bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity and Accuracy of High-Resolution Ultrasound for Diagnosis of Flexor Tendon Repair Integrity.
Authors: Hinckley Nathaniel B. , Renfree Sean , Dahiya Nirvikar , Zhang Nan , Renfree Kevin J.
Published: May 2023

Purpose:

Is ultrasound sensitivity, specificity, and accuracy in identifying intact repairs or flexor tendon gapping following zone II repair affected by the number of suture strands crossing the repair or gap, and/or imaging modality (static versus dynamic)?

Methods:

One hundred and forty-four fresh-frozen cadaveric digits (thumbs excluded) were randomized to either an intact repair (0-mm gap) or simulated “failed” repair (4 mm gap), as well as to either a 2 or 8 strand locked cruciate repair of a Zone 2 flexor digitorum profundus tendon laceration using 4-0 Fiberwire. Examinations were performed by a blinded musculoskeletal ultrasonographer in static and dynamic modes using an 18 MHz transducer. Gaps were remeasured after scanning, and the final gap width recorded. McNemar’s exact test was used to determine if there were differences between sensitivity, specificity, and accuracy affected by modality (static vs. dynamic), and Chi-square test was used to compare sensitivity, specificity and accuracy between number of strands (2 vs. 8) crossing the intact repair or repair gap (>/=4mm).

Results:

Sensitivity, specificity and accuracy improved with: 1. increased number of suture strands crossing repair/gap (8 vs 2), irrespective of modality (static vs. dynamic), and 2. dynamic compared to static scanning modes, irrespective of number of suture strands crossing repair or gap site.

Conclusion:

The most sensitive and accurate means of assessing flexor tendon repair integrity and gapping was seen using dynamic scanning mode. Increased number of suture strands does not negatively affect sensitivity, specificity, nor accuracy, regardless of scanning mode (dynamic vs. static).
Incidental Detection of Ectopic Ovary Varices by 99mTc–Red Blood Cell Bleeding Scintigraphy in a Patient With Cirrhosis
Authors: Lu Xia , Feng Lijuan , Wang Wei , Yang Jigang
Published: May 2023

A 72-year-old woman with cirrhosis underwent a99mTc-labeled red blood cell (RBC) bleeding scan because of recurrent gastrointestinal bleeding. The images showed abnormal99mTc-RBC accumulation in a mass in the region of the left ovary. Contrast-enhanced CT showed expansion of left ovary vein from the left renal vein, which twisted into an enhanced round mass in the left ovary area. Finally, a diagnosis of ectopic ovary varices was made, which is secondary to cirrhosis with portal hypertension. Ovary varices should be included as differential diagnoses of99mTc-RBC bleeding scintigraphy.
Encouraging Study in Health Sciences
Authors: Moro Christian , Phelps Charlotte
Published: May 2023

Introduction

Although commonly considered postgraduate-level study, universities are increasingly providing options for direct undergraduate entry into health professional programs. This presents a need to inform high school students about the wide variety of careers available in the medical and allied health professions.

Methods

To accomplish this, the developed “Health Simulation Experience” uses a case-based learning approach to introduce high school students to careers in health through the management and care of simulated patients. Participants worked through 3 simulated scenarios during the 1-day event and reported their perceptions on written feedback forms at the conclusion. A qualitative research approach was used to identify whether the simulation-based structure was an appropriate approach to assist with enhancing their understanding of career options within the primary and allied healthcare systems.

Results

Of the 528 student attendees who engaged with the program between 2018–2022, 333 provided ratings of their experience (94% overall satisfaction) and written feedback. From qualitative analysis of written comments, the following 3 key themes emerged: the approach provided insights into health professions careers; they enjoyed the authentic and immersive approach to learning; and the event developed an understanding of commonly performed clinical skills.

Conclusions

Overall, the use of case-based learning with interprofessional hands-on experiences is an effective approach to introduce students to future study options and career pathways in primary and allied health.
Operationalizing the Culture of Burnout and Well-Being: Multicenter Study of Value Congruence and Flourishing in General Surgery Residency
Authors: Cevallos Jenny R , Gonzales Paul Adam , Berler Michael H , Greenberg Anya L , Lebares Carter C ,   for the General Surgery Research Collaborative on Resident Well-being
Published: May 2023

BACKGROUND:

Value congruence (VC) is the degree of alignment between worker and workplace values and is strongly associated with reduced job strain and retention. Within general surgery residency, the impact of VC and how to operationalize it to improve workplace well-being remain unclear.

STUDY DESIGN:

This 2-part mixed-methods study comprised 2 surveys of US general surgery residents and qualitative interviews with program directors. In Part 1, January 2021, mixed-level surgical residents from 16 ACGME-accredited general surgery residency programs participated in survey #1. This survey was used to identify shared or conflicting perspectives on VC concerning well-being initiatives and resources. In April 2021, interviews from 8 institutions were conducted with 9 program directors or their proxies. In Part 2, May to June 2022, a similar cohort of surgical residents participated in survey #2. Unadjusted logistic and linear regression models were used in this survey to assess the association between VC and individual-level global well-being (ie flourishing), respectively.

