bluuebunny/crossref_metadata_2025 huggingface dataset:
A case report of cerebellar hemangioblastoma simulated brain metastasis shown by magnetic resonance imaging
Authors: Xue Jiaxing , Mo Chenlong
Published: February 2024

Rationale:

Hemangioblastomas occur both sporadically and as an important component of von Hippel-Lindau (VHL) disease. The typical MRI features of hemangioblastoma are cysts with enhanced cystic wall nodules in the cerebellum or lesions with uniform enhancement on the surface or inside the spinal cord. If there is edema around hemangioblastoma, it is easy to be misdiagnosed as brain metastasis on MRI.

Patient concerns:

A 41-year-old male patient was found to have a lump in the pancreas during a health examination 3 months ago. Subsequently, the patient underwent surgical treatment. The postoperative pathology suggests that the pancreatic lesion is a neuroendocrine tumor. The patient subsequently came to our hospital for consultation on further treatment plans. Abnormal signals were found in the right cerebellum during pituitary magnetic resonance imaging (MRI) before the development of a treatment plan for neuroendocrine tumors. Subsequently, the patient underwent cerebellar mass resection surgery. The pathological result after the surgery was hemangioblastoma.

Diagnosis:

The patient underwent surgery to remove the tumor and was diagnosed with hemangioblastoma by pathological examination. Subsequently, the patient’s genetic testing results confirmed the diagnosis of VHL syndrome.

Interventions:

The patient underwent cerebellar mass resection surgery.

Outcomes:

The patient recovered after surgical resection.

Lessons:

In this report, we emphasize the atypical MRI manifestations of hemangioblastoma. For patients with VHL syndrome-related hemangioblastoma, genetic testing is necessary for the patient and their family members.
Efficacy and Rationale of Endoscopic Ultrasound–Guided Thrombin Injection in Visceral Artery Pseudoaneurysm Not Amenable to Angioembolization
Authors: Jhajharia Ashok , Singh Shashank , Chaudhary Monika , Ameta Mayank , Ashdhir Prachis , Nijhawan Sandeep
Published: February 2024

Background

Pseudoaneurysm usually occurs after vascular injuries or erosions such as in trauma or inflammation like pancreatitis and is associated with high morbidity and mortality.

Aim

The aim of study is to assess efficacy and safety of EUS-guided thrombin injection in pseudoaneurysm.

Materials and Methods

Prospective data collection was done at SMS Hospital, Jaipur, from January 2015 to March 2023. All patients with pseudoaneurysm were consecutively enrolled.

Results

Twenty patients (M/F, 18:2) with median age of 41 years (25–58 years), were studied. Underlying etiology of pseudoaneurysm was chronic pancreatitis in 75% of the patients, blunt trauma abdomen in 15% of the patients, recurrent acute pancreatitis in 5%, and idiopathic in 5% of the patients. At the time of admission, mean hemoglobin was 6.7 g/dL (3.4–8.2), with median blood transfusion requirement was 2 units (0–6 units). Hemoglobin values after 4–6 weeks showed a significant improvement (t = 9.21, P < 0.05).

Mean dose of human thrombin required for complete obliteration of pseudoaneurysm was 520 ± 188.6 IU per patient (300–800 IU). Amount of thrombin (IU) dose needed to achieve complete obliteration correlated well significantly with the dimension of pseudoaneurysm, P value less than 0.05 (R = 0.80). Median follow-up duration in this study was 44 months (3–84 months), which was the longest follow-up period by far.

Conclusions

Endoscopic ultrasound–guided thrombin injection in visceral artery pseudoaneurysm is a safe and effective alternative for patients not amenable for digital subtraction angiography–guided angioembolization.
The epidemiology of neck and low back pain in Iran: a national and sub-national analysis from 1990 to 2019
Authors: Khadembashiri Mohamad M. , Khadembashiri Mohamad A. , Khonji Mohammad S. , Ahadi Tannaz , Forogh Bijan , Mirdamadi Niloofar , Ahmadi Mohammad , Bagherzadeh Cham Masumeh , Soleymanzadeh Hosna , Raissi Gholamreza
Published: February 2024

Background:

Neck pain (NP) is a condition influenced by multiple factors. It places a significant burden on individuals suffering from NP and on social and economic systems. On a global scale, low back pain (LBP) stands out as a significant contributor to years lost to disability, and this burden is on the rise due to population growth and aging.

Methods:

The Global Burden of Disease database was used to collect data on the prevalence, incidence, and years lived with disability (YLD) of NP and LBP between 1990 and 2019. Various factors, including age group, gender, Iran, and its 31 provinces, were used to classify the data.

