bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation of Sinonasal NKT From Diffuse Large B-Cell Lymphoma Using Machine Learning and MRI-Based Radiomics
Authors: Zhang Yiyin , Lin Naier , Xiao Hanyu , Xin Enhui , Sha Yan
Published: July 2023

Purpose

The aim of this study was to construct and validate a noninvasive radiomics method based on magnetic resonance imaging to differentiate sinonasal extranodal natural killer/T-cell lymphoma from diffuse large B-cell lymphoma.

Methods

We collected magnetic resonance imaging scans, including contrast-enhanced T1-weighted imaging and T2-weighted imaging, from 133 patients with non-Hodgkin lymphoma (103 sinonasal extranodal natural killer/T-cell lymphoma and 30 diffuse large B-cell lymphoma) and randomly split them into training and testing cohorts at a ratio of 7:3. Clinical characteristics and image performance were analyzed to build a logistic regression clinical-image model. The radiomics features were extracted on contrast-enhanced T1-weighted imaging and T2-weighted imaging images. Maximum relevance minimum redundancy, selectKbest, and the least absolute shrinkage and selection operator algorithms (LASSO) were applied for feature selection after balancing the training set. Five machine learning classifiers were used to construct the single and combined sequences radiomics models. Sensitivity, specificity, accuracy, precision, F1score, the area under receiver operating characteristic curve, and the area under precision-recall curve were compared between the 15 models and the clinical-image model. The diagnostic results of the best model were compared with those of 2 radiologists.

Results

The combined sequence model using support vector machine proves to be the best, incorporating 7 features and providing the highest values of specificity (0.903), accuracy (0.900), precision (0.727), F1score (0.800), and area under precision-recall curve (0.919) with relatively high sensitivity (0.889) in the testing set, along with a minimum Brier score. The diagnostic results differed significantly (P < 0.05) from those of radiology residents, but not significantly (P > 0.05) from those of experienced radiologists.

Conclusions

Magnetic resonance imaging based on machine learning and radiomics to identify the type of sinonasal non-Hodgkin lymphoma is effective and has the potential to help radiology residents for diagnosis and be a supplement for biopsy.
Patients with both traumatic brain injury and hemorrhagic shock benefit from resuscitation with whole blood
Authors: Hatton Gabrielle E. , Brill Jason B. , Tang Brian , Mueck Krislynn M. , McCoy C. Cameron , Kao Lillian S. , Cotton Bryan A.
Published: July 2023

BACKGROUND

Hemorrhagic shock in the setting of traumatic brain injury (TBI) reduces cerebral blood flow and doubles mortality. The optimal resuscitation strategy for hemorrhage in the setting of TBI is unknown. We hypothesized that, among patients presenting with concomitant hemorrhagic shock and TBI, resuscitation including whole blood (WB) is associated with decreased overall and TBI-related mortality when compared with patients receiving component (COMP) therapy alone.

METHODS

An a priori subgroup of prospective, observational cohort study of injured patients receiving emergency-release blood products for hemorrhagic shock is reported. Adult trauma patients presenting November 2017 to September 2020 with TBI, defined as a Head Abbreviated Injury Scale of ≥3, were included. Whole blood group patients received any cold-store low-titer Group O WB units. The COMP group received fractionated blood components alone. Overall and TBI-related 30-day mortality, favorable discharge disposition (home or rehabilitation), and 24-hour blood product utilization were assessed. Univariate and inverse probabilities of treatment-weighted multivariable analyses were performed.

RESULTS

Of 564 eligible patients, 341 received WB. Patients who received WB had a higher injury severity score (median, 34 vs. 29), lower scene blood pressure (104 vs. 118), and higher arrival lactate (4.3 vs. 3.6, all p < 0.05). Univariate analysis noted similar overall mortality between WB and COMP; however, weighted multivariable analyses found WB was associated with decreased overall mortality and TBI-related mortality. There were no differences in discharge disposition between the WB group and COMP group.

