bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial Experiences of Spanish-Speaking Parents of Children With Craniofacial Microsomia
Authors: Rahman Muhammad , Avila Sandra , Heike Carrie L. , Stock Nicola M. , Stueckle Laura , Schefer Amy , Johns Alexis L.
Published: May 2024

Craniofacial microsomia (CFM) and microtia psychosocial research in the US is primarily with English-speaking participants. Given that 19% of the US is Latino, and there is a higher prevalence of CFM in Latino populations, this study aims to describe psychosocial experiences related to CFM among Spanish-speaking Latino caregivers to better inform health care. Narrative interviews (mean 73±17 min) were completed in Spanish with parents of children with CFM aged 3 to 17 (mean age 10.8±4.8 years). Transcripts were analyzed using quantitative linguistic analyses and reflexive thematic analysis. Participants (N=12) were mostly mothers (83%) who had immigrated to the US and had low socioeconomic status. Based upon analysis of grouped word counts, participants spent approximately half of their narratives discussing the first two years of their child’s life. Themes selected based on US Latino sociodemographics and cultural values included the Impact of Language, Healthcare Challenges, Supportive Healthcare Experiences, Caregiver Coping with CFM, Family Roles, and Addressing Social Implications of CFM. Results highlighted that the first years of care are of critical importance to parents and suggest this is an optimal time to focus on education and support services for families. Additional treatment suggestions include providing interpretation and informational materials in Spanish, addressing care barriers, supporting familial and child coping, accounting for the role of extended family, and helping address social concerns. Ongoing research with Latino families can further assist in guiding culturally sensitive CFM health care.
Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer
Authors: Pan Hong-Feng , Zheng Zhi-Fang , Zhao Ze-Yi , Liu Zhun , Huang Sheng-Hui , Chi Pan
Published: May 2024

Background:

The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC.

Methods:

Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored.

Results:

Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy.

Conclusions:

Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.
A Near Miss in the Emergency Department
Authors: Toole Kimberly P. , Frank Catherine
Published: May 2024

Acute coronary syndrome is an umbrella term encompassing three types of coronary artery disease that affect millions worldwide annually. Despite the availability of diagnostic tests (blood analysis, imaging, electrocardiogram, and screening tools), the diagnosis of myocardial infarction (MI) is still sometimes missed. According to the Centers for Disease Control and Prevention, the reported prevalence of heart disease is higher among males than females, with adults over the age of 75 having the highest prevalence. Typical “heart attack” features include chest pain that feels like pressure or squeezing, pain or discomfort in one or both arms that can radiate to the neck or jaw, shortness of breath, diaphoresis, nausea, vomiting, and lightheadedness. However, there are three subgroups where the typical warning signs do not always present: the elderly, individuals with diabetes, and females. The following is an atypical case presentation of unstable angina and non-ST-elevation MI.
Lumbar Puncture
Authors: Carman Margaret J.
Published: May 2024

Lumbar puncture (LP) is a procedural skill that is required for practice in the emergency care setting, most often for diagnostic purposes. Rarely, it can also be used therapeutically, to alleviate the pain of patients presenting to the emergency department with acute headache from idiopathic intracranial hypertension. In either case, LP constitutes an invasive procedure in which the subarachnoid space is entered in order to obtain a sample of cerebrospinal fluid from one of the most vulnerable areas of the human anatomy. It is essential for the emergency clinician to carefully weigh the risks and benefits of LP, to ensure informed consent when possible, and to proceed in a manner that ensures optimal patient safety and effectiveness. This article reviews current recommendations and considerations around performing LP, in addition to the process for performing the procedure.
Improving Nurse Practitioner Students’ Knowledge and Confidence in the Identification and Management of Human Trafficking Victims
Authors: Shue-McGuffin Katherine D. , Jordan Kathleen S.
Published: May 2024

Human trafficking is a global public health problem affecting millions of people worldwide. In the United States, many trafficking victims seek medical care for physical, sexual, and mental health concerns. Unfortunately, many of these individuals go unrecognized by health care providers as being victims of human trafficking and return to their trafficker without interventions for their safety and protection. To provide effective quality care for this patient population, health care providers must be knowledgeable regarding the identification of signs of trafficking, trauma-informed interventions to ensure the safety and protection of the victim(s), and methods to collaborate with interprofessional partners for the provision of appropriate medical and socioeconomic care following the exit from their trafficking situation. The purpose of this pilot study was to evaluate best practices in teaching Family Nurse Practitioner (FNP) students to identify and implement appropriate interventions for victims of human trafficking. The study was conducted in two phases using a mixed-method research design with repeated measures. In the first phase, education was provided through the validated HOPE Training modules produced by the Safe House Project using a pretest, posttest design. In the second phase, the students observed an interprofessional simulation followed by focus groups using a phenomenological approach to explore students’ perceptions. Knowledge and confidence increased significantly following the implementation of this study. The results provide essential information regarding incorporating human trafficking education into FNP curricula. This study also contributes to the body of knowledge regarding the vital role that nurse practitioners play in the interprofessional management of human trafficking victims.
Micrometeorite collections: a review and their current status
Authors: van Ginneken Matthias , Wozniakiewicz Penelope J. , Brownlee Donald E. , Debaille Vinciane , Della Corte Vincenzo , Delauche Lucie , Duprat Jean , Engrand Cecile , Folco Luigi , Fries Marc , Gattacceca Jérôme , Genge Matthew J. , Goderis Steven , Gounelle Matthieu , Harvey Ralph P. , Jonker Guido , Krämer Ruggiu Lisa , Larsen Jon , Lever James H. , Noguchi Takaaki , Peterson Scott , Rochette Pierre , Rojas Julien , Rotundi Alessandra , Rudraswami N. G. , Suttle Martin D. , Taylor Susan , Van Maldeghem Flore , Zolensky Michael
Published: May 2024

Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth’s surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks—summits outcropping from the icesheet—and moraines. Collections extracted from deep-sea sediments (DSS) produced a large number of micrometeorites, in particular, iron-rich cosmic spherules that are rarer in other collections. Collections from the old and stable surface of the Atacama Desert show that finding large numbers of micrometeorites is not restricted to polar regions or DSS. The advent of rooftop collections marks an important step into involving citizen science in the study of micrometeorites, as well as providing potential sampling locations over all latitudes to explore the modern flux. We explore their strengths of the collections to address specific scientific questions and their potential weaknesses. The future of micrometeorite research will involve the finding of large fossil micrometeorite collections and benefit from recent advances in sampling cosmic dust directly from the air.

This article is part of the theme issue ‘Dust in the Solar System and beyond’.
Transport of dust across the Solar System: Constraints on the spatial origin of individual micrometeorites from cosmic-ray exposure
Authors: Feige J. , Airo A. , Berger D. , Brückner D. , Gärtner A. , Genge M. , Leya I. , Habibi Marekani F. , Hecht L. , Klingner N. , Lachner J. , Li X. , Merchel S. , Nissen J. , Patzer A. B. C. , Peterson S. , Schropp A. , Sager C. , Suttle M. D. , Trappitsch R. , Weinhold J.
Published: May 2024

The origin of micrometeorites (MMs) from asteroids and comets is well-established, but the relative contribution from these two classes remains poorly resolved. Likewise, determining the precise origin of individual MMs is an open challenge. Here, cosmic-ray exposure ages are used to resolve the spatial origins of 12 MMs collected from urban areas and Antarctica. Their
26
Al and
10
Be concentration, produced during cosmic-ray irradiation in space, were measured by accelerator mass spectrometry. These data are compared to results from a model simulating the transport and irradiation of the MM precursors in space. This model, for the first time, considers a variety of orbits, precursor particle sizes, compositions and densities and incorporates non-isotropic solar and galactic cosmic-ray flux profiles, depth-dependent production rates, as well as spherical evaporation during atmospheric entry. While the origin for six MMs remains ambiguous, two MMs show a preferential tendency towards an origin in the Inner Solar System (Near Earth Objects to the Asteroid Belt) and four towards an origin in the Outer Solar System (Jupiter Family Comets to the Kuiper Belt). These findings challenge the notion that dust originating from the Outer Solar System is unlikely to survive long-term transport and delivery to the terrestrial planets.

This article is part of the theme issue ‘Dust in the Solar System and beyond’.
Atypical presentation of varicella-zoster virus reactivation in a lung transplant patient: a case report
Authors: Hoff Ingrid , Rath Eivind , Pena-Karan Slobodanka , Sivy Nginamau Elisabeth , Holm Are Martin , Thune Turid , Mustafa Tehmina
Published: May 2024

Background: Varicella zoster virus (VZV) is a human neurotropic virus which commonly causes infection during childhood. Later in life it may reactivate as herpes zoster. We report a rare manifestation of reactivation of VZV infection presenting as cutaneous vasculitis and varicella pneumonia in a lung transplant recipient. 
Case presentation: A 65 year old man was lung transplanted bilaterally for emphysema. Nine months post-transplant he presented with dyspnea and a cutaneous vasculitis-like eruption. VZV reactivation was not suspected due to absence of the typical vesicular eruptions. The diagnosis was confirmed by VZV PCR from the swabs of the ulcer after skin punch biopsy of a lesion and from bronchoalveolar lavage (BAL). The histology of skin biopsy demonstrated epithelial and vascular damage but no typical epithelial virus associated changes. The patient responded to antiviral therapy with total remission of rash and VZV DNA was not detectable from repeated BAL after 29 days of therapy. However, the pulmonary radiological features and dyspnea persisted due to reasons possibly unrelated to the VZV infection.
Conclusion: Had it not been for the patient to mention the resemblance of the vasculitic rash with his primary VZV infection, the diagnosis would easily have been overlooked. In this case, the biopsy did not show typical histopathologic findings of VZV-vasculitis. What led the diagnosis was PCR from the wound swab taken after punch biopsy. This case serves as a reminder for atypical presentation of common conditions in immunosuppressed patients and that extensive diagnostic sampling may be warranted in this group.
Mannheimia indoligenes sp. nov., proposed for clade V organisms of Mannheimia
Authors: Christensen Henrik , Kuhnert Peter , Foster Geoff , Bisgaard Magne
Published: May 2024

