bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of computed tomography findings for hollow viscus injuries following thoracoabdominal gunshot wounds
Authors: Lian Tiffany , Ashbrook Matthew , Myers Lee , Chiba Hiroto , Ghafil Cameron , Silverstein Madeleine , Lee Eugenia , Inaba Kenji , Matsushima Kazuhide
Published: July 2022

BACKGROUND

Selective nonoperative management (SNOM) of abdominal gunshot wounds (GSWs) is increasingly used as computed tomography (CT) has become a diagnostic adjunct for the evaluation of intraabdominal injuries including hollow viscus injuries (HVIs). Currently, there is scarce data on the diagnostic accuracy of CT for identifying HVI. The purpose of this study was to determine the diagnostic accuracy of different CT findings in the diagnosis of HVI following abdominal GSW.

METHODS

This retrospective single-center cohort study was performed from January 2015 to April 2019. We included consecutive patients (≥18 years) with abdominal GSW for whom SNOM was attempted and an abdominal CT was obtained as a part of SNOM. Computed tomography findings including abdominal free fluid, diffuse abdominal free air, focal gastrointestinal wall thickness, wall irregularity, abnormal wall enhancement, fat stranding, and mural defect were used as our index tests. Outcomes were determined by the presence of HVI during laparotomy and test performance characteristics were analyzed.

RESULTS

Among the 212 patients included for final analysis (median age: 28 years), 43 patients (20.3%) underwent a laparotomy with HVI confirmed intraoperatively whereas 169 patients (79.7%) were characterized as not having HVI. The sensitivity of abdominal free fluid was 100% (95% confidence interval [CI]: 92–100). The finding of a mural defect had a high specificity (99%, 95% CI: 97–100). Other findings with high specificity were abnormal wall enhancement (97%, 95% CI: 93–99) and wall irregularity (96%, 95% CI: 92–99).

CONCLUSION

While there was no singular CT finding that confirmed the diagnosis of HVI following abdominal GSW, the absence of intraabdominal free fluid could be used to rule out HVI. In addition, the presence of a mural defect, abnormal wall enhancement, or wall irregularity is considered as a strong predictor of HVI.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria; Level II.
Recombinant human MG53 protein attenuates brain lesion size in a large animal model of traumatic brain injury
Authors: Jin Guang , Ho Jessie W. , Keeney-Bonthrone Toby Philip , Ober Rebecca Ariel , Liu Baoling , Chtraklin Kiril , Wang Xiao-Liang , Zhou Xinyu , Cai Chuanxi , Li Yongqing , Tan Tao , Ma Jianjie , Alam Hasan B.
Published: July 2022

BACKGROUND

MG53, a member of the tripartite motif (TRIM) protein family, plays an essential role in cell membrane repair and promotes cell survival. Recent studies show that systemic delivery of recombinant human MG53 (rhMG53) protein markedly attenuates tissue injury/inflammation, and facilitates healing. This study was performed to test whether intravenous administration of rhMG53 protein would decrease the lesion size in a clinically relevant large animal model of traumatic brain injury (TBI).

METHOD

Yorkshire swine (40–45 kg; n = 5/group) were subjected to controlled cortical impact TBI and randomized to either: (1) rhMG53 protein (2 mg/kg, intravenous) or (2) normal saline control. Hemodynamics, intracranial pressure, and brain oxygenation were monitored for 7 hours. Brains were then harvested and sectioned into 5-mm slices and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size. Blood-brain barrier permeability of MG53 in the brain was determined by Western blot and immunohistochemistry. Bcl-2 and phospho-GSK β levels were measured as makers of prosurvival pathway activation.

RESULTS

Hemodynamic parameters were similar in both groups, but the lesion size in the rhMG53-treated group (2,517 ± 525.4 mm3) was significantly (p < 0.05) smaller than the control group (3,646 ± 740.1 mm3). In the treated animals, rhMG53 was detected in the regions surrounding the TBI, but it was absent in the saline-treated control animals. Bcl-2 and phospho-GSK β levels in the brains were upregulated in the rhMG53-treated animals.

CONCLUSION

Intravenously administered rhMG53 localizes to the injured areas of the brain, with the treated animals demonstrating a significant attenuation in the brain lesion size following TBI.
Detecting Traumatic Brain Injury-Induced Coagulopathy: What We Are Testing and What We Are Not
Authors: Dong Jing-fei , Zhang Fangyi , Zhang Jianning
Published: July 2022

Coagulopathy after traumatic brain injury (TBI) is common and has been closely associated with poor clinical outcomes for the affected patients. TBI-induced coagulopathy (TBI-IC) is consumptive in nature and evolves rapidly from an injury-induced hypercoagulable state. TBI-IC defined by laboratory tests is significantly more frequent than clinical coagulopathy, which often manifests as secondary, recurrent, or delayed intracranial or intracerebral hemorrhage. This disparity between laboratory and clinical coagulopathies has hindered progress in understanding the pathogenesis of TBI-IC and developing more accurate and predictive tests for this severe TBI complication. In this review, we discuss laboratory tests used in clinical and research studies to define TBI-IC, with specific emphasis on what the tests detect and what they do not. We also offer perspective on developing more accurate and predictive tests for this severe TBI complication.