CONCLUSION

In patients with concomitant hemorrhagic shock and TBI, WB transfusion was associated with decreased overall mortality and TBI-related mortality. Whole blood should be considered a first-line therapy for hemorrhage in the setting of TBI.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
TLR4-MyD88 signaling is involved in the spinal neurons during the full length of recovery from transection of the motor branch of the femoral nerve in mice
Authors: Wei Xiaoyan , Ding Yumeng , Wang Lichao , Zhang Qixingmao , Wang Chunhuai , Chen Chen , You Siwei , Wu Mingmei , Kuang Fang
Published: July 2023

This study was designed to see the expression of toll-like receptor 4 (TLR4) and downstream molecules including myeloid differentiation factor 88 (MyD88) and interleukin 1-β (IL-1β) in the spinal cord as peripheral nerve injury recovered in mice. We established a model of femoral nerve injury (FNI) in C57BL/6 mice by transection of the motor branch of the femoral nerve, followed by retrograde labeling to show the according motor neurons in the anterior horn of the spinal cord pars lumbar. We observed the motor function recovery of the injured hind limbs using behavioral tests. The expression of TLR4, MyD88, and IL-1β was examined by immunofluorescent staining and western blot. According to the behavior test, the FNI animals fully recovered within 6–8 weeks. TLR4, MyD88, and IL-1β were expressed in the ventral horn of the spinal cord both at 72 h till 6 weeks after the femoral nerve transection surgery, and these proteins were mostly co-localized with neurons. IL-1β also tended to rise in the same surgery groups, but more intimate with microglia surrounding nearby retrograde labeled neurons. And western blot results were consistent with histological findings. The results indicate that peripheral nerve injury may induce innate immune reactions of the central neurons and critical signaling like TLR4/MyD88 in the spinal cord may reflect the recovery of the injury. These findings suggest that peripheral nerve injury triggered the TLR4/MyD88 signal in the soma of spinal neurons may be involved in function and nerve restoration through neuron-glia crosstalk.
Reclassification of Sabulilitoribacter multivorans and Sabulilitoribacter arenilitoris as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov., respectively, based on genome sequence analysis
Authors: Liu Ang , Dong Xinyue , Wang Wanting , Qin Jiayi , Leng Hongyu , Yan Chenlong , Zhao Longyu
Published: July 2023

Rapid advancements in DNA sequencing technologies are providing new approaches for bacterial taxonomy. The genus

Sabulilitoribacter

is a member of the family

Flavobacteriaceae

, which consists of more than 150 genera. In this study, genome sequence analysis was conducted to revisit the taxonomic status of

Sabulilitoribacter arenilitoris

and

Sabulilitoribacter multivorans

, the only two species of this genus. Genome sequence based phylogeny analysis showed that the genus

Sabulilitoribacter

was non-monophyletic:

S. multivorans

, the type species of genus

Sabulilitoribacter

, was clustered with the type species of the genus

Flaviramulus

, whereas

S. arenilitoris

formed a robust cluster with the only two species of the genus

Wocania

. The values of average amino acid identity, genome-wide average nucleotide identity, alignment fractions and some phenotypic features showed that

S. multivorans

was more closely related with the type species of the genus

Flaviramulus

than with

S. arenilitoris

, and

S. arenilitoris

was more closely related with the only two species of the genus

Wocania

than with

S. multivorans

. Based on these results, we consequently propose that

S. multivorans

and

S. arenilitoris

should be reclassified as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov. respectively.
A genome wide association study to identify germline variants associated with cancer-associated cachexia - a preliminary analysis
Authors: Narasimhan Ashok , Kumaran Mahalakshmi , Gioulbasanis Ioannis , Skipworth Richard J E , Bathe Oliver F , Kaasa Stein , Strasser Florian , Gagnon Bruno , Baracos Vickie , Damaraju Sambasivarao
Published: July 2023

Background

Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host-tumor interactions. While much emphasis has been made in understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify Copy Number Variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.

Methods

A total of 174 age-matched patients with esophagogastric or lung cancer were classified as weight losing (>10% weight loss) or weight stable participants (<2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with >5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.

Results

Among the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at >5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non-redundant CNV/CNVRs which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK-STAT signaling, Oncostatin M signaling, Wnt signaling and PI3K-Akt signaling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1 and PCSK6 to name a few.

Conclusion

This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weight loss in patients with cancer cachexia.
Systemic hypoxemia catalyzes cerebral oxidative-nitrosative stress during extreme apnea in humans: implications for cerebral bioenergetic function
Authors: Bailey Damian M. , Bain Anthony R. , Hoiland Ryan L. , Barak Otto F. , Drvis Ivan , Stacey Benjamin S. , Iannetelli Angelo , Davison Gareth W. , Dahl Rasmus H. , Berg Ronan M.G. , MacLeod David B. , Dujic Zeljko , Ainslie Philip N.
Published: July 2023

BACKGROUND

Voluntary asphyxia induced by apnea in competitive breath hold (BH) divers affords a unique opportunity to examine integrated mechanisms underlying the preservation of cerebral bioenergetic function. This study examined to what extent physiological extremes of oxygen (O2) demand and carbon dioxide (CO2) production impact redox homeostasis and corresponding red blood cell (RBC)-mediated cerebral vasodilation.

