bluuebunny/crossref_metadata_2025 huggingface dataset:
Disc Versus Vertebral Body Contribution to Lumbar Lordosis in Asymptomatic Subjects
Authors: Khalifé Marc , Lafage Renaud , Ferrero Emmanuelle , Elysée Jonathan , Assi Ayman , Gille Olivier , Finoco Mikael , Skalli Wafa , Guigui Pierre , Vergari Claudio , Lafage Virginie
Published: September 2024

Study Design.

Retrospective study of a multicentric prospective database.

Objective.

This study aimed at describing the relative contribution of vertebral bodies versus discs to lumbar lordosis, and its variation with age and pelvic incidence.

Summary of Background Data.

While studies sought to determine the physiological magnitude and distribution of lumbar lordosis, data regarding its anatomical composition is lacking.

Methods.

This study included healthy volunteers with full-body stereoradiographs in free-standing position, without lumbosacral transitional vertebra or age under 18. The following parameters were analyzed: age, sex, pelvic incidence (PI), lumbar lordosis (LL). Posterior heights and sagittal Cobb angles between upper and lower endplate for each lumbar disc and each vertebral body were measured from L1 to S1. Ratios of contribution to LL were calculated for each disc and vertebral body. The cohort was divided into four age groups and four PI groups.

Results.

645 subjects were included, mean age was 37.6±16.3, 51% of females. There was a significant decrease in total lumbar disc lordosis with age (−48.9±9.7° to −42.9±10.2°), occurring in lower LL. Vertebral bodies were significantly more kyphotic in Seniors than Youngs (−8.9±8.4° vs. −5.0±9.4°, P=0.03), driven by a significant increase in kyphosis of L1 and L2 bodies. Vertebral body contribution to LL significantly increased between groups as PI increased, from a median of 8.0% to 20.5% (P<0.001). This decrease in disc contribution in favor of vertebral bodies mainly took place in lower LL.

Conclusion.

This study highlights the importance of vertebral contribution to lumbar lordosis, ranging from 8 to 21% among PI groups. Lumbar lordosis decreased with aging through decreased disc lordosis in the lower lumbar spine and increased body kyphosis in the upper lumbar spine. These results may help surgeons in the assessment of sagittal alignment and the selection of operative technique to achieve surgical correction.
The role of international renal disaster preparedness working groups in difficult settings: bridge over troubled water
Authors: Yoo Kyung Don , Chao Chia-Ter , Lee Jung Pyo , Abu-Alfa Ali K.
Published: September 2024

Purpose of review

Disasters, natural and man-made, are rising in frequency and pose significant challenges to the provision of renal care worldwide. Patients with kidney disease, particularly those on dialysis, are extremely vulnerable during disasters. This timely review summarizes the potential roles international renal disaster preparedness working groups have in addressing these challenges.

Recent findings

The vulnerability of kidney patients has galvanized the evolution of global response mechanisms and the contemporary efforts of various organizations. In this review, the importance of preparedness, networking, and collaborations at all levels are highlighted, citing recent crises. It will also note key areas for improvement, including an enhanced engagement with global health organizations. Finally, it is imperative to urge the international community to recognize that individuals with kidney disease are often among the first patient groups to suffer in disaster zones. These messages are intended to persuade global stakeholders that kidney patients, including pediatric ones, should be prioritized as requiring immediate support during disasters.

The unique and life-threatening challenges faced by individuals with kidney disease in natural disaster- or war-torn areas demand special consideration in humanitarian efforts and international crisis response strategies. International organizations can play a major role in this regard.
The Impact of Leisure-Time Physical Activity and Sedentary Behavior on Mortality in Patients with Chronic Obstructive Pulmonary Disease
Authors: Yuan Lindong , Zhang Lihai , Wang Yan , Zhao Peige , Xie Xiang , Cao Dongming
Published: September 2024

Objective

This study sought to examine the association between inactive time, leisure-time physical activity (LTPA), and mortality in individuals diagnosed with chronic obstructive pulmonary disease (COPD).

Design

This study utilized a nationally representative sample of patients with COPD from National Health and Nutrition Examination Survey (NHANES) survey (n = 1817; weighted population, 23,698,840). Mortality was tracked from the date of interview and examination. LTPA and sedentary time were assessed using a Global Physical Activity Questionnaire.

Results

The study found that only 28% of patients with COPD achieved sufficient LTPA (LTPA ≥150 min/week), while 58% reported no physical activity and 47% sat for over six hours per day. Over a nine-year follow-up period, 501 deaths occurred, with 101 due to heart diseases. Adequate LTPA levels were associated with a decreased risk of mortality from any cause. Moreover, patients who engaged in sufficient LTPA and reduced sitting time had a lower risk of mortality from any cause compared to those who did not engage in sufficient LTPA.

