bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neutrophil-Lymphocyte Ratio in Pediatric Preseptal and Orbital Infectious Cellulitis
Authors: Law James J. , Orgul Sarp , Tomlinson Lauren A. , Wladis Edward J.
Published: December 2024

Purpose:

The neutrophil-lymphocyte ratio (NLR) is an important biomarker in a variety of systemic conditions, though its role in orbital disease remains unclear. We sought to investigate the utility of the NLR in distinguishing orbital cellulitis (OC) from preseptal cellulitis (PC) in a pediatric population.

Methods:

The earliest available NLRs of immunocompetent pediatric patients who presented to the emergency department with OC and PC were calculated from a single institution’s database. Demographic and interventional data related to each encounter were also gathered. NLRs were compared via the Mann–Whitney test between OC and PC cases. Among patients with OC, the relationship between presenting NLR and requirement for surgical intervention and between presenting NLR and subperiosteal abscess was similarly examined. All statistical analyses were performed in GraphPad Prism 9 (Insight Partners, New York, NY, U.S.A.).

Results:

Forty-three encounters of patients with OC and 23 encounters of patients with PC were identified. Median presenting NLR for the OC group was 4.18 (standard deviation: 5.44), whereas for the PC group, it was 1.96 (standard deviation: 2.38), representing a significant difference between the 2 groups (p < 0.001). The 26 patients with OC who required surgical intervention had significantly greater presenting NLR (median NLR: 6.53, standard deviation: 6.29) as compared to the 17 patients with OC who were managed medically (median NLR: 3.09, standard deviation: 2.37, p = 0.003). There was no statistically significant difference between 34 patients with OC who had a subperiosteal abscess (median NLR: 4.40, standard deviation: 5.91) and the 9 patients with OC who did not (median NLR: 3.84, standard deviation: 2.37, p = 0.401).

Conclusions:

An elevated NLR is a useful adjunct to the clinical examination in discerning OC from PC or in risk stratification for patients with OC who may need surgical treatment of their periocular infectious disease. In select cases, a reassuring NLR may allow the cost and radiation exposure associated with radiographic assessment to be avoided.
Aggressive Sebaceous Gland Hyperplasia in a Young Girl With MSH2 Gene Mutation: A Rare Presentation
Authors: Heroor Aniruddh , Vempuluru Vijitha S. , Jakati Saumya , Kaliki Swathi
Published: December 2024

Sebaceous gland hyperplasia is a benign cutaneous entity commonly seen in older men. Occasionally, it can develop in young patients on immunosuppression with cyclosporine or in adolescent boys in the peripubertal age group. It is extremely rare in young children with no reports of eyelid involvement. It is believed to have no systemic associations, unlike sebaceous adenoma, which is associated with Muir-Torre syndrome. Herein, we present a rare case of a young girl with recurrent and aggressive eyelid sebaceous hyperplasia who was treated by a wide local excision of the lesion. The histopathology showed intact nuclear expression of mismatch repair proteins MLH 1, MSH 2, MSH 6, and PMS 2, and the genetic testing revealed a missense mutation in the MSH2 gene.
Dermoid Cyst of Conjunctival Origin Attached to the Tarsus in a Pediatric Patient
Authors: Swain David L. , Gregston Alden , Proia Alan D. , Grace Sara F. , Enyedi Laura B.
Published: December 2024

Dermoid cysts of cutaneous origin are common orbital lesions, whereas dermoid cysts of conjunctival origin are rare. The authors present a case of a dermoid cyst of conjunctival origin that was attached to the tarsus in a pediatric patient. A 2-year-old boy presented to the clinic with an approximately 2 cm in diameter mobile nodule in the upper eyelid on the temporal side that distorted the eyelid architecture with temporal ptosis. During surgical excision, the lesion was firmly adherent to the tarsal plate. The mass was a conjunctival dermoid cyst lined by nonkeratinizing squamous epithelium with goblet cells and hair follicles on histological examination. This case represents the first report of a conjunctival dermoid cyst attached to the tarsus.
Combined artificial iris and intraocular lens double-flanged scleral fixation in a patient with posttraumatic aniridia and aphakia
Authors: Roth Kilian , Amon Michael
Published: December 2024