Level of evidence

published reports
The Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand
Authors: Howell Jess , Majumdar Avik , Fink Michael , Byrne Mandy , McCaughan Geoff , Strasser Simone I. , Crawford Michael , Hodgkinson Peter , Stuart Katherine A. , Tallis Caroline , Chen John , Wigg Alan , Jones Robert , Jaques Bryon , Jeffrey Gary , Adams Leon , Wallace Michael C. , Gane Ed , Thompson Alex , Gow Paul
Published: July 2022

Background.

Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown.

Methods.

This retrospective study included adult liver transplants between January 1‚ 1985‚ and December 31‚ 2019‚ from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression.

Results.

A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985–1989) to 302 (20%) during Era 7 (2015–2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14).

Conclusions.

Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.
Early-onset Alzheimer Disease Associated With Neuromyelitis Optica Spectrum Disorder
Authors: Fujisawa Chisato , Saji Naoki , Takeda Akinori , Kato Takashi , Nakamura Akinori , Sakurai Keita , Asanomi Yuya , Ozaki Kouichi , Takada Koji , Umegaki Hiroyuki , Kuzuya Masafumi , Sakurai Takashi
Published: July 2022

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. Although recent reports have noted that cognitive impairment is common in NMOSD, little longitudinal information is available on the trajectories of cognitive function in the disease. Here, we report a case of a 55-year-old woman with an 11-year history of NMOSD who visited our memory clinic for progressive memory loss. She was diagnosed with early-onset Alzheimer disease based on amyloid and tau positron emission tomography imaging biomarkers. This is the first report of early-onset Alzheimer disease in a patient with NMOSD. Complications of Alzheimer disease should be considered when patients with NMOSD exhibit rapid cognitive decline. More longitudinal studies of NMOSD with cognitive impairment are needed.
Retrospective Review of Trauma ICU Patients With and Without Palliative Care Intervention
Authors: Rotundo Erica , Braunreuther Elizabeth , Dale Miles , Vancheswaran Aparna , Sub Lee Joon , Hossain Raeesa H , Butler Jonathan , Lugassy Mara , Latifi Rifat , Finbarr Blood Vincent
Published: July 2022

BACKGROUND:

Older trauma patients present with poor preinjury functional status and more comorbidities. Advances in care have increased the chance of survival from previously fatal injuries with many left debilitated with chronic critical illness and severe disability. Palliative care (PC) is ideally suited to address the goals of care and symptom management in this critically ill population. A retrospective chart review was done to identify the impact of PC consults on hospital length of stay (LOS), ICU LOS, and surgical decisions.

STUDY DESIGN:

A Level 1 Trauma Center Registry was used to identify adult patients who were provided PC consultation in a selected 3-year time period. These PC patients were matched with non-PC trauma patients on the basis of age, sex, race, Glasgow Coma Scale, and Injury Severity Score. Chi-square tests and Student’s t-tests were used to analyze categorical and continuous variables, respectively. Any p value >0.05 was considered statistically significant.

RESULTS:

PC patients were less likely to receive a percutaneous endoscopic gastric tube or tracheostomy. PC patients spent less time on ventilator support, spent less time in the ICU, and had a shorter hospital stay. PC consultation was requested 16.48 days into the patient’s hospital stay. Approximately 82% of consults were to assist with goals of care.

CONCLUSION:

Specialist PC team involvement in the care of the trauma ICU patients may have a beneficial impact on hospital LOS, ICU LOS, and surgical care rendered. Earlier consultation during hospitalization may lead to higher rates of goal-directed care and improved patient satisfaction.
Validation of the Memorial Sloan Kettering Gastric Cancer Post-Resection Survival Nomogram: Does It Stand the Test of Time?
Authors: Nakauchi Masaya , Court Colin M , Tang Laura H , Gönen Mithat , Janjigian Yelena Y , Maron Steven B , Molena Daniela , Coit Daniel G , Brennan Murray F , Strong Vivian E
Published: July 2022

BACKGROUND:

The Memorial Sloan Kettering Cancer Center (MSK) nomogram combined both gastroesophageal junction (GEJ) and gastric cancer patients and was created in an era from patients who generally did not receive neoadjuvant chemotherapy. We sought to reevaluate the MSK nomogram in the era of multidisciplinary treatment for GEJ and gastric cancer.

STUDY DESIGN:

Using data on patients who underwent R0 resection for GEJ or gastric cancer between 2002 and 2016, the C-index of prediction for disease-specific survival (DSS) was compared between the MSK nomogram and the American Joint Committee on Cancer (AJCC) 8th edition staging system after segregating patients by tumor location (GEJ or gastric cancer) and neoadjuvant treatment. A new nomogram was created for the group for which both systems poorly predicted prognosis.

