bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality and Safety in Nursing: Recommendations From a Systematic Review
Authors: Patrician Patricia A. , Campbell Caitlin M. , Javed Mariyam , Williams Kathy M. , Foots Lozay , Hamilton Wendy M. , House Sherita , Swiger Pauline A.
Published: May 2024

As a consistent 24-hour presence in hospitals, nurses play a pivotal role in ensuring the quality and safety (Q&S) of patient care. However, a comprehensive review of evidence-based recommendations to guide nursing interventions that enhance the Q&S of patient care is lacking. Therefore, the purpose of our systematic review was to create evidence-based recommendations for the Q&S component of a nursing professional practice model for military hospitals. To accomplish this, a triservice military nursing team used Covidence software to conduct a systematic review of the literature across five databases. Two hundred forty-nine articles met inclusion criteria. From these articles, we created 94 recommendations for practice and identified eight focus areas from the literature: (1) communication; (2) adverse events; (3) leadership; (4) patient experience; (5) quality improvement; (6) safety culture/committees; (7) staffing/workload/work environment; and (8) technology/electronic health record. These findings provide suggestions for implementing Q&S practices that could be adapted to many healthcare delivery systems.
Liver transplantation for tumor entities
Authors: Patrono Damiano , De Stefano Nicola , Romagnoli Renato
Published: May 2024

Purpose of review

Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology.

Recent findings

Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection.

While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.
Myxoid Inflammatory Myofibroblastic Sarcoma
Authors: Papke David J. , Odintsov Igor , Dickson Brendan C. , Nucci Marisa R. , Agaimy Abbas , Fletcher Christopher D.M.
Published: May 2024

The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed “myxoid inflammatory myofibroblastic sarcoma,” which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative forALKrearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4PDGFRB, 2PML::JAK1, 1SEC31A::PDGFRA). Two instead harbored hot spotKRASmutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo–12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harboredSEC31A::PDGFRAwas treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.
Optimizing Triage
Authors: Levkowitz Eilan , Gibson Robert , Xu Hongyan , Zhang Li Fang , Eskine Katherine , Buck Brian , Bruno Michael , Seeyave Desiree
Published: May 2024

Objective

We investigated the diagnostic value of shock index, pediatric age-adjusted (SIPA) in predicting Emergency Severity Index level 3 patients' outcomes. Secondary objectives included exploring the impact of fever and participant variables on SIPA's predictive ability.

Methods

A retrospective chart review identified children aged 1 to 15 years triaged as a level 3 in the emergency department between January 2018 and December 2021. Shock index, pediatric age-adjusted thresholds based on age, 1 to 6 years (>1.2), 7 to 12 years (>1.0), and 13 to 17 years (>0.9), were used. We assessed elevated SIPA and SIPA corrected for fever to evaluate associations with outcomes and interventions.

Results

Our findings, involving 192 patients, revealed that elevated SIPA demonstrated enhanced discrimination relative to nonelevated SIPA. Patients with elevated SIPA had more average interventions: 1.14 versus 0.74, P < 0.016; average interventions using SIPA corrected for fever: 1.14 versus 0.77, P < 0.006; average interventions controlling for race and sex: 1.15 versus 0.71, P < 0.001; hospital admission: 64.4% versus 42.9%, P = 0.004; hospital length of stay (LOS): 3.06 days (SE, 0.42) versus 1.46 days (SE, 0.23); hospital LOS using SIPA corrected for fever: 2.75 days (SE, 0.44) versus 1.72 days (SE, 0.24); ventilatory support: 16.44% versus 3.36%, P < 0.002; fluid bolus: 28.77% versus 14.29%, P < 0.015; intravenous medications (antibiotics, antiepileptics, immune globulin, albumin): 45.21% versus 30.25%, P < 0.036. There was no difference between other interventions, pediatric intensive care admission, and LOS between the 2 groups. Importantly, SIPA was unaffected by fever, race, or sex.

Conclusions

Shock index, pediatric age-adjusted identifies level 3 Emergency Severity Index pediatric patients more likely to require hospital admission, longer LOS, and a lifesaving intervention especially ventilatory support, intravenous fluids, or specific intravenous medications. Shock index, pediatric age-adjusted's predictive ability remained unaffected by fever, race, or sex, making it a valuable tool in preventing mistriage and justifying inclusion in the Emergency Severity Index danger zone vitals criteria for up-triage.
Unnecessary Explantation of IDEAL IMPLANT Structured Saline Breast Implants Prompted byRadiologic Misdiagnosis of Rupture
Authors: Boston Rebecca S. , Hamas Robert S. , Mango Victoria L. , Nichter Larry S.
Published: May 2024