This article introduces a novel surgical approach to address traumatic aniridia and aphakia through combined artificial iris (AI) and intraocular lens (IOL) implantation using the Canabrava technique. The IOL is affixed to the AI through 2 prolene sutures, which are flanged in the sclera at 4 symmetrical points. Both the surgical procedures and the postoperative follow-up visits showed no complications. An improvement in function and visual outcomes was achieved. The studied alternative surgical method could improve the management of complex cases of traumatic aniridia and aphakia, offering both functional and aesthetic benefits to patients.
Femtosecond laser-assisted annular keratopigmentation using a novel duo-tunnel technique
Authors: Weill Yishay , Sela Tzahi , Baruch Shmuel , Munzer Gur , Kaiserman Igor
Published: December 2024

Keratopigmentation (KTP), or corneal tattooing, has evolved from a treatment for disfigured blind eyes to addressing functional pathologies and, more recently, cosmetic enhancement in sighted eyes. Advances in KTP now include the use of femtosecond laser-assisted intrastromal pockets, originally designed for intrastromal corneal ring segments and later adapted for pigment implantation. Various femtosecond laser platforms are used to create these precise stromal tunnels for femtosecond laser-assisted annular KTP. We introduce a novel technique using a femtosecond laser platform to join 2 adjacent small circular stromal tunnels, creating a large, unified, and consistent circular stromal pocket for pigment implantation. This method minimizes the need for manual dissection and holds promise for various clinical applications. A longer follow-up period is necessary to evaluate the potential refractive effects associated with the creation of complete 360-degree tunnels.
Genetic insights into the roles of fatty acids and gut microbiota in osteoarthritis: A Mendelian randomization study
Authors: Lu Yilei , Zhou Zekun , Pan Ding
Published: December 2024

Traditional observational studies have shown that fatty acids and gut microbiota are crucial in osteoarthritis (OA) progression, but their findings are often conflicting due to biases, confounding factors, and measurement errors. We conducted a two-sample Mendelian randomization analysis using genome-wide association study data on fatty acids from 136,016 individuals, the gut microbiota from 7738 individuals, and osteoarthritis from 314,870 individuals. Elevated levels of total (odds ratio [OR]: 0.92; 95% CI 0.84–1.00; P = .039), saturated fatty acids (OR: 0.91; 95% CI 0.84–0.99; P = .034), and linoleic acid (OR: 0.92; 95% CI 0.85–1.00; P = .040) were associated with reduced OA risk. In terms of gut microbiota, Bifidobacterium adolescentis (OR: 0.89; 95% CI 0.80–1.00; P = .048) and Escherichia (OR: 0.90; 95% CI 0.81–1.00; P = .042) demonstrated protective roles against OA. Conversely, Oscillibacter (OR: 1.16; 95% CI 1.00–1.34; P = .043), Bilophila (OR: 1.28; 95% CI 1.07–1.54; P = .007), Erysipelotrichaceae (OR: 1.08; 95% CI 1.00–1.16; P = .044), and Bilophila within the Desulfovibrionaceae family (OR: 1.19; 95% CI 1.04–1.36; P = .012) were associated with an increased risk of OA. The findings indicate that modulating dietary factors and gut microbiota can independently reduce the risk and progression of OA, potentially improving the quality of life and health management in aging populations.
Development and validation of a prognostic prediction model for endometrial cancer based on CD8+ T cell infiltration-related genes
Authors: Chen Chao , Pei Lipeng , Ren Wei , Sun Jingli
Published: December 2024