RESULTS:

In survey #1 (N = 300, 34% response rate), lack of VC was an emergent theme with subthemes of inaccessibility, inconsiderateness, inauthenticity, and insufficiency regarding well-being resources. Program directors expressed variable awareness of and alignment with these perceptions. In survey #2 (N = 251, 31% response rate), higher VC was significantly associated with flourishing (odds ratio 1.91, 95% CI 1.44 to 2.52, p < 0.001).

CONCLUSIONS:

Exploring the perceived lack of VC within general surgery residency reveals an important cultural variable for optimizing well-being and suggests open dialogue as a first step toward positive change. Future work to identify where and how institutional actions diminish perceived VC is warranted.
Astronomia ex machina: a history, primer and outlook on neural networks in astronomy
Authors: Smith Michael J. , Geach James E.
Published: May 2023

In this review, we explore the historical development and future prospects of artificial intelligence (AI) and deep learning in astronomy. We trace the evolution of connectionism in astronomy through its three waves, from the early use of multilayer perceptrons, to the rise of convolutional and recurrent neural networks, and finally to the current era of unsupervised and generative deep learning methods. With the exponential growth of astronomical data, deep learning techniques offer an unprecedented opportunity to uncover valuable insights and tackle previously intractable problems. As we enter the anticipated fourth wave of astronomical connectionism, we argue for the adoption of GPT-like foundation models fine-tuned for astronomical applications. Such models could harness the wealth of high-quality, multimodal astronomical data to serve state-of-the-art downstream tasks. To keep pace with advancements driven by Big Tech, we propose a collaborative, open-source approach within the astronomy community to develop and maintain these foundation models, fostering a symbiotic relationship between AI and astronomy that capitalizes on the unique strengths of both fields.
Description of the Pliocene marsupial
Ambulator keanei
gen. nov. (Marsupialia: Diprotodontidae) from inland Australia and its locomotory adaptations
Authors: van Zoelen Jacob D. , Camens Aaron B. , Worthy Trevor H. , Prideaux Gavin J.
Published: May 2023

Diprotodontids were the largest marsupials to exist and an integral part of Australian terrestrial ecosystems until the last members of the group became extinct approximately 40 000 years ago. Despite the frequency with which diprotodontid remains are encountered, key aspects of their morphology, systematics, ecology and evolutionary history remain poorly understood. Here we describe new skeletal remains of the Pliocene taxon
Zygomaturus keanei
from northern South Australia. This is only the third partial skeleton of a late Cenozoic diprotodontid described in the last century, and the first displaying soft tissue structures associated with footpad impressions. Whereas it is difficult to distinguish
Z. keanei
and the type species of the genus,
Z. trilobus
, on dental grounds, the marked cranial and postcranial differences suggest that
Z. keanei
warrants genus-level distinction. Accordingly, we place it in the monotypic
Ambulator
gen. nov. We, also recognize the late Miocene
Z. gilli
as a
nomen dubium
. Features of the forelimb, manus and pes reveal that
Ambulator keanei
was more graviportal with greater adaptation to quadrupedal walking than earlier diprotodontids. These adaptations may have been driven by a need to travel longer distances to obtain resources as open habitats expanded in the late Pliocene of inland Australia.
Copulatory behaviour and genital mechanics suggest sperm allocation by a non-intromittent sclerite in a pholcid spider
Authors: Izquierdo M. A. , Dederichs T. M. , Cargnelutti F. , Michalik P.
Published: May 2023

The male genitalia of pholcid spiders, which is one of the most species-rich spider families, are characterized by a procursus, which is a morphologically diverse projection of the copulatory organ. It has been shown that the procursus interacts with the female genitalia during copulation. Here, we investigate the function of the procursus in
Gertschiola neuquena
, a species belonging to the early branched and understudied subfamily Ninetinae, using behavioural and morphological data. Although many aspects of the copulatory behaviour of
G. neuquena
follow the general pattern described for the family, males use only one pedipalp during each copulation. Based on our micro-CT analysis of cryofixed mating pairs using virgin females, we can show that the long and filiform procursus is inserted deeply into the unpaired convoluted female spermatheca, and the intromittent sclerite, the embolus, is rather short and stout only reaching the most distal part of the female sperm storage organ. Histological data revealed that sperm are present in the most proximal part of the spermatheca, suggesting that the procursus is used to allocate sperm deeply into the female sperm storage organ. This represents the first case of a replacement of the sperm allocation function of the intromittent sclerite in spiders.
Trapping of an active Brownian particle at a partially absorbing wall
Authors: Bressloff Paul C.
Published: May 2023

