bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Utilization of a Nursing-Initiated Supportive Medication Order Panel in the Inpatient Setting
Authors: Tatara Alexandra W. , Lipten Samuel D.
Published: October 2023

Background:

Many medications are low-risk but must undergo the same ordering process as high-risk medications in the inpatient setting. Nurses identify the need for supportive medications and notify providers. An order panel and policy were developed to allow nurses to order low-risk, supportive medications.

Purpose:

The aim of this study was to increase order panel utilization from a 6% to a goal of 15%.

Methods:

This was a quality improvement study at a 1000-bed academic medical center. Five plan-do-study-act (PDSA) cycles were implemented. The primary end point was order panel utilization, and secondary end points were individual nursing unit utilization and the number of orders for each medication on the panel.

Results:

After each PDSA cycle, order panel utilization improved to 7.8%, 13.2%, 7.5%, 10.2%, and 10.6%, respectively. The units using the order panel most often were general medicine (n = 95, 28%), medical intensive care (n = 71, 21%), and inpatient oncology (n = 40, 12%). The medication most frequently ordered was lanolin alcohols–mineral oil with petrolatum (Eucerin) cream (n = 220, 28%).

Conclusions:

Order panel utilization improved from a baseline of 6% to an average of 9.9%. Increasing awareness of the order panel and adding medications will contribute to improvement in order panel utilization in the long-term.
Burnout Among Family Physicians in the United States: A Review of the Literature
Authors: Hoff Timothy , Trovato Kathryn , Kitsakos Aliya
Published: October 2023

Background and Objectives:

Burnout among physicians who work in primary care is an important problem that impacts health care quality, local communities, and the public's health. It can degrade the quality of primary care services in an area and exacerbate workforce shortages. This study conducted a review of the published research on burnout among family physicians working in the United States.

Methods:

We used a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided approach and several article databases to identify, filter, and analyze published research on US family physician burnout that uses data collected from 2015 onward.

Results:

Thirty-three empirical studies were identified with findings that included US family physician burnout prevalence and/or associations between burnout and specific personal and contextual drivers. Mean family physician burnout prevalence across studies that measured it was 35%. Almost half of the studies classified one-third or more of their family physician samples as burned out. Physician gender (being female), age (being younger), and job/work-related factors (workload, time pressures) were the most commonly identified correlates of family physician burnout. The vast majority of studies were cross-sectional and used secondary data.

Conclusions:

The extant research literature on family physician burnout in the United States shows that burnout is currently a meaningful problem. Several important correlates of the problem can be identified, some of which managers and health care organizations can proactively address. Other correlates require managers and health care organizations also viewing family physicians in differentiated ways. The collective literature can be improved through a more consistent focus on similar burnout correlates across studies; inclusion of interventions aimed at lessening the effects of key burnout correlates; employment of more robust longitudinal and quasi-experimental research designs; and additional pandemic-era data collection on burnout.
Intent matters: how flow and forms of information impact collective navigation
Authors: Hodgson T. M. , Johnston S. T. , Ottobre M. , Painter K. J.
Published: October 2023

The phenomenon of collective navigation has received considerable interest in recent years. A common line of thinking, backed by theoretical studies, is that collective navigation can improve navigation efficiency through the ‘many-wrongs’ principle, whereby individual error is reduced by comparing the headings of neighbours. When navigation takes place in a flowing environment, each individual’s trajectory is influenced by drift. Consequently, a potential discrepancy emerges between an individual’s intended heading and its actual heading. In this study, we develop a theoretical model to explore whether collective navigation benefits are altered according to the form of heading information transmitted between neighbours. Navigation based on each individual’s intended heading is found to confer robust advantages across a wide spectrum of flows, via both a marked improvement in migration times and a capacity for a group to overcome flows unnavigable by solitary individuals. Navigation based on individual’s actual headings is far less effective, only offering an improvement under highly favourable currents. For many currents, sharing actual heading information can even lead to journey times that exceed those of individual navigators.
Rapid, non-invasive,
in vivo
measurement of tissue mechanical properties using gravitational loading and a nonlinear virtual fields method
Authors: Evans S. L. , Keenan B. E. , Hill J. , Zappala S. , Bennion N. , Avril S.
Published: October 2023