A set of 25 strains belonging to clade V of Mannheimia mainly isolated from cattle was investigated and is proposed to represent Mannheimia indoligenes sp. nov. The species can be separated from the other validly published species of the genus by pheno- and genotype. Only indole separates M. indoligenes and Mannheimia varigena while two to seven characters separate M. indoligenes from other species of Mannheimia. Thirteen strains belonging to biogroups 6, 7, 8C, 9, 10, 12 and UG5 formed a monophyletic group based on 16S rRNA gene sequence comparisons with 98–100 % similarity. Eight of these strains were further included in the whole genome comparison. Digital DNA–DNA hybridization showed that the similarities between the suggested type strain M14.4T and the other strains of M. indoligenes were 62.9 % or higher. The average nucleotide identity was 95.5 % or higher between M14.4T and the other strains of the species. The rpoB gene sequence similarity was 95–100 % within M. indoligenes. MALDI-TOF allowed a clear separation from other Mannheimia species further supporting classification as a novel species and making it the diagnostic identification tool of choice for M. indoligenes. The type strain is M14.4T (=CCUG 77347T=DSM 116804T) isolated from a cattle tongue in Scotland.
Genomic characterization of Aeromonas spp. isolates from striped catfish with motile Aeromonas septicemia and human bloodstream infections in Vietnam
Authors: Truong Nhat Ha Minh , Nguyen Quynh , Voong Phat Vinh , Chau Vinh , Nguyen Nhi Huynh Thanh , Nguyen Tuan Hoa Minh , Vo Phuong Hong , Nguyen Luan Thanh , Ha Trinh Thi Phuong , Nguyen Lan Phu Huong , Le Phuoc Hong , Thanh Duy Pham , Nguyen Hoang Duc
Published: May 2024

Aeromonas spp. are commonly found in the aquatic environment and have been responsible for motile Aeromonas septicemia (MAS) in striped catfish, resulting in significant economic loss. These organisms also cause a range of opportunistic infections in humans with compromised immune systems. Here, we conducted a genomic investigation of 87 Aeromonas isolates derived from diseased catfish, healthy catfish and environmental water in catfish farms affected by MAS outbreaks in eight provinces in Mekong Delta (years: 2012–2022), together with 25 isolates from humans with bloodstream infections (years: 2010–2020). Genomics-based typing method precisely delineated Aeromonas species while traditional methods such as aerA PCR and MALDI-TOF were unable identify A. dhakensis. A. dhakensis was found to be more prevalent than A. hydrophila in both diseased catfish and human infections. A. dhakensis sequence type (ST) 656 followed by A. hydrophila ST251 were the predominant virulent species-lineages in diseased catfish (43.7 and 20.7 %, respectively), while diverse STs were found in humans with bloodstream infections. There was evidence of widespread transmission of ST656 and ST251 on striped catfish in the Mekong Delta region. ST656 and ST251 isolates carried a significantly higher number of acquired antimicrobial resistance (AMR) genes and virulence factors in comparison to other STs. They, however, exhibited several distinctions in key virulence factors (i.e. lack of type IV pili and enterotoxin ast in A. dhakensis), AMR genes (i.e. presence of imiH carbapenemase in A. dhakensis), and accessory gene content. To uncover potential conserved proteins of Aeromonas spp. for vaccine development, pangenome analysis has unveiled 2202 core genes between ST656 and ST251, of which 78 proteins were in either outer membrane or extracellular proteins. Our study represents one of the first genomic investigations of the species distribution, genetic landscape, and epidemiology of Aeromonas in diseased catfish and human infections in Vietnam. The emergence of antimicrobial resistant and virulent A. dhakensis strains underscores the needs of enhanced genomic surveillance and strengthening vaccine research and development in preventing Aeromonas diseases in catfish and humans, and the search for potential vaccine candidates could focus on Aeromonas core genes encoded for membrane and secreted proteins.
Single–cell transcriptional and epigenetic mapping reveals cellular and molecular mechanisms driving non-ischemic cardiac fibrosis
Authors: Krstevski Crisdion , Farrugia Gabriella E. , Hsu Ian , Dona Malathi S. I. , Gaynor Taylah L. , Cohen Charles D. , Harper Rebecca L. , Harrison Thomas I. , Claridge Bethany , Drack Auriane , Lelliott Patrick , Kiriazis Helen , Brown Aascha , McMullen Julie R. , Donner Daniel G. , Lal Sean , Greening David W. , Pinto Alexander R.
Published: May 2024

