activity tracking device. A stepped-wedge design was applied to compare levels of psychological distress (Kessler-6) during baseline, to intervention by comparing slopes of change. Secondary pre-post outcomes included mental health symptoms, physical activity, quality of life, social support to exercise, sleep quality and suicidal ideation.

Results

N=90 participants (n=47 emergency service workers and n=43 support partners) were recruited in 4 separate cohorts (mean age 42.3(SD=11.5) years, 51% male). Levels of psychological distress did not change significantly during the baseline (control) slope and reduced significantly during the first 6 weeks of intervention (intervention slope 1). The interaction between slopes were significant, b=-0.351, p = 0.003, (i.e., the trajectories of change were significantly different) and improvements plateaued until the 4-week follow-up. Retention was high (92%) and improvements in mental health symptoms, minutes of physical activity, sedentary time and quality of life were observed.

Conclusions

A physical activity intervention delivered via social media is effective in improving psychological distress among emergency service workers and support partners.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN): 12619000877189.
Supporting first FSH dosage for ovarian stimulation with Machine Learning
Authors: Correa N. , Cerquides J. , Arcos J.L. , Vassena R.
Published: February 2022

Research question

Is it possible to identify accurately the optimal first dose of FSH in controlled ovarian stimulation (COS) by means of a machine learning (ML) model?

Design

Observational study (2011 to 2021) including first In Vitro Fertilization (IVF) cycles with own oocytes. 2713 patients from five private reproductive centers were included in the development phase of the model (2011 to 2019), and 774 in the validation phase (2020 to 2021). Predictor variables included: age, Body Mass Index (BMI), Antimullerian Hormone (AMH), Antral Follicle Count (AFC), and previous live births. Performance of the developed model was measured with a proposed score based on the number of MII retrieved and the dose received and/or recommended.

Results

The cycles included were from women 37.2±4.9 years old [18-45], with a BMI of 23.7±4.2, AMH of 2.4±2.3, AFC of 11.8±7.7; and an average number of MII obtained 7.2±5.3. The model reached a mean performance score of 0.87 (95% CI 0.86 to 0.88) in the development phase; this value was significantly better than the one for the doses prescribed by the clinicians for the same patients (0.83 [0.82, 0.84]; p-value= 2.44 e-10). The mean performance score of the model recommendations was 0.89 (95% CI 0.88 to 0.90) in the validation phase, also significantly better than clinicians (0.84 [0.82, 0.86]; p-value = 3.81 e-05). With these results the model was shown to surpass the performance of the standard practice.

Conclusion(s)

The ML model developed could be deployed as a training and learning tool for new clinicians and serve as quality control for experienced ones; further, it could be used as second opinion, for instance by providing information in peer-to-peer case discussions.

Key Message

A Machine Learning model was trained to recommend first FSH doses for ovarian stimulation. When compared to clinicians the model developed had consistently better performance scores. The model could be used as a second opinion and as learning tool for new clinicians; to avoid as many non-optimal outcomes as possible.
Reward Responsiveness across Autism and Autistic Traits – Evidence from Neuronal, Autonomic, and Behavioural Levels
Authors: Matyjek Magdalena , Bayer Mareike , Dziobek Isabel
Published: February 2022