METHODS

Ten ultra-elite apneists (6 men, 4 women) aged 33 ± 9 (mean ± SD) years old performed two maximal dry apneas preceded by, [1] normoxic normoventilation resulting in severe hypoxemic hypercapnia apnea (HHA) and [2] hyperoxic hyperventilation designed to prevent hypoxemia resulting in isolated hypercapnic apnea (IHA). Transcerebral exchange kinetics of ascorbate radicals (A·-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH, spectrophotometry) and nitric oxide metabolites (NO, tri-iodide reductive chemiluminescence) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients determined at eupnea and after apnea.

RESULTS

Apnea duration increased from 306 ± 62 s during HHA to 959 ± 201 s during IHA (P = <0.001), resulting in individual nadirs of 29 mmHg and 40 % for PaO2and SaO2respectively in HHA and PaCO2peak of 68 mmHg in IHA. Apnea resulted in a more pronounced elevation in the net cerebral output (v>a) of A·-and LOOH in HHA (P = <0.05 vs. IHA). This coincided with a lower apnea-induced increase in gCBF (P = <0.001 vs. IHA) and related suppression in plasma nitrite () uptake (a>v) (P = < 0.05 vs. IHA), implying reduced consumption and delivery of NO consistent with elevated cerebral oxidative-nitrosative stress (OXNOS). While apnea-induced gradients consistently reflected plasmaconsumption (a>v) and RBC iron nitrosylhemoglobin formation (v>a), we failed to observe equidirectional gradients consistent withS-nitrosohemoglobin consumption and plasmaS-nitrosothiol delivery.

CONCLUSIONS

These findings highlight a key catalytic role for hypoxemia in cerebral OXNOS withreduction the more likely mechanism underlying endocrine NO vasoregulation with the capacity to transduce physiological O2-CO2gradients into graded vasodilation.
Performance of progressive generations of GPT on an exam designed for certifying physicians as Certified Clinical Densitometrists
Authors: Valdez Dustin , Bunnell Arianna , Lim Sian Y. , Sadowski Peter , Shepherd John A.
Published: July 2023

Background

Artificial intelligence (AI) large language models (LLMs) such as ChatGPT have demonstrated the ability to pass standardized exams. These models are not trained for a specific task, but instead trained to predict sequences of text from large corpora of documents sourced from the internet. It has been shown that even models trained on this general task can pass exams in a variety of domain-specific fields, including the United States Medical Licensing Examination. We asked if LLMs would perform as well on a much narrower subdomain tests designed for medical specialists. Furthermore, we wanted to better understand how progressive generations of GPT (generative pre-trained transformer) models may be evolving in the completeness and sophistication of their responses even while generational training remains general. In this study, we evaluated the performance of two versions of GPT (GPT 3 and 4) on their ability to pass the certification exam given to physicians to work as osteoporosis specialists and become a certified clinical densitometrists.

Methods

A 100-question multiple-choice practice exam was obtained from a 3rdparty exam preparation website that mimics the accredited certification tests given by the ISCD (international society for clinical densitometry). The exam was administered to two versions of GPT, the free version (GPT Playground) and ChatGPT+, which are based on GPT-3 and GPT-4, respectively (OpenAI, San Francisco, CA). The systems were prompted with the exam questions verbatim. If the response was purely textual and did not specify which of the multiple-choice answers to select, the authors matched the text to the closest answer. Each exam was graded and an estimated ISCD score was provided from the exam website. In addition, each response was evaluated by a rheumatologist CCD and ranked for accuracy using a 5-level scale. The two GPT versions were compared in terms of response accuracy and length.

Results

The average response length was 11.6 ±19 words for GPT-3 and 50.0±43.6 words for GPT-4. GPT-3 answered 62 questions correctly resulting in a failing ISCD score of 289. However, GPT-4 answered 82 questions correctly with a passing score of 342. GPT-3 scored highest on the “Overview of Low Bone Mass and Osteoporosis” category (72% correct) while GPT-4 scored well above 80% accuracy on all categories except “Imaging Technology in Bone Health” (65% correct). Regarding subjective accuracy, GPT-3 answered 23 questions with nonsensical or totally wrong responses while GPT-4 had no responses in that category.