Conclusion

Participating in an adequate amount of LTPA was linked to a reduced risk of death from any cause in patients with COPD. However, irrespective of the extent of the LTPA, there was no significant correlation between sedentary behavior and the risk of mortality.
Optimizing Quantum Iterative Reconstruction for Ultra–high-resolution Photon-counting Computed Tomography of the Lung
Authors: Tóth Adrienn , Chamberlin Jordan H. , Puthoff Gregory , Baruah Dhiraj , O’Doherty Jim , Maisuria Dhruw , McGuire Aaron M. , Schoepf U. Joseph , Munden Reginald F. , Kabakus Ismail M.
Published: September 2024

Purpose:

The aim of this study was to find the optimal strength level of QIR for ultra–high-resolution (UHR) PCCT of the lung.

Materials and Methods:

This retrospective study included 24 patients who had unenhanced chest CT with the novel UHR scan protocol on the PCCT scanner between March 24, 2023 and May 18, 2023. Two sets of reconstructions were made using different slice thicknesses: standard resolution (SR, 1 mm) and ultra–high-resolution (UHR, 0.2 mm), reconstructed with all strength levels of QIR (0 to 4). Attenuation of the lung parenchyma, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were assessed as objective criteria of image quality. Two fellowship-trained radiologists compared image quality and noise level, sharpness of the images, and the airway details using a 5-point Likert scale. Wilcoxon signed-rank test was used for statistical analysis of reader scores, and one-way repeated measures analysis of variance for comparing the objective image quality scores.

Results:

Objective image quality linearly improved with higher strength levels of QIR, reducing image noise by 66% from QIR-0 to QIR-4 (P<0.001). Subjective image noise was best for QIR-4 (P<0.001). Readers rated QIR-1 and QIR-2 best for SR, and QIR-2 and QIR-3 best for UHR in terms of subjective image sharpness and airway detail, without significant differences between them (P=0.48 and 0.56, respectively).

Conclusions:

Higher levels of QIR provided excellent objective image quality, but readers’ preference was for intermediate levels. Considering all metrics, we recommend QIR-3 for ultra–high-resolution PCCT of the lung.
Esophageal actinobacillosis mimicking a diverticulum in a cow: a case report
Authors: Kumar Rahul , Kumar Gulshan , Pandey R. P.
Published: September 2024

Present case report describes a case of an atypical oesophageal actinobacillosis in an adult cow presented to the university hospital with a history of inability to drink and swallow. Clinical examination revealed a five-inch swelling in the jugular groove. Skiagram revealed the presence of a small and slightly radio opaque round growth. Exploratory surgical excision of the growth was adapted as palliative treatment and the extirpated tissue was fixed in 10% buffered formalin. Histopathological examination revealed pyogranulomatous inflammation with radiating eosinophilic club shaped bodies surrounding small colonies of coccobacilli. Gram and Ziehl-Neelsen stains confirmed the presence of Gram-negative and non-acid-fast coccobacilli. Histopathology confirmed the pathognomonic lesion and proved to be a modality of choice for pathologists to reach at a diagnosis of atypical oesophageal actinobacillosis in a cow. After the exhaustive search of relevant literature on atypical actinobacillosis, the authors claim this to be the second report of oesophageal actinobacillosis worldwide.
How to set up and run a Bad Bugs Bookclub group
Authors: Verran Joanna
Published: September 2024

The Bad Bugs Bookclub is a public engagement initiative that enables scientists (microbiologists) and non-scientists to discuss the role of infectious disease and microorganisms in novels of fiction. The bookclub began in 2009, but since 2020, the meetings have taken place online, enabling international membership and occasional author participation. The bookclub has been shown, through peer-reviewed publications, to have impact and value to its members. For each book (the number now exceeds 100), a reading guide (questions to provoke discussion) and a meeting report (narrative of the discussion) were produced. Previously hosted on a website, the reading guides from this rich archive and resource are now presented alongside this paper, which provides tips on how to run a similar reading group.
Clinicopathological Heterogeneity of Lewy Body Diseases: The Profound Influence of Comorbid Alzheimer’s Disease
Authors: Beach Thomas G. , Serrano Geidy E. , Zhang Nan , Driver-Dunckley Erika D. , Sue Lucia I. , Shill Holly A. , Mehta Shyamal H. , Belden Christine , Tremblay Cecilia , Choudhury Parichita , Atri Alireza , Adler Charles H.
Published: September 2024

In recent years, proposals have been advanced to redefine or reclassify Lewy body disorders by merging the long-established entities of Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). These proposals reject the International DLB Consortium classification system that has evolved over three decades of consensus collaborations between neurologists, neuropsychologists and neuropathologists. While the Consortium’s “one year rule” for separating PD and DLB has been criticized as arbitrary, it has been a pragmatic and effective tool for splitting the continuum between the two entities. In addition to the decades of literature supporting the non-homogeneity of PD and DLB, it has become increasingly apparent that Lewy body disorders may fundamentally differ in their etiology. Most PD subjects, as well as most clinically-presenting DLB subjects, might best be classified as having a “primary synucleinopathy” while most clinically-unidentified DLB subjects, who also have concurrent neuropathology-criteria AD (AD/DLB), as well as those with neuropathological AD and amygdala-predominant LBD insufficient for a DLB diagnosis, may best be classified as having a “secondary synucleinopathy. Importantly, the DLB Consortium recognized the importance of comorbid AD pathology by defining “Low”, “Intermediate” and “High” subdivisions of DLB based on the relative brain stages of both Lewy body and AD pathology. If the one-year rule for separating PD from DLB, and for then dividing DLB into subtypes based on the presence and severity of comorbid AD pathology, is effective, then the divided groups should statistically differ in important ways. In this study we used the comprehensive clinicopathological database of the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) to empirically test this hypothesis. Furthermore, we used multivariable statistical models to test the hypothesis that comorbid AD neuropathology is a major predictor of the presence and severity of postmortem Lewy synucleinopathy. The results confirm the clinicopathological heterogeneity of Lewy body disorders as well as the profound influence of comorbid AD pathology.
Biological sex affects functional variation across the human genome
Authors: Jones Angela G. , Connelly Guinevere G. , Dalapati Trisha , Wang Liuyang , Schott Benjamin H. , San Roman Adrianna K. , Ko Dennis C.
Published: September 2024