Atypicalities in processing of social rewards have been suggested to lie at the root of social difficulties in autism spectrum conditions (ASC). While evidence for atypical reward function in ASC is mounting, it remains unclear whether it manifests specifically in hypo- or hyper-responsiveness, and whether it appears only in the social domain or more generally. Moreover, stimuli used as social rewards in studies often lack familiarity and relevance, which are known to enhance reward-related responses. In this study, we investigated behavioural (reaction times and ratings), neuronal (event-related potentials), and autonomic (pupil sizes) responses to three conditions – relevant social rewards, money, and neutral informative outcomes – in 26 ASC and 53 non-autistic subjects varying in levels of autistic traits, as measured with the Autism Spectrum Quotient (AQ). We used both a population-based approach (low AQ vs. high AQ) and a psychopathological approach (low AQ vs. ASC) to investigate the effects of both sub-clinical and clinical autistic traits on reward responsiveness. As hypothesised and preregistered, autism and autistic traits did not differently influence responses to social, monetary, and neutral outcomes on behavioural, neuronal or autonomic level. Although the ASC group rated the stimuli’s motivational and rewarding values lower than the other groups, the task performance was similar for all participants. Moreover, the ASC group in contrast to low AQ group showed enhanced brain responses (the CNV) in early anticipation and larger pupil constrictions in reward reception. Both effects were also predicted by autistic traits (AQ). Together, our results do not offer evidence for specifically social reward deficits in ASC. Instead, the data suggest enhanced neuronal and autonomic reward responsiveness linked to autism with simultaneously typical performance and reduced self-reported motivational and rewarding values of stimuli. Together, these results emphasise the need to investigate multiple processing levels for a broader picture of reward responsiveness in ASC.
Single-cell Bayesian deconvolution
Authors: Torregrosa Gabriel , Oriola David , Trivedi Vikas , Garcia-Ojalvo Jordi
Published: February 2022

Individual cells exhibit substantial heterogeneity in protein abundance and activity, which is frequently reflected in broad distributions of fluorescently labeled reporters. Since all cellular components are intrinsically fluorescent to some extent, the observed distributions contain background noise that masks the natural heterogeneity of cellular populations. This limits our ability to characterize cell-fate decision processes that are key for development, immune response, tissue homeostasis, and many other biological functions. It is therefore important to separate the contributions from signal and noise in single-cell measurements. Addressing this issue rigorously requires deconvolving the noise distribution from the signal, but approaches in that direction are still limited. Here we present a non-parametric Bayesian formalism that performs such a deconvolution efficiently on multidimensional measurements, in a way that allows us to estimate confidence intervals. We use the approach to study the expression of the mesodermal transcription factor Brachyury in mouse embryonic stem cells undergoing differentiation.
Experimental and analytical framework for “mix-and-read” assays based on split luciferase
Authors: McArthur Nikki , Cruz-Teran Carlos , Thatavarty Apoorva , Reeves Gregory T. , Rao Balaji M.
Published: February 2022

The use of immunodetection assays including the widely used enzyme-linked immunosorbent assay (ELISA) in applications such as point-of-care detection is often limited by the need for protein immobilization and multiple binding and washing steps. Here, we describe an experimental and analytical framework for the development of simple and modular “mix-and-read” enzymatic complementation assays based on split luciferase that enable sensitive detection and quantification of analytes in solution. In this assay, two engineered protein binders targeting non-overlapping epitopes on the target analyte were each fused to non-active fragments of luciferase to create biosensor probes. Binding proteins to two model targets, lysozyme and Sso6904, were isolated from a combinatorial library of Sso7d mutants using yeast surface display. In the presence of the analyte, probes were brought into close proximity, reconstituting enzymatic activity of luciferase and enabling detection of low picomolar concentrations of the analyte by chemiluminescence. Subsequently, we constructed an equilibrium binding model that relates binding affinities of the binding proteins for the target, assay parameters such as the concentrations of probes used, and assay performance (limit of detection and concentration range over which the target can be quantified). Overall, our experimental and analytical framework provide the foundation for the development of split luciferase assays for detection and quantification of various targets.
Diversity begets diversity under microbial niche construction
Authors: Estrela Sylvie , Diaz-Colunga Juan , Vila Jean C.C. , Sanchez-Gorostiaga Alicia , Sanchez Alvaro
Published: February 2022

Microbial interactions are expected to modulate microbial diversity, but whether they inhibit or stimulate further diversity in complex microbial communities, and how, remains poorly understood. By assembling microbial communities in multiple identical habitats with a single limiting nutrient, here we provide direct evidence for the role of microbial niche construction and cross-feeding in driving a positive relationship between community diversity and focal lineage diversity in microbial communities. Combining these experiments with simulations, we show that this positive relationship is not inevitable but depends on the underlying metabolic structure of by-product secretions and uptake between different taxonomic levels.
scShapes: A statistical framework for identifying distribution shapes in single-cell RNA-sequencing data
Authors: Dharmaratne Malindrie , Kulkarni Ameya S , Fard Atefeh Taherian , Mar Jessica C
Published: February 2022

Background

Single cell RNA sequencing (scRNA-seq) methods have been advantageous for quantifying cell-to-cell variation by profiling the transcriptomes of individual cells. For scRNA-seq data, variability in gene expression reflects the degree of variation in gene expression from one cell to another. Analyses that focus on cell-cell variability therefore are useful for going beyond changes based on average expression and instead, identifying genes with homogenous expression versus those that vary widely from cell to cell.