The unique dual-lumen and baffle design of the IDEAL IMPLANT Structured Saline breast implant gives it specific advantages over both silicone gel–filled and the original saline-filled implants. This internal baffle structure also gives it an appearance on various radiologic imaging studies that may be misinterpreted as a rupture because of similarities to the well-known radiologic appearance of a ruptured silicone gel implant. Patients may present with various misinterpreted imaging studies, highlighting the need for plastic surgeons and radiologists to be familiar with the normal appearance of the intact IDEAL IMPLANT and be able to distinguish it from a ruptured IDEAL IMPLANT. The radiology findings must be correlated with the clinical findings, or an intact IDEAL IMPLANT misdiagnosed as ruptured, may cause unnecessary patient worry, and may prompt unnecessary surgery for removal or replacement.
Promoting Growth in Behavioral Neurology: A Path Forward
Authors: Bateman James R. , Josephy-Hernandez Sylvia , Apostolova Liana G. , Benjamin Sheldon , Barrett A.M. , Boeve Bradley F. , Budson Andrew E. , Chemali Zeina , Lin Chi-Ying R. , Daffner Kirk R. , Geschwind Michael D. , Heilman Kenneth M. , Hillis Argye E. , Holden Samantha K. , Jaffee Michael S. , Kletenik Isaiah , Love Marissa Natelson , Moo Lauren R. , Pelak Victoria S. , Press Daniel Z. , Ramirez-Gomez Liliana , Rosen Howie J. , Schmahmann Jeremy D. , Vaishnavi Sanjeev N. , Windon Charles C. , Hamilton Roy H. , Perez David L.
Published: May 2024

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain–behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist’s perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP—efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.
Using Photovoice to engage students in a non-major microbiology course
Authors: Kelly Bridget
Published: May 2024

In the past decade, it has become increasingly difficult to engage and encourage critical thinking and deeper learning in students who participate in higher education, particularly in non-major subjects. Photovoice is a participatory action research methodology that has been used in community based research in many different areas including social science, health science and education. In this study, photovoice was used as a pedagogical tool in a third year BSc Bioscience non-major microbiology module at Dundalk Institute of Technology. In order to ascertain if photovoice was an effective way of engaging these students, a qualitative descriptive methodological approach, in the form of a focus group, was employed. Six of the thirteen students who took the module participated in the focus group, reporting a positive experience overall of using photovoice. Further analysis of the focus group data resulted in the overarching theme of choice, with creativity and critical thinking and research skills as sub-themes to emerge. These findings suggest that photovoice is an effective way to engage students in microbiology as a non-major subject. However, as it was a small sample size, future research would need to use a larger cohort of students to provide further evidence of using photovoice as a pedagogical engagement tool for non-major subjects.
Coraliomargarita algicola sp. nov., isolated from a marine green alga
Authors: Lee Jae Kyeong , Choi Dae Gyu , Choi Byeong Jun , Kim Jeong Min , Jeon Che Ok
Published: May 2024

A Gram-stain-negative, facultative aerobic, catalase- and oxidase-positive, non-motile, non-flagellated, and coccus-shaped bacterium, strain J2-16T, isolated from a marine green alga, was characterized taxonomically. Strain J2-16T grew at 20–40 °C (optimum, 30 °C), pH 6.0–10.0 (optimum, pH 7.0), and 1.0–4.0 % (w/v) NaCl (optimum, 3.0 %). Menaquinone-7 was identified as the sole respiratory quinone, and major fatty acids (>5 %) were C18 : 1
 ω9c, iso-C14 : 0, C14 : 0, anteiso-C15 : 0, C18 : 0, C16 : 0, and C17 : 1
 ω8c. The polar lipids of strain J2-16T consisted of phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, and three unidentified lipids. The genome size of strain J2-16T was 5384 kb with a G+C content of 52.0 mol%. Phylogenetic analyses based on 16S rRNA gene and 120 protein marker sequences revealed that strain J2-16T formed a distinct phyletic lineage within the genus Coraliomargarita, closely related to Coraliomargarita sinensis WN38T and Coraliomargarita akajimensis DSM 45221T with 16S rRNA gene sequence similarities of 95.7 and 94.4 %, respectively. Average nucleotide identity and digital DNA–DNA hybridization values between strain J2-16T and Coraliomargarita species were lower than 71.2 and 20.0 %, respectively. The phenotypic, chemotaxonomic, and molecular features support that strain J2-16T represents a novel species of the genus Coraliomargarita, for which the name Coraliomargarita algicola sp. nov. is proposed. The type strain is J2-16T (=KACC 22590T=JCM 35407T).
Assessing the change in the epidemiology of seasonal respiratory viruses with the onset of the COVID-19 pandemic
Authors: Kara Yalcin , Kizil Mahmut Can , İşeri Nepesov Merve , Kaçmaz Ebru , Kiral Eylem , Bozan Gurkan , Durmaz Gül , Us Tercan , Kiliç Ömer , Dinleyici Ener Çağrı
Published: May 2024

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.

Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.

Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.

Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.
Ezrin defines TSC complex activation at endosomal compartments through EGFR-AKT signaling
Authors: Giamundo Giuliana , Intartaglia Daniela , Prete Eugenio Del , Polishchuk Elena , Andreone Fabrizio , Ognibene Marzia , Buonocore Sara , Mele Bruno Hay , Salierno Francesco Giuseppe , Monfregola Jlenia , Antonini Dario , Grumati Paolo , Eva Alessandra , de Cegli Rossella , Conte Ivan
Published: May 2024

Endosomes have emerged as major signaling hubs where different internalized ligand-receptor complexes are integrated and the outcome of signaling pathways are organized to regulate the strength and specificity of signal transduction events. Ezrin, a major membrane-actin linker that assembles and coordinates macromolecular signaling complexes at membranes, has emerged recently as an important regulator of lysosomal function. Here, we report that endosomal-localized EGFR/Ezrin complex interacts with and triggers the inhibition of the Tuberous Sclerosis Complex (TSC complex) in response to EGF stimuli. This is regulated through activation of the AKT signaling pathway. Loss of Ezrin was not sufficient to repress TSC complex by EGF and culminated in translocation of TSC complex to lysosomes triggering suppression of mTORC1 signaling. Overexpression of constitutively active EZRINT567Dis sufficient to relocalize TSC complex to the endosomes and reactivate mTORC1. Our findings identify EZRIN as a critical regulator of autophagy via TSC complex in response to EGF stimuli and establish the central role of early endosomal signaling in the regulation of mTORC1. Consistently, Medaka fish deficient for Ezrin exhibit defective endo-lysosomal pathway, attributable to the compromised EGFR/AKT signaling, ultimately leading to retinal degeneration. Our data identify a pivotal mechanism of endo-lysosomal signaling involving Ezrin and its associated EGFR/TSC complex, which are essential for retinal function.
Multi-omics Reveals Immune Response and Metabolic Profiles during High-Altitude Mountaineering
Authors: Yin Jianhua , Lv Jingzhi , Yang Shichen , Wang Yang , Huang Zhuoli , Wang Xue , Hou Guixue , Zhou Wenwen , Liu Ying , Wang Weikai , Lin Xiumei , Huang Yunting , Zheng Yuhui , Wei Chen , Yuan Yue , Huang Yaling , Liu Chang , Tao Haoran , Liu Huanhuan , Liu Ruquan , Zhang Yan , Zeng Guodan , Gao Peng , Liu Longqi , Cao Jun , Liu Chuanyu , Jin Xin , Wang Jian
Published: May 2024

The physiological perturbations induced by high-altitude exposure in mountain climbers, manifesting as metabolic and immunologic deviations, have been previously reported but are not fully understood. In this study, we obtained longitudinal multi-omic profiles of blood samples for healthy mountain climbers during two mountaineering stages (acclimatization and extreme altitude mountaineering). Our integrative assay included metabolomics and lipidomics profiling of plasma coupled with single-cell transcriptomic analysis of 375,722 immune cells. Longitudinal analysis revealed dynamic immune response profiles, during the acclimatization period, characterized by the downregulation of inflammatory responses in monocytes and classical dendritic cells (cDCs) and an increase in the proportion of cytotoxic CD8+T cells with enhanced immune effector processes. In contrast, during extreme altitude mountaineering, the activation of inflammatory responses and impairment of T cell effector function were observed, concomitant with an increased cellular response to hypoxia and oxidative stress pathways. Furthermore, we found upregulated glycolysis and antioxidant gene expression during extreme altitude mountaineering, which was primarily orchestrated byHIF1AandNFE2L2, while decreased expression of these genes was observed in dysregulated plasmacytoid dendritic cells (pDCs). Finally, high-resolution plasma metabolic analysis revealed significant alterations in the metabolism of climbers, involving enhanced glutamine and fatty acid metabolism.
Neutrophil percentages in bronchoalveolar lavage fluid: Implications for diagnosing bacterial pneumonia in patients with immunocompromise and neutropenia
Authors: Grudzinski Kevin M. , Fenske Samuel , Peltekian Alec , Markov Nikolay S. , Pawlowski Anna , Kang Mengjia , Walter James M. , Pickens Chiagozie I. , Nadig Nandita R. , Agrawal Ankit , Singer Benjamin D. , Wunderink Richard G. , Gao Catherine A.
Published: May 2024

Rationale

Pneumonia is the most common infection in ICU patients and a leading cause for death. Assessment of bronchoalveolar lavage fluid (BALF) cellularity can aid in pneumonia diagnosis. Low percentages (<50%) of BALF neutrophils have a high negative predictive value for bacterial pneumonia in a general medical ICU population. The operating characteristics in patients with immunocompromise and neutropenia are less clear.