Humans display sexual dimorphism across many traits, but little is known about underlying genetic mechanisms and impacts on disease. We utilized single-cell RNA-seq of 480 lymphoblastoid cell lines to reveal that the vast majority (79%) of sex-biased genes are targets of transcription factors that display sex-biased expression. Further, we developed a two-step regression method that identified sex-biased expression quantitative trait loci (sb-eQTL) across the genome. In contrast to previous work, these sb-eQTL are abundant (n=10,754; FDR 5%) and reproducible (replication up to π1=0.56). These sb-eQTL are enriched in over 600 GWAS phenotypes, including 120 sb-eQTL associated with the female-biased autoimmune disease multiple sclerosis. Our results demonstrate widespread genetic impacts on sexual dimorphism and identify possible mechanisms and clinical targets for sex differences in diverse diseases.
Understanding Bilateral Motor Coordination in Stroke Using the Towel Folding Task: An Exploratory Biomechanical Study
Authors: Wu Jingyi , Kwong Patrick Wai-Hang , Sidarta Ananda , Zhang Jack Jiaqi , Zhuang Jingwen , Li Yining , Fong Kenneth NK
Published: September 2024

Objectives

Coordination deficits in bilateral upper limbs make daily activities more difficult for stroke survivors. Previous studies showed worse kinematics during unilateral tasks compared to healthy individuals, but this was unclear for bimanual tasks. We aim to assess the potential of the towel folding task from the Wolf Motor Function Assessment as a measure of bimanual control by examining kinematic differences between stroke survivors and healthy individuals and correlating these differences with clinical parameters in the stroke group.

Methods

This was a cross-sectional design. Seventeen people with stroke and sixteen healthy individuals participated. Vicon motion capture obtained kinematics of bilateral upper limbs during the task, including movement time, initiation delay, velocity, trunk displacement, smoothness, and inter-/intra-limb coordination. Statistical analyses compared groups and correlated kinematic variables with clinical parameters.

Results

Stroke survivors had longer movement times (P< .001, Cohen’s d = 1.396), slower initiation (P< .001, Cohen’s d = 0.797), lower max velocity (P= .026, Cohen’s d = −.815;P< .001, Cohen’s d = −2.156; andP= .005, Cohen’s d = −.736; respectively), greater trunk displacement (P< .001, Cohen’s d = 2.173 andP< .001, Cohen’s d = 1.727, respectively), less smoothness (P= .031, Cohen’s d = 0.883 andP< .001, Cohen’s d = .725, respectively), and altered inter-/intra-limb coordination. Regarding bilateral elbow-elbow coordination, stroke group exhibited decreased in-phase patterns (P< .001, partial η² = .368) and increased anti-phase and non-hemiplegic elbow dominancy patterns (P= .001, partial η² = .298 andP= .004, partial η² = .244, respectively). Regarding bilateral shoulder-shoulder coordination, stroke group showed decreased hemiplegic shoulder leading patterns (P= .010, partial η² = .196) and increased anti-phase and non-hemiplegic shoulder dominancy patterns (P= .001, partial η² = .315 andP< .001, partial η² = .463, respectively). For hemiplegic shoulder-elbow coordination, stroke group showed decreased anti-phase patterns (P< .001, partial η² = .382) and increased elbow dominancyPatterns (P< .001, partial η² = .324). Fugl-Meyer Assessment scores positively correlated with smoothness and hemiplegic shoulder-elbow coordination (r = −.500,P= .039 and r = .600,P= .010, respectively), while Action Research Arm Test scores negatively correlated with movement initiation delay (r = −.600,P= .010).