Cardiac fibrosis is a major cause of cardiac dysfunction. Recently, single-cell genomic approaches have revealed in unprecedented resolution the orchestrated cellular responses driving cardiac fibrosis. Yet, the fibrosis-causing phenotypes that emerge in the heart following non-ischemic cardiac stress, and the transcriptional circuits that govern cell identity and drive fibrosis, are not well understood. Applying a paired multiomic approach, we reveal key transcriptional circuits, in mouse and human hearts, which are associated with fibrosis development following non-ischemic cardiac insults, independent of disease model, species or biological sex. Strikingly, we find the key regulatory events driving fibrosis are reversible at the single-cell transcriptional and epigenomic level, further pointing to key factors regulating fibrosis development and resolution. The transcriptional regulators identified in this study represent promising targets to ameliorate the development of fibrosis in the context of chronic stressors such as aging and hypertension.
The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell divisionin vivo
Authors: Memar Nadin , Sherrard Ryan , Sethi Aditya , Fernandez Carla Lloret , Schmidt Henning , Lambie Eric , Poole Richard , Schnabel Ralf , Conradt Barbara
Published: May 2024

The mechanisms that enable differential gene expression in daughter cells produced by asymmetric cell divisions are not well understood. We discovered that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for this process inC. elegans. DuringC. elegansdevelopment, some dividing cells give rise to a daughter that survives and a daughter that dies. We found that PSF-2 GINS2, a component ofC. elegansCMG, is necessary for the transcriptional burst of the pro-apoptotic geneegl-1BH3-only, which occurs in the daughter that dies immediately following mother cell division. We present evidence that this requirement is independent of the function of CMG in DNA unwinding. We propose that the recently described histone chaperone activity of CMG causes epigenetic changes at theegl-1locus during replication in mother cells, and that these changes are required for the increase inegl-1transcription in the daughter that dies. We also find that PSF-2 is required for the divergence of other cell fates duringC. elegansdevelopment, suggesting that this function is not restricted to the regulation ofegl-1expression. Our work uncovers a new and unexpected role of CMG in cell fate and a novel intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.
Fast adaptive super-resolution lattice light-sheet microscopy for rapid, long-term, near-isotropic subcellular imaging
Authors: Qiao Chang , Li Ziwei , Wang Zongfa , Lin Yuhuan , Liu Chong , Zhang Siwei , Liu Yong , Feng Yun , Wang Xinyu , Dong Xue , Guo Jiabao , Jiang Tao , Wang Qinghua , Dai Qionghai , Li Dong
Published: May 2024

Lattice light-sheet microscopy (LLSM) provides a crucial observation window into intra- and inter-cellular physiology of living specimens with high speed and low phototoxicity, however, at the diffraction-limited resolution or anisotropic super-resolution with structured illumination. Here we present the meta-learning-empowered reflective lattice light-sheet virtual structured illumination microscopy (Meta-rLLS-VSIM), which instantly upgrades LLSM to a near-isotropic super resolution of ∼120-nm laterally and ∼160-nm axially, more than twofold improvement in each dimension, without any modification of the optical system or sacrifice of other imaging metrics. Moreover, to alleviate the tremendous demands on training data and time necessitated by existing deep-learning (DL) methods, we devised an adaptive online training approach by synergizing the front-end imaging system and back-end meta-learning framework, which reduced the total time for data acquisition and model training down to tens of seconds. With this method, a new model can be well-trained with tenfold less data and three orders of magnitude less time than current standard supervised learning. We demonstrate the versatile functionalities of Meta-rLLS-VSIM by imaging a variety of bioprocesses with ultrahigh spatiotemporal resolution for long duration of hundreds of multi-color volumes, characterizing the dynamic regulation of contractile ring filaments during mitosis and the growth of pollen tubes, and delineating the nanoscale distributions, dispersion, and interaction pattern of multiple organelles in embryos and eukaryotic cells.
Ligandability at the membrane interface of GPx4 revealed through a reverse micelle fragment screening platform
Authors: Labrecque Courtney L. , Fuglestad Brian
Published: May 2024

While they account for a large portion of drug targets, membrane proteins (MPs) present a unique challenge for drug discovery. Peripheral membrane proteins (PMPs), a class of proteins that bind reversibly to membranes, are also difficult targets, particularly those that function only while bound to membranes. The protein-membrane interface in PMPs is often where functional interactions and catalysis occur, making it a logical target for inhibition. However, interfaces are underexplored spaces in inhibitor design and there is a need for enhanced methods for small-molecule ligand discovery. In an effort to better initiate drug discovery efforts for PMPs, this study presents a screening methodology using membrane-mimicking reverse micelles (mmRM) and NMR-based fragment screening to assess ligandability in the protein-membrane interface. The proof-of-principle target, glutathione peroxidase 4 (GPx4), is a lipid hydroperoxidase which is essential for the oxidative protection of membranes and thereby the prevention of ferroptosis. GPx4 inhibition is promising for therapy-resistant cancer therapy, but current inhibitors are generally covalent ligands with limited clinical utility. Presented here is the discovery of non-covalent small-molecule ligands for membrane-bound GPx4 revealed through the mmRM fragment screening methodology. The fragments were tested against GPx4 in bulk aqueous conditions and displayed little to no binding to the protein without embedment into the membrane. The 9 hits had varying affinities and partitioning coefficients and revealed properties of fragments that bind within the protein-membrane interface. Additionally, a secondary screen confirmed the potential to progress the fragments by enhancing the affinity from > 200 µM to ∼15 µM with the addition of certain hydrophobic groups. This study presents an advancement of screening capabilities for membrane associated proteins, reveals ligandability within the GPx4 protein-membrane interface, and may serve as a starting point for developing non-covalent inhibitors of GPx4.
Impedance-based assay for pan-cancer early and rapid detection of cell-free DNA
Authors: Dube Tejal , Prasad Puja , Swami Pragya , Singh Ankita , Verma Meenakshi , Tanwar Parul , Chowdhury Shantanu , Gupta Shalini
Published: May 2024