Active matter concerns the self-organization of energy consuming elements such as motile bacteria or self-propelled colloids. A canonical example is an active Brownian particle (ABP) that moves at a constant speed while its direction of motion undergoes rotational diffusion. When ABPs are confined within a channel, they tend to accumulate at the channel walls, even when inter-particle interactions are ignored. Each particle pushes on the boundary until a tumble event reverses its direction. The wall thus acts as a sticky boundary. In this article, we consider a natural extension of sticky boundaries that allow for a particle to be permanently absorbed (killed) whilst attached to a wall. In particular, we investigate the first passage time (FPT) problem for an ABP in a two-dimensional channel where one of the walls is partially permeable. Calculating the exact FPT statistics requires solving a non-trivial two-way diffusion boundary value problem. We follow a different approach by separating out the dynamics away from the absorbing wall from the dynamics of absorption and escape whilst attached to the wall. By using probabilistic methods, we derive an explicit expression for the mean first passage time of absorption, assuming that the arrival statistics of particles at the wall are known. Our method also allows us to incorporate a more general encounter-based model of absorption.
Genetic characterization of Escherichia coli and Klebsiella spp. from Humans and Poultry in Nigeria
Authors: Jesumirhewe Christiana , CABAL-ROSEL Adriana , ALLERBERGER Franz , SPRINGER Burkhard , RUPPITSCH Werner
Published: May 2023

The emergence of antibiotic resistance in food producing animals is of major public health significance arising from the risk of these bacteria entering the food chain. In this study, the genetic characteristics of antibiotic resistant Escherichia coli and Klebsiella spp. isolates from humans and poultry in Edo state, Nigeria were investigated. In April 2017, 45 Klebsiella spp. and 46 Escherichia coli isolates were obtained from urine, clinical wounds, nasal and chicken fecal samples. Isolates were recovered and identified as previously described. Species identification was achieved by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and ribosomal multilocus sequence typing. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method for 12 antibiotics. Double disc synergy test was used to screen for ESBL production. Whole genome sequencing was performed for strain characterization of the isolates. Thirteen Klebsiella spp. isolates yielded positive results by the ESBL phenotypic test and harbored ESBL genes. Out of the 46 E. coli isolates, 21 human and 13 poultry isolates were resistant to at least one of the tested antibiotics. Four human E. coli isolates harbored ESBL genes and revealed positive results when applying ESBL double disc synergy tests. ESBL genes in the Klebsiella spp. and E. coli isolates include bla CTX-M-15 and bla SHV-28 . Whole genome based cgMLST of the Klebsiella spp. and E. coli isolates revealed a close relatedness among the isolates. An integrated “One Health” surveillance system is required to monitor transmission of antimicrobial resistance in Nigeria.
Point-of-Care Biomarker Assay for Rapid Multiplexed Detection of CRP and IP-10
Authors: Wilson Claire S. , Vashi Bhavya , Genzor Pavol , Gregory Melissa K. , Yau Jason , Wolfe Lauren , Lochhead Michael J. , Myatt Chris , Pettrone Kristen , Blair Paul W. , Krishnan Subramaniam , Chenoweth Josh G. , Clark Danielle V.
Published: May 2023

Rapid and accurate measurements of immune protein markers are essential for diagnosis and treatment in all clinical settings. The recent pandemic has revealed a stark need for developing new tools and assays that could be rapidly used in diverse settings and provide useful information to clinicians. Here, we describe the development and test application of a novel one-step CRP/IP-10 duplex assay for the LightDeck platform capable of delivering reproducible and accurate measurements in under eight minutes. We used the optimized assay to measure CRP and IP-10 levels in human blood and serum samples from healthy, COVID-19-positive, and influenza-like illness (ILI) presenting patients. Our results agreed with previously published analyte levels and enabled us to make statistically significant comparisons relevant to multiple clinical parameters. Our duplex assay is a simple and powerful tool for aiding diagnostic decisions in diverse settings.
Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers
Authors: Rose KN , Zorlu M , Xue X , Fassini A , Cai W , Lin S , Webb P , Schwarzschild MA , Chen X , Gomperts SN
Published: May 2023

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson’s disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with a neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO modulated pathways to slow symptom onset and limit pathology in PD patients.
Transcranial stimulation of alpha oscillations modulates brain state dynamics in sustained attention
Authors: Brown Joshua A. , Clancy Kevin J. , Chen Chaowen , Zeng Yimeng , Qin Shaozheng , Ding Mingzhou , Li Wen
Published: May 2023