Endometrial cancer (EC) is the most common gynecologic malignancy with increasing incidence and mortality. The tumor immune microenvironment significantly impacts cancer prognosis. Weighted Gene Co-Expression Network Analysis (WGCNA) is a systems biology approach that analyzes gene expression data to uncover gene co-expression networks and functional modules. This study aimed to use WGCNA to develop a prognostic prediction model for EC based on immune cell infiltration, and to identify new potential therapeutic targets. WGCNA was performed using the Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma dataset to identify hub modules associated with T-lymphocyte cell infiltration. Prognostic models were developed using LASSO regression based on genes in these hub modules. The Search Tool for the Retrieval of Interacting Genes/Proteins was used for protein–protein interaction network analysis of the hub module. Gene Set Variation Analysis identified differential gene enrichment analysis between high- and low-risk groups. The relationship between the model and microsatellite instability, tumor mutational burden, and immune cell infiltration was analyzed using The Cancer Genome Atlas data. The model’s correlation with chemotherapy and immunotherapy resistance was examined using the Genomics of Drug Sensitivity in Cancer and Cancer Immunome Atlas databases. Immunohistochemical staining of EC tissue microarrays was performed to analyze the relationship between the expression of key genes and immune infiltration. The green-yellow module was identified as a hub module, with 4 genes (ARPC1B, BATF, CCL2, and COTL1) linked to CD8+ T cell infiltration. The prognostic model constructed from these genes showed satisfactory predictive efficacy. Differentially expressed genes in high- and low-risk groups were enriched in tumor immunity-related pathways. The model correlated with EC-related phenotypes, indicating its potential to predict immunotherapeutic response. Basic leucine zipper activating transcription factor-like transcription factor(BATF) expression in EC tissues positively correlated with CD8+ T cell infiltration, suggesting BATF’s crucial role in EC development and antitumor immunity. The prognostic model comprising ARPC1B, BATF, CCL2, and COTL1 can effectively identify high-risk EC patients and predict their response to immunotherapy, demonstrating significant clinical potential. These genes are implicated in EC development and immune infiltration, with BATF emerging as a potential therapeutic target for EC.
Symptom Management Guideline Implementation Among Nurses in Cancer-Specific Outpatient Settings
Authors: Teggart Kylie , Silva Amina , Lopez Christian J. , Bryant-Lukosius Denise , Neil-Sztramko Sarah E. , Ganann Rebecca
Published: December 2024

Background

Oncology outpatients experience high levels of distressing cancer-related symptoms. Nurses can provide high-quality outpatient cancer symptom management following clinical practice guideline recommendations; however, these guidelines are inconsistently used in practice. Understanding contextual factors influencing implementation is necessary to develop tailored implementation strategies.

Objectives

To identify and describe (1) barriers and facilitators influencing symptom management guideline adoption, implementation, and/or sustainability among nurses in cancer-specific outpatient settings and (2) components of strategies used to enhance guideline implementation.

Methods

A scoping review was conducted following Joanna Briggs Institute methodology. CINAHL, EMBASE, EMCARE, MEDLINE, and gray literature sources were searched. Eligibility screening and data extraction were performed in duplicate. The updated Consolidated Framework for Implementation Research and Expert Recommendations for Implementing Change taxonomy informed data extraction and descriptive analysis.

Results

Thirty-six projects from 2004 to 2023 were included; most used quality improvement (n = 14) or quasi-experimental (n = 10) designs. Determinants were most often mapped to the “inner setting” and “individuals—roles/characteristics” Consolidated Framework for Implementation Research domains. Most projects used multiple discrete implementation strategies within the “train and educate stakeholders” (n = 29, 85%) and/or “develop stakeholder interrelationships” (n = 20, 59%) categories.

Conclusions

Nurses may face several barriers to symptom management guideline implementation within cancer-specific outpatient setting workflows and may have limited opportunity to implement guidelines within their current roles. Most projects used educational strategies, which alone may be insufficient to address reported barriers.

Implications for Practice

By identifying barriers, facilitators, and strategies, this scoping review can be used to design tailored strategies to implement symptom management guidelines within outpatient oncology nursing care.
Physical, Social, Psychological, and Environmental Predictors of Life Satisfaction Among Older Adults
Authors: Siegmund Lee Anne , Siedlecki Sandra L. , Bena James F.
Published: December 2024

Life satisfaction is a multidimensional construct impacted by many variables and needs to be explored within that context. A correlational design was used to survey community-dwelling older adults to determine perceptions of life satisfaction and its association with physical, social, psychological, and environmental factors. The sample was primarily White (n = 474 [93%]) but balanced between male (n = 253 [50%]) and female (n = 258 [50%]). The mean age was 73.1 (SD, 4.8) years. Associations with life satisfaction were evaluated using linear regression models. In multivariable modeling, social isolation, living alone, depression, sleep disturbance, social vulnerability, and physical ability predicted life satisfaction. Physical ability was the only predictor of high life satisfaction. Findings underscore the importance of helping older adults with improvements in physical ability and addressing social, psychological, and environmental influences that may lead to low life satisfaction.
Garbage Out: A Radiologist's Guide to Hospital Waste Streams
Authors: White-Dzuro Claire E. , Doyle Patrick W. , Larson Michael C. , Frederick-Dyer Katherine C.
Published: December 2024