Results

We present a novel statistical framework scShapes for identifying differential distributions in single-cell RNA-sequencing data using generalized linear models. Most approaches for differential gene expression detect shifts in the mean value. However, as single cell data are driven by over-dispersion and dropouts, moving beyond means and using distributions that can handle excess zeros is critical. scShapes quantifies gene-specific cell-to-cell variability by testing for differences in the expression distribution while flexibly adjusting for covariates if required. We demonstrate that scShapes identifies subtle variations that are independent of altered mean expression and detects biologically-relevant genes that were not discovered through standard approaches.

Conclusions

This analysis also draws attention to genes that switch distribution shapes from a unimodal distribution to a zero-inflated distribution and raises open questions about the plausible biological mechanisms that may give rise to this, such as transcriptional bursting. Overall, the results from scShapes helps to expand our understanding of the role that gene expression plays in the transcriptional regulation of a specific perturbation or cellular phenotype. Our framework scShapes is incorporated into Bioconductor R package (https://github.com/Malindrie/scShapes).
Patterns of Polysubstance use among Adults in Malaysia – A Latent Class Analysis
Authors: Wan Shakira R.H , Tania Gyle R. L , Shubash S. G , Nur Liana A.M , Muhammad Fadhli MY
Published: February 2022

Introduction

Polysubstance use is the use of more than one non-prescribed licit or illicit substance at one time. This is a common phenomenon, but little is known about the severity and the various substances used by adults in Malaysia.

Objective

To determine the pattern of polysubstance use and its associated factors among general adults in Malaysia.

Methodology

This was a secondary data analysis from the National Health and Morbidity Survey (NHMS) 2019), a cross-sectional population survey with a two-stage stratified random sampling design. A total of 10,472 Malaysians aged 18 years and above participated in this survey. Polysubstance use was defined as concurrent use of more than one substance, either alcohol, tobacco, or drugs (opioid, marijuana, amphetamine/ methamphetamine or kratom). A latent class analysis (LCA) was used to identify the membership of polysubstance groups. The association of class membership with demographic profiles was examined using Multinomial Logistic Regression analysis.

Results

Fit indices (AIC =16458.9, BIC = 16443.6) from LCA supported 3 classes solution: i) Combination of tobacco and alcohol (Tob+Alc) use (2.4%), ii) multi-drug use including kratom (0.3%) and iii) non/negligible user (97.3%). The multinomial model showed young adults (18-40 years) had a higher likelihood of being polysubstance users both for Tob+Alc class (OR=4.1) and multi-drug class (OR=3.9) compared to older age (≥60 years). Chinese (OR = 18.9), Indian (OR =23.3), Indigenous Sabah & Sarawak (OR =34.6) and others ethnicity (OR =8.9) showed higher odds of being Tob+Alc users than Malays. The greater odds of Tob+Alc. use for male (OR =35.5), working group (OR =1.5) and low education level group (OR=3.2).