Conclusions

This study enhances understanding of the folding towel task and may provide metrics to quantify bilateral coordination task performance in stroke survivors.
In-cell architecture of the mitochondrial respiratory chain
Authors: Waltz Florent , Righetto Ricardo D. , Kelley Ron , Zhang Xianjun , Obr Martin , Khavnekar Sagar , Kotecha Abhay , Engel Benjamin D.
Published: September 2024

Mitochondria produce energy through oxidative phosphorylation, carried out by five membrane-bound complexes collectively known as the respiratory chain. These complexes work in concert to transfer electrons and pump protons, leading to ATP regeneration. The precise organization of these complexes in native cells is debated, notably their assembly into higher-order supercomplexes called respirasomes. Here, we usein situcryo-electron tomography to visualize the native structures and organization of several major mitochondrial complexes insideChlamydomonas reinhardtiicells. ATP synthases and respiratory complexes are segregated into curved and flat crista membrane domains, respectively. Respiratory complexes I, III, and IV assemble into a single type of respirasome, from which we determined a native 5 Å-resolution structure showing the binding of electron carrier cytochromec. Combined with single-particle cryo-electron microscopy reconstruction at 2.4 Å resolution, we assemble a detailed model of how the respiratory complexes interact with each other inside native mitochondria.
Integrin-activating Yersinia protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets
Authors: Wijnakker Joost J.A.P.M. , van Son Gijs J. F. , Krueger Daniel , van de Wetering Willine , Lopez-Iglesias Carmen , Schreurs Robin , van Rijt Fenna , Lim Sangho , Lin Lin , Peters Peter J. , Isberg Ralph R. , Yanda Claudia , de Lau Wim , Clevers Hans
Published: September 2024

Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells (ASC)1,2. Here, we show that interaction between Matrigel’s major component Laminin111 with epithelial α6β1-integrin is crucial for this process. The outer membrane protein Invasin ofYersiniais known to activate multiple integrin-β1 complexes, including integrin-α6β1. A C-terminal integrin-binding fragment of Invasin, coated on culture plates, mediated gut epithelial cell adhesion. Addition of organoid growth factors allowed multi-passage expansion in 2D. Polarization, junction formation and generation of enterocytes, goblet cells, Paneth cells, and enteroendocrine cells was stable over time. Sustained expansion of other human-, mouse-, and even snake epithelia was accomplished under comparable conditions. The 2D ‘organoid sheet’ format holds advantages over the 3D ‘in gel’ format in terms of imaging, accessibility of basal and apical domains and automation for high throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel/BME.
Modeling disorders of consciousness at the patient level reveals the network's influence on the diagnosis vs the local node parameters role in prognosis
Authors: Zonca Lou , Escrichs Anira , Patow Gustavo A. , Manasova Dragana , Sanz Perl Yonatan , Annen Jitka , Gosseries Olivia , Sitt Jacobo , Deco Gustavo
Published: September 2024

The study of disorders of consciousness (DoC) is very complex because patients are suffering from a wide variety of lesions, affected brain mechanisms, different symptom severity and are unable to communicate. Combining neuroimaging data and mathematical modeling can help us quantify and better describe some of these alterations. This study's goal is to provide a novel analysis and modeling pipeline for fMRI data leading to new diagnosis and prognosis biomarkers at the individual patient level. To do so, we project patient's fMRI data into a low dimension latent-space. We define the latent space's dimension as the smallest dimension able to maintain the complexity, non-linearities, and information carried by the data, according to different criteria that we detail in the first part. This dimensionality reduction procedure then allows us to build biologically inspired latent whole-brain models that can be calibrated at the single-patient level. In particular, we propose a new model inspired by the astrocyte regulation of neuronal activity in the brain. This modeling procedure leads to two types of model-based biomarkers (MBBs) that provide novel insight at different levels: (1) the connectivity matrices bring us information about the severity of the patient's diagnosis, and, (2) the local node parameters, correlate to the patient's etiology, age and prognosis.
A workflow for practical training in ecological genomics using Oxford Nanopore long-read sequencing
Authors: Foster Robert , Weerd Heleen De , Medd Nathan , Booth Tim , Newman Caitlin , Ritch Helen , Santoyo-Lopez Javier , Trivedi Urmi , Twyford Alex D.
Published: September 2024

Long-read single molecule sequencing technologies continue to grow in popularity for genome assembly and provide an effective way to resolve large and complex genomic variants. However, uptake of these technologies for teaching and training is hampered by the complexity of high molecular weight DNA extraction protocols, the time required for library preparation and the costs for sequencing, as well as challenges with downstream data analyses. Here, we present a full long-read workflow optimised for teaching, that covers each stage from DNA extraction, to library preparation and sequencing, to data QC and genome assembly and characterisation, that can be completed in under two weeks. We use a specific case study of plant identification, where students identify an anonymous plant sample by sequencing and assembling the genome and comparing it to other samples and to reference databases. In testing, long-read genome skimming of nine wild-collected plant species extracted with a modified kit-based approach produced an average of 8Gb of Oxford Nanopore data, enabling the complete assembly of plastid genomes, and partial assembly of nuclear genomes. In the classroom, all students were able to complete the protocols, and to correctly identify their plant samples based on BOLD searches of barcoding loci extracted from the plastid genome, coupled with phylogenetic analyses of whole plastid genomes. We supply all the learning material and raw data allowing this to be adapted to a range of teaching settings.
Compensatory role of KatG in defending H2O2stress inmsrdeletion strain ofSalmonellaTyphimurium
Authors: Lalhmangaihzuali Lalhmangaihzuali , Upreti Suchitra , Sahoo Raj , Chauhan Tapan Kumar Singh , Mahawar Manish
Published: September 2024