What happens to trash after disposal? The management and processing of discarded items is often opaque and taken for granted, but an understanding of hospital waste streams is important for radiology departments and hospital systems for economic, regulatory, and environmental reasons. In this paper, we discuss the numerous waste pathways including general, hazardous, pharmaceutical, radioactive, and electronic waste as well as sustainable waste streams including laundry services, composting, and recycling. Costs, regulatory issues, and environmental considerations associated with each pathway are reviewed. We also describe radiology's specific contributions to each waste stream as well as variations in department practices, tips for optimal use, and future research investigations that could impact waste volume. Healthcare garbage disposal pathways will only increase in importance as our healthcare needs and systems continue to grow, and waste optimization efforts yield benefits to operation costs, environmental ecosystems, and human health.
Does the Use of the Allen Test is an Absolute Myth?—A Novel Look at the Preoperative Evaluation of the Routine Procedure Before Harvesting Radial Forearm Free Flap
Authors: Bula Daniel , Opyrchał Jakub , Walczak Dominik , Krakowczyk Łukasz , Maciejewski Adam
Published: December 2024

Radial forearm free flap (RFFF) is one of the most popular free flaps in the history of reconstructive microsurgery. Due to its characteristics, it has found its main application in reconstructions in the head and neck region. Before harvesting this flap due to the removal of 1 of the 2 major forearm arteries, an Allen test has historically been recommended. However, is it necessary to use this test in every patient? During the period of 2013 to 2023, 237 RFFF reconstructions were performed on 220 patients. Each surgeon performing a given procedure received a questionnaire to complete, which concentrated on only 2 questions, each had 2 possible answers. The first, whether the Allen test was performed before harvesting the radial forearm free flap, and second, if there was, whether it ever resulted in the change of the approach to reconstruction. In a whole analyzed group of 237 harvested flaps, there were no acute or chronic ischemic complications regarding the hand itself. Three surgeons who performed the RFFF most frequently stated that they had never done Allen test during the last decade. The remaining number of operators have assured that they always have used Allen test, but the result has never forced them to change the approach. Our study shows that the Allen test has limited utility in patients where the radial forearm flap was harvested from a previously intact donor site.
Optimal dose of tranexamic acid in traumatic brain injury: Systematic review and network meta-analysis of randomized controlled trials
Authors: Utsumi Shu , Kawakami Akiko , Amemiya Yu
Published: December 2024

BACKGROUND

Tranexamic acid (TXA) has been used to treat traumatic brain injury (TBI); however, no definitive conclusions have been drawn regarding its effectiveness or dosage. This study evaluated the optimal TXA dose for treating TBI using a network meta-analysis (NMA).

METHODS

Five databases were searched for peer-reviewed randomized controlled trials (RCTs) published from inception to May 2024. The inclusion criteria were as follows: (1) RCTs, (2) patients older than 1 month with TBI, (3) interventions of TXA and control, (4) primary outcomes of mortality and poor neurological outcomes and secondary outcomes of vascular occlusive events, and (5) full-text peer-reviewed articles. Two reviewers independently screened and extracted the data and assessed the risk of bias. Frequency-based NMA was performed using the Grading of Recommendations, Assessment, Development, and Evaluation working-group approach.

RESULTS

We included 10 RCTs comprising 11,237 patients with TBI. Placebo showed higher mortality compared with that of a 2-g bolus of TXA (risk ratio, 1.53; 95% confidence interval, 1.08–2.17). Higher mortality was observed with a 1-g bolus of TXA followed by 1-g maintenance TXA compared with that of a 2-g bolus of TXA (risk ratio, 1.44; 95% confidence interval, 1.02–2.03). No significant differences in poor neurological outcomes or vascular occlusive events were observed between the treatment groups.