Objective

To compare BALF % neutrophils operating characteristics in patients with and without immunocompromise or neutropenia.

Methods

This was a single center observational cohort study. Patients were categorized into three groups: (1) patients with neutropenia, (2) patients with underlying immunocompromise, and (3) patients with neither. BAL-level analysis reflected neutropenia and immunocompromise state on day of BAL sampling. Operating characteristics of BALF % neutrophils were calculated using varying thresholds of alveolar neutrophilia. Median [Q1,Q3] are reported for nonparametric data and compared using Mann-Whitney U tests.

Results

688 mechanically ventilated patients had 1736 BAL samples. Among bacterial pneumonia episodes, no difference was found in BALF % neutrophils between patients with underlying immunocompromise and patients with neither neutropenia nor immunocompromise on day of sampling: 82.0% [61.0, 91.0] vs 81.0% [66.0, 91.0], p=0.859. However, when neutropenic on day of sampling, the median BALF % neutrophils was 35.0% [8.8, 67.5] (p<0.001 compared with other categories). In patients with neutropenia, a BALF % neutrophil threshold of 7% had a sensitivity of 90% for excluding bacterial pneumonia.

Conclusions

We found that among patients with bacterial pneumonia, BALF % neutrophil was not significantly lower in patients with a broad spectrum of immunocompromised states but was significantly lower when measured during acute neutropenia. We found varying thresholds of BALF % neutrophils across the three groups. Patients with neutropenia who mount even a low percent of alveolar neutrophils should raise concern for bacterial pneumonia.
Prediction of antibiotic resistance mechanisms using a protein language model
Authors: Yagimoto Kanami , Hosoda Shion , Sato Miwa , Hamada Michiaki
Published: May 2024

Motivation

Antibiotic resistance has emerged as a major global health threat, with an increasing number of bacterial infections becoming difficult to treat. Predicting the underlying resistance mechanisms of antibiotic resistance genes (ARGs) is crucial for understanding and combating this problem. However, existing methods struggle to accurately predict resistance mechanisms for ARGs with low similarity to known sequences and lack sufficient interpretability of the prediction models.

Results

In this study, we present a novel approach for predicting ARG resistance mechanisms using Protein-BERT, a protein language model based on deep learning. Our method outperforms state-of-the-art techniques on diverse ARG datasets, including those with low homology to the training data, highlighting its potential for predicting the resistance mechanisms of unknown ARGs. Attention analysis of the model reveals that it considers biologically relevant features, such as conserved amino acid residues and antibiotic target binding sites, when making predictions. These findings provide valuable insights into the molecular basis of antibiotic resistance and demonstrate the interpretability of protein language models, offering a new perspective on their application in bioinformatics.

Availability

The source code is available for free athttps://github.com/hmdlab/ARG-BERT. The output results of the model are published athttps://waseda.box.com/v/ARG-BERT-suppl.

Contact

mhamada@waseda.jp
Singular Odorant Receptor Expression Orchestrated by Promoter Activation Specificity inApis MelliferaOlfactory Sensory Neurons
Authors: Zhang Weixing , Nie Yage , Li Yiheng , Xu Yicong , Xu Tao , Shi Peiyu , Liu Fang , Zhao Hongxia , Ma Qing , Xu Jin
Published: May 2024

Honeybee, positioned as an outgroup of flies and mosquitos, have exhibited intriguing duplications and expansions of OR genes in genomic studies. However, little is known about how the OR genes are expressed and regulated in honeybee olfactory sensory neurons (OSNs). In this study, we utilized a single-cell multi-omics approach to profile the transcriptome and chromatin accessibility inApis melliferaantennal nuclei, aiming to elucidate OR gene expression and its underlying regulatory mechanisms. Our systematical analysis unveiled a similar singular expression pattern of ligand-specific receptors inApis melliferaOSNs, parallel with those observed inDrosophila melanogaster. Mechanistically, we discovered that promoter activation of OR genes orchestrates receptor expression patterns. For instance, although multiple adjacent OR genes are co-expressed with a single active promoter through polycistronic transcription, only the first OR gene could produce functional receptor protein, as supported by transcriptome quantification in OSNs. Additionally, we found that co-expression of receptor proteins might occur only when co-expressed OR genes possess multiple accessible promoters. This scenario is less common than expected, considering the number and evolutionary age of OR genes inApis mellifera, suggesting a selection favoring the specialization of rapidly expanded OR genes inApis mellifera. Overall, our study provides significant insights into the insect olfaction system and the regulatory mechanisms of OR genes expression.
Linking intercontinental biogeographic events to decipher how European vineyards escaped Pierce’s disease
Authors: Moralejo Eduardo , Giménez-Romero Àlex , Matías Manuel A.
Published: May 2024