Results:

Iran accounted for 0.86 million incident cases of NP in 2019, with age-standardized incident rate per 100 000 population of 934.1. Tehran has the maximum age-standardized prevalence, incidence, and YLD. Iran accounted for the age-standardized incidence rate for LBP per 100 000 population of 3492.9, and it reduced to −8.35% from 1990. Mazandaran exhibits the highest levels of prevalence, incidence, and YLD for LBP in 2019. In Iran, the point prevalence of NP in 2019 was higher in females and increased with age up to 50–54 years for females and 70–74 years for males. However, there is only a slight difference between females and males in Iran regarding LBP prevalence.

Conclusions:

In this study, the authors report the prevalence, incidence, YLD, and age-standardized rates for NP and LBP in the world’s general population and Iran’s population based on its sub-nations in 1990 and 2019.
A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial
Authors: Gholamrezaei Ali , Magee Michael R. , McNeilage Amy G. , Dwyer Leah , Sim Alison , Ferreira Manuela L. , Darnall Beth D. , Brake Timothy , Aggarwal Arun , Craigie Meredith , Hollington Irina , Glare Paul , Ashton-James Claire E.
Published: February 2024

Introduction:

Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support.

Objectives:

We evaluated the feasibility, acceptability, and potential efficacy of a codesigned digital health intervention to support patients with chronic pain during voluntary prescription opioid tapering.

Methods:

In a pilot randomised controlled trial, participants received a psychoeducational video and 28 days of text messages (2 SMS/day) in addition to their usual care (intervention) or usual care alone (control). The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy.

Results:

Of 28 randomised participants, 26 completed the study (13 per group). Text message delivery was high (99.2%), but fidelity of video delivery was low (57.1%). Most participants rated the messages as useful, supportive, encouraging, and engaging; 78.5% would recommend the intervention to others; and 64.2% desired a longer intervention period. Tapering self-efficacy (Cohen d = 0.74) and pain self-efficacy (d = 0.41) were higher, and pain intensity (d = 0.65) and affective interference (d = 0.45) were lower in the intervention group at week 4.

Conclusion:

First evidence supports the feasibility, acceptability, and potentially efficacy of a psychoeducational video and SMS text messaging intervention to support patients with chronic pain during voluntary prescription opioid tapering. Definitive trials with longer intervention duration are warranted.
Multi-Institution Survey of Accepting Physicians’ Perception of Appropriate Reasons for Interhospital Transfer: A Mixed-Methods Evaluation
Authors: Nguyen Khanh T. , Lee Tiffany M. , Mueller Stephanie K.
Published: February 2024

Objectives

There is a lack of evidence-based guidelines to direct best practices in interhospital transfers (IHTs). We aimed to identify frontline physicians’ current and ideal reasons for accepting IHT patients to inform future IHT research and guidelines.

Methods

We conducted a cross-sectional survey of hospitalist physicians across 11 geographically diverse hospitals. The survey asked respondents how frequently they currently consider and should consider various factors when triaging IHT requests. Responses were dichotomized into “highly considered” and “less considered” factors. Frequencies of the “highly considered” factors (current and ideal) were analyzed. Write-in responses were coded into themes within a priori domains in a qualitative analysis.

Results

Of the 666 hospitalists surveyed, 238 (36%) responded. Respondents most frequently identified the need for specialty procedural and nonprocedural care and bed capacity as factors that should be considered when triaging IHT patients in current and ideal practice, whereas the least frequently considered factors were COVID-related care, insurance/financial considerations, and patient/family preference. More experienced respondents considered patient/family preference more frequently in current and ideal practice compared with less experienced respondents (33% versus 11% [P = 0.0001] and 26% versus 9% [P = 0.01], respectively). Qualitative analysis identified several themes in the domains of Criteria for Acceptance, Threshold for Acceptance, and Indications for Physician-to-Physician Communication.

Conclusions

This geographically diverse sample of hospitalist physicians responsible for accepting IHT patients showed general agreement between primary factors that are currently and that should be considered for IHT acceptance, with greatest weight placed on patients’ need for specialty care.
Complications of a Barbed Thread in Rhinoplasty
Authors: Lee Sae Bin , Min Hyun Jin
Published: February 2024

Rhinoplasty using threads has been popular for the benefits of being free from anesthesia, shortness of post-surgical recovery process, and surgery-related complications. Compared with its beneficial aspects, studies that evaluated thread rhinoplasty-related complications are relatively limited. Recently, we experienced a patient who underwent barbed thread rhinoplasty in 12 months before visiting our clinic. She presented with a firm mass-like lesion palpated through the nasal dorsum, making hump-looking appearance. During revision rhinoplasty, we found that previously inserted threads were identified from the nasal dorusam and tip area not being resorted. Threads and soft tissue on nasal dorsal area formed firm mass-like lesion and were firmly attached to surrounding soft tissues. Herein, we introduce our case in which the formation of nasal mass on dorsal area is a later complication of thread rhinoplasty.
Using Bibliometric Analysis to Map the Impact of a Simulation Program's Published Scholarly Works
Authors: Rodgers David L. , Bohrer Maxwell B. , Morales Adrian A. , Needler Matthew D. , VandeKoppel Paul
Published: February 2024