CONCLUSION

Placebo and a 1-g bolus followed by 1-g maintenance TXA were associated with higher mortality rates than those of a 2-g bolus of TXA. No difference in vascular occlusive events was observed with either treatment, indicating that our NMA recommends 2 g of TXA. However, the data for the 2-g bolus of TXA were from a single study, and further research is needed to draw definitive conclusions.

LEVEL OF EVIDENCE

Systematic Review/Meta-Analysis; Level III.
The Effect of Cranial Sutures Should Be Considered in Transcranial Electrical Stimulation
Authors: Carroll Alistair , Rae Caroline D. , Martin Donel , Dokos Socrates , Loo Colleen
Published: December 2024

Background

Computational modeling is used to optimize transcranial electrical stimulation (tES) approaches, and the precision of these models is dependent on their anatomical accuracy. We are unaware of any computational modeling of tES that has included cranial sutures.

Objectives

The aims of the study were to review the literature on the timing of closure of the coronal and squamous sutures, which are situated under electrode placements used in tES; to review the literature regarding differences in skull and suture conductivity and to determine a more accurate conductivity for sutures; and to identify magnetic resonance image (MRI) techniques that could be used to detect cranial sutures.

Methods

A scoping review of medical literature was conducted. We conducted computational modeling of a cranial bone plug using COMSOL Multiphysics finite element software, utilizing methodology and results from a previous study. We assessed use of the “3D Slicer” software to identify sutures in routine T1-weighted MRI scans.

Results

Reports from forensic examinations and computed tomography (CT) scans showed suture closure does not correlate with age. Our computational modeling determined a cranial suture conductivity of 0.32 S/m, which is much higher than for skull (compact skull 0.004 S/m, standard trilayer 0.013 S/m). 3D slicer enabled rapid and precise identification of the anatomy and location of cranial sutures.

Conclusions

Cranial sutures persist throughout the lifespan and have a far higher conductivity than skull bone. Cranial sutures can be localized quickly and precisely using a combination of MRI and readily available modeling software. Sutures should be included in tES computational modeling and electroencephalography source imaging to improve the accuracy of results.
Unveiling three novel actinobacterial species (Streptomyces cavernicola sp. nov., Streptomyces solicavernae sp. nov. and Streptomyces luteolus sp. nov.) in soil samples in Phu Pha Phet Cave, Thailand
Authors: Chamroensaksri Nitcha , Muangham Supattra , Suriyachadkun Chanwit , Phornsiricharoenphant Worawich , Phongsopitanun Wongsakorn , Suetrong Satinee , Tanasupawat Somboon
Published: December 2024

Three strains of actinobacteria, designated as B-S-A6T, B-S-A8T and B-S-A12T, were isolated from soil samples collected in the Phu Pha Phet Cave located in the Satun UNESCO Global Geopark, Satun Province, Thailand. A comprehensive polyphasic approach was used to describe these strains. Strains B-S-A6T, B-S-A8T and B-S-A12T were identified within the genus Streptomyces based on a comparative examination of 16S rRNA gene sequences. Strains B-S-A8T and B-S-A12T showed a high genetic similarity to Streptomyces spectabilis NBRC 13424T (99.0%, for both) and to Streptomyces deserti C63T (98.6 and 98.7 %, respectively). Meanwhile, strain B-S-A6T exhibited 98.6% sequence similarity with S. spectabilis NBRC 13424T and Streptomyces koyangensis VK-A6 T. However, upon further comparison, the 16S rRNA gene sequence of strain B-S-A6T showed a similarity of 99.6% to B-S-A8T and 99.7% to B-S-A12T. Contrastingly, B-S-A8T showed a very high similarity of 99.8% with B-S-A12T. The use of digital DNA–DNA hybridization, along with the analysis of average nt identities and aa identities, comparing the three strains to their closest known type strains, validated that each of these strains represents a new and distinct species. Three newly identified strains exhibited phenotypic characteristics and chemotaxonomic properties consistent with the members of the genus Streptomyces. The primary menaquinones identified in these strains were MK-9(H6) and MK-9(H8). The major fatty acids were iso-C15 : 0 and anteiso-C15 : 0. Their polar lipid profiles included diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The comprehensive phenotypic and genomic analyses of the Streptomyces strains strongly suggest that strains B-S-A6T, B-S-A8T and B-S-A12T represent three new species for which the names Streptomyces cavernicola sp. nov. (type strain B-S-A6T =TBRC 17074T =NBRC 116118T), Streptomyces solicavernae sp. nov. (type strain B-S-A8T =TBRC 17072T =NBRC 116117T) and Streptomyces luteolus sp. nov. (type strain B-S-A12T =TBRC 17060T =NBRC 116116T) are proposed.
Lymphatic drainage of cerebrospinal fluid using lymph node seeker64Cu-labeled Gram-negative bacterial extracellular vesicles PET
Authors: Kim Kyuwan , Lee Changjin , Yoo Ran Ji , Choi Yoori , Lee Chanwoo , Lee Jaewook , Suh Minseok , Lee Yun-Sang , Gho Yong Song , Lee Dong Soo
Published: December 2024