Conclusion

Our study highlights patterns and demographics related to the use of polysubstance among adults in Malaysia. These results would help formulate specific prevention programmes for these high risk groups.
Interpretation of southern hemisphere humpback whale diet via stable isotopes; implications of tissue-specific analysis
Authors: Eggebo June , Groβ Jasmin , Bengtson Nash Susan
Published: February 2022

Blubber and skin are commonly used tissues in stable isotope analysis for the purpose of investigating cetacean diet. Critical comparison of tissue-specific isotopic signals is, however, lacking resulting in uncertainty surrounding the representativeness and therefore utility of different tissues for accurate determination of recent foraging. This study used remotely biopsied blubber and skin tissues from southern hemisphere humpback whales for strategic comparison of δ13C and δ15N values. Samples were collected 2008-2018 as part of long-term monitoring under the Humpback Whale Sentinel Program. Blubber tissues were lipid-extracted prior to analysis, whilst mathematical lipid-correction was performed on skin samples. Isotopic values from paired blubber and skin samples from the same individuals were compared to assess whether tissues could be used interchangeably for isotope analysis and dietary interpretation. Significant differences were observed for both δ13C and δ15N, flagging previously undocumented methodological considerations, and the need for method validation and standardisation in application of these approaches. This study therefore advances methodological aspects of cetacean dietary analysis. This is of elevated importance in the context of rapidly changing ocean ecosystems.
uniPort: a unified computational framework for single-cell data integration with optimal transport
Authors: Cao Kai , Gong Qiyu , Hong Yiguang , Wan Lin
Published: February 2022

Single-cell data integration can provide a comprehensive molecular view of cells. Here we introduce uniPort, a unified single-cell data integration framework which combines a coupled Variational Autoencoder (coupled-VAE) and Minibatch Unbalanced Optimal Transport (Minibatch-UOT). It leverages both highly variable common and dataset-specific genes for integration and is scalable to large-scale and partially overlapping datasets. uniPort jointly embeds heterogeneous single-cell multi-omics datasets into a shared latent space. It can further construct a reference atlas for online prediction across datasets. Meanwhile, uniPort provides a flexible label transfer framework to deconvolute spatial heterogeneous data using optimal transport space, instead of embedding latent space. We demonstrate the capability of uniPort by integrating a variety of datasets, including single-cell transcriptomics, chromatin accessibility and spatially resolved transcriptome data. uniPort software is available athttps://github.com/caokai1073/uniPort.
Lung evolution in vertebrates and the water-to-land transition
Authors: Cupello Camila , Hirasawa Tatsuya , Tatsumi Norifumi , Yabumoto Yoshitaka , Gueriau Pierre , Isogai Sumio , Matsumoto Ryoko , Saruwatari Toshiro , King Andrew , Hoshino Masato , Uesugi Kentaro , Okabe Masataka , Brito Paulo M.
Published: February 2022

A crucial evolutionary change in vertebrate history was the Palaeozoic (Devonian ~400 million years ago) water-to-land transition, allowed by key morphological and physiological modifications including the acquisition of lungs. Nonetheless, the origin and early evolution of vertebrate lungs remain highly controversial, particularly whether the ancestral state was paired or unpaired. Due to the rarity of fossil soft tissue preservation, lung evolution can only be traced based on the extant phylogenetic bracket. Here we investigate, for the first time, lung morphology in extensive developmental series of key living lunged osteichthyans using synchrotron X-ray microtomography and histology. Our results shed light on the primitive state of vertebrate lungs as unpaired, evolving to be truly paired in the lineage towards the tetrapods. The water-to-land transition confronted profound physiological challenges and paired lungs were decisive for increasing the surface area and the pulmonary compliance and volume, especially during the air-breathing on land.
The exchange rates of amide and arginine guanidinium CEST in the mouse brain
Authors: Wang Kexin , Sui Ran , Chen Lin , Li Yuguo , Xu Jiadi
Published: February 2022

Purpose

To develop a pipeline for measuring the exchange rates and concentrations of in vivo excgangeable protons, and to demonstrate this for the amide and arginine (Arg) guanidinium (Guan) protons in mobile proteins in the mouse brain.

Methods

An ultra-short echo (UTE) CEST sequence with a continuous wave presaturation (preRadCEST) was applied to acquire Z-spectra with robustness to motion and physiological fluctuations. AmideCEST and Arginine guanCEST (ArgCEST) were extracted and their proton concentrations and exchange rates obtained using a two-step multi-B1Bloch fitting approach that included the semisolid macromolecular background. To minimize contamination from the amine protons from creatine and phosphocreatine, ArgCEST measurements were performed on the Guanidinoacetate N-methyltransferase deficiency (GAMT-/-) mouse characterized by low creatine and phosphocreatine concentrations in the brain.