Conclusion

If this had been an actual certification exam, GPT-4 would now have a CCD suffix to its name even after being trained using general internet knowledge. Clearly, more goes into physician training than can be captured in this exam. However, GPT algorithms may prove to be valuable physician aids in the diagnoses and monitoring of osteoporosis and other diseases.
GWAS of cataract in Puerto Ricans identifies a novel large-effect variant in ITGA6
Authors: Shi Jingchunzi , O’Connell Jared , Hicks Barry , Wang Wei , Bryc Katarzyna , Brady Jennifer J. , Vacic Vladimir , Freyman Will , Abul-Husn Noura S. , Auton Adam ,   23andMe Research Team, Shringarpure Suyash
Published: July 2023

Cataract is a common cause of vision loss and affects millions of people worldwide. Genome-wide association studies (GWAS) and family studies of cataract have demonstrated a role for genetics in cataract susceptibility. However, most of these studies have been conducted in populations of European or Asian descent, leaving the genetic etiology of cataract among Hispanic/Latino (HL) populations unclear. Here we perform the first GWAS of cataract in a Puerto Rican population of research participants derived from the customer base of 23andMe, Inc. In our analysis with 3,060 self-reported cases and 41,890 controls, we found a novel association of large effect size with a rare coding variant in the ITGA6 gene (rs200560853, p-value=2.9×10−12, OR=12.7, 95% CI=[6.5, 24.7]). ITGA6 is part of the integrin alpha chain in the laminin receptor subfamily, and likely contributes to eye lens homeostasis, transparency, and cell survival. We found that this coding variant is associated with a 13.7 year earlier disease onset on average, as well as a 4.3-fold higher rate of cataract events in the Puerto Rican population. The variant has a minor allele frequency (MAF) of 0.089% in Puerto Rico and is extremely rare elsewhere in the world. Population genetic analyses showed that the variant is only found in individuals with ancestry from the Americas and countries bordering the Mediterranean Sea, suggesting a North African origin. Our discovery identifies a novel genetic risk factor for cataract in Puerto Ricans and highlights the importance of including underrepresented populations in genomics research to improve our understanding of disease in all populations.
Wagers for work: Decomposing the costs of cognitive effort
Authors: Master Sarah L. , Curtis Clayton E. , Dayan Peter
Published: July 2023

Some aspects of cognition are more taxing than others. Accordingly, many people will avoid cognitively demanding tasks in favor of simpler alternatives. Which components of these tasks are costly, and how much, remains unknown. Here, we use a novel task design in which subjects request wages for completing cognitive tasks and a computational modeling procedure that decomposes their wages into the costs driving them. Using working memory as a test case, our approach revealed that gating new information into memory and protecting against interference are costly. Critically, other factors, like memory load, appeared less costly. Other key factors which may drive effort costs, such as error avoidance, had minimal influence on wage requests. Our approach is sensitive to individual differences, and could be used in psychiatric populations to understand the true underlying nature of apparent cognitive deficits.

Author Summary

Anyone who has tried to mentally calculate how much to tip at a restaurant knows that cognitive effort can feel aversive. Doing math in your head, like most high-level cognitive abilities, depends critically on working memory (WM). We know that WM is sometimes effortful to use, but we don’t know which aspects of WM use drive these effort costs. To address this question, we had participants request wages in exchange for performing various tasks that differed in their specific WM demands. Using computational models of their wage demands, we demonstrated that some aspects of WM are costly, such as bringing new information into memory and preventing interference. Other factors, like the amount of information in memory and attempts to avoid mistakes, were less costly. Our approach identified which specific subcomponents of WM are aversive. Future research could use these methods to test theories about how motivational problems might be masquerading as cognitive deficits in psychiatric populations.
Autologous iPSC- and MSC-derived Chondrocyte Implants for Cartilage Repair in a Miniature Pig Model
Authors: Lee Ming-Song , Sivapatham Athillesh , Leiferman Ellen M. , Jiao Hongli , Lu Yan , Nemke Brett W. , Leiferman Matthew , Markel Mark D. , Li Wan-Ju
Published: July 2023

Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) have greater potential for generating chondrocytes without hypertrophic and fibrotic phenotypes compared to bone marrow-derived mesenchymal stem/stromal cells (BMSCs). However, there is a lack of research demonstrating the use of autologous iMSCs for repairing articular chondral lesions in large animal models. In this study, we aimed to evaluate the effectiveness of autologous miniature pig (minipig) iMSC-chondrocyte (iMSC-Ch)-laden implants in comparison to autologous BMSC-chondrocyte (BMSC-Ch)-laden implants for cartilage repair in porcine femoral condyles. iMSCs and BMSCs were seeded into fibrin glue/nanofiber constructs and cultured with chondrogenic induction media for 7 days before implantation. To assess the regenerative capacity of the cells, 19 skeletally mature Yucatan minipigs were randomly divided into microfracture control, acellular scaffold, iMSC, and BMSC subgroups. A cylindrical defect measuring 7 mm in diameter and 0.6 mm in depth was created on the articular cartilage surface without violating the subchondral bone. The defects were then left untreated or treated with acellular or cellular implants. Both cellular implant-treated groups exhibited enhanced joint repair compared to the microfracture and acellular control groups. Immunofluorescence analysis yielded significant findings, showing that cartilage treated with iMSC-Ch implants exhibited higher expression of COL2A1 and minimal to no expression of COL1A1 and COL10A1, in contrast to the BMSC-Ch-treated group. This indicates that the iMSC-Ch implants generated more hyaline cartilage-like tissue compared to the BMSC-Ch implants. These results contribute to filling the knowledge gap regarding the potential of autologous iPSC derivatives for cartilage repair in translational animal models.
Parallel EEG assessment of different sound predictability levels in tinnitus
Authors: Brinkmann Pia , Devos Jana V. P. , van der Eerden Jelle H. M. , Smit Jasper V. , Janssen Marcus L. F. , Kotz Sonja A. , Schwartze Michael
Published: July 2023

Objective

Tinnitus denotes perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g. type) and temporal sound characteristics facilitates the filtering of irrelevant information (“sensory gating”, SG). Here, we explored if and how parallel manipulations of formal and temporal predictability affect sensory gating in persons with and without tinnitus.

Methods

Age-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone “oddball” sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA).

Results

SG was observed in P50- and N100-like activity (amplitude suppression for the 2ndtone in the pair) in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only in persons without tinnitus N100-like activity in response to deviants was enhanced with isochronous relative to random timing.

Conclusions

Persons with tinnitus do not benefit similarly as persons without tinnitus from temporally predictable context in deviance processing.

Significance

The current results indicate altered temporal sensitivity and selective attention allocation in persons with tinnitus.

Highlights

-

Persons with tinnitus display altered auditory predictions affecting the processing of unexpected auditory input

-

Position predictions did not differ between persons with tinnitus and without

-

Temporal predictability facilitated deviance processing for P50-like activity in persons with tinnitus and without
Dynamic local mRNA distribution and translation influence the postnatal molecular maturation of perivascular astrocytic processes
Authors: Avila-Gutierrez Katia , Slaoui Leila , Alvear Rodrigo , Kozlowski Esther , Oudart Marc , Augustin Emma , Mailly Philippe , Monnet Héloïse , Mignon Virginie , Saubaméa Bruno , Boulay Anne-Cécile , Cohen-Salmon Martine
Published: July 2023

Astrocytes (the main glial cells in the brain) are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain’s blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA distribution and local translation influence the cell’s polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. Furthermore, we found that distribution of mRNAs in PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Lastly, we found that some polysomal mRNAs polarized progressively towards the PvAPs. Our results indicate that dynamic mRNA distribution and local translation influence the postnatal maturation of PvAPs.

Summary statement

Local translation operates during the postnatal development of perivascular astrocyte processes and might contribute to their molecular maturation.
Rastermap: a discovery method for neural population recordings
Authors: Stringer Carsen , Zhong Lin , Syeda Atika , Du Fengtong , Kesa Maria , Pachitariu Marius
Published: July 2023