Measuring the mechanical properties of soft tissues
in vivo
is important in biomechanics and for diagnosis and staging of diseases, but challenging because it is difficult to control the boundary conditions. We present a novel, non-invasive method for measuring tissue properties using gravitational loading. MRI images of an organ in different positions are registered to measure tissue displacements due to gravitational forces in different positions. Considering equilibrium between stresses and gravity, we established a nonlinear virtual fields method to identify the tissue properties. The method was applied to the human brain as a proof of concept, using an Ogden model. Sensitivity analysis showed that the bulk modulus could be identified accurately while the shear modulus was identified with greater uncertainty; the strains were too small to identify the strain stiffening exponent. The measured properties agreed well with published
in vitro
data. The technique offers very promising perspectives, allowing the non-invasive measurement of otherwise inaccessible tissues and providing new information such as the bulk modulus under static loading, which has never previously been measured
in vivo
.
A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays
Authors: Shajib Md. Shafiullah , Futrega Kathryn , Davies Anthony M. , Franco Rose Ann G. , McKenna Eamonn , Guillesser Bianca , Klein Travis J. , Crawford Ross W. , Doran Michael R.
Published: October 2023

If it were possible to purchase tumour-spheroids as a standardised product, ready for direct use in assays, this may contribute to greater research reproducibility, potentially reducing costs and accelerating outcomes. Herein, we describe a workflow where uniformly sized cancer tumour-spheroids are mass-produced using microwell culture, cryopreserved with high viability, and then cultured in neutral buoyancy media for drug testing. C4-2B prostate cancer or MCF-7 breast cancer cells amalgamated into uniform tumour-spheroids after 48 h of culture. Tumour-spheroids formed from 100 cells each tolerated the cryopreservation process marginally better than tumour-spheroids formed from 200 or 400 cells. Post-thaw, tumour-spheroid metabolic activity was significantly reduced, suggesting mitochondrial damage. Metabolic function was rescued by thawing the tumour-spheroids into medium supplemented with 10 µM
N
-Acetyl-
l
-cysteine (NAC). Following thaw, the neutral buoyancy media, Happy Cell ASM, was used to maintain tumour-spheroids as discrete tissues during drug testing. Fresh and cryopreserved C4-2B or MCF-7 tumour-spheroids responded similarly to titrations of Docetaxel. This protocol will contribute to a future where tumour-spheroids may be available for purchase as reliable and reproducible products, allowing laboratories to efficiently replicate and build on published research, in many cases, making tumour-spheroids simply another cell culture reagent.
An oil-absorbing resin with a simple polymerization system with benzyl methacrylate as a functional monomer
Authors: Zhou Yanjia , Zhang Ming , Liu Yongqiang , Xu Bo , Qiu Haiyan , Che Xiuli , Lan Guihong
Published: October 2023

To solve the problem of the low absorbency of oil-absorbing resins, oil-absorbing resins (PAMs) were fabricated in this study by introducing commercially available benzyl methacrylate (BZMA) as a functional monomer copolymerized with stearyl methacrylate (SMA) and butyl acrylate (BA). The internal network structure of the PAMs expanded more easily when absorbing oils or organic solvents after introducing rigid groups of the benzene ring by an uncomplex polymerization process, which provided the oil-absorbing resin with good absorbency. The reagents were all commercially available, and there was no other pretreatment or posttreatment process. Then, the optimum parameters for the monomer feed ratio, water/oil mass ratio, and concentrations of initiator, stabilizer and crosslinker were studied. Simultaneously, the reusability, oil retention and thermal stability of PAMs were investigated in this article. The PAMs swelled in various oils and organic solvents (the values of oil absorbency were 44.52, 56.13, 25.54, 28.21, 32.85, 24.56, 14.17, 15.02 and 29.07 g g
−1
for CCl
4
, CHCl
3
, CH
2
Cl
2
, benzene, toluene, xylene, n-hexane, 0# diesel oil and 93# gasoline, respectively) and displayed good oil absorbency, which met the absorption requirements for common oils or organic solvents.
Stochastic modelling of intersectional pay gaps in universities
Authors: Barrett-Walker Tessa , Buelow Franca , Te Atu O Tu MacDonald Lindsey , Brower Ann , James Alex
Published: October 2023