Results

For the amideCEST proton pool, the exchange rate and concentrations were found to be 59.6 ± 9.0 s-1and 41.7 ± 7.0 mM, respectively, with the maximum signal observed at B1= 0.8 μT. For the ArgCEST proton, the guanidinium exchange these were 70.1 ± 5.5 s-1and 10.1 ± 1.3 mM, respectively, with the maximum effect observed at B1= 0.9 μT. The current study suggests that the inverse pH dependence in GuanCEST of brain is led by the CrCEST component, not ArgCEST.

Conclusion

The current pipeline is expected to have general use forin vivoCEST quantitation and optimization of visible CEST resonances.
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Authors: Farley Scotland E. , Kyle Jennifer E. , Leier Hans C. , Bramer Lisa M. , Weinstein Jules , Bates Timothy A. , Lee Joon-Yong , Metz Thomas O. , Schultz Carsten , Tafesse Fikadu G.
Published: February 2022

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. We mapped alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We found that SARS-CoV-2 rewires host lipid metabolism, altering 409 lipid species up to 64-fold relative to controls. We correlated these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We found that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We found that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.
Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 –tubulin complex
Authors: Taguchi Shinya , Nakano Juri , Imasaki Tsuyoshi , Kita Tomoki , Saijo-Hamano Yumiko , Sakai Naoki , Shigematsu Hideki , Okuma Hiromichi , Shimizu Takahiro , Nitta Eriko , Kikkawa Satoshi , Mizobuchi Satoshi , Niwa Shinsuke , Nitta Ryo
Published: February 2022

Kinesin superfamily proteins are microtubule-based molecular motors driven by the energy of ATP hydrolysis. Among them, the kinesin-4 family is a unique motor that inhibits microtubule dynamics. Although mutations of kinesin-4 cause several diseases, its molecular mechanism is unclear because of the difficulty of visualizing the high-resolution structure of kinesin-4 working at the microtubule plus-end. Here, we report that KLP-12, a C. elegans kinesin-4 ortholog of KIF21A and KIF21B, is essential for proper length control of C. elegans axons, and its motor domain represses microtubule polymerization in vitro. The crystal structure of the KLP-12 motor domain complexed with tubulin, which represents the high-resolution structural snapshot of inhibition state of microtubule-end dynamics, revealed the bending effect of KLP-12 for tubulin. Comparison with the KIF5B-tubulin and KIF2C-tubulin complexes, which represent the elongation and shrinking forms of microtubule ends, respectively, showed the curvature of tubulin introduced by KLP-12 is in between them. Taken together, KLP-12 controls the proper length of axons by modulating the curvature of the microtubule ends to inhibit the microtubule dynamics.
Strong phylogenetic and ecological effects on host competency for avian influenza in Australian wild birds
Authors: Wille Michelle , Lisovski Simeon , Roshier David , Ferenczi Marta , Hoye Bethany J. , Leen Trent , Warner Simone , Fouchier Ron A. M. , Hurt Aeron C. , Holmes Edward C. , Klaassen Marcel
Published: February 2022

Host susceptibility to parasites is mediated by intrinsic and external factors such as genetics, age or season. While key features have been revealed for avian influenza A virus (AIV) in waterfowl of the Northern Hemisphere, the role of host phylogeny has received limited attention. Herein, we analysed 12339 oropharyngeal and cloacal swabs and 10826 serum samples collected over 11 years from wild birds in Australia. As well as describing species-level differences in prevalence and seroprevalence, we reveal that host phylogeny is a key driver in susceptibility. We confirm the role of age in AIV seroprevalence and viral prevalence. Seasonality effects appear less pronounced than in the Northern Hemisphere, while annual variations are potentially linked to El Niño– Southern Oscillation. Taken together, our study provides new insights into evolutionary ecology of AIV in its avian hosts, defining distinctive processes on the continent of Australia and expanding our understanding of AIV globally.
4th Dose COVID mRNA Vaccines’ Immunogenicity & Efficacy Against Omicron VOC
Authors: Regev-Yochay Gili , Gonen Tal , Gilboa Mayan , Mandelboim Michal , Indenbaum Victoria , Amit Sharon , Meltzer Lilac , Asraf Keren , Cohen Carmit , Fluss Ronen , Biber Asaf , Nemet Ital , Kliker Limor , Joseph Gili , Doolman Ram , Mendelson Ella , Freedman Laurence S. , Harats Dror , Kreiss Yitshak , Lustig Yaniv
Published: February 2022