RESULTS:

During the study period, 886 patients (645 gastric and 241 GEJ cancer) underwent up-front surgery, and 999 patients (323 gastric and 676 GEJ) received neoadjuvant treatment. Compared with the AJCC staging system, the MSK nomogram demonstrated a comparable C-index in gastric cancer patients undergoing up-front surgery (0.786 vs 0.753) and a better C-index in gastric cancer patients receiving neoadjuvant treatment (0.796 vs 0.698). In GEJ cancer patients receiving neoadjuvant chemotherapy, neither the MSK nomogram nor the AJCC staging system performed well (C-indices 0.647 and 0.646). A new GEJ nomogram was created based on multivariable Cox regression analysis and was validated with a C-index of 0.718.

CONCLUSIONS:

The MSK gastric cancer nomogram’s predictive accuracy remains high. We developed a new GEJ nomogram that can effectively predict DSS in patients receiving neoadjuvant treatment.
Genomic diversity of genus Limosilactobacillus
Authors: Ksiezarek Magdalena , Grosso Filipa , Ribeiro Teresa Gonçalves , Peixe Luísa
Published: July 2022

The genus

Limosilactobacillus

(formerly

Lactobacillus

) contains multiple species considered to be adapted to vertebrates, yet their genomic diversity has not been explored. In this study, we performed comparative genomic analysis of

Limosilactobacillus

(22 species; 332 genomes) isolated from different niches, further focusing on human strains (11 species; 74 genomes) and their adaptation features to specific body sites. Phylogenomic analysis of

Limosilactobacillus

showed misidentification of some strains deposited in public databases and existence of putative novel

Limosilactobacillus

species. The pangenome analysis revealed a remarkable genomic diversity (only 1.3 % of gene clusters are shared), and we did not observe a strong association of the accessory genome with different niches. The pangenome of

Limosilactobacillus reuteri

and

Limosilactobacillus fermentum

was open, suggesting that acquisition of genes is still occurring. Although most

Limosilactobacillus

were predicted as antibiotic susceptible (83%), acquired antibiotic-resistance genes were common in

L. reuteri

from food-producing animals. Genes related to lactic acid isoform production (>95 %) and putative bacteriocins (70.2%) were identified in most

Limosilactobacillus

strains, while prophages (55.4%) and CRISPR-Cas systems (32.0%) were less prevalent. Among strains from human sources, several metabolic pathways were predicted as conserved and completed. Their accessory genome was highly variable and did not cluster according to different human body sites, with some exceptions (urogenital

Limosilactobacillus vaginalis

,

Limosilactobacillus portuensis

,

Limosilactobacillus urinaemulieris

and

Limosilactobacillus coleohominis

or gastrointestinal

Limosilactobacillus mucosae

). Moreover, we identified 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues that were significantly enriched in strains from particular body sites. We concluded that evolution of the highly diverse

Limosilactobacillus

is complex and not always related to niche or human body site origin.
Simultaneous Spectral Differentiation of Multiple Fluorophores in Super-resolution Imaging Using a Glass Phase Plate
Authors: Fernando Sanduni I. , Martineau Jason T. , Hobson Robert J. , Vu Thien N. , Baker Brian , Mueller Brian D. , Menon Rajesh , Jorgensen Erik M. , Gerton Jordan M.
Published: July 2022

Multicolor localization microscopy typically relies on sequential imaging and bandpass filters to distinguish fluorescent tags, which introduces temporal delays during live imaging, and decreases photon yield. By engineering the point-spread function (PSF), different fluors can be imaged simultaneously and distinguished by their unique patterns, without discarding photons. Here, we insert a silicon-dioxide phase plate at the Fourier plane of the detection path of a wide-field fluorescence microscope to produce distinguishable PSFs (X-PSFs) at different wavelengths. We demonstrate that the resulting PSFs can be localized spatially and spectrally using a statistics-based computational algorithm and can be utilized for hyper-spectral super-resolution microscopy of biological samples. Single PSFs in fixed U2OS cells were acquired using dSTORM with simultaneous illumination of fluors without emission filters. The modified PSF achieves ∼21 nm lateral localization precision (FWHM), ∼17 nm axial precision (FWHM) with an average of 1,800 - 3,500 photons per PSF and a background as high as 130 - 400 photons per pixel. The modified PSF can distinguish up to three fluorescent probes with ∼80 nm peak-to-peak separation between consecutive spectra.
Fully Quantitative Measurements of the Antibody Levels for SARS-CoV-2 Infections and Vaccinations calibrated against the NISTmAb Standard IgG Antibody
Authors: James-Pemberton Philip H. , Helliwell Mark W. , Olkhov Rouslan V. , Kohli Shivali , Westlake Aaron C. , Farrar Benjamin M. , Shaw Andrew M.
Published: July 2022