The gender and ethnicity pay gaps are well publicised for academics. The majority of research relies on observations representing a point in time or uses models to consider a standard academic lifespan. We use a stochastic mathematical model to ask what drives differences in lifetime earnings of university academics and highlight a new question: how best should we quantify a working lifetime? The model observes and accounts for patterns in age when entering and leaving the workforce, and differing salary trajectories during an academic career. It is parameterized with data from a national dataset in Aotearoa New Zealand. We compare the total lifetime earnings of different gender and ethnicity groups with and without accounting for the different lengths of time spent in academia. The lifetime earnings gaps are considerably larger when we account for different hiring and leaving ages. We find that overall, for every ethnicity, women have shorter careers and are more likely to leave academia. All minority ethnic groups—and women—earn considerably less than their male white, European colleagues.
The essential habitat role of a unique coastal inlet for a widely distributed apex predator
Authors: De Wysiecki Agustín M. , Barnett Adam , Cortés Federico , Wiff Rodrigo , Merlo Pablo J. , Jaureguizar Andrés J. , Awruch Cynthia A. , Trobbiani Gastón A. , Irigoyen Alejo J.
Published: October 2023

Essential habitats support specific functions for species, such as reproduction, feeding or refuge. For highly mobile aquatic species, identifying essential habitats within the wider distribution range is central to understanding species ecology, and underpinning effective management plans. This study examined the movement and space use patterns of sevengill sharks (
Notorynchus cepedianus
) in Caleta Valdés (CV), a unique coastal habitat in northern Patagonia, Argentina. Seasonal residency patterns of sharks were evident, with higher detectability in late spring and early summer and lower during autumn and winter. The overlap between the residency patterns of sharks and their prey, elephant seals, suggests that CV functions as a seasonal feeding aggregation site for
N. cepedianus
. The study also found sexual differences in movement behaviour, with males performing abrupt departures from CV and showing increased roaming with the presence of more sharks, and maximum detection probability at high tide. These movements could be related to different feeding strategies between sexes or mate-searching behaviour, suggesting that CV may also be essential for reproduction. Overall, this study highlights the importance of coastal sites as essential habitats for
N. cepedianus
and deepens our understanding of the ecological role of this apex predator in marine ecosystems.
Drop dead! Female mate avoidance in an explosively breeding frog
Authors: Dittrich Carolin , Rödel Mark-Oliver
Published: October 2023

Males’ and females’ reproductive strategies may differ, potentially leading to sexual conflict. Increased efforts by males (harassment, forced copulation, intimidation) to gain access to females could even negatively affect female survival and thus lead to reproductive failure for both individuals. In anurans, a higher mortality risk of mating females has been reported in explosive breeding species. During these mating events, several males cling to a female, which are mostly unable to get rid of the unwanted males. This can lead to the female's death. From the literature, it seems that females of explosive breeding frogs have no means to reject unwanted males. Here we describe female mate avoidance behaviours in the European common frog. We observed three female avoidance behaviours, namely ‘rotation’, ‘release call(s)’ and tonic immobility (death feigning). These behaviours were significantly associated with smaller female body size, and smaller females were more successful in escaping amplexus. Tonic immobility as a tactic to avoid mating or male harassment has only been observed in a handful of species and only in one other amphibian. Our observations show that females in explosive breeding frogs may not be as passive and helpless as previously thought.
Emotions and mathematics: anxiety profiles and their influence on arithmetic performance in university students
Authors: Rossi Serena , Xenidou-Dervou Iro , Cipora Krzysztof
Published: October 2023

Mathematics anxiety (MA), general and test anxieties affect mathematics performance. However, little is known about how different anxiety profiles (i.e. individual configurations of anxiety forms) influence the relationship between MA and mathematics performance in university students. To the best of our knowledge, studies that have categorized participants based on their anxiety profiles and investigated how such groups differ in mathematics performance and other individual characteristics have all been conducted only with children and adolescents. Using latent profile analysis, we identified five different anxiety profiles in UK university students (N= 328) based on their MA, test anxiety (TA) and trait general anxiety levels (GA). Beyond extreme profiles (high or low levels in all forms of anxiety), we found groups characterized by more specific anxiety forms (MA profile, TA profile and high anxiety with low MA learning profile). These profiles were differentially related to arithmetic performance (but not the performance in a non-mathematics task), and individual factors (e.g. self-concept and self-efficacy). Results can inform the design of interventions tailored to individuals' unique anxiety profiles and highlight the necessity to further study the underpinning mechanisms that drive the MA developmental trajectory from childhood to adulthood.
Learning in ensembles of proteinoid microspheres
Authors: Mougkogiannis Panagiotis , Adamatzky Andrew
Published: October 2023