Summary Statement

Bibliometrics quantitatively evaluates the targeted literature sources and can help define research and scholarly publications' impact and demonstrate connections for authors, departments, or universities. This article presents a methodology for simulation programs to evaluate their influence in terms of both impact and scope of their published simulation-based healthcare scholarly output. Using the authors' home university and healthcare system as an example, the article outlines a methodology to map research and scholarly works networks within the systems, identify and map connections outside the system, and quantifiably score the overall impact of the simulation program's scholarly output using a common scoring metric, the h-index. This generates an objective measure of impact, rather than a subjective opinion of an organization's research and scholarly impact. The combination of an institutional h-index with mapping of simulation-based healthcare scholarly output provides a full, objective description of the institution's output and provides a benchmark for other simulation programs for comparison.
Linking geodiversity and geosystem services to human well-being for the sustainable utilization of the subsurface and the urban environment
Authors: van Ree D. , van Beukering P. J. H. , Hofkes M. W.
Published: February 2024

Because the functions of the subsurface are hidden from view, its important role in society is often ignored or taken for granted. The subsurface is, however, an essential part of the global ecosystem with important contributions to human well-being. Geodiversity is an important characteristic in this respect. Material supply is the more obvious role of the subsurface with projections of a doubling of global material use in 2060 as compared to 2017. Moreover, creating underground spaces and infrastructure are gaining importance in the urban environment. The main reason for the inadequate protection of geodiversity is the lack of a comprehensive and integrative framework. Linking socio-economic activities to biophysical system characteristics of the subsurface is facilitated by the geosystem services approach. Sustainable urban development strategies require including geodiversity in decision-making on human well-being and setting conditions for land use change. Spatial plans and decisions on the use of natural endowments should look at processes over much longer timeframes. In this paper, we explore the links between human well-being and the subsurface with an emphasis on the role of geodiversity. We set out a methodological framework and describe possible long term three-dimensional land use planning consequences for sustainable utilization of the subsurface.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
The status and future of essential geodiversity variables
Authors: Schrodt Franziska , Vernham Grant , Bailey Joseph , Field Richard , Gordon John E. , Gray Murray , Hjort Jan , Hoorn Carina , Hunter Jr. Malcom L. , Larwood Jonathan , Lausch Angela , Monge-Ganuzas Manu , Miller Stephanie , van Ree Derk , Seijmonsbergen Arie Christoffel , Zarnetske Phoebe L. , Daniel Kissling W.
Published: February 2024

Rapid environmental change, natural resource overconsumption and increasing concerns about ecological sustainability have led to the development of ‘Essential Variables' (EVs). EVs are harmonized data products to inform policy and to enable effective management of natural resources by monitoring global changes. Recent years have seen the instigation of new EVs beyond those established for climate, oceans and biodiversity (ECVs, EOVs and EBVs), including Essential Geodiversity Variables (EGVs). EGVs aim to consistently quantify and monitor heterogeneity of Earth-surface and subsurface abiotic features, including geology, geomorphology, hydrology and pedology. Here we assess the status and future development of EGVs to better incorporate geodiversity into policy and sustainable management of natural resources. Getting EGVs operational requires better consensus on defining geodiversity, investments into a governance structure and open platform for curating the development of EGVs, advances in harmonizing
in situ
measurements and linking heterogeneous databases, and development of open and accessible computational workflows for global digital mapping using machine-learning techniques. Cross-disciplinary collaboration and partnerships with governmental and private organizations are needed to ensure the successful development and uptake of EGVs across science and policy.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
The influence of scale-dependent geodiversity on species distribution models in a biodiversity hotspot
Authors: Gerstner Beth E. , Blair Mary E. , Bills Patrick , Cruz-Rodriguez Cristian A. , Zarnetske Phoebe L.
Published: February 2024

Improving models of species' distributions is essential for conservation, especially in light of global change. Species distribution models (SDMs) often rely on mean environmental conditions, yet species distributions are also a function of environmental heterogeneity and filtering acting at multiple spatial scales. Geodiversity, which we define as the variation of abiotic features and processes of Earth's entire geosphere (inclusive of climate), has potential to improve SDMs and conservation assessments, as they capture multiple abiotic dimensions of species niches, however they have not been sufficiently tested in SDMs. We tested a range of geodiversity variables computed at varying scales using climate and elevation data. We compared predictive performance of MaxEnt SDMs generated using CHELSA bioclimatic variables to those also including geodiversity variables for 31 mammalian species in Colombia. Results show the spatial grain of geodiversity variables affects SDM performance. Some variables consistently exhibited an increasing or decreasing trend in variable importance with spatial grain, showing slight scale-dependence and indicating that some geodiversity variables are more relevant at particular scales for some species. Incorporating geodiversity variables into SDMs, and doing so at the appropriate spatial scales, enhances the ability to model species-environment relationships, thereby contributing to the conservation and management of biodiversity.