Unlike most grapevine diseases of American origin, the vector-borne bacteriumXylella fastidiosa(Xf) responsible for Pierce’s disease (PD) has not yet spread to continental Europe. The reasons for this lack of invasiveness remain unclear. Here, we present phylogenetic, epidemiological and historical evidence to explain how European vineyards escaped Xf. Using Bayesian temporal reconstruction, we show that the export of American grapevines to France as rootstocks to combat phylloxera (∼1872-1895) preceded the spread of the Xf grapevine lineage in the US. In the dated tree, the time of the most recent common ancestor places the introduction of Xf into California around 1875, which agrees with the emergence of the main PD outbreak and the onset of its expansion into the southeastern US around 1895. We also show that between 1870 and 1990, climatic conditions in continental Europe were mostly below the threshold for PD epidemics. This lack of spatiotemporal concurrence between factors that could facilitate the establishment of the Xf grapevine lineage would explain the historical absence of PD in continental Europe. However, our model indicates that there has been an inadvertent expansion of risk in southern European vineyards since the 1990s, which is accelerating with global warming. Our temporal approach identifies the biogeographic conditions that have so far prevented PD, and gives continuity to predictions of increased risk in important southern European wine-producing areas under a forthcoming scenario of +2 and +3°C temperature increases.
Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain
Authors: Martin Laurent , Stratton Harrison J. , Gomez Kimberly , Do Le Duy , Loya-Lopez Santiago , Tang Cheng , Calderon-Rivera Aida , Ran Dongzhi , Nunna Venkatrao , Bellampalli Shreya S. , François-Moutal Liberty , Dumaire Nicolas , Salih Lyuba , Luo Shizhen , Porreca Frank , Ibrahim Mohab , Rogemond Véronique , Honnorat Jérôme , Khanna Rajesh , Moutal Aubin
Published: May 2024

Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.
Disentangling associations between complex traits and cell types withseismic
Authors: Lai Qiliang , Dannenfelser Ruth , Roussarie Jean-Pierre , Yao Vicky
Published: May 2024

Abstract

Integrating single-cell RNA sequencing (scRNA-seq) with Genome-Wide Association Studies (GWAS) can help reveal GWAS-associated cell types, furthering our understanding of the cell-type-specific biological processes underlying complex traits and disease. However, current methods have technical limitations that hinder them from making systematic, scalable, interpretable disease-cell-type associations. In order to rapidly and accurately pinpoint associations, we develop a novel framework,seismic, which characterizes cell types using a new specificity score. We compareseismicwith alternative methods across over 1,000 cell type characterizations at different granularities and 28 traits, demonstrating thatseismicboth corroborates findings and identifies trait-relevant cell groups which are not apparent through other methodologies. Furthermore, as part of theseismicframework, the specific genes driving cell type-trait associations can easily be accessed and analyzed, enabling further biological insights. The advantages ofseismicare particularly salient in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, where disease pathology has not only cell-specific manifestations, but also brain region-specific differences. Interestingly, a case study of Alzheimer’s disease reveals the importance of considering GWAS endpoints, as studies relying on clinical diagnoses consistently identify microglial associations, while GWAS with a tau biomarker endpoint reveals neuronal associations. In general,seismicis a computationally efficient, powerful, and interpretable approach for identifying associations between complex traits and cell type-specific expression.
CLONALITY AND POLYPLOIDY CONTRIBUTE TO THE SPREAD OFAVRAINVILLEA LACERATA(BRYOPSIDALES, CHLOROPHYTA) IN HAWAIʻI
Authors: Thornton Brinkley M. , Spalding Heather L. , Stoeckel Solenn , Harris Melissa L. , Wade Rachael M. , Krueger-Hadfield Stacy A.
Published: May 2024