Humanised recombinant antibodies specific to the SARS-CoV-2 Spike protein were calibrated against the NISTmAb standard human antibody to produce a fully quantitative antibody assay. The assay allows comparative studies between patient cohorts to be performed from which common properties may be derived. Two cohorts comparing patient vaccine response to AstraZeneca ChAdOx1-S (AZ, 35 patients) and Pfizer/BioNTech BNT162b2 (Pfizer, 25 patients) shows close association of the 31st percentile of the AZ distribution (2.90 ± 1.10 mg/L) and the 7th percentile of the Pfizer distribution (1.11 ± 1.10 mg/L) corresponding to the efficacy of the vaccines at preventing infection. The AZ IgG response distribution varies from 0.6 mg/L–25.4 mg/L with an average (mode) of 3.3 ± 1.0 mg/L; the Pfizer response distribution varies from 0.6 mg/L to 33.1 mg/L with a mode of 3.7 ± 1.0 mg/L. A third patient cohort looked at the recovery of 195 SARS-CoV-2 RT-PCR-positive patient samples and 200 pre-pandemic patient samples. A fourth patient cohort reviewed the NIBSC Anti-SARS-CoV-2 Verification Panel. The diagnostic cut-off for RT-PCR-positive patient samples was 1.34 ± 1.10 mg/L and the NIBSC panel separated seropositive and seronegative samples at 1.90 ± 1.10 mg/L. The mean value of the two prevention and two recovery thresholds is 1.8 mg/L with 95% confidence limits of 0.2–3.4 mg/L. In recovery and, critically, infection prevention, an antibody concentration threshold estimate of 3.4 mg/L appears mechanistically important. An antibody immunity threshold predicting a mucosal concentration preventing SARS-CoV-2 colonisation of the nasopharyngeal cavity is discussed.
Prospective Observational Cohort Study Of Tenecteplase Versus Alteplase In Routine Clinical Practice
Authors: Warach Steven J , Dula Adrienne N , Milling Truman J , Miller Samantha , Allen Leigh , Zuck Nathan D , Miller Collin , Jesser Christine A , Misra Lotika R , Miley Jefferson T , Mawla Manzure , Ding Ming-Chieh , Bertelson John A , Tsui Annie Y , Jefferson John R , Davison Holly M , Shah Darshan N , Padrick Matthew M , Nova Alan S. , Ellington Kent T , Krishna Vivek R , Davis Lisa A , Paydarfar David
Published: July 2022

Background and Purpose

A 10-hospital regional network transitioned to tenecteplase as the standard of care stroke thrombolytic in September 2019 because of its workflow advantages and reported non-inferior clinical outcomes relative to alteplase in meta-analyses of randomized trials. We assessed whether tenecteplase use in routine clinical practice reduces thrombolytic workflow times with non-inferior clinical outcomes.

Methods

We designed a prospective registry-based observational, sequential cohort comparison tenecteplase (n=234) to alteplase (n=354) treated stroke patients. We hypothesized: (1) an increase in the proportion of patients meeting target times for target door to needle (DTN) and transfer door-in-door-out (DIDO), and (2) non-inferior favorable (discharge to home with independent ambulation) and unfavorable (symptomatic intracranial hemorrhage, in-hospital mortality or discharge to hospice) in the tenecteplase group. Total hospital cost associated with each treatment was also compared.

Results

Target DTN within 45 minutes was superior for tenecteplase, 41% versus 29%; aOR 1.76 (95% CI 1.24, 2.52), P = 0.002. Target DIDO within 90 minutes was superior for tenecteplase 37% (15/43) versus 14% (9/65); OR 3.69 (95% CI 1.47, 9.7), P =0.006, overall, and 67% (12/18) versus 14% (2/14) for those transferred for thrombectomy after thrombolytic treatment (P =0.009). Favorable outcome for tenecteplase fell within the 6.5% non-inferiority margin; aOR 1.28 (95% CI 0.92, 1.77). Unfavorable outcome was less for tenecteplase 7.7% versus 11.9%, aOR 0.79 (95% CI 0.46, 1.32), but did not fall within the pre-specified 1% non-inferior boundary. Net benefit (%favorable – %unfavorable) was greater for the tenecteplase sample: 36% v 27%. P =0.022. Median cost per hospital encounter was less for tenecteplase cases ($13,382 vs $15,841; P <0.001).

Conclusions

Switching to tenecteplase in routine clinical practice in a 10-hospital network was associated with shorter DTN and DIDO times, non-inferior favorable clinical outcomes at discharge, and reduced hospital costs. Evaluation in larger, multicenter cohorts is recommended to determine if these observations generalize.
B1+-correction of MT saturation maps optimized for 7TpostmortemMRI of the brain
Authors: Lipp I. , Kirilina E. , Edwards L.J. , Pine K.J. , Jäger C. , Gräßle T. ,   EBC consortium, Weiskopf N. , Helms G.
Published: July 2022

Purpose

Magnetization transfer saturation (MTsat) is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased-inhomogeneity at ≥ 7T and significantly larger saturation pulse flip angles which are often used forpostmortemstudies exceed the limits where previous MTsatcorrection methods are applicable. Here, we develop a calibration-based correction model and procedure, and validate and evaluate it inpostmortem7T data of whole chimpanzee brains.