Proteinoids are thermal proteins which form microspheres in water in the presence of salt. Ensembles of proteinoid microspheres exhibit passive nonlinear electrical properties and active neuron-like spiking of electrical potential. We propose that various neuromorphic computing architectures can be prototyped from the proteinoid microspheres. A key feature of a neuromorphic system is a learning. Through the use of optical and resistance measurements, we study mechanisms of learning in ensembles of proteinoid microspheres. We analyse 16 types of proteinoids study and their intrinsic morphology and electrical properties. We demonstrate that proteinoids can learn, memorize and habituate, making them a promising candidate for novel computing.
The affinities of the Late Triassic
Cryptovaranoides
and the age of crown squamates
Authors: Brownstein Chase D. , Simões Tiago R. , Caldwell Michael W. , Lee Michael S. Y. , Meyer Dalton L. , Scarpetta Simon G.
Published: October 2023

Most living reptile diversity is concentrated in Squamata (lizards, including snakes), which have poorly known origins in space and time. Recently, †
Cryptovaranoides microlanius
from the Late Triassic of the United Kingdom was described as the oldest crown squamate. If true, this result would push back the origin of all major lizard clades by 30–65 Myr and suggest that divergence times for reptile clades estimated using genomic and morphological data are grossly inaccurate. Here, we use computed tomography scans and expanded phylogenetic datasets to re-evaluate the phylogenetic affinities of †
Cryptovaranoides
and other putative early squamates. We robustly reject the crown squamate affinities of †
Cryptovaranoides
, and instead resolve †
Cryptovaranoides
as a potential member of the bird and crocodylian total clade, Archosauromorpha. Bayesian total evidence dating supports a Jurassic origin of crown squamates, not Triassic as recently suggested. We highlight how features traditionally linked to lepidosaurs are in fact widespread across Triassic reptiles. Our study reaffirms the importance of critically choosing and constructing morphological datasets and appropriate taxon sampling to test the phylogenetic affinities of problematic fossils and calibrate the Tree of Life.
Tail shape and the swimming speed of sharks
Authors: Iliou Anthony S. , Vanderwright Wade , Harding Lucy , Jacoby David M. P. , Payne Nicholas L. , Dulvy Nicholas K.
Published: October 2023

Trait-based ecology is a rapidly growing approach for developing insights and predictions for data-poor species. Caudal tail fin shape has the potential to reveal much about the energetics, activity and ecology of fishes and can be rapidly measured from field guides, which is particularly helpful for data-sparse species. One outstanding question is whether swimming speed in sharks is related to two morphological traits: caudal fin aspect ratio (CFAR, height
2
/tail area) and caudal lobe asymmetry ratio (CLAR). We derived both metrics from the species drawings in
Sharks of the world
(Ebert
et al.
2013
Sharks of the world:
a fully illustrated guide
) and related fin shape to two published datasets of (1) instantaneous swimming speeds (Jacoby
et al.
2015
Biol. Lett.
11
, 20150781 (
doi:10.1098/rsbl.2015.0781
)) and (2) cruising speeds (Harding
et al.
2021
Funct. Ecol.
35
, 1951–1959 (
doi:10.1111/1365-2435.13869
)) for 28 total unique shark species. Both estimates of swimming speed were positively related to CFAR (and weakly negatively to CLAR). Hence, shark species with larger CFAR and more symmetric tails (low CLAR) tended to be faster-moving and have higher average speeds. This relationship demonstrates the opportunity to use tail shape as an easily measured trait to index shark swimming speed to broader trait-based analyses of ecological function and extinction risk.
Distinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex
Authors: Zak Joseph D. , Reddy Gautam , Konanur Vaibhav , Murthy Venkatesh N.
Published: October 2023

Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Odorant mixtures of increasing complexity evoked progressively denser OSN activity, yet cortical feedback activity was of similar sparsity for all stimuli. Representations of complex mixtures were similar in OSNs but were decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibited a sigmoidal relationship, cortical axonal responses were complex and non-monotonic, which could be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to both local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.
Stromal localization of inactive CD8+T cells in metastatic mismatch repair deficient colorectal cancer
Authors: Küçükköse Emre , Baars Matthijs J.D. , Amini Mojtaba , Schraa Suzanna J. , Floor Evelien , Bol Guus M. , Rinkes Inne H.M. Borel , Roodhart Jeanine M.L. , Koopman Miriam , Laoukili Jamila , Kranenburg Onno , Vercoulen Yvonne
Published: October 2023

Background

The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC.