Aberrant DNA methylation is a hallmark of cancer, and plasma cell-free DNA (cfDNA) containing these abnormal methylation patterns has emerged as a promising non-invasive biomarker for pan-cancer detection. However, intrinsic challenges remain that continue to limit its broad clinical application. Here we show a simple and rapid impedance biosensor called Asima™ Rev that can detect cancer cfDNA in under 5 min without the need for any molecular labelling, electrode modification, signal amplification, or target enrichment steps. Using 216 clinical samples (50 healthy) from 15 different cancer types (all stages) we show an overall sensitivity and specificity of 96.4% and 94.0%, respectively. Differences in methylation content between cancerous and healthy cfDNA lead to distinct solvation behaviour and electro-physicochemical property that remain consistent across cancer types regardless of the distribution patterns of methyl cytosine. Our test exploits this inherent difference.
Model for chromosome congression based on motor proteins in microtubule overlaps
Authors: Sigmund Ivan , Božan Domagoj , Šarić Ivana , Pavin Nenad
Published: May 2024

Mitotic spindle, a micromachine composed of microtubules and associated proteins, plays a pivotal role in ensuring the accurate segregation of chromosomes. During spindle assembly, initially randomly distributed chromosomes are transported toward the equatorial plate and experiments suggest that several competing mechanisms can contribute to this process of chromosome congression. However, a systematic theoretical study of forces relevant to chromosome congression is still lacking. Here we show, by introducing a physical model, that length-dependent forces generated by motor proteins transport chromosomes toward the spindle equator. Passive crosslinkers, on the other hand, can generate off-centering forces that impair chromosome congression. Our mean-field approach also reveals that stable points can exist in the vicinity of spindle poles, in addition to the one in the center, and thus provides an explanation for erroneous spindles with polar chromosomes. Taken together, our study provides a comprehensive approach to understanding how different spindle components interact with each other and generate forces that drive chromosome congression.
Xylem perforation plate phenotypes affect water use and drought adaptation in maize (Zea maysL.)
Authors: Strock Christopher F. , DePew Cody L. , Sidhu Jagdeep S. , Xu Tianyu , Lynch Jonathan P.
Published: May 2024

Rationale: Xylem morphology in annual monocots is important for water use strategies in many agronomically important species.

Methods:We assess how xylem perforation plates affect water use strategies in maize (Zea maysL.) throughin silicomodeling, empirical studies under water deficit in controlled environments, and in the field.

Key Result: Significant genotypic variation for the prominence and frequency of perforation plates was observed in maize germplasm. Perforation plate phenotypes had high heritability, were associated with several QTL, and were pleiotropic across leaves, aerial nodal roots, and subterranean nodal roots. Perforation plate phenotypes did not affect vulnerability to cavitation, but modeling predicted that they should affect axial water transport, which was supported byin situmeasurements of root segments. Metaxylem vessel length was correlated with the rate of root elongation, root depth, and deep-water utilization in mesocosms. Under drought stress in the field, variation in xylem vessel length was associated with leaf roll, leaf temperature, transpiration, photosynthesis, and grain yield.

Main Conclusion:Phenotypic variation for xylem perforation plate phenotypes in maize directly affects axial water conductance and is part of a pleiotropic syndrome with greater root elongation and deeper rooting that improves adaptation to water deficit stress.
Towards high throughput in-field detection and quantification of wheat foliar diseases with deep learning
Authors: Zenkl Radek , McDonald Bruce A. , Walter Achim , Anderegg Jonas
Published: May 2024

1

Reliable, quantitative information on the presence and severity of crop diseases is critical for site-specific crop management and resistance breeding. Successful analysis of leaves under naturally variable lighting, presenting multiple disorders, and across phenological stages is a critical step towards high-throughput disease assessments directly in the field.

Here, we present a dataset comprising 422 high resolution images of flattened leaves captured under variable outdoor lighting with polygon annotations of leaves, leaf necrosis and insect damage as well as point annotations of Septoria tritici blotch (STB) fruiting bodies (pycnidia) and rust pustules. Based on this dataset, we demonstrate the capability of deep learning for keypoint detection of pycnidia (F1 = 0.76) and rust pustules (F1 = 0.77) combined with semantic segmentation of leaves (IoU= 0.96), leaf necrosis (IoU= 0.77) and insect damage(IoU= 0.69) to reliably detect and quantify the presence of STB, leaf rusts, and insect damage under natural outdoor conditions. An analysis of intra- and inter-annotator agreement on selected images demonstrated that the proposed method achieved a performance close to that of annotators in the majority of the scenarios.