Neurophysiology has long progressed through exploratory experiments and chance discoveries. Anecdotes abound of researchers setting up experiments while listening to spikes in real time and observing a pattern of consistent firing when certain stimuli or behaviors happened. With the advent of large-scale recordings, such close observation of data has become harder because high-dimensional spaces are impenetrable to our pattern-finding intuitions. To help ourselves find patterns in neural data, our lab has been openly developing a visualization framework known as “Rastermap” over the past five years. Rastermap takes advantage of a new global optimization algorithm for sorting neural responses along a one-dimensional manifold. Displayed as a raster plot, the sorted neurons show a variety of activity patterns, which can be more easily identified and interpreted. We first benchmark Rastermap on realistic simulations with multiplexed cognitive variables. Then we demonstrate it on recordings of tens of thousands of neurons from mouse visual and sensorimotor cortex during spontaneous, stimulus-evoked and task-evoked epochs, as well as on whole-brain zebrafish recordings, widefield calcium imaging data, population recordings from rat hippocampus and artificial neural networks. Finally, we illustrate high-dimensional scenarios where Rastermap and similar algorithms cannot be used effectively.
Systematic assessment of long-read RNA-seq methods for transcript identification and quantification
Authors: Pardo-Palacios Francisco J. , Wang Dingjie , Reese Fairlie , Diekhans Mark , Carbonell-Sala Sílvia , Williams Brian , Loveland Jane E. , De María Maite , Adams Matthew S. , Balderrama-Gutierrez Gabriela , Behera Amit K. , Gonzalez Jose M. , Hunt Toby , Lagarde Julien , Liang Cindy E. , Li Haoran , Meade Marcus Jerryd , Amador David A. Moraga , Prjibelski Andrey D. , Birol Inanc , Bostan Hamed , Brooks Ashley M. , Çelik Muhammed Hasan , Chen Ying , Du Mei R.M. , Felton Colette , Göke Jonathan , Hafezqorani Saber , Herwig Ralf , Kawaji Hideya , Lee Joseph , Li Jian-Liang , Lienhard Matthias , Mikheenko Alla , Mulligan Dennis , Nip Ka Ming , Pertea Mihaela , Ritchie Matthew E. , Sim Andre D. , Tang Alison D. , Wan Yuk Kei , Wang Changqing , Wong Brandon Y. , Yang Chen , Barnes If , Berry Andrew , Capella Salvador , Dhillon Namrita , Fernandez-Gonzalez Jose M. , Ferrández-Peral Luis , Garcia-Reyero Natàlia , Goetz Stefan , Hernández-Ferrer Carles , Kondratova Liudmyla , Liu Tianyuan , Martinez-Martin Alessandra , Menor Carlos , Mestre-Tomás Jorge , Mudge Jonathan M. , Panayotova Nedka G. , Paniagua Alejandro , Repchevsky Dmitry , Rouchka Eric , Saint-John Brandon , Sapena Enrique , Sheynkman Leon , Smith Melissa Laird , Suner Marie-Marthe , Takahashi Hazuki , Youngworth Ingrid Ashley , Carninci Piero , Denslow Nancy D. , Guigó Roderic , Hunter Margaret E. , Tilgner Hagen U. , Wold Barbara J. , Vollmers Christopher , Frankish Adam , Au Kin Fai , Sheynkman Gloria M. , Mortazavi Ali , Conesa Ana , Brooks Angela N.
Published: July 2023

Abstract

The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well asde novotranscript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
Management of splenic injury in children and young adults: a survey of surgeons investigating factors responsible for variations in care using the Theoretical Domains Framework
Authors: Adams Susan E , Holland Andrew JA , Brown Julie
Published: July 2023

STRUCTURED ABSTRACT

Objective: To identify differences in practice and behavioural drivers in adult and paediatric surgeons related to the management of splenic injury in children and young people.

Background: Despite the existence of guidelines, there are variations in the care of children with splenic injuries. There are no specific guidelines for the care of young adults, who may be managed according to either paediatric or adult practices. The drivers of variation in trauma management between adult and paediatric surgeons have not been examined through an implementation science lens.

Methods: The COM-B model of behaviour and theoretical domains framework were used to construct a survey which was delivered to a cross-section of adult general surgeons and paediatric surgeons working in public hospitals throughout NSW, Australia. The capability, opportunity, and motivation for management decisions were analysed. Outcome variables were compared between the practitioner groups. Statistical significance was set at p < 0.05.

Results: Eighty (26.4%) responses met the inclusion criteria. Significant differences between adult and paediatric surgeons were identified in terms of: capability (surgeon training and experience); opportunity (hospital, personnel, and resources); and motivation (comfort with splenic injury care at different ages). In managing splenic injury, pediatric surgeons tended to follow pediatric guidelines while adult surgeons followed adult guidelines, making some adjustments for age. All agreed guidelines had the potential to improve care.

Conclusions: This study identified several behavioural drivers for observed variations in the care of splenic injury in children and young adults. The results indicate that contextually relevant guidelines for managing splenic injury in children and young people across any setting may be needed to reduce disparities in care. These should be underpinned by interventions designed to further address the drivers of surgeon behaviour to optimise uptake. Furthermore, splenic injury care is a clinical indicator of the quality of trauma care more broadly. Addressing variation in its care has the potential to translate to other trauma system improvements.

HIGHLIGHTS

Unwarranted variations in splenic injury management have been reported.

This is the first examination of surgeon behaviour in the provision of trauma care through an implementation science lens.

Differences in the capability, opportunity, and motivation of surgeons in providing evidence-based care to children and young adults with splenic injury were found.