This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Promoting diversity in geoheritage evaluation: creating an evaluation method for the scientific value of Quaternary sites in arid environments
Authors: Sayama Kenta
Published: February 2024

A rigorous assessment is an essential part of geoconservation, and choosing an appropriate evaluation method is essential for this process. Globally, an increasing number of sites are being assessed for their geoheritage values, but the most popular methods have been created by researchers with experiences centred in Europe, without considerations of regional differences. To understand whether regional perspectives are required in the evaluation process, this study developed a new method targeting the scientific value of Quaternary geoheritage sites in arid environments, using input from 49 researchers in geosciences and related disciplines with interests in arid landscapes. The results demonstrated the need for a new or modified method, given the different preferences in the weighting system and the necessity to include additional criteria specific to the type of sites targeted by the study. The strong preference to include a new criterion on connections with archaeology/anthropology highlighted the significance of the interdisciplinary scientific values of Quaternary geoheritage sites in arid environments. These findings imply the need for regional diversity or adjustments in geoheritage evaluation. Future research is required to consider such differences for geoheritage values beyond the scientific dimension, such as educational values and touristic values in diverse geographical settings.

This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.
Speluncibacter jeojiensis gen. nov. sp. nov., a novel bacterium of the order Mycobacteriales isolated from a cave and a proposal of Speluncibacteraceae fam. nov.
Authors: Lee Soon Dong , Yang Hong-Lim , Han Jong-Heon , Kim In Seop
Published: February 2024

Two Gram-stain-positive, aerobic, non-spore-forming, non-motile, irregular rod-shaped actinobacteria, designated as D2-41T and D3-21, were isolated from soil samples collected in a natural cave in Jeju, Republic of Korea. Both of the isolates were shown to share 100 % 16S rRNA sequence identity. The cell wall contained meso-diaminopimelic acid, arabinose and galactose. The predominant menaquinone was MK-8(H2). The polar lipids contained phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified aminolipid, an unidentified aminoglycolipid, an unidentified phospholipid and two unidentified lipids. The predominant fatty acids were C16 : 0 and summed feature 3 (C16 : 1
 ω7c and/or iso-C15 : 0 2-OH). Mycolic acids of C30–C38 were present. The 16S rRNA gene trees showed that the organisms occupied a distinct position remotely located from recognized genera within the order Mycobacteriales, albeit with the 16S rRNA gene similarities of 97.0–97.1 % with Rhodococcus olei, Rhodococcus rhodnii and Rhodococcus triatomae. The genome sizes and DNA G+C contents of strains D2-41T and D3-21 were 4.77–4.88 Mbp and 69.8 mol%, respectively. Both of the isolates shared an average nucleotide identity of 99.4 % and digital DNA–DNA hybridization of 95.2 % to each other, revealing that strains D2-41T and D3-21 belonged to the same species. In the core genome-based phylogenomic tree, both of the isolates were found to be closely associated with members of the genus Tomitella. However, strains D2-41T and D3-21 revealed the highest amino acid identity values (mean 66.5 %, range 66.2–67.0 % with the genus Prescottella of the family Nocardiaceae, followed by the genus Tomitella (mean 64.1 %, range 63.6–64.7 %) of the family Tomitellaceae. Based on the combined data obtained here, the novel isolates belong to a new genus of the new family for which the name Speluncibacter jeojiensis gen. nov. sp. nov. is proposed, with Speluncibacteraceae fam. nov. The type strain is strain D2-41T (=KACC 17930T=DSM 101875T).
Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing
Authors: Fiflis David N. , Rey Nicolas A. , Venugopal-Lavanya Harshitha , Sewell Beatrice , Mitchell-Dick Aaron , Clements Katie N. , Milo Sydney , Benkert Abigail R. , Rosales Alan , Fergione Sofia , Asokan Aravind
Published: February 2024

Type VI CRISPR enzymes have been developed as programmable RNA-guided Cas proteins for eukaryotic RNA editing. Notably, Cas13 has been utilized for site-targeted single base edits, demethylation, RNA cleavage or knockdown and alternative splicing. However, the ability to edit large stretches of mRNA transcripts remains a significant challenge. Here, we demonstrate that CRISPR-Cas13 systems can be repurposed to assist trans-splicing of exogenous RNA fragments into an endogenous pre-mRNA transcript, a method termedCRISPRAssisted mRNAFragmentTrans-splicing (CRAFT). Using split reporter-based assays, we evaluate orthogonal Cas13 systems, optimize guide RNA length and screen for optimal trans-splicing site(s) across a range of intronic targets. We achieve markedly improved editing of large 5’ and 3’ segments in different endogenous mRNAs across various mammalian cell types compared to other spliceosome-mediated trans-splicing methods. CRAFT can serve as a versatile platform for attachment of protein tags, studying the impact of multiple mutations/single nucleotide polymorphisms, modification of untranslated regions (UTRs) or replacing large segments of mRNA transcripts.
Morphologic characterization and cytokine response of chicken bone-marrow derived dendritic cells to infection with high and low pathogenic avian influenza virus
Authors: Mo Jongsuk , Segovia Karen , Chrzastek Klaudia , Briggs Kelsey , Kapczynski Darrell R.
Published: February 2024