Theory

Thedependence of MTsat was investigated by varying the off-resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments onpostmortemtissue, the dependence was close to linear. A linear model with a single calibration constantCis proposed to correct bias in MTsat by mapping it to the reference value of the saturation pulse flip angle.

Methods

Cwas estimated voxel-wise in fivepostmortemchimpanzee brains. “Individual-based global parameters” were obtained by calculating the meanCwithin individual specimen brains and “group-based global parameters” by calculating the means of the individual-based global parameters across the five brains.

Results

The linear calibration model described the data well, thoughCwas not entirely independent of the underlying tissue and. Individual-based and group-based global correction parameters (C= 1.2) led to visible, quantifiable reductions of-biases in high resolution MTsat maps.

Conclusion

The presented model and calibration approach effectively corrects forin-homogeneities inpostmortem7T data.
Mink on the brink: Comparing survey methods for detecting a Critically Endangered carnivore, the European minkMustela lutreola
Authors: Croose Elizabeth , Hanniffy Ruth , Harrington Andrew , Põdra Madis , Gómez Asun , Bolton Polly L. , Lavin Jenna V. , Browett Samuel S. , Ruiz Javier Pinedo , Arnaez David Lacanal , Galdos Iñaki , Ugarte Jon , Torre Aitor , Wright Patrick , MacPherson Jenny , McDevitt Allan D. , Carter Stephen P. , Harrington Lauren A.
Published: July 2022

Monitoring rare and elusive species is critical in guiding appropriate conservation management measures. Mammalian carnivores are challenging to monitor directly, due to their generally nocturnal and solitary lifestyle, and relatively large home ranges. The European minkMustela lutreolais a Critically Endangered, small, semi-aquatic carnivore and is one of the most threatened mammal species in Europe. In northern Spain, the European mink population is monitored regionally using different methods and approaches, making assessment of national population status difficult. There is an urgent need to 1) assess the efficacy of survey methods, and 2) identify a standard monitoring methodology that can be deployed rapidly and inexpensively over large areas of the mink’s range. We deployed four methods – camera trapping, hair tubes, live trapping, and environmental DNA (eDNA) from water samples – to compare the probability of detecting European mink when present at 25 sampling sites within five 10×10km squares, and the economic cost and time required for each method. All four methods successfully detected European mink but the probability of detection varied by method. Camera trapping and hair tubes had the highest probability of detection; however, eDNA and live trapping detected mink in one 10×10km square where the latter two methods did not. For future European mink monitoring programmes, we recommend a combination of at least two methods, and suggest that camera traps or hair tubes are combined with live trapping or eDNA (depending on the scale and aims of the study), to gather critical information on distribution, occupancy and conservation status.
Through a Dog’s Eyes: fMRI Decoding of Naturalistic Videos from Dog Cortex
Authors: Phillips Erin M. , Gillette Kirsten D. , Dilks Daniel D. , Berns Gregory S.
Published: July 2022

Recent advancements using machine learning and fMRI to decode visual stimuli from human and nonhuman cortex have resulted in new insights into the nature of perception. However, this approach has yet to be applied substantially to animals other than primates, raising questions about the nature of such representations across the animal kingdom. Here, we used awake fMRI in two domestic dogs and two humans, obtained while each watched specially created dog-appropriate naturalistic videos. We then trained a neural net (Ivis) to classify the video content from a total of 90 minutes of recorded brain activity from each. We tested both an object-based classifier, attempting to discriminate categories such as dog, human and car, and an action-based classifier, attempting to discriminate categories such as eating, sniffing and talking. Compared to the two human subjects, for whom both types of classifier performed well above chance, only action-based classifiers were successful in decoding video content from the dogs. These results demonstrate the first known application of machine learning to decode naturalistic videos from the brain of a carnivore and suggest that the dog’s-eye view of the world may be quite different than our own.
Restoring morphology of light sheet microscopy data based on magnetic resonance histology
Authors: Tian Yuqi , Cook James J. , Johnson G. Allan
Published: July 2022