Contextually relevant guidelines, underpinned by supporting interventions addressing these behavioural drivers, are needed to reduce disparities in care.
High connectivity and human movement limits the impact of travel time on infectious disease transmission
Authors: John Reju Sam , Miller Joel C. , Muylaert Renata L. , Hayman David T. S.
Published: July 2023

The speed of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic highlights the importance of understanding how infections are transmitted in a highly connected world. Prior to vaccination, changes in human mobility patterns were used as non-pharmaceutical interventions to eliminate or suppress viral transmission. The rapid spread of respiratory viruses, various intervention approaches, and the global dissemination of SARS-CoV-2 underscore the necessity for epidemiological models that incorporate mobility to comprehend the spread of the virus. Here, we introduce a metapopulation susceptible–exposed–infectious–recovered (SEIR) model parameterised with human movement data from 340 cities in China. Our model replicates the early case trajectory in the COVID-19 pandemic. We then use machine learning algorithms to determine which network properties best predict spread between cities and find travel time to be most important, followed by the human movement Weighted Personalised PageRank. However, we show that travel time is most influential locally, after which the high connectivity between cities reduces the impact of travel time between individual cities on transmission speed. Additionally, we demonstrate that only significantly reduced movement substantially impacts infection spread times throughout the network.
The Eye-image Features of Patients with Coronary Heart Disease Assed: A prospective, observational study of traditional Chinese medicine combined with modern medicine
Authors: Gao Zhanqun , Zhang Dirui , Weng Ziqian , Liu Minghao , Gao Yubo , Hao Wei , Zhao Chen , Zeng Ming , Feng Xue , Wang Shengfang , Yi Boling , Xie Chunqi , Qin Yuhan , He Luping , Xu Yishuo , Jia Haibo , Fang Chao , Zhang Zhi , Hu Sining , Yu Bo
Published: July 2023

BACKGROUND

Coronary heart disease (CHD) significantly impacts human health. Traditional Chinese medicine (TCM) suggests a possible correlation between eye-image and CHD, but this relationship has not been fully explored in Western medicine.

PURPOSE

We aim to investigate the potential causal relationship between eye-image features and CHD, as examined by coronary angiography (CAG).

METHODS

The study selected patients hospitalized in the Department of Cardiology from November 15, 2021, to February 27, 2022. The selected patients were divided into two groups based on their CAG findings: the CHD group (at least one coronary lesion stenosis≥ 50%) and the control group (lesion stenosis<50%)

RESURTS

The final analysis included 342 patients out of a total of 426 participants, of these, 165 patients (48.2%) were diagnosed with CHD. The study found that certain characteristics in the left region 5(L5) and right region ( R5) were associated with CHD, including L5 pink dark speckle (OR: 4.143, 95%CI: 1.135-15.124,P=0.031), L5 vascular tortuosity (OR: 0.234, 95%CI: 0.077-0.71,P=0.010) R5 dark red blood vessels (known as Xue mai in TCM) (OR: 1.683, 95%CI: 1.035-2.738,P=0.036), and R5 yellowish mounds (OR: 2.083, 95%CI: 1.221-3.554,P= 0.007). Multivariate regression analyses showed that L5 vascular tortuosity had a negative correlation with CHD.

CONCLUSION

Our study revealed that four types of eye-image features, namely pink dark speckle, vascular tortuosity, dark red blood vessels, and yellowish mounds are associated with CHD. Among these features, vascular tortuosity showed a negative correlation with CHD, which could potentially aid in the diagnosis of the disease.
Ribosomal Protein SA (RPSA) is required for localized translation and sarcomere maintenance in mice
Authors: Haddad Rami , Sadeh Omer , Ziv Tamar , Erlich Itai , Haimovich-Caspi Lilac , Shemesh Ariel , van der Velden Jolanda , Kehat Izhak
Published: July 2023

Cardiomyocyte sarcomeres contain localized ribosomes, but the factors responsible for their localization and the significance of localized translation are unknown. Using proximity labeling, we identified Ribosomal Protein SA (RPSA) as a Z-line protein. In cultured cardiomyocytes, the loss of RPSA led to impaired local protein translation and reduced sarcomere integrity. By employing CAS9 expressing mice along with adeno-associated viruses expressing CRE recombinase and single-guide RNAs targetingRpsa, we knocked outRpsain vivo and observed mis-localization of ribosomes and diminished local translation. These genetic mosaic mice withRpsaknockout in a subset of cardiomyocytes developed dilated cardiomyopathy, featuring atrophy of RPSA-deficient cardiomyocytes, compensatory hypertrophy of unaffected cardiomyocytes, left ventricular dilation, and impaired contractile function. We demonstrate that RPSA C-terminal domain is sufficient for localization to the Z-lines and that if the microtubule network is disrupted RPSA loses its sarcomeric localization. These findings highlight RPSA as a ribosomal factor essential for ribosome localization to the Z-line, facilitating local translation and sarcomere maintenance.
A distributed brain response predicting the facial expression of acute nociceptive pain
Authors: Picard Marie-Eve , Kunz Miriam , Chen Jen-I , Coll Michel-Pierre , Vachon-Presseau Étienne , Wager Tor D. , Rainville Pierre
Published: July 2023