KatG and Msrs are important enzymes associated with ROS homeostasis and bacterial survival under oxidative stress. Consistent to this notion, mutant strains in these enzymes showed hypersensitivity to oxidants and accumulates elevated levels of ROS. In current study we observed that a panmsrdeletion (Δ5msrmutant) strain ofS.Typhimurium accumulates significantly higher levels of ROS. However, unexpectedly, as compared toS.Typhimurium, the Δ5msrmutant strain exhibits more than 2000 folds resistance to H2O2. Transcriptional and mass spectrometry analyses reveal the upregulation of KatG in Δ5msrmutant strain. Further, Δ5msrmutant strain exhibits ∼6 folds higher KatG activity. Supplementation of Δ5msrmutant culture with reduced glutathione resulted in ROS neutralization, decreased KatG activity and abrogation of H2O2resistance. However, Δ5msrmutant strain showed negligible KatE and KatN activities. The findings of current study suggest that theSalmonellahave evolved the mechanism to upregulate one antioxidant gene in absence of others to mitigate oxidative stress.
The Aquaporin-4 expression and localization in the olfactory epithelium modulate the odorant-evoked responses and olfactory driven behavior
Authors: Lobraico Donatella , Abbrescia Pasqua , Fioriello Maria Grazia , Barile Barbara , Palazzo Claudia , Valente Onofrio , Nicchia Grazia Paola , Dibattista Michele , Frigeri Antonio
Published: September 2024

Aquaporin-4 (AQP4) is a water-selective channel expressed in glial cells throughout the central nervous system. It serves as the main water channel in the neuropil, and is involved in various physiological functions, ranging from regulating water homeostasis by adjusting cell volume to modulating neuronal activity. Different isoforms of AQP4 are expressed in glial-like cells known as sustentacular cells (SUSs) of the olfactory epithelium (OE). Interestingly, mice lacking all AQP4 isoforms exhibit impaired olfactory abilities. Hence, we aim to uncover the physiological role of two AQP4 isoforms, the perivascular AQP4ex isoform and the Orthogonal Array of Particle (OAP)-forming isoform (AQP4M23) in the OE. Primarily, we investigated the impact of AQP4 isoforms on OE protein expression, finding reduced levels of mature olfactory sensory neurons (OSNs) in mice lacking AQP4ex (AQP4ex-KO) or OAPs (OAP-null). Moreover, the reduced number of OSNs, SUSs, and globose basal cells (GBCs) suggests that AQP4 isoforms are involved in maintaining an optimal microenvironment in the OE, preserving the overall cell density. Then, we explored the role of AQP4 in modulating odorant-evoked responses through electro-olfactogram recordings, finding reduced odorant responses in mice lacking AQP4 isoforms. Olfactory ability assessments revealed deficits in odor-guided food-seeking test in AQP4ex-KO and OAP-null mice. Furthermore, AQP4ex-KO mice showed a reduced ability to discriminate between different odorants, while OAP-null mice were unable to recognize them as distinct. Overall, our data highlight the role of AQP4 isoforms in modulating neuronal homeostasis, affecting odorant-evoked responses and cell density in the OE. These results shed light on SUSs involvement in mediating these processes and establish a foundation for further understanding their role in controlling OE physiology.
Pre and Post antibiotic epoch: insights into the historical spread of antimicrobial resistance
Authors: Cazares Adrian , Figueroa Wendy , Cazares Daniel , Lima Leandro , Turnbull Jake D. , McGregor Hannah , Dicks Jo , Alexander Sarah , Iqbal Zamin , Thomson Nicholas R.
Published: September 2024

Plasmids are now the primary vectors of antimicrobial resistance, but our understanding of how human industrialisation of antibiotics influenced this is limited by a paucity of data predating the antibiotic era (PAE). By investigating plasmids from clinically relevant bacteria isolated between 1917 and 1954 and comparing them to modern plasmids, we captured over 100 years of evolution. We show that while all PAE plasmids were devoid of resistance genes and most never acquired them, a small minority evolved to drive the global spread of resistance to first-line and last-resort antibiotics in Gram-negative bacteria. They have evolved through complex microevolution and fusion events into a distinct group of highly recombinogenic, multi-replicon, self-transmissible plasmids that now pose the highest risk to resistance dissemination, and therefore human health.

One Sentence Summary

Pre-antibiotic era bacteria reveal the origin and evolution of drug-resistance vectors.
Evolution of drought resistance strategies following the introduction of white clover (Trifolium repens L.)
Authors: Hendrickson Brandon T , Stamps Caitlyn , Patterson Courtney M , Strickland Hunter , Foster Michael J , Albano Lucas J , Kim Audrey , Kim Paul , Kooyers Nicholas J
Published: September 2024