The combination of cellular-resolution whole brain light sheet microscopy (LSM) images with an annotated atlas enables quantitation of cellular features in specific brain regions. However, most existing methods register LSM data with existing canonical atlases, e.g. The Allen Brain Atlas (ABA), which limits the precision of measuring regional volumes and eliminates the individual difference in brain partitions for different strains, ages, and environmental exposures. Thus, these approaches obscure valuable anatomical information. Here, we present a method to combine LSM data with magnetic resonance histology (MRH) of the same brain restoring the morphology of the LSM images to the in-skull morphology. Our pipeline which maps 3D LSM data (terabyte level per dataset) to magnetic resonance histology of the same mouse brain provides accurate registration with low displacement error in 10 hours with limited manual input. Optimization and validation, from initialization of the data, designing the quantitative loss function, optimizing the 20+ image processing variables on multiple resolution scales, and finalizing the application on full resolution data has been integrated through a structured workflow. Excellent agreement has been seen between registered data and reference data both locally and globally. This workflow has been applied to a collection of datasets with varied MRH and LSM contrast providing a routine method for streamlined registration of LSM images to MRH.
On the role of tail in stability and energetic cost of bird flapping flight
Authors: Ducci Gianmarco , Vitucci Gennaro , Chatelain Philippe , Ronsse Renaud
Published: July 2022

Migratory birds travel over impressively long distances. Consequently, they have to adopt flight regimes being both efficient - in order to spare their metabolic resources - and robust to perturbations.

This paper investigates the relationship between both aspects, i.e. mechanical performance and stability in flapping flight of migratory birds. Relying on a poly-articulated wing morphing model and a tail-like surface, several families of steady flight regime have been identified and analyzed. These families differ by their wing kinematics and tail opening. A systematic parametric search analysis has been carried out, in order to evaluate power consumption and cost of transport. A framework tailored for assessing limit cycles, namely Floquet theory, is used to numerically study flight stability.

Our results show that under certain conditions, an inherent passive stability of steady and level flight can be achieved. In particular, we find that progressively opening the tail leads to passively stable flight regimes. Within these passively stable regimes, the tail can produce either upward or downward lift. However, these configurations entail an increase of cost of transport at high velocities penalizing fast forward flight regimes.

Our model-based predictions suggest that long range flights require a furled tail configuration, as confirmed by field observations, and consequently need to rely on alternative mechanisms to stabilize the flight.
PanomiR: A systems biology framework for analysis of multi-pathway targeting by miRNAs
Authors: Yeganeh Pourya Naderi , Teo Yue Yang , Karagkouni Dimitra , Pita-Juárez Yered , Morgan Sarah L. , Slack Frank J. , Vlachos Ioannis S. , Hide Winston A.
Published: July 2022

Charting microRNA (miRNA) regulation across pathways is central to characterizing their role in disease. Yet, current methods reveal only individual miRNA-pathway interactions. We have developed a systems biology approach,Pathway networks of miRNA Regulation(PanomiR), that overcomes these limitations to identify miRNA targeting of groups of interacting pathways using gene expression. The approach does not depend on statistically significant enrichment of miRNA target genes in individual pathways or significant differentially expressed genes. Rather, it directly captures differential activity of pathways between states, determining their up-or-down regulation while sensitively detecting biologically-meaningful signals. PanomiR analyzes the co-activity of differentially regulated pathways to determine coordinate functional groups and uses these co-activated grouped pathways to uncover miRNAs that target them. Incorporating both experimentally-supported or predicted miRNA-mRNA interactions, PanomiR robustly identifies miRNAs central to the regulation of disease functions. We applied PanomiR to a liver cancer dataset and showed that it can organize liver cancer pathways and their regulating miRNAs into coordinated transcriptional programs, reflecting the pathogenic mechanisms of hepatocellular carcinoma. PanomiR recapitulated known central miRNAs in liver cancer with a biologically meaningful assignment of pathways under their regulation, unbiased by the number of genes targeted by each miRNA. PanomiR is a granular framework for detecting broad-scale multi-pathway programs under miRNA regulation. It is accessible as an open-source R/Bioconductor package: .
Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system
Authors: Walsh Alexander D. , Stone Sarrabeth , Aprico Andrea , Kilpatrick Trevor J. , Ansell Brendan A. , Binder Michele D.
Published: July 2022

Microglia regulate multiple processes in the central nervous system, exhibiting a significant level of cellular plasticity which is facilitated by an equally dynamic transcriptional environment. While many gene networks that regulate microglial functions have been characterised, the influence of epigenetic regulators such as small non-coding microRNAs (miRNAs) is less well defined. We have sequenced the miRNAome and mRNAome of mouse microglia during brain development and adult homeostasis, identifying unique profiles of known and novel miRNAs. Microglia express both a consistently enriched miRNA signature as well as temporally distinctive subsets of miRNAs. We generated robust miRNA-mRNA networks related to fundamental developmental processes, in addition to networks associated with immune function and dysregulated disease states. There was no apparent influence of sex on miRNA expression. This study reveals a unique developmental trajectory of miRNA expression in microglia during critical stages of CNS development, establishing miRNAs as important modulators of microglial phenotype.
Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods
Authors: Winnett Alexander Viloria , Akana Reid , Shelby Natasha , Davich Hannah , Caldera Saharai , Yamada Taikun , Reyna John Raymond B. , Romano Anna E. , Carter Alyssa M. , Kim Mi Kyung , Thomson Matt , Tognazzini Colten , Feaster Matthew , Goh Ying-Ying , Chew Yap Ching , Ismagilov Rustem F.
Published: July 2022