Cerebrospinal fluid (CSF) is drained into the systemic lymphatics via paravertebral lymph nodes. Superficial and deep cervical lymph nodes collect CSF in mice, but the exact and quantified routes are unknown. Recently, we simultaneously visualized cervical, sacral and iliac lymph nodes via serial imaging on the intrathecal [64Cu]Cu-albumin positron emission tomography. Paravertebral lymph nodes might act as sentinels to monitor the CSF, brain, and spinal cord. We used64Cu-labeledEscherichia coliextracellular vesicles, outer membrane vesicles (OMVs), as lymph node seekers for intrathecal administration with an optimized volume/rate and quantified the differential amounts of various paravertebral lymph nodes along the axis of the brain and spinal cord in mice. The quantified results revealed 77.3% in superficial and deep cervical lymph nodes, 11.4% in abdominal/pelvic lymph nodes and 11.3% in sacral lymph nodes. Click-labeled [64Cu]Cu-OMVs were drained to reach and stop at the lymph nodes on serial quantification. The cervical lymph nodes drained most of the OMV-laden CSF, which is proportional to the surface areas of the brain (70%) and spinal cord in mice. We propose that all paravertebral lymph nodes monitor the segmental regions of the brain and spinal cord as immediate sentinel lymph nodes against the central nervous system.
Social and Mental Health Pathways to Institutional Trust: A Cohort Study
Authors: Paquin Vincent , Miconi Diana , Aversa Samantha , Johnson-Lafleur Janique , Côté Sylvana , Geoffroy Marie-Claude , Gülöksüz Sinan
Published: December 2024

Objective

Trust in institutions such as the government is lower in the context of mental health problems and socio-economic disadvantage. However, the roles of structural inequality, interpersonal factors, and mental health on institutional trust remain unclear. This study aimed to examine the associations of social and mental health factors, from early life to adulthood, with institutional trust.

Method

Participants (n=1347; 57.2% female) were from the population-based Québec Longitudinal Study of Child Development (1997-2021). Trust in 13 institutions was self-reported at age 23. Predictors were 20 social and mental health factors during early life, adolescence, and adulthood. Associations were examined with linear regressions corrected for false discovery rate. Pathways were explored using the temporal Peter-Clark algorithm.

Results

Early-life factors associated with lower levels of trust were male sex, racialized minority status, low household income, and maternal history of depression and antisocial behaviors. After adjusting for early-life factors, adolescence factors associated with lower levels of trust were internalizing and externalizing problems, bullying exposure, and school difficulties. Independently of early-life or adolescence factors, adulthood factors associated with lower levels of trust were perceived stress, psychotic experiences, suicidal ideas, and seeking professional help, whereas greater social capital was associated with greater trust. Temporal Peter-Clark analyses identified social capital and psychotic experiences as potential proximal determinants of institutional trust.