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.
Analysis of RyR2 distribution in HEK293 cells and mouse cardiac myocytes using 3D MINFLUX microscopy
Authors: Clowsley Alexander H , Meletiou Anna , Lučinskaitė Evelina , Jansen Isabelle , Jones Peter P. , Louch William E. , Soeller Christian
Published: July 2023

The cardiac type 2 ryanodine receptor (RyR2) is a large homotetramer of a ∼560 kD subunit and is the molecular pathway through which the majority of Ca2+enters the cytosol during cardiac activation. It constitutes the molecular basis of the process of calcium induced calcium release where activation of RyR2s can be locally regenerative giving rise to local release events termed Ca2+sparks. Accordingly, the molecular distribution of RyR2 in cardiac myocytes has been of great interest. Here we present the first purely optical data of RyR2 distribution with sub-molecular resolution by applying 3D MINFLUX fluorescence super-resolution microscopy. We demonstrate that by using single-domain antibodies (sdABs) against fluorescent protein domains in engineered RyR2 fluorescent protein fusions we can determine the location of individual RyR2 subunits with high precision (∼3 nm) in all directions. This allows determining not only the location but also the 3D orientation of individual RyR2 channels in intact cells. In practice, this capability is currently limited by a relatively modest effective labeling efficiency (∼10 % subunit detection efficiency translating into ∼35% RyR2 labeling efficiency) which we measurein-situusing a novel procedure enabled by the true molecular resolution of MINFLUX microscopy. The new data suggests a resolution to apparent discrepancies between previous data from electron microscopy and super-resolution data that may be at least partially explained by effects of labeling efficiency. The methodology developed here will be critical to reveal the full complexity of RyR2 and related Ca2+handling proteins in 3D as well as their relationship to contractile function. Our new approaches may be applicable to other multi-subunit complexes in cardiac muscle and other cell types.
Functional hierarchies in brain dynamics characterized by signal reversibility in ferret cortex
Authors: Idesis Sebastian , Geli Sebastian , Faskowitz Joshua , Vohryzek Jakub , Perl Yonatan Sanz , Pieper Florian , Galindo-Leon Edgar , Engel Andreas K. , Deco Gustavo
Published: July 2023

Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep periods, using custom micro-electrocorticographic (μECoG) arrays implanted in ferrets. In contrast to humans, ferrets remain less time in each state across the sleep-wake cycle. We deployed a diverse set of metrics in order to measure the levels of complexity of the different behavioral states. In particular, brain irreversibility, which allows us to quantify the level of non-equilibrium captured by the arrow of time of the signal, revealed the hierarchical organization of the ferret’s cortex. We found different signatures of irreversibility and functional hierarchy of large-scale dynamics in three different brain states (active awake, quiet awake, and deep sleep), showing a lower level of irreversibility in the deep sleep stage, compared to the other. Irreversibility also allowed us to disentangle the influence of different brain regions and frequency bands in this process, showing a predominance of the parietal area and the theta band. Furthermore, when inspecting the embedded dynamic through a Hidden Markov Model, the deep sleep stage was revealed to have a lower switching rate and lower entropy production. These results suggest functional hierarchies in organization that can be revealed through thermodynamic features and information theory metrics.
Investigating the neural basis of schematic false memories by examining schematic and lure pattern similarity
Authors: Carpenter Catherine M. , Dennis Nancy A.
Published: July 2023

Schemas allow us to make assumptions about the world based upon previous experiences and aid in memory organization and retrieval. However, a reliance on schemas may also result in increased false memories to schematically related lures. Prior neuroimaging work has linked schematic processing in memory tasks to activity in prefrontal, visual, and temporal regions. Yet, it is unclear what type of processing in these regions underlies memory errors. The current study examined where schematic lures exhibit greater neural similarity to schematic targets, leading to this memory error, as compared to neural overlap with non-schematic lures, which, like schematic lures, are novel items at retrieval. Results showed that patterns of neural activity in ventromedial prefrontal cortex, medial frontal gyrus, middle temporal gyrus, hippocampus, and occipital cortices exhibited greater neural pattern similarity for schematic targets and schematic lures than between schematic lures and non-schematic lures. As such, results suggest that schematic membership, and not object history, may be more critical to the neural processes underlying memory retrieval in the context of a strong schema.