Methods

We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of stromal and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry.

Results

High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+T cells in non-metastatic tumors. CD8+T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort.

Conclusion

We conclude that localization of phenotypically distinct CD8+T cells within stroma may predict metastasis formation in MSI-H CRC.
Changes in electrophysiological aperiodic activity during cognitive control in Parkinson’s disease
Authors: Monchy Noémie , Modolo Julien , Houvenaghel Jean-François , Voytek Bradley , Duprez Joan
Published: October 2023

Cognitive symptoms in Parkinson’s disease (PD) are common and can significantly affect patients’ quality of life. Therefore, there is an urgent clinical need to identify a signature derived from behavioral and/or neuroimaging indicators that could predict which patients are at increased risk for early and rapid cognitive decline. Recently, converging evidence identified electroencephalogram (EEG) aperiodic activity as meaningful physiological information associated with age, development, cognitive and perceptual states or pathologies. In this study, we aimed to investigate aperiodic activity in PD during cognitive control and characterize its possible association with behavior.

Here, we recorded high-density EEG (HD-EEG) in 30 healthy controls and 30 PD patients during a Simon task. We analyzed task-related behavioral data in the context of the activation-suppression model and extracted aperiodic parameters (offset, exponent) at both scalp and source levels.

Our results showed behavioral alterations of cognitive control as well as higher offsets in patients in the parieto-occipital areas, suggesting increased excitability in PD. A small congruence effect on aperiodic parameters in pre- and post-central brain areas was also found, possibly associated with task execution. Significant differences in aperiodic parameters between the resting state, pre- and post-stimulus phases all across the scalp and cortex confirmed that the observed changes in aperiodic activity are linked to task execution. No correlation was found between aperiodic activity and behavior or clinical features.

Our findings provide evidence that EEG aperiodic activity in PD is characterized by greater offsets, and that aperiodic parameters differ depending on arousal state. However, our results do not support the hypothesis that the behavior-related differences observed in PD are related to aperiodic changes. Overall, this study highlights the importance of considering aperiodic activity contributions in brain disorders and further investigating the relationship between aperiodic activity and behavior.
Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT)
Authors: Brunet J. , Cook A. C. , Walsh C. L. , Cranley J. , Tafforeau P. , Engel K. , Berruyer C. , Burke O’Leary E. , Bellier A. , Torii R. , Werlein C. , Jonigk D. D. , Ackermann M. , Dollman K. , Lee P. D.
Published: October 2023

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one ‘control’ without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac ‘blueprint’ with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.
Do calcium channel blockers applied to cardiomyocytes cause increased channel expression resulting in reduced efficacy?
Authors: Jæger Karoline Horgmo , Charwat Verena , Wall Samuel , Healy Kevin E. , Tveito Aslak
Published: October 2023

In the initial hours following the application of the calcium channel blocker (CCB) nifedipine to microtissues consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we observe notable variations in the drug’s efficacy. Here, we investigate the possibility that these temporal changes in CCB effects are associated with adaptations in the expression of calcium ion channels in cardiomyocyte membranes. To explore this, we employ a recently developed mathematical model that delineates the regulation of calcium ion channel expression by intracellular calcium concentrations. According to the model, a decline in intracellular calcium levels below a certain target level triggers an upregulation of calcium ion channels. Such an upregulation, if instigated by a CCB, would then counteract the drug’s inhibitory effect on calcium currents. We assess this hypothesis using time-dependent measurements of hiPSC-CMs dynamics and by refining an existing mathematical model of myocyte action potentials incorporating the dynamic nature of the number of calcium ion channels. The revised model forecasts that the CCB-induced reduction in intracellular calcium concentrations leads to a subsequent increase in calcium ion channel expression, thereby attenuating the drug’s overall efficacy. The data and fit models suggests that dynamic changes in cardiac cells in the presence of CCBs may be explainable by induced changes in protein expression, and that this may lead to challenges in understanding calcium based drug effects on the heart unless timings of applications are carefully considered.
A target-free approach to estimate thermal camera pose in LiDAR scenes of feature-deficient environments
Authors: Jandeleit Julian , Beleyur Thejasvi , Goldlüecke Bastian
Published: October 2023