Dendritic cells (DCs) are professional antigen-presenting cells, which are key components of the immune system and involved in the early immune response. DCs are specialized in capturing, processing, and presenting antigens to facilitate immune interactions. Chickens infected with avian influenza virus (AIV) demonstrate a wide range of clinical symptoms, based on pathogenicity of the virus. Low pathogenic avian influenza (LPAI) viruses typically induce mild clinical signs, whereas high pathogenic avian influenza (HPAI) induce more severe disease, which can lead to death within days. For this study, chicken bone marrow-derived DC (ckBM-DC)s were produced and infected with high and low pathogenic avian influenza viruses of H5N2 or H7N3 subtypes to characterize innate immune responses, study effect on cell morphology, and evaluate virus replication. A strong proinflammatory response, including chicken interleukin-1β, and stimulation of the interferon response pathway were observed at 8 hours post infection. Microscopically, the DCs underwent morphological changes from classic elongated dendrites to a more general rounded shape that eventually lead to cell death with the presence of scattered cellular debris. Differences in onset of morphologic changes were observed between H5 and H7 subtypes. Increases in viral titers demonstrated that both HPAI and LPAI are capable of infecting and replicating in DCs. The elevated expression of infected DCs may be indicative with a dysregulation of the immune response typically seen with HPAI infections.
Single-Cell Transcriptomic Profiling Unveils Critical Metabolic Alterations and Signatures in Progression of Atherosclerosis
Authors: Ma Limei , Zhao Ying , Xiang Peng , Chen Qingqiu , Hassan Moustapha , Yu Chao
Published: February 2024

Metabolic dysregulation is recognized as a fundamental characteristic of cardiovascular diseases (CVDs), therefore mining metabolic patterns in these diseases would help to identify the possible pathogenic mechanisms and potential intervention targets. Atherosclerosis (AS), serving as the foundational pathology in numerous CVDs, represents a paramount global health concern. However, a systematic integrated analysis of the metabolic networks of AS is still lacking. In this study, we investigated and integrated single-cell RNA sequencing datasets from calcified atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery tissue to generate metabolic flux profiling at single-cell level. Using scFEA and scWGCNA analyses, we discerned common metabolic changes in endothelial cells (ECs), myeloid cells, and smooth muscle cells. These altered metabolic modules were predominantly enriched in glucose-related pathways and were predicted to potentially facilitate metabolic bypass. Of particular interest, we observed an enrichment of metabolites produced from glucose/sialic acid metabolism pathway in both ECs and myeloid cells. This observation may partially account for their positive involvement in plaque formation, as previously discovered. Furthermore, we predicted that metabolic genes such asHK1,ENO1,PFKL,LDHA,PGK1,andNANSmay be implicated in the detected metabolic flux disorder during AS progression. Additionally, we uncovered interactions between various cell types at single-cell level using CellChat. We noted heightened interactions between endothelial/SMC as well as myeloid/ECs in AC group, with ITGB2/VCAM and CD44/CD74 receptors potentially participating in these interactions, thereby fostering the development of pro-inflammatory plaque microenvironment. In conclusion, our study unveils metabolic shifts at single-cell level and identifies key gene signatures associated with metabolic disorders and cell-cell communication in atherosclerosis.
Experimental Snowball Earth Viscosity Drives the Evolution of Motile Multicellularity
Authors: Halling Andrea , Goodson Brysyn , Hirschmann Anna , Wing Boswell A. , Simpson Carl
Published: February 2024

During the 70-million-year span of the Cryogenian Snowball Earth glaciations, low ocean temperatures beneath global sea ice increased water viscosity up to fourfold. In the absence of adaptation, unicellular organisms living in this viscous environment were limited in their ability to move and acquire nutrients. We experimentally test the hypothesis that multicellularity evolved in order to overcome this viscosity-induced metabolic deficit. In the presence of Snowball Earth viscosities, we find that populations of unicellular green algae evolve motile multicellular phenotypes in addition to other phenotypes that optimize different combinations of size and speed. As the Snowball Earth subsided and warm seas returned, the novelty of motile multicellularity permitted these organisms to take physical control over their local environment for the first time. This innovation may underpin the evolution of dominant multicellular lineages on Earth today.