The brain operates an advanced complex system to support mental activities. Cognition is thought to emerge from dynamic states of the complex brain system, which are organized spatially through large- scale neural networks and temporally via neural synchrony. However, specific mechanisms underlying these processes remain obscure. Applying high-definition alpha-frequency transcranial alternating-current stimulation (HD α-tACS) in a continuous performance task (CPT) during functional resonance imaging (fMRI), we causally elucidate these major organizational architectures in a key cognitive operation— sustained attention. We demonstrated that α-tACS enhanced both electroencephalogram (EEG) alpha power and sustained attention, in a correlated fashion. Akin to temporal fluctuations inherent in sustained attention, our hidden Markov modeling (HMM) of fMRI timeseries uncovered several recurrent, dynamic brain states, which were organized through a few major neural networks and regulated by the alpha oscillation. Specifically, during sustain attention, α-tACS regulated the temporal dynamics of the brain states by suppressing a Task-Negative state (characterized by activation of the default mode network/DMN) and Distraction state (with activation of the ventral attention and visual networks). These findings thus linked dynamic states of major neural networks and alpha oscillations, providing important insights into systems-level mechanisms of attention. They also highlight the efficacy of non-invasive oscillatory neuromodulation in probing the functioning of the complex brain system and encourage future clinical applications to improve neural systems health and cognitive performance.
Maintenance of pig brain function under extracorporeal pulsatile circulatory control (EPCC)
Authors: Shariff Muhammed , Dobariya Aksharkumar , Albaghdadi Obada , Awkal Jacob , Moussa Hadi , Reyes Gabriel , Syed Mansur , Hart Robert , Longfellow Cameron , Douglass Debra , El Ahmadieh Tarek Y. , Good Levi B. , Jakkamsetti Vikram , Kathote Gauri , Angulo Gus , Ma Qian , Brown Ronnie , Dunbar Misha , Shelton John M. , Evers Bret M. , Patnaik Sourav , Hoffmann Ulrike , Hackmann Amy E. , Mickey Bruce , Peltz Matthias , Jessen Michael E. , Pascual Juan M.
Published: May 2023

Selective vascular access to the brain is desirable in metabolic tracer, pharmacological and other studies aimed to characterize neural properties in isolation from somatic influences from chest, abdomen or limbs. However, current methods for artificial control of cerebral circulation can abolish pulsatility-dependent vascular signaling or neural network phenomena such as the electrocorticogram even when preserving individual neuronal activity. Thus, we set out to mechanically render cerebral hemodynamics fully regulable to replicate or modify native pig brain perfusion. To this end, blood flow to the head was surgically separated from the systemic circulation and full extracorporeal pulsatile circulatory control (EPCC) delivered via a modified aorta or brachiocephalic artery. This control relied on a computerized algorithm that maintained, for several hours, blood pressure, flow and pulsatility at near-native values individually measured before EPCC. Continuous electrocorticography and brain depth electrode recordings were used to evaluate brain activity relative to the standard offered by awake human electrocorticography. Under EPCC, this activity remained unaltered or minimally perturbed compared to the native circulation state, as did cerebral oxygenation, pressure, temperature and microscopic structure. Thus, our approach enables the study of neural activity and its circulatory manipulation in independence of most of the rest of the organism.
Improving the prediction of protein stability changes upon mutations by geometric learning and a pre-training strategy
Authors: Xu Yunxin , Liu Di , Gong Haipeng
Published: May 2023

Abstract

Accurate prediction of the fitness and stability of a protein upon mutations is of high importance in protein engineering and design. Despite the rapid development of deep learning techniques and accumulation of experimental data, the multi-labeled nature of fitness data hinders the training of robust deep-learning-based models for the fitness and stability prediction tasks. Here, we propose three geometric-learning-based models, GeoFitness, GeoDDG and GeoDTm, for the prediction of the fitness score, ΔΔGand ΔTmof a protein upon mutations, respectively. In the optimization of GeoFitness, we designed a novel loss function to allow supervised training of a unified model using the large amount of multi-labeled fitness data in the deep mutational scanning (DMS) database. By this means, GeoFitness efficiently learns the general functional effects of protein mutations and achieves better performance over the other state-of-the-art methods. To further improve the downstream tasks of ΔΔG/ΔTmprediction, we re-utilized the encoder of GeoFitness as a pre-trained module in GeoDDG and GeoDTm to overcome the challenge of lack of sufficient amount of specifically labeled data. This pre-training strategy in combination with data expansion remarkably improves model performance and generalizability. When evaluated on the benchmark test sets (S669 for ΔΔGprediction and a newly collected set S571 for ΔTmprediction), GeoDDG and GeoDTm outperform the other state-of-the-art methods by at least 30% and 70%, respectively, in terms of the Spearman correlation coefficient between predicted and experimental values. An online server for the suite of these three predictors, GeoStab-suite, is available athttp://structpred.life.tsinghua.edu.cn/server_geostab.html.
Genome-wide profiling reveals a dual role for histone H2A monoubiquitylation at Polycomb-repressed and enhancer chromatin
Authors: MacGillivray Kailynn , Fusca Daniel , Tan Luomeng , Aram Reta , Saltzman Arneet L.
Published: May 2023