SARS-CoV-2 viral load measurements from a single specimen type are used to establish diagnostic strategies, interpret clinical-trial results for vaccines and therapeutics, model viral transmission, and understand virus-host interactions. However, measurements from a single specimen type are implicitly assumed to be representative of other specimen types. We quantified viral-load timecourses from individuals who began daily self-sampling of saliva, anterior nares (nasal), and oropharyngeal (throat) swabs before or at the incidence of infection with the Omicron variant. Viral loads in different specimen types from the same person at the same timepoint exhibited extreme differences, up to 109copies/mL. These differences were not due to variation in sample self-collection, which was consistent. For most individuals, longitudinal viral-load timecourses in different specimen types did not correlate. Throat-swab and saliva viral loads began to rise up to 7 days earlier than nasal-swab viral loads in most individuals, leading to very low clinical sensitivity of nasal swabs during the first days of infection. Individuals frequently exhibited presumably infectious viral loads in one specimen type while viral loads were low or undetectable in other specimen types. Therefore, defining an individual as infectious based on assessment of a single specimen type underestimates the infectious period, and overestimates the ability of that specimen type to detect infectious individuals. For diagnostic COVID-19 testing, these three single specimen types have low clinical sensitivity, whereas a combined throat-nasal swab, and assays with high analytical sensitivity, were inferred to have significantly better clinical sensitivity to detect presumed pre-infectious and infectious individuals.

Significance Statement

In a longitudinal study of SARS-CoV-2 Omicron viral loads in three paired specimen types (saliva, anterior-nares swabs, and oropharyngeal swabs), we found extreme differences among paired specimen types collected from a person at the same timepoint, and that viral loads in different specimen types from the same person often do not correlate throughout infection. Individuals often exhibited high, presumably infectious viral loads in oral specimen types before nasal viral loads remained low or even undetectable. Combination oropharyngeal-nasal swabs were inferred to have superior clinical sensitivity to detect infected and infectious individuals. This demonstrates that single specimen type reference standard tests for SARS-CoV-2, such as in clinical trials or diagnostics evaluations may miss infected and even infectious individuals.
Augmented Pain-Evoked Primary Sensorimotor Cortex Activation in Adolescent Girls with Juvenile Fibromyalgia
Authors: Tong Han , Maloney Thomas C. , Payne Michael F. , Suñol Maria , King Christopher D. , Ting Tracy V. , Kashikar-Zuck Susmita , Coghill Robert C. , López-Solà Marina
Published: July 2022

Objective

Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM.

Methods

Thirty-three adolescent girls with JFM and thirty-three healthy adolescent girls underwent functional MRI scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm2 and rated pain intensity and unpleasantness on a computerized visual analogue scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses, and computed pain-evoked brain responses within seven major cortical networks.

Results

The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities (p<0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm2 (Z>3.1, cluster-corrected p<0.05), and the peak S1 activation magnitudes correlated with Widespread Pain Index scores (r=0.35, p=0.048). In the JFM group, we also found augmented activation of the somatomotor network in response to 2.5 kg/cm2, and greater primary sensorimotor cortex activation in response to 4kg/cm2 mediated the between-group differences in pain intensity ratings (p<0.001).

Conclusion

We found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input.
Genome evolution and early introductions of the SARS-CoV-2 Omicron Variant in Mexico
Authors: Castelán-Sánchez Hugo G. , Martínez-Castilla León P. , Sganzerla-Martínez Gustavo , Torres-Flores Jesús , López-Leal Gamaliel
Published: July 2022

A new variant of SARS-CoV-2 Omicron (Pango lineage designation B.1.1.529), was first reported to the World Health Organization (WHO) by South African health authorities on November 24, 2021. The Omicron variant possesses numerous mutations associated with increased transmissibility and immune escape properties. In November 2021, Mexican authorities reported Omicron’s presence in the country. In this study, we infer the first introductory events of Omicron and the impact that human mobility can have on the spread of the virus. We also evaluated the adaptive evolutionary processes in Mexican SARS-CoV-2 genomes during the first month of circulation of Omicron.

We infer 173 introduction events of Omicron in Mexico in the first two months of detection; subsequently, of the introductions, there was an increase in the prevalence for January.

This higher prevalence of the novel variant results in a peak of cases reported, on average, six weeks after a higher mobility trend was reported. The peak of cases reported is due to the BA.1.1 Omicron sub-lineage dominated, followed by BA.1 and BA.15 sub-lineages in the country from January to February 2022.

Additionally, we identified the presence of diversifying natural selection in the genomes of Omicron and found mainly five non-synonymous mutations in the RDB domain of the Spike protein, all of them related to evasion of the immune response. In contrast, the other proteins in the genome are highly conserved—however, there are homoplasies mutations in non-structural proteins, indicating a parallel evolution.
Exploring regression dilution bias using repeat measurements of 2858 variables in up to 49 000 UK Biobank participants
Authors: Rutter Charlotte E , Millard Louise AC , Borges Maria Carolina , Lawlor Deborah A
Published: July 2022

Background

Measurement error in exposures and confounders can bias exposure-outcome associations but is rarely considered. Our aim was to assess measurement error between repeat measures of all continuous variables in UK Biobank, and explore approaches to mitigate its impact on exposure-outcome associations.