Modern animal behaviourists are able to collect vast amounts of data from multiple sensors. Sensor fusion however still remains a challenge given the unique sensor types biologists use. Here we study thermal camera-LiDAR alignment. While LiDAR-RGB scene alignment is well-established in feature-rich scenes with reliable inter-camera correspondences, thermal scenes are often captured with low-resolution devices and suffer from halo and history effects, and thus require sensor-specific algorithms. To deal with this, we present the depth-map correspondence (DMCP) algorithm. DMCP is a semi-automatic algorithm to fuse Li-DAR with feature-deficient thermal scenes without explicit calibration objects. The user annotates at least 4 corresponding points on the thermal image and a depth map of the LiDAR scene, which allows us to compute the position and orientation of the thermal camera within the scene. We quantify the accuracy of alignment using 2D reprojection error and 3D nearest-neighbour distances of known world points across experimental trials. A median reprojection error of 7.7 (95%ile: 3.7-23.5) pixels was achieved. Known objects lying on the LiDAR mesh showed a median nearest-neighbour mesh distance of 0.12 m (95%ile: 0.007-5.61 m). We present the first such alignment of feature-deficient thermal scenes and LiDAR data. DMCP has two advantages 1) it is computationally straightforward to implement and 2) requires minimal user annotation to work. DMCP could be broadly applied to any type of mesh-image alignment problem. Finally we provide DMCP and the Ushichka dataset as a baseline for further research on the challenging problem of subterranean thermal-LiDAR alignment.
Systemic Metabolic Depletion of Intestine Microbiome Undermines Melanoma Immunotherapy Effectiveness
Authors: Zakharevich Natalia V. , Morozov Maxim D. , Kanaeva Vera A. , Ivanov Artem B. , Ulyantsev Vladimir I. , Klimina Ksenia M. , Olekhnovich Evgenii I.
Published: October 2023

Immunotherapy has proven to be a boon for patients grappling with metastatic melanoma, significantly enhancing their clinical condition and overall quality of life. A compelling connection was discovered between the composition of the intestinal microbiome and the effectiveness of immunotherapy substantiated in both animal models and human patients. Nonetheless, the precise biological mechanisms through which gut microbes influence melanoma treatment outcomes remain poorly understood. This study conducted a high-resolution metagenomic meta-analysis, employing cutting-edge bioinformatics techniques including genome-resolved metagenomics, strain profiling, comparative genomics, and metabolic reconstruction. According to the obtained results, the systemic metabolic depletion of the gut microbiome causes a lack of response to immunotherapy. Specifically, the presence of bacteria adept at utilizing polysaccharides, as well as those responsible for cobalamin, amino acids, and fatty acids production, decreased in patients who experienced unfavorable treatment outcomes. In contrast, patients who had successful outcomes after immunotherapy exhibited a prevalence of amino acids and cobalamin prototrophs, while autotrophy in these substances characterized the microbiomes of patients with unsuccessful outcomes. The metabolic reconstruction of short-chain fatty acid biosynthesis pathways did not differentiate bacteria linked to treatment outcomes based on their ability to produce acetate, butyrate, or propionate. However, the cobalamin-dependent Wood-Ljungdahl pathway of acetate synthesis was directly associated with immunotherapy effectiveness.
Comparing Neural Correlates of Memory Encoding and Maintenance for Foveal and Peripheral Stimuli
Authors: Kandemir G. , Olivers C.N.L.
Published: October 2023

Visual working memory is believed to rely on top-down attentional mechanisms that sustain active sensory representations in early visual cortex. However, both bottom-up sensory input and top-down attentional modulations thereof have been shown to be biased towards the fovea, at the expense of the periphery, and initially peripheral percepts may even be assimilated by foveal processing. This raises the question whether and how visual working memory differs for central and peripheral input. To address this, we conducted a delayed orientation recall task in which an orientation stimulus was presented either at the center of the screen or at 15° eccentricity to the left or right. Response accuracy, electroencephalographic (EEG) activity and gaze position were recorded from 30 participants. Accuracy was slightly but significantly higher for foveal versus peripheral memories. Orientation decoding analyses of the EEG signals revealed a clear dissociation between early sensory and later maintenance signals. While sensory signals were clearly decodable for the central location, they were not for peripheral locations. In contrast, maintenance signals were decodable to an equal extent for both foveal and peripheral memories, suggesting comparable top-down components regardless of eccentricity. Moreover, while memory representations were initially spatially specific and reflected in voltage fluctuations, later in the maintenance period they generalized across locations, as emerged in alpha oscillations, thus revealing a dynamic transformation within memory. Moreover, these transformed representations remained accessible through sensory impulse-driven perturbations, unveiling the underlying memory state. The eccentricity-driven dissociation between disparate sensory and common maintenance representations indicates that storage activity patterns as measured by EEG reflect signals beyond primary visual cortex.
Divergent evolutionary strategies preempt tissue collision in fly gastrulation
Authors: Dey Bipasha , Kaul Verena , Kale Girish , Scorcelletti Maily , Takeda Michiko , Wang Yu-Chiun , Lemke Steffen
Published: October 2023