Histone modifications are an integral component of eukaryotic genome regulation. Polycomb Repressive Complex 1 (PRC1) is responsible for depositing histone H2A lysine 119 monoubiquitylation (H2AK119ub) and can work cooperatively with PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) to maintain gene repression. However, H3K27me3-independent functions and roles in gene activation have also been described for PRC1. Thus, the extent to which Polycomb complexes and their corresponding histone modifications function together or independently and the conservation of these roles in different organisms is unclear. UsingC. elegansas a model, we investigated the relationship between H2AK119ub and H3K27me3. Here we show that the majority of H2AK119ub and H3K27me3 enrichment across the genome in embryos is distinct, and that the bulk levels of these modifications are regulated independently. We identify many genes related to nervous system development and functionality that have H2AK119ub-enriched promoters and are misregulated in H2AK119ub-deficient mutants, including a subset of genes that are normally H3K27me3-repressed. Surprisingly, we also find an enrichment of H2AK119ub at enhancers, including enhancers proximal to genes which are both up-regulated and down-regulated following the loss of this histone modification. Together, our results indicate a dual role for H2AK119ub in the regulation of both H3K27me3-repressed and enhancer chromatin states.
Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis
Authors: Wang Lianlei , Liu Zhaoyang , Zhao Sen , Xu Kexin , Aceves Valeria , Qiu Cheng , Troutwine Benjamin , Liu Lian , Ma Samuel , Niu Yuchen , Wang Shengru , Yuan Suomao , Li Xiaoxin , Zhao Lina , Liu Xinyu , Wu Zhihong , Zhang Terry Jianguo , Gray Ryan S. , Wu Nan
Published: May 2023

SOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation ofSOX9is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of howSOX9variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants ofSOX9identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain ofSOX9. Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated aSox9hypomorphic mutant mouse model bearing a microdeletion within the TAM domain (Sox9Asp272del). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. HomozygousSox9Asp272delmice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs inSox9Asp272delmutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant ofSOX9within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.
Joint cell type identification in spatial transcriptomics and single-cell RNA sequencing data
Authors: Geras Agnieszka , Domżał Kacper , Szczurek Ewa
Published: May 2023

Understanding the intricate composition of tissues in complex living organisms is crucial for unraveling the mechanisms underlying health and disease. This study addresses the challenge of dissecting cell types within tissues by integrating information from two powerful experimental techniques: single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST). While scRNA-seq offers insights into transcriptional heterogeneity at the cellular level, ST provides spatial information within tissues. Current methods for cell-type annotation in scRNA-seq and mixture decomposition in ST data are often conducted independently, resulting in reduced statistical power and accuracy. To bridge this gap, we propose ST-Assign, a novel hierarchical Bayesian probabilistic model that jointly performs cell-type annotation in scRNA-seq data and cell-type mixture decomposition in ST data. ST-Assign accounts for shared variables such as gene expression profiles and leverages prior knowledge about marker genes, amplifying statistical strength and mitigating experimental noise. The model’s excellent performance is demonstrated on simulated and real mouse brain data, showcasing accurate cell-type mixture decomposition and cell-type assignment. In comparison to existing tools, ST-Assign demonstrates superior capabilities, particularly in the task of assigning cell types to individual cells. ST-Assign enables exploring the spatial composition of cell types and holds the potential for enhancing our comprehension of diverse biological systems.
Permeabilization status affects the relationship between basal metabolic rate and mitochondrial respiration in great tit blood cells
Authors: Thoral Elisa , García Díaz Carmen C. , Persson Elin , Chamkha Imen , Elmér Eskil , Ruuskanen Suvi , Nord Andreas
Published: May 2023

Although mitochondrial respiration is believed to explain a substantial part of the variation in whole-animal basal (BMR) or resting metabolic rate (RMR), few studies have addressed the relationship between organismal and cellular metabolism and how this may vary in environments where individual demands for energy differ. We investigated the relationship between whole-individual metabolic rate, measured in temperatures ranging thermoneutrality to far below thermoneutrality, and mitochondrial respiration of intact or permeabilized blood cells in two separate studies on wild great tits (Parus majorL.). Our results show that, in permeabilized cells, there are significant positive relationships between BMR or RMR and several mitochondrial traits, including phosphorylating respiration rate through both complexes I and II (i.e., OXPHOS respiration). However, surprisingly, the LEAK respiration (i.e., basal respiration that mainly counteract for proton leakage) was not related to BMR or RMR. When measurements were performed using intact blood cells, BMR was positively related to ROUTINE respiration (i.e., mitochondrial respiration on endogenous substrates) in one of the two studies, but no other mitochondrial traits could explain variation in BMR or RMR in any thermal environment. These studies seem to show that the level of activation of mitochondrial metabolism as well as the permeabilization status of blood cells play a primary role on the extent to which blood metabolism might explain variations in the whole-individual metabolic rate.
Huge narwhal displacement following shipping of iron ore in the Canadian Arctic Archipelago
Authors: Witting Lars
Published: May 2023