Significance statement

Beginning 720-million years ago, two global glaciations — together known as the Snowball Earth — covered the planet with a thick layer of ice for a total of 70-million years. Several groups of complex multicellular organisms independently radiated at this time, including animals, green algae, and red algae. All of these clades include lineages with large bodies made of thousands of cells, multiple cell types, and spatial organization. At first glance, it seems that life merely survived despite the Snowball Earth glaciations. We find experimental evidence that the Snowball Earth glaciations were instead an evolutionary trigger for the diversification of complex multicellular groups.
vSPACE: Exploring Virtual Spatial Representation of Articular Chondrocytes at the Single-Cell Level
Authors: Zhang Chenyu , Wang Honglin , Hong Seung-Hyun , Olmer Merissa , Swahn Hannah , Lotz Martin K. , Maye Peter , Rowe David , Shin Dong-Guk
Published: February 2024

Single cell RNA sequencing technology has been dramatically changing how gene expression studies are performed. However, its use has been limited to identifying subtypes of cells by comparing cells’ gene expression levels in an unbiased manner to produce a 2D plot (e.g., UMAP/tSNE). We developed a new method of placing cells in 2D space. This system, called vSPACE, shows a virtual spatial representation of scRNAseq data obtained from human articular cartilage by emulating the concept of spatial transcriptomics technology, but virtually. This virtual 2D plot presentation of human articular cartage cells generates several zonal distribution patterns, in one or multiple genes at a time, reveling patterns that scientists can appreciate as imputed spatial distribution patterns along the zonal axis. The discovered patterns are explainable and remarkably consistent across all six healthy doners despite their respectively different clinical variables (age and sex), suggesting the confidence of the discovered patterns.
Prelude to Malignancy: A Gene Expression Signature in Normal Mammary Gland from Breast Cancer Patients Suggests Pre-tumorous Alterations and Is Associated with Adverse Outcomes
Authors: Andreou Maria , Jąkalski Marcin , Duzowska Katarzyna , Filipowicz Natalia , Kostecka Anna , Davies Hanna , Horbacz Monika , Ławrynowicz Urszula , Chojnowska Katarzyna , Bruhn-Olszewska Bożena , Jankau Jerzy , Śrutek Ewa , Las-Jankowska Manuela , Bała Dariusz , Hoffman Jacek , Hartman Johan , Pęksa Rafał , Skokowski Jarosław , Jankowski Michał , Szylberg Łukasz , Zegarski Wojciech , Nowikiewicz Magdalena , Nowikiewicz Tomasz , Dumanski Jan P. , Mieczkowski Jakub , Piotrowski Arkadiusz
Published: February 2024

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes is still missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes(FOXA1, RAB25, NRG1, SPDEF, TRIM29, andGABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.
In vivovalidation of anin situcalibration bead as a reference for backscatter coefficient calculation
Authors: Zhao Yuning , Czarnota Gregory J. , Park Trevor H. , Miller Rita J. , Oelze Michael L.
Published: February 2024

Objectives

The study aims to assess the capability of Quantitative Ul-trasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantifying fatty liver disease. We evaluate the effectiveness of anin situtitanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation.

Methods

Traditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmis-sion losses through tissues. To address this issue, we use anin situtitanium (Ti) bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of thein situcalibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N = 21). Specifically, mammary tumors were grown in rabbits and when a tumor reached 1 cm or greater in size, a 2-mm Ti bead was implanted into the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with a L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenu-ation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead.

Results

For ESD estimation, the 95% confidence interval between measure-ments with and without the pork belly layer was (6.0,27.4) using thein situbead and (114, 135.1) with the external reference phantom. For EAC esti-mation, the 95% confidence interval were (−8.1, 0.5) for the bead and (−41.5, −32.2) for the phantom. These results indicate that thein situbead method shows reduced bias in QUS estimates due to intervening tissue losses.

Conclusions

The use of anin situTi bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.
USE OF MACHINE LEARNING TO PREDICT INDIVIDUAL POSTPRANDIAL GLYCEMIC RESPONSES TO FOOD AMONG INDIVIDUALS WITH TYPE 2 DIABETES IN INDIA
Authors: Choudhry Niteesh K. , Priyadarshini Shweta , Swamy Jaganath , Mehta Mridul
Published: February 2024

Background

Type 2 diabetes (DM2) is a leading cause of premature morbidity and mortality globally and affects more than 100 million people in the world’s most populous country, India. Nutrition is a critical and evidence-based component of effective blood sugar control and most dietary advice emphasizes carbohydrate and calorie reduction. Emerging global evidence demonstrates marked inter-individual differences in post-prandial glucose response (PPGR) although no such data exists in India and prior studies have primarily evaluated PPGR variation in individuals without diabetes.

Methods

This prospective cohort study seeks to characterize the PPGR variability in Indians with diabetes and to identify factors associated with these differences. Adults with type 2 diabetes and a hemoglobin A1c ≥7 are being enrolled from 14 sites around India. Subjects wear a continuous glucose monitor, eat a series of standardized meals, and record all free-leaving foods, activities, and medication use for a 14-day period. The study’s primary outcome is PPGR, calculated as the incremental area under the curve 2 hours after each logged meal.