The relative rates of sexual versus asexual reproduction influence the partitioning of genetic diversity within and among populations. During range expansions, uniparental reproduction often facilitates colonization and establishment. The arrival of the green algaAvrainvillea laceratahas caused shifts in habitat structure and community assemblages since its discovery in 1981 offshore of west Oʻahu, Hawai‘i. Field observations suggest this species is spreading via vegetative reproduction. To characterize the reproductive system ofA. laceratain Hawai‘i, we developed seven microsatellite loci and genotyped 321 blades collected between 2018 and 2023 from two intertidal sites at Maunalua Bay and ʻEwa Beach. We found one to four alleles at multiple loci, suggestingA. laceratais tetraploid. Each site was characterized by high genotypic richness (R > 0.8). However, clonal rates were also high at both sites, suggesting vegetative spread ofA. lacerataplays a significant role. The importance of clonal reproduction for the persistence ofA. laceratain Hawai‘i is consistent with the ecological data collected for this species, and observations of other abundant macroalgal invaders in Hawaiʻi and other regions of the world. These data demonstrate the necessity for implementing appropriate population genetic methods and provide insights into the biology of this alga that will contribute to future studies on effective management strategies incorporating its reproductive system. This study represents one of the few investigating green algal population genetic patterns and contributes to our understanding of algal reproductive system evolution.
The Peruvian Genome Project: expanding the global pool of genome diversity from South America
Authors: Guio Heinner , Caceres Omar , Sanchez Cesar , Padilla Carlos , Trujillo Omar , Borda Victor , Jaramillo-Valverde Luis , Poterico Julio A. , Silva-Carvalho Carolina , Horton Mary , Lanata Cristina M , Carnevale Alessandra , Romero-Hidalgo Sandra , Canizales-Quinteros Samuel , Acuña-Alonzo Víctor , Machacuay-Romero Marco , Novoa Pedro , Frisancho Roberto , Shady Ruth , Flores-Villanueva Pedro , O’Connor Timothy D. , Corpas Manuel , Tarazona-Santos Eduardo
Published: May 2024

The process of inhabiting the Americas by ancestral native American populations involved many individuals settling in the Peruvian Andes and Amazonian regions. Due to Latin American countries representing less than 1% of the human genome data available in public reference databases, the evolution and migration processes involved in adapting to this unique geography have not yet been fully explained. The Peruvian Genome Project is an initiative, started in 2011, to address the underrepresentation of genomic data from native South American populations. This project has collected 1,149 samples from 17 traditional native and 13 mestizo (mixed of native, African, and European ancestry) communities. Currently, 150 whole genomes and 873 array-genotyped individuals have been sequenced from across the geography of Western South America, including coastal, Andes, and Amazonian regions. We discovered 1.6 million novel genetic variants with varying frequencies, indicative of local environmental adaptations and population drift. These novel variants allow us to infer local evolutionary traits and population-specific allele frequencies for people living at different altitudes, as well as varying adaptations to pathogens and living conditions. The Peruvian Genome Project is the result of over a decade of work in sample selection, logistics, and approved regulatory community engagement, designed to enhance the human genome pool of diversity of native Americans. The data collected here enable the targeted characterization of endemic diseases, trait adaptations, and new variants of clinical significance in South America. The Peruvian Genome Project represents a step forward in international and multidisciplinary efforts to make precision medicine more inclusive and accessible for underrepresented communities in Latin America, offering significant potential for drug development and diagnostics in a neglected continent.
Precise Generation of Conformational Ensembles for Intrinsically Disordered Proteins via Fine-tuned Diffusion Models
Authors: Zhu Junjie , Li Zhengxin , Zhang Bo , Zheng Zhuoqi , Zhong Bozitao , Bai Jie , Hong Xiaokun , Wang Taifeng , Wei Ting , Yang Jianyi , Chen Hai-Feng
Published: May 2024

Intrinsically disordered proteins (IDPs) play pivotal roles in various biological functions and are closely linked to many human diseases including cancer, diabetes and Alzheimer disease. Structural investigations of IDPs typically involve a combination of molecular dynamics (MD) simulations and experimental data to correct for intrinsic biases in simulation methods. However, these simulations are hindered by their high computational cost and a scarcity of experimental data, severely limiting their applicability. Despite the recent advancements in structure prediction for structured proteins, understanding the conformational properties of IDPs remains challenging partly due to the poor conservation of disordered protein sequences and limited experimental characterization. Here, we introduce IDPFold, a method capable of generating conformational ensembles for IDPs directly from their sequences using fine-tuned diffusion models. IDPFold bypasses the need for Multiple Sequence Alignments (MSA) or experimental data, achieving accurate predictions of ensemble properties across numerous IDPs. By sampling conformations at the backbone level, IDPFold provides more detailed structural features and more precise property estimation compared to other state-of-the-art methods. IDPFold is ready to be used in the elucidate the sequence-disorder-function paradigm of IDPs.
Assessing the subarachnoid space anatomy on clinical imaging: utilizing normal and pathology to understand compartmentalization of the subarachnoid space
Authors: Almohaimede Khaled , Alibrahim Yusuf , Butt Abu Bakar , Maralani Pejman , Heyn Chris , Kapadia Anish
Published: May 2024

BACKGROUND

The goad of the study is to use CT imaging in patients with aSAH to evaluate the anatomic distribution of hemorrhage and compartmentalization of subarachnoid space to investigate potential in vivo visualization of recently discovered layer named subarachnoid lymphatic-like membrane (SLYM).

METHODS

We conducted a retrospective cohort study of cases with aneurysmal SAH (aSAH) at our institution between January 2015 and June 2022. Subarachnoid hemorrhage distribution into superficial and deep subarachnoid spaces was classified based on proximity to the dural or pial surfaces, respectively, as seen on multiplanar CT head.