Background and Aims: Success during colonization likely depends on growing quickly and tolerating novel and stressful environmental conditions. However, rapid growth, stress avoidance, and stress tolerance are generally considered divergent physiological strategies. Methods: We evaluate how white clover (Trifolium repens) has evolved to a divergent water regime following introduction to North America. We conduct RNAseq within a dry-down experiment utilizing accessions from low and high latitude populations from native and introduced ranges, and assess variation in dehydration avoidance (avoidance of wilting) and dehydration tolerance (ability to survive wilting). Key Results: Introduced populations are better at avoiding dehydration, but poorer at tolerating dehydration than native populations. There is a strong negative correlation between avoidance and tolerance traits and expression of most drought-associated genes exhibits similar tradeoffs. Candidate genes with expression strongly associated with dehydration avoidance are linked to stress signaling, closing stomata and producing osmoprotectants. However, genes with expression linked to dehydration tolerance are associated with avoiding excessive ROS production and toxic bioproducts of stress responses. Several candidate genes show differential expression patterns between native and introduced ranges, and could underlie differences in drought resistance syndromes between ranges. Conclusions: These results suggest there has been strong selection following introduction for deyhydration avoidance at the cost of surviving dehydration.
Sensory context of initiation-cue modulates action goal-relevant neural representations
Authors: Kreter Nicholas , Dundon Neil M. , Smith Jolinda , Marneweck Michelle
Published: September 2024

The ability to produce goal-directed movement relies on the integration of diverse sources of sensory information specific to the task goal. Neural representations of goal-relevant features, such as target location and gaze direction, have been well studied in sensorimotor areas. It remains less clear whether goal-relevant motor representations are influenced by sensory changes to initiation-relevant information, such as a go-cue that provides no information about target location. We used Bayesian pattern component modelling of fMRI data during a delayed reach task with either visual or audiovisual go-cues to explore whether neural representations of goal-related features in sensorimotor areas are modulated by changes to initiation-relevant sensory information. We found that representations of target direction and gaze direction in the primary sensory areas, motor areas, and posterior parietal cortex, were sensitive to whether a reach was cued with a visual or audiovisual go-cue. These findings indicate that the central nervous system flexibly delegates the tasks of ‘where’ to move and ‘when’ to move based on available sensory context, even if initiation-relevant stimuli provide no additional information about target location.
Description of a novel extremophile green algae, Chlamydomonas pacifica, and its potential as a biotechnology host
Authors: Dutra Molino Joao Vitor , Oliver Aaron , Sethuram Harish , Kang Kalisa , Saucedo Barbara , Diaz Crisandra Jade , Gupta Abhishek , Jen Lee Jong , Torres-tiji Yasin , Hidasi Nora , Badary Amr , Jenkins Hunter , Fields Francis J. , Simkovsky Ryan , Mayfield Stephen
Published: September 2024

We present the comprehensive characterization of a newly identified microalga, Chlamydomonas pacifica, originally isolated from a soil sample in San Diego, CA, USA. This species showcases remarkable biological versatility, including a broad pH range tolerance (6-11.5), high thermal tolerance (up to 42 degree celsius), and salinity resilience (up to 2% NaCl). Its amenability to genetic manipulation and sexual reproduction via mating, particularly between the two opposing strains CC-5697 & CC-5699, now publicly available through the Chlamydomonas Resource Center, underscores its potential as a biotechnological chassis. The biological assessment of C. pacifica revealed versatile metabolic capabilities, including diverse nitrogen assimilation capability, motility and phototaxis. Genomic and transcriptomic analyses identified 17,829 genes within a 121 Mb genome, featuring a GC content of 61%. The codon usage of C. pacifica closely mirrors that of C. reinhardtii, indicating a conserved genetic architecture that supports a trend in codon preference with minor variations. Phylogenetic analyses position C. pacifica within the core-Reinhardtinia clade yet distinct from known Volvocales species. The lipidomic data revealed an abundance of triacylglycerols (TAGs), promising for biofuel applications and lipids for health-related benefits. Our investigation lays the groundwork for exploiting C. pacifica in biotechnological applications, from biofuel generation to synthesizing biodegradable plastics, positioning it as a versatile host for future bioengineering endeavors.
Circadian meal timing is heritable and associated with insulin sensitivity
Authors: Vahlhaus Janna , Peters Beeke , Hornemann Silke , Ost Anne-Cathrin , Kruse Michael , Busjahn Andreas , Pfeiffer Andreas F.H. , Pivovarova-Ramich Olga
Published: September 2024

Background

Although the contribution of the circadian clock to metabolic regulation is widely recognized, the role of meal timing in glucose metabolism and diabetes risk remains insufficiently studied. This study aimed (i) to investigate the link between individual circadian meal timing pattern and glucose homeostasis and (ii) to explore the contribution of genetic and environmental factors to meal timing parameters.

Methods

In the German NUtriGenomic Analysis in Twins (NUGAT) cohort, which includes 92 adult twins, glucose metabolism parameters were assessed using fasting samples and the oral glucose tolerance test (OGTT). Parameters of meal timing pattern (meal timing itself, daily calorie distribution, and meal number) were extracted from five-day food records. Circadian eating timing was determined relative to the individual’s chronotype (MSFsc) assessed by the Munich chronotype questionnaire. The heritability of meal timing components was estimated using the ACE model.