Discussion

This study will provide the first large scale examination variability in blood sugar responses to food in India and will be among the first to estimate PPGR variability for individuals with DM2 in any jurisdiction. Results from our study will generate data to facilitate the creation of machine learning models to predict individual PPGR responses and to facilitate the prescription of personalized diets for individuals with DM2.
Insights into the nature of the microalgal toxins from theChrysochromulina leadbeateriblooms in Northern Norwegian fjords
Authors: Wang Xinhui , Fon Mathias , Andersen Aaron J.C. , Solhaug Anita , Ingebrigtsen Richard A. , Samdal Ingunn A. , Uhlig Silvio , Miles Christopher O. , Edvardsen Bente , Larsen Thomas O.
Published: February 2024

In May–June 2019, the microalgaChrysochromulina leadbeatericaused a massive fish-killing event in several fjords in Northern Norway, resulting in the largest direct impact ever on aquaculture in northern Europe due to toxic algae. Motivated by the fact that no algal toxins have previously been described fromC. leadbeateri, we set out to investigate the chemical nature and toxicity of secondary metabolites in extracts of two strains (UIO 393, UIO 394) isolated from the 2019 bloom, as well as one older strain (UIO 035) isolated during a bloom in Northern Norway in 1991. Initial LC–DAD–MS/MS-based molecular networking analysis of the crude MeOH extracts of the cultivated strains showed that their profiles of small organic molecules, including a large number of known lipids, were very similar, suggesting that the same class of toxin(s) were likely the causative agents of the two harmful algal bloom (HAB) events. Next, bioassay-guided fractionation using the RTgill-W1 cell line and metabolomics analysis pointed to a major compound affording [M+H]+ions atm/z1399.8333 as a possible toxin, corresponding to a compound with the formula C67H127ClO27. Moreover, our study unveiled a series of minor analogues exhibiting distinct patterns of chlorination and sulfation, together defining a new family of compounds, which we propose to name leadbeaterins. Remarkably, these suspected toxins were detectedin situin samples collected during the 2019 bloom close to Tromsø, thereby substantiating their likely role in fish kills. The elemental compositions of the putativeC. leadbeateriichthyotoxins strongly indicate them to be long linear polyhydroxylated polyketides, structurally similar to sterolysins, reported from a number of dinoflagellates.
The Genotype and Phenotypes in Families (GPF) platform manages the large and complex data at SFARI
Authors: Chorbadjiev Liubomir , Cokol Murat , Weinstein Zohar , Shi Kevin , Fleisch Chris , Dimitrov Nikolay , Mladenov Svetlin , Xu Simon , Hall Jake , Ford Steven , Lee Yoon-ha , Yamrom Boris , Marks Steven , Munoz Adriana , Lash Alex , Volfovsky Natalia , Iossifov Ivan
Published: February 2024

The exploration of genotypic variants impacting phenotypes is a cornerstone in genetics research. The emergence of vast collections containing deeply genotyped and phenotyped families has made it possible to pursue the search for variants associated with complex diseases. However, managing these large-scale datasets requires specialized computational tools tailored to organize and analyze the extensive data. GPF (Genotypes and Phenotypes in Families) is an open-source platform (https://github.com/iossifovlab/gpf) that manages genotypes and phenotypes derived from collections of families. The GPF interface allows interactive exploration of genetic variants, enrichment analysis forde novomutations, and phenotype/genotype association tools. In addition, GPF allows researchers to share their data securely with the broader scientific community. GPF is used to disseminate two large-scale family collection datasets (SSC, SPARK) for the study of autism funded by the SFARI foundation. However, GPF is versatile and can manage genotypic data from other small or large family collections. Our GPF-SFARI GPF instance (https://gpf.sfari.org/) provides protected access to comprehensive genotypic and phenotypic data for the SSC and SPARK. In addition, GPF-SFARI provides public access to an extensive collection ofde novomutations identified in individuals with autism and related disorders and to gene-level statistics of the protected datasets characterizing the genes’ roles in autism. Here, we highlight the primary features of GPF within the context of GPF-SFARI.
Model-guided metabolic engineering of curcuminoid Production inPseudomonas putida
Authors: Martin-Pascual Maria , Moreno-Paz Sara , van Rosmalen Rik P. , Dorigo Julia , Demaria Francesca , van Kranenburg Richard , Martins dos Santos Vitor A.P. , Suarez-Diez Maria
Published: February 2024