We validated the generalization capabilities of the proposed method by testing it on images of unstructured canopies acquired directly in the field and with-out manual interaction with single leaves. The corresponding imaging procedure can be adapted to support automated data acquisition. Model predictions were in good agreement with visual assessments of in-focus regions in these images, despite the presence of new challenges such as variable orientation of leaves and more complex lighting. This underscores the principle feasibility of diagnosing and quantifying the severity of foliar diseases under field conditions using the proposed imaging setup and image processing methods. By demonstrating the ability to diagnose and quantify the severity of multiple diseases in highly natural complex scenarios, we lay out the groundwork for a significantly more efficient, non-invasive in-field analysis of foliar diseases that can support resistance breeding and the implementation of core principles of precision agriculture.
Legionella uses host Rab GTPases and BAP31 to create a unique ER niche
Authors: Chadha Attinder , Yanai Yu , Oide Hiromu , Wakana Yuichi , Inoue Hiroki , Saha Saradindu , Tagaya Mitsuo , Arasaki Kohei , Mukherjee Shaeri
Published: May 2024

Upon entry into host cells, the facultative intracellular bacteriumLegionella pneumophila(L.p.) uses its type IV secretion system, Dot/Icm, to secrete ~330 bacterial effector proteins into the host cell. Some of these effectors hijack endoplasmic reticulum (ER)-derived vesicles to form theLegionella-containing vacuole (LCV). Despite extensive investigation over decades, the fundamental question persists: Is the LCV membrane distinct from or contiguous with the host ER network? Here, we employ advanced photobleaching techniques, revealing a temporal acquisition of both smooth and rough ER (sER and rER) markers on the LCV. In the early stages of infection, the sER intimately associates with the LCV. Remarkably, as the infection progresses, the LCV evolves into a distinct niche comprising an rER membrane that is independent of the host ER network. We discover that theL.p.effector LidA binds to and recruits two host proteins of the Rab superfamily, Rab10, and Rab4, that play significant roles in acquiring sER and rER membranes, respectively. Additionally, we identify the pivotal role of a host ER-resident protein, BAP31, in orchestrating the transition from sER to rER. While previously recognized for shuttling between sER and rER, we demonstrate BAP31’s role as a Rab effector, mediating communication between these ER sub-compartments. Furthermore, using genomic deletion strains, we uncover a novelL.p.effector, Lpg1152, essential for recruiting BAP31 to the LCV and facilitating its transition from sER to rER. Depletion of BAP31 or infection with an isogenicL.p.strain lacking Lpg1152 results in a growth defect. Collectively, our findings illuminate the intricate interplay between molecular players from both host and pathogen, elucidating howL.p.orchestrates the transformation of its residing vacuole membrane from a host-associated sER to a distinct rER membrane that is not contiguous with the host ER network.
Hypophosphatemia Is Associated with Post-Operative Ileus After Right Colon Resection
Authors: Yu Allen T. , Malhotra Simran , Abeshouse Marnie , Yoo Esther , Sullivan Joseph , Huang Alex , Plietz Michael C. , Khaitov Sergey , Greenstein Alexander J. , Sylla Patricia , Hahn Sue J.
Published: May 2024

Background

Electrolyte imbalances are known to contribute to intestinal ileus. However, the direct impact of hypophosphatemia on post-operative ileus (POI) is unknown.

Objective

To describe post-operative phosphate dynamics and if hypophosphatemia is associated with POI after a right colon resection.

Design

Comparative retrospective cohort study

Settings

High-volume tertiary referral center

Patients

Patients who underwent right colon resection, which includes right hemicolectomies and ileocolic resections between 2020 and 2022.

Main Outcome Measures

POI incidence, post-surgical phosphate dynamics, and post-operative phosphate deficit and recovery.

Results

A total of 396 patients were reviewed, where 68% of resections were for inflammatory bowel disease. Patients had a mean return of bowel function on POD 3.78 ± 1.45. 17.4% of patients overall had POI. Serum phosphate was the most dynamic post-operative electrolyte, with statistically significant differences between POI and non-POI on POD 1, 3, and 7 (p< 0.05). Serum phosphate recovery in patients with POI was impaired at 0.11 mg/dL/day versus 0.17 mg/dL/day (p< 0.001). Patients with POI had a phosphate deficit that persisted beginning on POD 2, with statistically significant deficits on POD 3-5 (p< 0.01), as well as POD 7 (p< 0.001). On multivariate analysis, a phosphate deficit on POD 3 (ORadj9.04, 95% CI 1.38-59.2), POD 5 (ORadj7.05, 1.13-44.1), and POD 7 (ORadj47.2, 2.98-749.4) were the only independent risk factors for POI.

Limitations

Generalizability of these findings may be limited outside of right colon resections.