Methods

Intraclass correlation coefficients (ICC) were calculated for all continuous variables with repeat measures. Regression calibration was used to correct for measurement error in both exposures and confounders, using the association of C-Reactive Protein (CRP) with mortality as an illustrative example.

Results

The 2858 continuous variables with repeat measures, varied in sample size from 109 to 49 121. They fell into three groups: (i) baseline visit measures (529 variables; median ICC=0.64, IQR= [0.57, 0.83]); (ii) online dietary measures (22 variables; median ICC=0.35, IQR=[0.30, 0.40]) and (iii) imaging measures (2307 variables; median ICC=0.85, IQR=[0.73, 0.94]). Highest ICC were for anthropometric and medical history measures, and lowest for dietary and heart magnetic resonance imaging.

The ICC for CRP was 0.29 (95% CI=[0.27, 0.30]), and for body mass index and smoking pack-years (confounders), were 0.93 (95% CI=[0.92, 0.93]) and 0.85 (95% CI=[0.84, 0.86]) respectively. The association of CRP with all-cause mortality (Hazard Ratio (HR)=1.029 per mg/L, 95% CI=[1.028, 1.031]) increased when correction for RDB was applied to the exposure (HR=1.119, 95% CI=[1.095, 1.143]). Confounder correction did not influence estimates.

Conclusions

Measurement error varies widely and is often non-negligible. For UK Biobank we provide relevant statistics and adaptable code to help other researchers explore and correct for bias due to measurement error.

Key Messages

Random measurement error in the exposure and confounders can bias the association between exposure and outcome towards or away from the null.

Some prospective studies, including UK Biobank, provide repeat measures of variables in a sub-sample for exploring bias due to random measurement error; these are rarely used.

Our results demonstrate that measurement error is often non-negligible and may bias estimates.

Agreement between repeated measures varies by category. In UK Biobank, dietary measures and heart magnetic resonance imaging are least stable while anthropometric and medical history variables are most stable.

We have provided intraclass correlation coefficients for 2858 continuous variables from UK Biobank and adaptable code to support researchers to correct for bias due to random error in exposures and confounders.
Detection of pneumococcus during hospitalization for SARS-CoV-2
Authors: Watkins Anne E. , Glick Laura R. , Ott Isabel M. , Craft Samuel B. , Yolda-Carr Devyn , Harden Christina A. , Nakahata Maura , Farhadian Shelli F. , Grant Lindsay R. , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D. , Weinberger Daniel M. , Wyllie Anne L.
Published: July 2022

Background

Infections with respiratory viruses (e.g., influenza, RSV) can increase the risk of severe pneumococcal infections. Likewise, pneumococcal co-infection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 co-infection and the role of co-infection in influencing COVID-19 severity.

Methods

The study included patients admitted to Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease).

Results

Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 (OR: 2.20; 95% CI: [0.72, 7.48]); however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died.

Conclusions

Pneumococcal LRTI, as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.

One Sentence Summary

Pneumococcal lower respiratory tract infection, as detected by positive UAD, occurred in patients hospitalized with COVID-19 at rates similar to those reported prepandemic.
Predicting expression divergence and its evolutionary parameters between single-copy genes in two species
Authors: Piya Antara Anika , DeGiorgio Michael , Assis Raquel
Published: July 2022

Predicting gene expression divergence and its evolutionary parameters is integral to understanding the emergence of new gene functions and associated traits. Whereas several sophisticated methods have been developed for these tasks, their applications are either limited to duplicate genes or require expression data from more than two species. Thus, here we present PiXi, the first machine learning framework for predicting expression divergence and its evolutionary parameters between single-copy genes in two species. In particular, PiXi models gene expression evolution as an Ornstein-Uhlenbeck process, and overlays this model with multi-layer neural network, random forest, and support vector machine architectures for making predictions. We show that PiXi has high power and accuracy in predicting gene expression divergence and its underlying parameters across a wide range of evolutionary scenarios, with the globally best performance achieved by a multi-layer neural network. Moreover, application of our best performing PiXi predictor to empirical data from single-copy genes residing at different loci in two species ofDrosophilareveals that expression divergence occurs in approximately 20% of these positionally relocated genes and is driven by a combination of neutral and selective forces. Further analysis shows that several of these genes are involved in the electron transport chain of the mitochondrial membrane, suggesting that new chromatin environments may impact energy production inDrosophila. Thus, by providing a toolkit for predicting expression divergence and its evolutionary parameters between single-copy genes in two species, PiXi can shed light on the origins of novel phenotypes across diverse biological processes and study systems.