With 100,000 narwhals inhabiting populations in the Canadian Arctic Archipelago, the Northwest Passage runs through the largest aggregation of narwhals in the world. I use a metapopulation analysis that covers eight of the narwhal populations in the area to estimate that about 25,000 narwhals have emigrated from Eclipse Sound to Admiralty Inlet since 2007, causing almost total population collapse in Eclipse Sound following shipping of iron ore through Milne Inlet and Eclipse Sound. It is estimated that up to about 30,000 narwhals may vanish in the long run, unless shipping is increasingly regulated, or narwhals adapt to the disturbance and reinhabits the abandoned areas. Reflecting only a local disturbance, these population effects warn against intense shipping in other fjords with narwhals, and against a potentially much larger impact from increased shipping through the Northwest Passage in the future.
Antibodies against SARS-CoV-2 control complement-induced inflammatory responses to SARS-CoV-2
Authors: Bermejo-Jambrina Marta , van der Donk Lieve E.H. , van Hamme John L. , Wilflingseder Doris , de Bree Godelieve , Prins Maria , de Jong Menno , Nieuwkerk Pythia , van Gils Marit J. , Kootstra Neeltje A. , Geijtenbeek Teunis B.H.
Published: May 2023

Dysregulated immune responses contribute to pathogenesis of COVID-19 leading to uncontrolled and exaggerated inflammation observed during severe COVID-19. However, it remains unclear how immunity to SARS-CoV-2 is induced and subsequently controlled. Notably, here we have uncovered an important role for complement in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonized SARS-CoV-2 via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently interacted with dendritic cells (DCs), inducing type I IFN and pro-inflammatory cytokine responses, which were inhibited by antibodies against the complement receptors (CR)3 and CR4. These data suggest that complement is important in inducing immunity via DCs in the acute phase against SARS-CoV-2. Strikingly, serum from COVID-19 patients as well as monoclonal antibodies against SARS-CoV-2 attenuated innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking the FcyRII, CD32, restored complement-induced immunity. These data strongly suggest that complement opsonization of SARS-CoV-2 is important for inducing innate and adaptive immunity to SARS-CoV-2. Subsequent induction of antibody responses is important to limit the immune responses and restore immune homeostasis. These data suggest that dysregulation in complement and FcyRII signalling might underlie mechanisms causing severe COVID-19.
Human plasma-like medium facilitates metabolic tracing and enables upregulation of immune signaling pathways in glioblastoma explants
Authors: Shami Mohamad El , Savani Milan R , Gattie Lauren C , Smith Bailey , Hicks William H , Rich Jeremy N , Richardson Timothy E , McBrayer Samuel K , Abdullah Kalil G
Published: May 2023

Purpose

Metabolism within the tumor microenvironment (TME) represents an increasing area of interest to understand glioma initiation and progression. Stable isotope tracing is a technique critical to the study of tumor metabolism. Cell culture models of this disease are not routinely cultured under physiologically relevant nutrient conditions and do not retain cellular heterogeneity present in the parental TME. Moreover, in vivo, stable isotope tracing in intracranial glioma xenografts, the gold standard for metabolic investigation, is time consuming and technically challenging. To provide insights into glioma metabolism in the presence of an intact TME, we performed stable isotope tracing analysis of patient-derived, heterocellular Surgically eXplanted Organoid (SXO) glioma models in human plasma-like medium (HPLM).

Methods

Glioma SXOs were established and cultured in conventional media or transitioned to HPLM. We evaluated SXO cytoarchitecture and histology, then performed spatial transcriptomic profiling to identify cellular populations and differential gene expression patterns. We performed stable isotope tracing with15N2-glutamine to evaluate intracellular metabolite labeling patterns.

Results

Glioma SXOs cultured in HPLM retain cytoarchitecture and cellular constituents. Immune cells in HPLM-cultured SXOs demonstrated increased transcription of immune-related signatures, including innate immune, adaptive immune, and cytokine signaling programs.15N isotope enrichment from glutamine was observed in metabolites from diverse pathways, and labeling patterns were stable over time.

Conclusion

To enable ex vivo, tractable investigations of whole tumor metabolism, we developed an approach to conduct stable isotope tracing in glioma SXOs cultured under physiologically relevant nutrient conditions. Under these conditions, SXOs maintained viability, composition, and metabolic activity while exhibiting increased immune-related transcriptional programs.
The Bergen Breakfast Scanning Club dataset: a deep brain imaging dataset
Authors: Wang Meng-Yun , Korbmacher Max , Eikeland Rune , Specht Karsten
Published: May 2023

Populational brain imaging methods based on group averages provide valuable insights into the general functions of the brain. However, they often overlook the inherent inter- and intra-subject variability, limiting our understanding of individual differences. To address this limitation, researchers have turned to big datasets and deep brain imaging datasets. Big datasets enable the exploration of inter-subject variations, while deep brain imaging datasets, involving repeated scanning of multiple subjects over time, offer detailed insights into intra-subject variability. Despite the availability of numerous big datasets, the number of deep brain imaging datasets remains limited. In this article, we present a deep brain imaging dataset derived from the Bergen Breakfast Scanning Club (BBSC) project. The dataset comprises data collected from three subjects who underwent repeated scanning over the course of approximately one year. Specifically, three types of data chunks were collected: behavioral data, functional brain data, and structural brain data. Functional brain images, encompassing magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI), along with their anatomical reference T1-weighted brain images, were collected twice a week during the data collection period. In total, 38, 40, and 25 sessions of functional data were acquired for subjects 1, 2, and 3, respectively. On the other hand, structural brain images, including T2-weighted brain images, diffusion-weighted images (DWI), and fluid-attenuated inversion recovery (FLAIR) images, were obtained once a month. A total of 10, 9, and 6 sessions were collected for subjects 1, 2, and 3, respectively.