BACKGROUND

Following the emergence of the Omicron variant of concern, we investigated immunogenicity, efficacy and safety of BNT162b2 or mRNA1273 fourth dose in an open-label, clinical intervention trial.

METHODS

Primary end-points were safety and immunogenicity and secondary end-points were vaccine efficacy in preventing SARS-CoV-2 infections and COVID-19 symptomatic disease. The two intervention arms were compared to a matched control group. Eligible participants were healthcare-workers (HCW) vaccinated with three BNT162b2 doses, and whose IgG antibody levels were ≤700 BAU (40-percentile). IgG and neutralizing titers, direct neutralization of live VOCs, and T-cell activation were assessed. All participants were actively screened for SARS-CoV-2 infections on a weekly basis.

RESULTS

Of 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ∼9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively.

CONCLUSIONS

The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development.

Trial registration number

clicaltrials.gov: NCT05231005, NCT05230953
Urinary collagen-derived peptides as sensitive markers for bone resorption and bisphosphonate treatment in kidney transplant patients
Authors: Marx David , Anglicheau Dany , Caillard Sophie , Moulin Bruno , Kochman Audrey , Mischak Harald , Pejchinowski Martin , Latosinska Agnieszka , Bienaimé Frank , Prié Dominique , Marquet Pierre , Perrin Peggy , Gwinner Wilfried , Metzger Jochen
Published: February 2022

Kidney transplant recipients (KTR) are at increased risk of fractures. Total urinary hydroxyproline excretion used to be a marker for bone resorption (BR) but faded into the background when more specific markers like Beta-CrossLaps (CTX) became available. Proteomic studies identified numerous hydroxyproline-containing urinary collagen peptides but their origin remains unknown. We followed the hypothesis that some of the urinary collagen peptides are associated with BR and are markers for pathophysiological changes in bone metabolism of KTR. Clinical and laboratory data including serum levels of CTX in 96 KTR from two French centers (Strasbourg, n=38; Paris-Necker, n=58) were correlated with the signal intensity of urinary peptides identified by capillary electrophoresis (CE) coupled to mass spectrometry (MS) and tandem-MS. The effect of oral bisphosphonates on urinary peptides was studied in an independent group of 11 KTR. Eighty-two urinary peptides were identified to be significantly correlated with serum CTX levels in both cohorts. Statistical association with parameters other than BR markers were not significant. Collagen α-1(I) chain (COL1A1) was the most frequently identified peptide source. COL1A1 peptides associated with BR were significantly more hydroxylated than those showing no association (55.9% versus 45,2%, p<0.0003 by a χ2-test). From the 82 urinary peptides correlated to CTX, 17 were significantly associated with bisphosphonate treatment. All of these 17 peptides showed a marked reduction in their excretion levels after 410 ± 344 days of bisphosphonate treatment compared to baseline levels. We studied the cleavage sites of these COL1A1 peptides and observed a signature of Cathepsin K and Matrix Metallopeptidase 9. This study provides strong evidence for the occurrence of collagen peptides in the urine of KTR that are associated with BR and that are sensitive to bisphosphonate treatment. Their assessment might become a valuable tool to monitor bone status in KTR.
Leveraging genetics to improve Body Mass Index increase prediction in the first-episode of psychosis
Authors: Muntané Gerard , Vázquez-Bourgon Javier , Sada Ester , Martorell Lourdes , Papiol Sergi , Bosch Elena , Navarro Arcadi , Crespo-Facorro Benedicto , Vilella Elisabet
Published: February 2022

Background

Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with reduction in psychiatric and physical health. Although genetics is assumed to be a significant contributor to this weight gain, its exact role is unknown.