RESULTS

A total of 97 patients with aSAH were included. Patients with lower modified Fisher score (MFS) of 1-2 were more likely to have SAH compartmentalizing in the “deep” pial-adjacent subarachnoid space. Patients with higher MFS of 3-4 were more likely to have SAH in both “superficial” and “deep” compartments along the brainstem. There is a significant association between the severity of aSAH - quantified by the MFS - and the distribution of the blood. Patients with higher MFS scores were roughly 7.6 times (p-value = 0.049) more likely to have hemorrhage at the “Superficial” juxta-dural subarachnoid compartment when compared to those with lower MFS scores.

CONCLUSION

This study suggests an imaging correlate to the recently discovered “SLYM”, potentially influencing aSAH compartmentalization, particularly in low-grade bleeds. While compartmentalization is limited in high-grade cases, these findings warrant further investigation with advanced imaging techniques to validate this membrane’s role and potential impact on CSF flow and aSAH pathophysiology.
Distances from ligands as main predictive features for pathogenicity and functional effect of variants in NMDA receptors
Authors: Montanucci Ludovica , Brünger Tobias , Bhattarai Nisha , Boßelmann Christian M , Kim Sukhan , Allen James P. , Zhang Jing , Klöckner Chiara , Fariselli Piero , May Patrick , Lemke Johannes R. , Myers Scott J. , Yuan Hongjie , Traynelis Stephen F. , Lal Dennis
Published: May 2024

Genetic variants in genesGRIN1,GRIN2A,GRIN2B, andGRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic diseases. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects are therefore crucial for accurate diagnosis and therapeutic applications. We assembled missense variants: 201 from patients, 631 from general population, and 159 characterized by electrophysiological readouts showing whether they can enhance or reduce the receptor function. This includes new functional data from 47 variants reported here, for the first time. We found that pathogenic/benign variants and variants that increase/decrease the channel function were distributed unevenly on the protein structure, with spatial proximity to ligands bound to the agonist and antagonist binding sites being key predictive features. Leveraging distances from ligands, we developed two independent machine learning-based predictors for NMDAR missense variants: a pathogenicity predictor which outperforms currently available predictors (AUC=0.945, MCC=0.726), and the first binary predictor of molecular function (increase or decrease) (AUC=0.809, MCC=0.523). Using these, we reclassified variants of uncertain significance in the ClinVar database and refined a previous genome-informed epidemiological model to estimate the birth incidence of molecular mechanism-defined GRIN disorders. Our findings demonstrate that distance from ligands is an important feature in NMDARs that can enhance variant pathogenicity prediction and enable functional prediction. Further studies with larger numbers of phenotypically and functionally characterized variants will enhance the potential clinical utility of this method.
Multi-Organ System Metabolic Stress and Sex-Divergent Vascular Associations
Authors: Kwan Alan C. , Wang Minhao , Ji Hongwei , Claggett Brian , Ouyang David , Trivedi Hirsh , Sharma Sonia , Shyy John , Velazquez Amanda , Ebinger Joseph E. , Cheng Susan
Published: May 2024

Introduction

Women experience excess cardiovascular risk compared to men in the setting of similar metabolic disease burden. This consistent finding could be related to sex differences in the vascular response to various forms of metabolic stress. In this study we examine the association of both systemic and organ-specific metabolic stress with vascular health in women and men.

Methods

We conducted an observational study of 4,299 adult participants (52% women, aged 59±13 years) of the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cohort and 110,225 adult outpatients (55% women, aged 64±16 years) of the Cedars-Sinai Medical Center (CSMC) 2019 cohort. We used natural splines to examine the association of systemic and organ-specific measures of metabolic stress including body mass index (BMI), hemoglobin A1c (HbA1c), hepatic FIB-4 score, and CKD-EPI estimated glomerular filtration rate (eGFR) on systolic blood pressure (SBP). Piecewise linear models were generated using normal value thresholds (BMI <25 kg/m2, HbA1c <5.7%, FIB-4 <1.3, and eGFR ≥90 ml/min), which approximated observed spline breakpoints. The primary outcome was increase in SBP (relative to a sex-specific physiologic baseline SBP) in association with increase in level of each metabolic measure.

Results

Women compared to men demonstrated larger magnitudes and an earlier onset of increase in SBP per increment increase across all metabolic stress measures. The slope of SBP increase per increment of each metabolic measure was greater for women than men particularly for metabolic measures within the normal range, with slope differences of 1.71 mmHg per kg/m2 of BMI, 9.61 mmHg per %HbA1c, 6.45 mmHg per FIB-4 unit, and 0.37 mmHg per ml/min decrement of eGFR in the NHANES cohort (P difference <0.05 for all). Overall results were consistent in the CSMC cohort.