The primary objective of this article is to provide a comprehensive description of the data acquisition protocol employed in the BBSC project, as well as detailed insights into the preprocessing steps applied to the acquired data.
Comparison of eDNA, bulk-sample metabarcoding, and morphological approaches: A case study of riverine benthic macroinvertebrate communities
Authors: Doloiras-Laraño Arnelyn D. , Yaegashi Sakiko , Serrana Joeselle M. , Ishitani Naoto , Watanabe Kozo
Published: May 2023

Freshwater biomonitoring is essential for aquatic biodiversity conservation. Advances in high-throughput sequencing allowed parallel sequencing of community samples containing DNA from environmental samples, i.e., metabarcoding. Two approaches of DNA-based method are widely used, bulk-sample metabarcoding the use of bulk tissues such as insects and eDNA the use of environmental samples such as air, water and soil. Despite the novelty of this approach for routine freshwater biomonitoring, questions still need to be answered about its applicability and reliability due to confounding factors, e.g., sample type, laboratory technicalities, and limitations of databases. Hence, studies on direct comparisons are essential to validate the efficiency of these molecular approaches compared to the conventional morphological approach to accurately assessed biodiversity for riverine benthic macroinvertebrate biomonitoring. This study used three approaches to estimate diversity and composition of benthic macroinvertebrates. We also evaluated the relationship between benthic macroinvertebrate communities and environmental factors. We morphologically identified 8,052 individuals from 35 families, 31 genera, and 29 species. eDNA metabarcoding identified 51 families, 84 genera, and 90 species, while 37 families, 55 genera, and 107 species were detected through bulk-sample metabarcoding. We report that bulk-sample metabarcoding showed finer taxonomic resolution than other approaches. Our study highlights the use of bulk-sample metabarcoding for macroinvertebrate biodiversity assessment.
Turing pattern formation in reaction-cross-diffusion systems with a bilayer geometry
Authors: Diez Antoine , Krause Andrew L. , Maini Philip K. , Gaffney Eamonn A. , Seirin-Lee Sungrim
Published: May 2023

Conditions for self-organisation via Turing’s mechanism in biological systems represented by reaction-diffusion or reaction-cross-diffusion models have been extensively studied. Nonetheless, the impact of tissue stratification in such systems is under-explored, despite its ubiquity in the context of a thin epithelium overlying connective tissue, for instance the epidermis and underlying dermal mesenchyme of embryonic skin. In particular, each layer can be subject to extensively different biochemical reactions and transport processes, with chemotaxis – a special case of cross- diffusion – often present in the mesenchyme, contrasting the solely molecular transport typically found in the epidermal layer. We study Turing patterning conditions for a class of reaction-cross- diffusion systems in bilayered regions, with a thin upper layer and coupled by a linear transport law. In particular, the role of differential transport through the interface is explored together with the presence of asymmetry between the homogeneous equilibria of the two layers. A linear stability analysis is carried out around a spatially homogeneous equilibrium state in the asymptotic limit of weak and strong coupling strengths, where quantitative approximations of the bifurcation curve can be computed. Our theoretical findings, for an arbitrary number of reacting species, reveal quantitative Turing conditions, highlighting when the coupling mechanism between the layered regions can either trigger patterning or stabilize a homogeneous equilibrium regardless of the inde- pendent patterning state of each layer. We support our theoretical results through direct numerical simulations, and provide an open source code to explore such systems further.
Learning dynamic image representations for self-supervised cell cycle annotation
Authors: Ulicna Kristina , Kelkar Manasi , Soelistyo Christopher J , Charras Guillaume T , Lowe Alan R
Published: May 2023

Time-based comparisons of single-cell trajectories are challenging due to their intrinsic heterogeneity, autonomous decisions, dynamic transitions and unequal lengths. In this paper, we present a self-supervised framework combining an image autoencoder with dynamic time series analysis of latent feature space to represent, compare and annotate cell cycle phases across singlecell trajectories. In our fully data-driven approach, we map similarities between heterogeneous cell tracks and generate statistical representations of single-cell trajectory phase durations, onset and transitions. This work is a first effort to transform a sequence of learned image representations from cell cycle-specific reporters into an unsupervised sequence annotation.
Functional clustering of splice-altering variants in whole genome sequencing data reveals hidden heritability in rare variant disorder
Authors: Wang Yan , van Dijk Charlotte , Timpanaro Ilia , Hop Paul , Kenna Brendan , Kooyman Maarten , Aronica Eleonora , Pasterkamp R. Jeroen , van den Berg Leonard , Cooper-Knock Johnathan ,   Project MinE ALS sequencing consortium,   NYGC ALS consortium, Veldink Jan , Kenna Kevin
Published: May 2023