Conclusions

We have established baseline phosphate dynamics in patients who undergo ileocolic anastomoses. We found POI was associated with a delayed serum phosphate recovery, as well as lower overall phosphate levels. Thus, a potential post-surgical window for intervention with timed phosphate repletion may have the potential to reduce post-operative ileus, need for nasogastric decompression, and ultimately decrease hospital length of stay.
Disparities in Lung Cancer Screening Utilization at Two Health Systems in the Southeastern US
Authors: Niranjan Soumya J , Rivers Desiree , Ramachandran Rekha , Edward Murrell J , Curry Kayleigh C , Mubasher Mohammed , Flenaugh Eric , Dransfield Mark T , Bae Sejong , Scarinci Isabel C
Published: May 2024

Purpose

Low-dose computed tomography lung cancer screening is effective for reducing lung cancer mortality. It is critical to understand the lung cancer screening practices for screen-eligible individuals living in Alabama and Georgia where lung cancer is the leading cause of cancer death. High lung cancer incidence and mortality rates are attributed to high smoking rates among underserved, low income, and rural populations. Therefore, the purpose of this study: (1) to define sociodemographic and clinical characteristics of patients who were screened for lung cancer at an Academic Medical Center (AMC) in Alabama and a Safety Net Hospital (SNH) in Georgia.

Methods

A retrospective cohort study of patient electronic health records who received lung cancer screening between 2015 to 2020 was performed to identify the study population and outcome variable measures. Chi-square tests and Student t-tests were used to compare screening uptake across patient demographic and clinical variables. Bivariate and multivariate logistic regressions determined significant predictors of lung cancer screening uptake.

Results

At the AMC, 67,355 were identified as eligible for LCS and 1,129 were screened. In bivariate analyses, there were several differences between those who were screened and those who were not screened. Screening status in the site at Alabama varied significantly by age (P<0.01), race (P<0.001), marital status (P<0.01), smoking status (P<0.01) health insurance (P<0.01), median income (P<0.01), urban status (P<0.01) and distance from UAB (P<0.01). Those who were screened were more likely to have lesser comorbidities (2.31 vs. 2.53; P<0.001). At the SNH, 11,011 individuals were identified as screen-eligible and 500 were screened. In the site at Georgia, screening status varied significantly by race (P<0.01), health insurance (P<0.01), and distance from site (P<0.01). At the AMC, the odds of being screened increased significantly if the individual was a current smoker compared to former smoker (OR=3.21; P<0.01). At the SNH, the odds of being screened for lung cancer increased significantly with every unit increase in co-morbidity count (OR = 1.12; P=0.01)

Conclusion

The study provides evidence that LCS has not reached all subgroups and that additional targeted efforts are needed to increase lung cancer screening uptake. Furthermore disparity was noticed between adults living closer to screening institutions and those who lived farther.
Post-translational digital data encoding into the genomes of mammalian cell populations
Authors: Callisto Alec , Strutz Jonathan , Leeper Kathleen , Kalhor Reza , Church George , Tyo Keith E.J. , Bhan Namita
Published: May 2024

High resolution cellular signal encoding is critical for better understanding of complex biological phenomena. DNA-based biosignal encoders alter genomic or plasmid DNA in a signal dependent manner. Current approaches involve the signal of interest affecting a DNA edit by interacting with a signal specific promoter which then results in expression of the effector molecule (DNA altering enzyme). Here, we present the proof of concept of a biosignal encoding system where the enzyme terminal deoxynucleotidyl transferase (TdT) acts as the effector molecule upon directly interacting with the signal of interest. A template independent DNA polymerase (DNAp), TdT incorporates nucleotides at the 3’ OH ends of DNA substrate in a signal dependent manner. By employing CRISPR-Cas9 to create double stranded breaks in genomic DNA, we make 3’OH ends available to act as substrate for TdT. We show that this system can successfully resolve and encode different concentrations of various biosignals into the genomic DNA of HEK-293T cells. Finally, we develop a simple encoding scheme associated with the tested biosignals and encode the message “HELLO WORLD” into the genomic DNA of HEK-293T cells at a population level with 91% accuracy. This work demonstrates a simple and engineerable system that can reliably store local biosignal information into the genomes of mammalian cell populations.
Migration, proliferation, and elasticity of bladder cancer cells on lectin-coated surfaces
Authors: Luty Marcin , Szydlak Renata , Pabijan Joanna , Øvreeide Ingrid H , Prot Victorien E. , Zemła Joanna , Stokke Bjørn T. , Lekka Małgorzata
Published: May 2024

The alterations in migration, proliferation, and mechanics of cells observed during cancer progression can potentially be linked to enhanced tumor invasiveness. These properties are frequently attributed to the ability to form distant metastasis; however, the direct mutual connection between these properties is not always proven. Here, we studied the migratory, proliferative, and mechanical phenotype of three bladder cancer cells originating from various stages of cancer progression, i.e., non-malignant cell cancer of ureter (HCV29 cells), bladder carcinoma (HT1376 cells) and transitional bladder carcinoma (T24 cells). The results were linked with the organization of actin filaments because of their major role in cell migration. The results classified cells into non-malignant, non-invasive, and invasive, revealing the significant impact of actin filaments in bladder cancer invasion. Based on the reported changes in cancer cell glycosylation, the potential applicability of the observed cancer-related changes to identify invasive cells was demonstrated for the lectin-coated surfaces, which is the potential surface modification for biosensors.
Nuclear actin-dependent Meg3 expression suppresses metabolic genes by affecting the chromatin architecture at sites of elevated H3K27 acetylation levels
Authors: El Said Nadine Hosny , Abdrabou Wael , Mahmood Syed Raza , Venit Tomas , Idaghdour Youssef , Percipalle Piergiorgio
Published: May 2024