Metazoan development proceeds through a series of morphogenetic events that sculpt body plans and organ structures. In the early embryonic stages, morphogenetic processes involving growth and deformation occur concurrently. Forces generated in one tissue can thus increase mechanical stress in the neighboring tissue, potentially disrupting spatial patterning, morphological robustness, and consequently decreasing organismal fitness. How organisms evolved mechanisms to reduce or release inter-tissue stresses remains poorly understood. Here we combined phylogenetic survey across a whole insect order (Diptera), quantitative live imaging, and functional mechanical perturbation to investigate the evolution of mechanical stress management during epithelial expansions in the gastrulating fly embryos. We find that two distinct cellular mechanisms exist in Diptera to prevent the accumulation of compressive stress that can arise when the expanding head and trunk tissues collide. In Cyclorrhapha, a monophyletic dipteran subgroup including the fruit flyDrosophila melanogaster, the head-trunk boundary undergoes active out-of-plane deformation to form a transient epithelial fold, called the cephalic furrow (CF), which acts as a mechanical sink to preempt head-trunk collision. Genetic or optogenetic elimination of the CF leads to tissue buckling, yielding deleterious effects of axial distortion that likely results from unmitigated release of compressive stress. Non-cyclorrhaphan flies, by contrast, lack CF formation and instead display widespread out-of-plane division in the head, which shortens the duration of its expansion and reduces surface area increase. Reorienting head mitosis inDrosophilafrom in-plane to out-of-plane partially suppresses the need for epithelial out-of-plane deformation, suggesting that out-of-plane division can act as an alternative mechanical sink to prevent tissue collision. Our data suggest that programs of mechanical stress management can emerge abruptly under selective pressure of inter-tissue mechanical conflict in early embryonic development.
Mapping lung hematopoietic progenitors: Developmental kinetics and response to Influenza A viral infection
Authors: Mincham Kyle T. , Lauzon-Joset Jean-Francois , Read James F. , Holt Patrick G. , Stumbles Philip A. , Strickland Deborah H.
Published: October 2023

The bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood. These lung progenitors display distinct microenvironment-specific developmental kinetics compared to their bone marrow counterparts, exemplified by a rapid shift from a common myeloid to megakaryocyte-erythrocyte progenitor dominated niche with increasing age. In adult mice, Influenza A viral infection results in a transient reduction in multipotent progenitors within the lungs, with a parallel increase in downstream granulocyte-macrophage progenitors and dendritic cell populations associated with acute viral infections. Our findings suggest lung hematopoietic progenitors play a role in re-establishing immunological homeostasis in the respiratory mucosa, which may have significant clinical implications for maintaining pulmonary health following inflammatory perturbation.
Menstrual cycle-driven hormone concentrations co-fluctuate with white and grey matter architecture changes across the whole brain
Authors: Rizor Elizabeth J. , Babenko Viktoriya , Dundon Neil M. , Beverly-Aylwin Renee , Stump Alexandra , Hayes Margaret , Herschenfeld-Catalan Luna , Jacobs Emily G. , Grafton Scott T.
Published: October 2023

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA), while follicle-stimulating hormone (FSH) was directly proportional to cortical thickness. Within several individual regions, FSH and progesterone demonstrated opposing associations with mean diffusivity and cortical thickness. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Lastly, progesterone was associated with increased tissue and decreased CSF volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and cortical thickness coinciding with menstrual cycle-driven hormone rhythms. Strong brain-hormone interaction effects may not be limited to classically known HPG-axis receptor-dense regions.
Parental infertility and offspring cardiometabolic trajectories up to 25 years: a pooled analysis of three European cohorts
Authors: Hernáez Álvaro , Elhakeem Ahmed , Barros Henrique , Vrijkotte Tanja G. M. , Fraser Abigail , Lawlor Deborah A. , Magnus Maria C.
Published: October 2023

Objective

To assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring from childhood to 25 years of age.