Results

Multiple meal timing components showed associations with glucose metabolism parameters. Most associations were found for the calorie midpoint defined as the time point at which 50% of daily calories were consumed. Indices of insulin sensitivity, ISI Stumvoll (β = 0.334, p = 2.9 x 10-4) and HOMA-IR (β = -0.276, p = 0.007), as well as fasting insulin levels were significantly associated with the circadian caloric midpoint even after the model adjustment for gender, age, energy intake, and sleep duration. BMI and waist circumference also demonstrated robust associations with circadian caloric midpoint. High or moderate heritability was shown for all meal timing components. Meal timing pattern was also strongly related to individual sleep timing and chronotype, both of which also showed a marked genetic impact.

Conclusion

Circadian meal timing is associated with insulin sensitivity and shows significant genetic influences, sharing a common genetic architecture with sleep behaviour. Shifting the main calorie intake to earlier circadian time might protect against diabetes, although this could be challenging due to the high heritability of meal timing components.

Graphical abstract

Highlights

Circadian caloric midpoint shows a robust association with insulin sensitivity

It remains significant after the adjustment for energy intake and other cofounders

Meal timing, daily calorie distribution, and meal number show a high or moderate heritability

Meal timing strongly relates to the sleeping behaviour and chronotype
Effect of maximum voluntary isometric contraction of the triceps surae muscle on a subsequent drop jump
Authors: Ino Taiki , Ogawara Keita , Uchiyama Shuichi , Endo Shinya , Miyazaki Seiji , Yamada Hiroshi
Published: September 2024

Purpose

Pre-muscle contraction improves sports performance because post-activation potentiation (PAP), induced by a previous intense voluntary contraction (conditioning contraction), amplifies the subsequent target muscle contraction. This study aims to examine the influence of conditioning contraction on the performance of ballistic motion, particularly on the stretch-shortening cycle (SSC).

Methods

Fourteen male university students specializing in athletic jumping events performed a drop jump from a height of 0.3 m. Maximal voluntary isometric plantarflexion for 6 seconds was considered a conditioning contraction. We set two conditions: in the PAP condition, participants performed a conditioning contraction 10 s before the drop jump, and in the control condition, they simply performed the drop jump. After 10 minutes of rest from the reference drop jump, both conditions were performed. A 3D motion analysis system, force plates, and surface electromyography were used to record the jump data.

Results

In the PAP conditions, the jump height and velocity of the center of gravity increased by 4 cm and 14 cm/s, respectively. Lower limb torque increment was observed only in the ankle joint between the PAP and control conditions (0.31 Nm/kg). However, there was no change in the magnitude of muscle activity based on the electromyogram.

Conclusion

Our study showed that PAP could potentiate the contraction mechanism under excitation-contraction coupling, irrespective of the effect on the central nervous system. Therefore, PAP enhances jump performance by improving SSC.
Deep Learning Model and Multi Modal Late Fusion For Predicting Adverse Events Following Cardiothoracic Surgery in the ICU Using STS Data and Time Series Intraoperative Data
Authors: Korutla Rajashekar , Hicks Anne , Milosevic Marko , Kulkarni Dipti , Mazhude Felistas , Mortazawy Mehdi , Seyed Vahedein Yashar , Kelting Tyler , Rabib Jaime B , Jin Qingchu , Kramer Robert , Sawyer Douglas , Winslow Raimond L , Amal Saeed
Published: September 2024

Accurate prediction of post-operative adverse events following cardiothoracic surgery is crucial for timely interventions, potentially improving patient outcomes and reducing healthcare costs. By leveraging advanced deep learning techniques, this study highlights the transformative potential of incorporating intraoperative variables into predictive analytics models to enhance postoperative care for cardiothoracic surgery patients in the ICU. We developed deep learning predictive models for anticipating adverse events in patients following cardiothoracic surgery using a dataset from the Society of Thoracic Surgeons’ database (4) and intraoperative data. Our models perform late fusion by integrating static patient data and intra-operative time-series data, utilizing Fully Connected Neural Networks (FCNN) and long short-term memory (LSTM) networks, respectively. The hybrid model was validated through five-fold cross-validation, demonstrating robust performance with a mean AUC of 0.93, Sensitivity of 0.83 and Specificity of 0.89. This work represents a significant step forward in the proactive management of cardio thoracic surgery patients in the ICU by effectively predicting potential adverse events associated with mortality in the post operative period.
Automated Phonological Error Scoring for Children with Language and Hearing Impairment
Authors: Sundstrom Simon , Themistocleous Charalambos
Published: September 2024

Purpose: Phonological production impairments are prevalent in children with developmental language disorder (DLD) and hearing impairment (HI). This study aims to quantify and compare phonological errors in Swedish-speaking children using a novel automated assessment tool and provide an automatic machine learning classification algorithm of children with DLD and HI to age-matched controls based on phonological errors. Methods: 72 Swedish-speaking children (29 with DLD, 14 with HI, and 29 typically developing) participated. Phonological production was elicited using a 72-item confrontation naming task. A novel tool was developed to calculate a composite phonological error score and specific scores for different phonological errors (deletions, insertions, substitutions, and transpositions) from written speech productions. This tool leverages the International Phonetic Alphabet (IPA) and a form of the Normalized Damerau-Levenshtein Distance for accurate error analysis. Results: The composite score successfully differentiated between children with DLD and typically developing children, highlighting its sensitivity in detecting phonological impairment. Machine learning models can accurately differentiate between children with and without language disorders. However, children with DLD and HI differed in the phonemic deletion errors, which suggests that their phonemic production is relatively similar. Conclusions: Children with DLD and HI exhibit significantly higher phonological error rates compared to typically developing peers. Children with HI and DLC are comparably impaired in phonology (as manifested by the compositive phonological score). These findings highlight the potential of machine learning for early identification and targeted intervention in language disorders, improving outcomes for affected children and demonstrated the potential of a multilingual tool for scoring phonological errors.
Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers
Authors: Zobeck Mark , Khan Javed , Venkatramani Rajkumar , Okcu M. Fatih , Scheurer Michael E. , Lupo Philip J.
Published: September 2024