Methods

Reference GWAS from BMI and SCZ were obtained to evaluate the pleiotropic landscape between both traits using the pleioFDR software. In parallel, we gathered a population-based FEP cohort of 381 individuals and BMI Polygenic risk-scores (PRS) were evaluated on a sample of 224 individuals. Subsequently, the PRSs obtained from both BMI and the variants shared between the two traits were incorporated into risk models that included demographic and clinical variable to predict BMI increase (ΔBMI) on an independent sample of 157 patients.

Results

BMI PRS significantly improved the prediction of absolute BMI and ΔBMI during the first 12 months after the onset of psychotic symptoms. This improvement, was mainly explained by shared variants between SCZ and BMI. In contrast, absolute BMI was predicted mainly by non-shared variants.

Conclusions

We validated, for the first time, that genetic factors play a key in the determination of both BMI and ΔBMI in FEP. This finding has important clinical implications in identifying individuals who require specific treatment strategies. Improved risk classification may help prevent associated adverse metabolic events, and reduce overtreatment and costs for both individuals and the healthcare system. It also highlights the importance of studying genetic pleiotropy in the context of medically important comorbidities.
BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models
Authors: Park Su Mi , Roache Cooper E. , Iffland Philip H. , Moldenhauer Hans J. , Matychak Katia K. , Plante Amber E. , Lieberman Abby G. , Crino Peter B. , Meredith Andrea L.
Published: February 2022

KCNMA1 forms the pore of BK K+ channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous KCNMA1 variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of KCNMA1 mutations and the basis for clinical heterogeneity in PNKD3 has not been established. Here we evaluate the relative severity of three KCNMA1 patient variants in BK channels, neurons, and mice. In heterologous cells, BKN999S and BKD434G channels displayed gain-of-function (GOF) properties, whereas BKH444Q channels showed loss-of-function (LOF) properties. The relative degree of channel activity was BKN999S > BKD434G > WT > BKH444Q. BK currents and action potential firing were increased, and seizure thresholds decreased, in Kcnma1N999S/WT and Kcnma1D434G/WT transgenic mice but not Kcnma1H444Q/WT mice. In a novel behavioral test for paroxysmal dyskinesia, the more severely affected Kcnma1N999S/WT mice became immobile after stress, consistent with stress-induced immobility episodes observed in PNKD3-affected individuals. Homozygous Kcnma1D434G/D434G mice showed similar immobility, but in contrast, homozygous Kcnma1H444Q/H444Q mice displayed hyperkinetic behavior. These data establish the relative pathogenic potential of patient alleles as N999S > D434G > H444Q and validate Kcnma1N999S/WT mice as a model for PNKD3 with increased seizure propensity.
Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling
Authors: Agarwal Rupesh , Pi Min , Ye Ruisong , Smith Micholas Dean , Smith Jeremy C. , Quarles L. Darryl
Published: February 2022

GPRC6A is a member of the Family C G-protein coupled receptors that is activated by cations, L-amino acids, the osteocalcin (Ocn) peptide, and testosterone. GPRC6A functions as a master regulator of energy metabolism and sex hormone production. Based on homology to the related receptors mGluR5 and CaSR, GPRC6A’s multiple ligand specificity is likely based on an orthosteric ligand binding site in the bilobed Venus fly trap (VFT) domain together with two positive allosteric modulator (PAM) sites, one in the VFT and the other in the 7TM domain. Here, we show that Ocn acts as a PAM for GPRC6A by binding to a site in the VFT that is distinct from the orthosteric site for calcium and L-amino acids. In agreement with this finding, alternatively spliced GPRC6A isoforms 2 and 3, which lack regions of the VFT, and mutations in the predicted Ocn binding site, K352E and H355P, prevent Ocn activation of GPRC6A. These observations provide a structural framework for understanding the ability of multiple distinct classes of compounds to activate GPRC6A and set the stage to develop novel small molecules to activate and inhibit this receptor.