Conclusions

Women exhibited greater vascular sensitivity in the setting of multiple types of metabolic stress, particularly in periods representing the transition from metabolic health to disease. These findings underscore the importance of involving early metabolic health interventions as part of efforts to mitigate vascular risks in both women and men.
CLINICAL IMPLEMENTATION OF PREEMPTIVE PHARMACOGENOMICS TESTING FOR PERSONALIZED MEDICINE AT AN ACADEMIC MEDICAL CENTER
Authors: Tamraz Bani , Shin Jaekyu , Khanna Raman , Van Ziffle Jessica , Knowles Susan , Stregowski Susan , Wan Eunice , Kamath Rajesh , Collins Christopher , Phunsur Choeying , Tsai Benjamin , Kong Patsy , Calanoc Clari , Pollard Aleta , Sawhney Rajeev , Pleiman Jennifer , Devine Walter Patrick , Croci Rhiannon , Sashikanth Aparna , Kroon Lisa , Cucina Russ , Rajkovic Aleks
Published: May 2024

Objective

This paper describes the implementation of preemptive clinical pharmacogenomics (PGx) testing linked to an automated electronic clinical decision support (CDS) system delivering clinically actionable PGx information to clinicians at the point of care at UCSF Health, a large Academic Medical Center.

Methods

A multidisciplinary team developed the strategic vision for the PGx program. The drug-gene interactions of interest were compiled, and actionable alleles were identified. A genotyping platform was selected and validated at the in-house laboratory. Following HIPAA protocols, genotype results were electronically transferred and stored in EPIC. CDS was developed and integrated with electronic prescribing.

Results

We developed a customized clinical PGx program for 56 medications and 15 genes. 233 MWs and 15 BPAs, approved by clinicians, were built into EPIC to deliver actionable clinical PGx information to clinicians.

Conclusions

Our multidisciplinary team successfully implemented preemptive PGx testing linked to point-of-care electronic CDS to guide clinicians with precise medication decision-making.
ShapeMed-Knee: A Dataset and Neural Shape Model Benchmark for Modeling 3D Femurs
Authors: Gatti Anthony A. , Blankemeier Louis , Van Veen Dave , Hargreaves Brian , Delp Scott L. , Gold Garry E. , Kogan Feliks , Chaudhari Akshay S.
Published: May 2024

Analyzing anatomic shapes of tissues and organs is pivotal for accurate disease diagnostics and clinical decision-making. One prominent disease that depends on anatomic shape analysis is osteoarthritis, which affects 30 million Americans. To advance osteoarthritis diagnostics and prognostics, we introduceShapeMed-Knee, a 3D shape dataset with 9,376 high-resolution, medicalimaging-based 3D shapes of both femur bone and cartilage. Besides data, ShapeMed-Knee includes two benchmarks for assessing reconstruction accuracy and five clinical prediction tasks that assess the utility of learned shape representations. Leveraging ShapeMed-Knee, we develop and evaluate a novel hybrid explicit-implicit neural shape model which achieves up to 40% better reconstruction accuracy than a statistical shape model and two implicit neural shape models. Our hybrid models achieve state-of-the-art performance for preserving cartilage biomarkers (root mean squared error ≤ 0.05 vs. ≤ 0.07, 0.10, and 0.14). Our models are also the first to successfully predict localized structural features of osteoarthritis, outperforming shape models and convolutional neural networks applied to raw magnetic resonance images and segmentations (e.g., osteophyte size and localization 63% accuracy vs. 49-61%). The ShapeMed-Knee dataset provides medical evaluations to reconstruct multiple anatomic surfaces and embed meaningful disease-specific information. ShapeMed-Knee reduces barriers to applying 3D modeling in medicine, and our benchmarks highlight that advancements in 3D modeling can enhance the diagnosis and risk stratification for complex diseases. The dataset, code, and benchmarks are freely accessible.
Integrated surveillance of sandflies as vectors of leishmaniasis reveals the presence of a newLeishmaniaspecies with possible implication in human health in Europe
Authors: Ruiz-Arrondo Ignacio , Cervera-Acedo Cristina , Villa-López María Inés , Muelas Eva María , Méndez Manuel , Oteo José Antonio , Collantes Francisco
Published: May 2024

Leishmaniasis, endemic in Spain, displays rising incidence rates, notably in the Region of Murcia. Sandfly surveillance andLeishmaniascreening in 2021 uncoveredLeishmania infantumandL. adleri. While currentLeishmaniadiagnostic methods primarily targetL. infantum, our study underscores the importance of broaderLeishmaniaspecies surveillance for accurate diagnosis and understanding of disease dynamics. The detection ofL. adleri, previously undescribed in Europe, highlights the need for expanded research to investigate its presence and implications for human and animal health.