Purpose

Molecular markers, such asFOXO1fusion genes andTP53andMYOD1mutations, increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Patients and Methods

Clinical variables and somatic mutation data for 20 genes from 641 RMS patients in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The ‘Baseline Clinical’ (BC) model included treatment location, age, fusion status, and risk group. The ‘Gene Enhanced 2’ (GE2) model addedTP53andMYOD1mutations to the BC predictors. The ‘Gene Enhanced 6’ (GE6) model further includedNF1,MET,CDKN2A, andMYCNmutations, selected through LASSO regression. Model performance was assessed using likelihood ratio (LR) tests and optimism-adjusted, bootstrapped validation and calibration metrics.

Results

The GE6 model demonstrated superior predictive performance, offering 39% more predictive information than the BC model (LR p<0.001) and 15% more than the GE2 model (LR p<0.001). The GE6 model achieved the highest discrimination with a C-index of 0.7087, a Nagalkerke R2of 0.205, and appropriate calibration. Mutations inTP53,MYOD1,CDKN2A,MET, andMYCNwere associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative,NF1-positive disease was 50.0% (95% confidence interval: 39-64%) from BC but 76% (64-90%) from GE6.

Conclusion

Incorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared to traditional risk-classification schemas. Improved clinical variables and external validation are required prior to implementing these models into clinical practice.
Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls
Authors: Muir Ryan T. , Stukas Sophie , Cooper Jennifer G. , Beaudin Andrew E. , McCreary Cheryl R. , Gee Myrlene , Nelles Krista , Nukala Nikita , Valencia Janina , Kirmess Kristopher M , Black Sandra E. , Hill Michael D. , Camicioli Richard , Wellington Cheryl L. , Smith Eric. E
Published: September 2024

INTRODUCTION

Cerebral Amyloid Angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40,phosphorylated-tau (p-tau), neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls.

METHODS

Plasma Aβ42/40,p-tau-181, NfL and GFAP were quantified using Simoa and Aβ42/40was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS).

RESULTS

45 participants with CAA and 47 healthy controls had available plasma. Aβ42/40ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40(Simoa), p-tau-181, and NfL resulted in an AUC of 0.90 (95% CI: 0.80, 0.95).

DISCUSSION

Plasma Aβ42/40, p-tau-181 and NfL differ in those with CAA and together can discriminate CAA from healthy controls.
Dynamic Contrast Enhanced MRI Mapping of Vascular Permeability for Evaluation of Breast Cancer Neoadjuvant Chemotherapy Response Using Image-to-Image Conditional Generative Adversarial Networks
Authors: Arledge Chad A. , Zhao Alan H. , Topaloglu Umit , Zhao Dawen
Published: September 2024

Dynamic contrast enhanced (DCE) MRI is a non-invasive imaging technique that has become a quantitative standard for assessing tumor microvascular permeability. Through the application of a pharmacokinetic (PK) model to a series of T1-weighed MR images acquired after an injection of a contrast agent, several vascular permeability parameters can be quantitatively estimated. These parameters, including Ktrans, a measure of capillary permeability, have been widely implemented for assessing tumor vascular function as well as tumor therapeutic response. However, conventional PK modeling for translation of DCE MRI to PK vascular permeability parameter maps is complex and time-consuming for dynamic scans with thousands of pixels per image. In recent years, image-to-image conditional generative adversarial network (cGAN) is emerging as a robust approach in computer vision for complex cross-domain translation tasks. Through a sophisticated adversarial training process between two neural networks, image-to-image cGANs learn to effectively translate images from one domain to another, producing images that are indistinguishable from those in the target domain. In the present study, we have developed a novel image-to-image cGAN approach for mapping DCE MRI data to PK vascular permeability parameter maps. The DCE-to-PK cGAN not only generates high-quality parameter maps that closely resemble the ground truth, but also significantly reduces computation time over 1000-fold. The utility of the cGAN approach to map vascular permeability is validated using open-source breast cancer patient DCE MRI data provided by The Cancer Imaging Archive (TCIA). This data collection includes images and pathological analyses of breast cancer patients acquired before and after the first cycle of neoadjuvant chemotherapy (NACT). Importantly, in good agreement with previous studies leveraging this dataset, the percentage change of vascular permeability Ktransderived from the DCE-to-PK cGAN enables early prediction of responders to NACT.