Explaining missing heritability in rare disorders requires effective methods to interpret genetic variants. Sequence-to-function models such as SpliceAI support discovery of splice altering variants but filtering their output to identify pathogenic mutations remains challenging. We developed SpliPath to address 2 unmet needs in this process. First, SpliPath links the output of SpliceAI with reference transcriptomics data. This allows users to identify genetic variants that induce unannotated splice isoforms selectively expressed in disease models or patient tissue. Second, SpliPath aggregates variants with similar functional consequences into collapsed splicing quantitative trait loci (csQTLs) for more powerful genetic association analyses. We first used SpliPath to annotate whole genome sequencing (WGS) of 9,467 ALS patients and controls using RNAseq data from an iPSC model of TDP-43 dysfunction. Through this, SpliPath identified 53 variants predicted to enhance cryptic exon (CE) retention events associated with a core ALS pathomechanism. We then applied SpliPath to 294 ALS patients where both WGS and RNAseq were available and discovered missing genetic risk in the known ALS geneKIF5A. This revealed a first of kind intronic mutation hotspot that was validated using minigene reporter assays. Finally, using the same RNAseq data we then predicted 754 candidate csQTL for an independent WGS cohort of 6,625 ALS patients and 2,472 controls. Unbiased genomewide csQTL association testing successfully recoveredKIF5Aand nominatedEPG5as a potential pathogenic gene. These effects were undetectable using simplistic SpliceAI gene burden tests. Collectively, our study demonstrates the utility of SpliPath for uncovering missing heritability in rare disorders.
Prevalence of Erythromycin Resistantemm92-type Invasive Group A Streptococcal Infections in West Virginia, United States, 2021-2023
Authors: Powell Lillie M. , Choi Soo Jeon , Haught Breanna L. , Demkowicz Ryan , LaSala P. Rocco , Lukomski Slawomir
Published: May 2023

Background

Increasing incidence of invasive group AStreptococcus(iGAS) disease has been reported in Europe and United States over the past several years. Coupled with this are observations of higher rates of resistance to non-beta lactam antimicrobials.

Objectives

The aim of this study was to characterize iGAS and pharyngitis isolates from West Virginia (WV), a region outside of the US national active bacteria core surveillance purview, where risk factors associated with iGAS infections are prevalent.

Methods

Seventy-seven invasive group AStreptococcusisolates were collected from sixty-seven unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021-23. Invasive isolates and twenty unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibilities in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based onemm-type and detection of MLSBresistance determinants.

Results

Twenty-six (39%) isolates were of a singleemm-type,emm92. Allemm92isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSBresistance imparted by the plasmid-borneerm(T) gene. The majority ofemm92infections were associated with adult patients who reported intravenous drug use, whereas no pharyngitis infections were caused by anemm92strain. Overall, fifty-one (76%) of the sixty-seven iGAS isolates were determined to carry MLSBresistance.

Conclusions

Isolates ofemm-type 92 predominated in this collection, were uniformly erythromycin/clindamycin resistant, and were associated with adult intravenous drug use but not with pediatric pharyngitis.
Striatal dopamine regulates sleep states and narcolepsy-cataplexy
Authors: Toth Brandon A. , Chang Katie S. , Burgess Christian R.
Published: May 2023

Disruptions to sleep can be debilitating and have a severe effect on daily life. Patients with the sleep disorder narcolepsy suffer from excessive daytime sleepiness, disrupted nighttime sleep, and cataplexy - the abrupt loss of postural muscle tone (atonia) during wakefulness, often triggered by strong emotion. The dopamine (DA) system is implicated in both sleep-wake states and cataplexy, but little is known about the function of DA release in the striatum - a major output region of midbrain DA neurons - and sleep disorders. To better characterize the function and pattern of DA release in sleepiness and cataplexy, we combined optogenetics, fiber photometry, and sleep recordings in a murine model of narcolepsy (orexin−/−; OX KO) and in wildtype mice. Recording DA release in the ventral striatum revealed OX-independent changes across sleep-wake states as well as striking increases in DA release in the ventral, but not dorsal, striatum prior to cataplexy onset. Tonic low frequency stimulation of ventral tegmental efferents in the ventral striatum suppressed both cataplexy and REM sleep, while phasic high frequency stimulation increased cataplexy propensity and decreased the latency to rapid eye movement (REM) sleep. Together, our findings demonstrate a functional role of DA release in the striatum in regulating cataplexy and REM sleep.