Three-dimensional organization of the eukaryotic genome is directly affected by the nuclear β-actin pool that regulates enhancer function by affecting H3K27 acetylation levels. This actin-based mechanism, in turn, influences enhancer-dependent transcriptional regulation and plays a crucial role in driving gene expression changes observed upon compartment-switching. Using a combination of bulk RNA-seq and qPCR analyses performed on total RNA from WT mouse embryonic fibroblasts (MEFs), β-actin heterozygous (HET) MEFs, and β-actin KO MEFs, in this study we demonstrate that expression of several lncRNAs is directly affected by β-actin depletion. Among these lncRNAs, Meg3 expression increases in a β-actin dosage-dependent manner. Using ChIRP-seq, ChIRP-MS and f-RIP-qPCR, we show that β-actin depletion leads to alterations in Meg3 genomic association. It also leads to Meg3 enrichment at or close to gene regulatory sites including enhancers and promoters concomitantly with increased H3K27 acetylation levels. At these sites, specific Meg3 association with H3K27 acetylation leads to loss of promoter-enhancer interactions as revealed by the Activity by Contact (ABC) model that builds on RNA-seq, H3K27acetylation ChIP-seq, ATAC-seq and HiC-seq obtained in WT and β-actin KO MEFs. Results from metabolomics experiments in WT, HET and β-actin KO MEFs show these mechanisms contribute to the repression of genes involved in metabolic biosynthetic pathways for chondroitin, heparan, dermatan sulfate, and phospholipases, hence impacting their synthesis. We propose that at sites of actin-dependent increase in H3K27acetylation levels Meg3 interferes with promoter-enhancer interactions, potentially impairing local genome organization (or DNA looping) and negatively regulating gene expression.
Gauge fixing for sequence-function relationships
Authors: Posfai Anna , Zhou Juannan , McCandlish David M. , Kinney Justin B.
Published: May 2024

Quantitative models of sequence-function relationships are ubiquitous in computational biology, e.g., for modeling the DNA binding of transcription factors or the fitness landscapes of proteins. Interpreting these models, however, is complicated by the fact that the values of model parameters can often be changed without affecting model predictions. Before the values of model parameters can be meaningfully interpreted, one must remove these degrees of freedom (called “gauge freedoms” in physics) by imposing additional constraints (a process called “fixing the gauge”). However, strategies for fixing the gauge of sequence-function relationships have received little attention. Here we derive an analytically tractable family of gauges for a large class of sequence-function relationships. These gauges are derived in the context of models with all-order interactions, but an important subset of these gauges can be applied to diverse types of models, including additive models, pairwise-interaction models, and models with higher-order interactions. Many commonly used gauges are special cases of gauges within this family. We demonstrate the utility of this family of gauges by showing how different choices of gauge can be used both to explore complex activity landscapes and to reveal simplified models that are approximately correct within localized regions of sequence space. The results provide practical gauge-fixing strategies and demonstrate the utility of gauge-fixing for model exploration and interpretation.

Significance Statement

Computational biology relies heavily on mathematical models that predict biological activities from DNA, RNA, or protein sequences. Interpreting the parameters of these models, however, remains difficult. Here we address a core challenge for model interpretation-the presence of ‘gauge freedoms’, i.e., ways of changing model parameters without affecting model predictions. The results unify commonly used methods for eliminating gauge freedoms and show how these methods can be used to simplify complex models in localized regions of sequence space. This work thus overcomes a major obstacle in the interpretation of quantitative sequence-function relationships.
Asymmetric binding of coactivator SRC1 to FXR-RXR and allosteric communication within the complex
Authors: Sheng Yanan , Guo Yaoting , Sun Mingze , Dong Yan , Yin Yue , Wang Yanwu , Peng Chao , Xu Yong , Wang Na , Liu Jinsong
Published: May 2024

Farnesoid X receptor (FXR) is a promising target for treatment of metabolic associated fatty liver disease (MAFLD). In this study, we employed an integrative approach to investigate the interaction between FXR-RXRα-hSHP-1 complex and the entire coactivator SRC1-NRID (nuclear receptor interaction domain). We constructed a multi-domain model of FXR120-RXRα98-hSHP-1, highlighting the interface between FXR-DBD and LBD. Using HDX-MS, XL-MS, and biochemical assays, we revealed the allosteric communications in FXR-RXRα-hSHP-1 upon agonist and DNA binding. We then demonstrated that SRC1 binds only to the coactivator binding surface of FXR within the FXR-RXRα heterodimer, with the NR-box2 and NR-box3 of SRC1 as the key binding motifs. Our findings, which provide the first model of SRC1-NRID in complex with FXR-RXRα-hSHP-1, shed light on the molecular mechanism through which the coactivator asymmetrically interacts with nuclear receptors and provide structural basis for further understanding the function of FXR and its implications in diseases.