Design

Pooled analysis of three European pregnancy cohort studies.

Subjects

Up to 14,609 singletons from three pregnancy cohorts (the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and their Development study).

Exposure

Parental infertility defined as time-to-pregnancy ≥12 months.

Main Outcome Measures

Trajectories of body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose from childhood to 25 years of age were compared in offspring of couples with and without infertility. Trajectories were modelled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, body mass index, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared by parental infertility.

Results

Offspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25: +1.09 kg/m2, 95% confidence interval [0.68 to 1.50]) and suggestively higher DBP at age 25 (+1.21 mmHg [0.00 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age 25, LDL-C: +4.07% [-0.79 to 8.93]; HDL-C: −2.78% [-6.99 to 1.43]). At middle-late adolescence, offspring of couples with infertility had higher waist circumference (age 17: +1.05 cm [0.11 to 1.99]) and SBP (age 17: +0.93 mmHg [0.044 to 1.81]), but these differences attenuated at later ages. No clear inter-group differences in triglyceride and glucose trajectories were observed. Further adjustment for paternal age, body mass index, smoking, and educational level, and both parent’s history of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate inter-group differences.

Conclusion

Offspring of couples with infertility have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.
Modeling Sepsis-Associated ARDS Using a Lung Endothelial Microphysiological System
Authors: Liang Nai-Wen , Wilson Carole , Davis Brooke , Wolf Ian , Qyli Tonela , Moy Joy , Beebe David J. , Schnapp Lynn M. , Kerr Sheena C. , Faust Hilary E.
Published: October 2023

Acute respiratory distress syndrome due to non-pulmonary causes exhibits prominent endothelial activation which is challenging to assess in critically ill patients. Preclinicalin vivomodels of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses. Use of microphysiological systems (MPS) offer improved fidelity to human biological responses and better predict pharmacological responses than traditional culture. We adapted a lung endothelial MPS based on the LumeNEXT platform to evaluate the effect of plasma from critically ill sepsis patients on endothelial permeability, adhesion molecule expression and inflammatory cytokine production. Lumens incubated with sepsis plasma exhibited areas of contraction, loss of cellular coverage, and luminal defects. Sepsis plasma-incubated lumens had significantly increased permeability compared to lumens incubated with healthy donor plasma. ICAM-1 expression increased significantly in lumens incubated with sepsis plasma compared with those incubated with healthy control plasma, while concentrations of IL-6, IL-18, and soluble VEGF-R1 increased in sepsis plasma before and after incubation in the MPS compared with healthy control plasma. Use of the lung endothelial MPS may enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients.
Cell specific single viral vector CRISPR/Cas9 editing and genetically encoded tool delivery in the central and peripheral nervous systems
Authors: Moffa Jamie C. , Bland India N. , Tooley Jessica R. , Kalyanaraman Vani , Heitmeier Monique , Creed Meaghan C. , Copits Bryan A.
Published: October 2023

Gene manipulation strategies using germline knockout, conditional knockout, and more recently CRISPR/Cas9 are crucial tools for advancing our understanding of the nervous system. However, traditional gene knockout approaches can be costly and time consuming, may lack cell-type specificity, and can induce germline recombination. Viral gene editing presents and an exciting alternative to more rapidly study genes of unknown function; however, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we have developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific editing across the nervous system. Expressing Cre-dependent Cas9 in specific cell types in transgenic mouse lines affords more space to package guide RNAs for gene editing together with Cre-dependent, genetically encoded tools to manipulate, map, or monitor neurons using a single virus.

We validated this strategy with three commonly used tools in neuroscience: ChRonos, a channelrhodopsin, for manipulating synaptic transmission using optogenetics; GCaMP8f for recording Ca2+ transients using fiber photometry, and mCherry for anatomical tracing of axonal projections. We tested these tools in multiple brain regions and cell types, including GABAergic neurons in the nucleus accumbens (NAc), glutamatergic neurons projecting from the ventral pallidum (VP) to the lateral habenula (LHb), dopaminergic neurons in the ventral tegmental area (VTA), and parvalbumin (PV)-positive proprioceptive neurons in the periphery. This flexible approach should be useful to identify novel genes that affect synaptic transmission, circuit activity, or morphology with a single viral injection.