Production of value-added, plant-derived compounds in microbes increasingly attracts commercially interest in food and pharmaceutical industries. However, plant metabolic pathways are complex, require a robust balance of enzymes, cofactors, ATP and other metabolites, and often result in low production when transplanted to bacteria. This is exemplified by the biosynthesis of curcuminoids from theCurcuma longaplant. Here, we combine dynamic pathway modeling, systematic testing of isoenzymes, and the optimization of gene expression levels and substrate concentrations for the biosynthesis of curcuminoids inPseudomonas putida, leading to unprecedented conversion rates of caffeic acid and tyrosine to curcumin. The development of kinetic ensemble models guided the design of production strains, emphasizing the necessity of high relative expression ofc3h, curs2anddcsand, the low relative expression oftal, comt, ccoaomt, and4cl4. This optimization resulted in a strain that achieved a 10.8 ±1.8% of the maximum theoretical yield of curcumin from tyrosine. This represents a 4.1-fold increase in production efficiency and the highest yield reported to date, demonstrating the potential ofP. putidaas a promising platform for curcuminoid production. Our findings highlight the effectiveness of our strategy not only in the advances in the production of curcuminoids but also in setting a framework for the biosynthesis of other complex compounds.
The utilization of contraceptives by teenagers in Lesotho: A descriptive cross-sectional survey
Authors: Khiba Rets’elisitsoe , Nyangu Isabel
Published: February 2024

Background

Contraceptive service provision to teenagers prevents pregnancy and childbirth complications, which are the leading causes of death among teenage girls globally.

Aim

The study aimed to assess how teenagers utilized the contraceptive services provided at selected healthcare facilities in Lesotho.

Methodology

A quantitative descriptive cross-sectional design was used to collect data from 194 teenagers who were conveniently sampled from two health facilities in Berea district, Lesotho. Permission to conduct the study was sought and granted from the Ministry of Health and written informed consent was sought from the participants before they completed selfadministered questionnaires. Data was captured and analyzed using the SPSS version 24.

Results

Most (64.5%) of the teenagers knew that contraceptives prevented pregnancy, whilst a fifth of them referred to them as the prevention of HIV or sexually transmitted infections. Utilization of contraceptives was reported by just over a third and about two-fifths were able to access them at the public health clinics daily. Injectables and condoms were the most preferred methods used by teenagers. Factors that enhanced contraceptive usage included nurses’ friendliness, as well as an understanding of why teenagers are not fully utilizing the contraceptive services provided. Most teenagers were found not to be utilizing contraceptive services due to the belief that they led to weight gain and unsatisfactory intercourse.

Conclusion

The study findings provided a need for and importance of contraceptive service provision to teenagers, including the need for education to improve their understanding and reduce myths.

Implications for nursing management

Healthcare service providers need to improve access to contraceptive services to improve their utilization by teenagers.
An increasing Arctic-boreal CO2sink offset by wildfires and source regions
Authors: Virkkala Anna-Maria , Rogers Brendan M. , Watts Jennifer D. , Arndt Kyle A. , Potter Stefano , Wargowsky Isabel , Schuur Edward A. G. , See Craig , Mauritz Marguerite , Boike Julia , Bret-Harte Syndonia M. , Burke Eleanor J. , Burrell Arden , Chae Namyi , Chatterjee Abhishek , Chevallier Frederic , Christensen Torben R. , Commane Roisin , Dolman Han , Elberling Bo , Emmerton Craig A. , Euskirchen Eugenie S. , Feng Liang , Goeckede Mathias , Grelle Achim , Helbig Manuel , Holl David , Järveoja Järvi , Kobayashi Hideki , Kutzbach Lars , Liu Junjie , Liujkx Ingrid , López-Blanco Efrén , Lunneberg Kyle , Mammarella Ivan , Marushchak Maija E. , Mastepanov Mikhail , Matsuura Yojiro , Maximov Trofim , Merbold Lutz , Meyer Gesa , Nilsson Mats B. , Niwa Yosuke , Oechel Walter , Park Sang-Jong , Parmentier Frans-Jan W. , Peichl Matthias , Peters Wouter , Petrov Roman , Quinton William , Rödenbeck Christian , Sachs Torsten , Schulze Christopher , Sonnentag Oliver , St.Louis Vincent , Tuittila Eeva-Stiina , Ueyama Masahito , Varlagin Andrej , Zona Donatella , Natali Susan M.
Published: February 2024

The Arctic-Boreal Zone (ABZ) is rapidly warming, impacting its large soil carbon stocks. We use a new compilation of terrestrial ecosystem CO2fluxes, geospatial datasets and random forest models to show that although the ABZ was an increasing terrestrial CO2sink from 2001 to 2020 (mean ± standard deviation in net ecosystem exchange: −548 ± 140 Tg C yr-1; trend: −14 Tg C yr-1, p<0.001), more than 30% of the region was a net CO2source. Tundra regions may have already started to function on average as CO2sources, demonstrating a critical shift in carbon dynamics. After factoring in fire emissions, the increasing ABZ sink was no longer statistically significant (budget: −319 ± 140 Tg C yr-1; trend: −9 Tg C yr-1), with the permafrost region becoming CO2neutral (budget: −24 ± 123 Tg C yr-1; trend: −3 Tg C yr-1), underscoring the importance of fire in this region.