Conclusion

This study identified factors associated with institutional trust reflecting an interplay between structural inequality, interpersonal relationships, and mental health over development. Interventions aimed at promoting social inclusion may improve institutional trust and population wellbeing.
Cognitive Dynamics of Verb-Particle Constructions: An Eye-Tracking Study
Authors: Kissane Hassane , Tziridis Konstantin , Schilling Achim , Krauss Patrick , Herbst Thomas
Published: December 2024

This study investigates the cognitive processing of verb-particle constructions (VPCs) using eye-tracking data analysis method to explore how English native speakers process different types of the sequence NP–verb–particle–NP during reading tasks. While previous research has focused on phrasal verbs, our study extends this examination to include patterns with prepositions, aiming to identify distinct cognitive engagement patterns and processing efficiencies associated with each. We employed the Provo Corpus to analyse eye movements while participants read sentences containing these constructions. we focused on metrics such as first fixation duration, gaze duration, go-past times, and total reading times. Our findings indicate similarities in the lexical verbs, and significant differences in particles, indicating how these two types of constructions are processed, with phrasal verbs sometimes processed more efficiently than the prepositional counterparts. This suggests that phrasal verbs might be more deeply entrenched in the linguistic repertoire of native speakers, possibly functioning as single lexical units. This research contributes to the understanding of complex structures processing and the cognitive mechanisms that support it, offering insights that could influence linguistic theory and language education.
NCPepFold: Accurate Prediction of Non-canonical Cyclic Peptide Structures via Cyclization Optimization with Multigranular Representation
Authors: Mao Qingyi , Shang Tianfeng , Xu Wen , Zhai Silong , Zhang Chengyun , Su An , Li Chengxi , Duan Hongliang
Published: December 2024

Artificial intelligence-based peptide structure prediction methods have revolutionized biomolecular science. However, restricting predictions to peptides composed solely of 20 natural amino acids significantly limits their practical application, as such peptides often demonstrate poor stability under physiological conditions. Here, we present NCPepFold, a computational approach that can utilize a specific cyclic position matrix to directly predict the structure of cyclic peptides with non-canonical amino acids. By integrating multi-granularity information at the residue- and atomic-level, along with fine-tuning techniques, NCPepFold significantly improves prediction accuracy, with the average peptide RMSD for cyclic peptides being 1.640 Å. In summary, this is a novel deep learning model designed specifically for cyclic peptides with non-canonical amino acids without length restrictions, offering great potential for peptide drug design and advancing biomedical research.
BioMedGraphica: An All-in-One Platform for Biomedical Prior Knowledge and Omic Signaling Graph Generation
Authors: Zhang Heming , Liang Shunning , Xu Tim , Li Wenyu , Huang Di , Dong Yuhan , Li Guangfu , Miller J. Philip , Goedegebuure S. Peter , Sardiello Marco , Cooper Jonathan , Buchser William , Dickson Patricia , Fields Ryan C. , Cruchaga Carlos , Chen Yixin , Province Michael , Payne Philip , Li Fuhai
Published: December 2024

Artificial intelligence (AI) is revolutionizing scientific discovery because of its super capability, following the neural scaling laws, to integrate and analyze large-scale datasets to mine knowledge. Foundation models, large language models (LLMs) and large vision models (LVMs), are among the most important foundations paving the way for general AI by pre-training on massive domain-specific datasets. Different from the well annotated, formatted and integrated large textual and image datasets for LLMs and LVMs, biomedical knowledge and datasets are fragmented with data scattered across publications and inconsistent databases that often use diverse nomenclature systems in the field of AI for Precision Health and Medicine (AI4PHM). These discrepancies, spanning different levels of biomedical organization from genes to clinical traits, present major challenges for data integration and alignment. To facilitate foundation AI model development and applications in AI4PHM, herein, we developedBioMedGraphica, an all-in-one platform and unified text-attributed knowledge graph (TAKG), consists of 3,131,788 entities and 56,817,063 relations, which are obtained from 11 distinct entity types and harmonizes 29 relations/edge types using data from 43 biomedical databases. All entities and relations are labeled a unique ID and associated with textual descriptions (textual features). Since covers most of research entities in AI4PHM, BioMedGraphica supports the zero-shot or few-shot knowledge discoveries via new relation prediction on the graph. Via a graphical user interface (GUI), researchers can access the knowledge graph with prior knowledge of target functional annotations, drugs, phenotypes and diseases (drug-protein-disease-phenotype), in the graph AI ready format. It also supports the generation of knowledge-multi-omic signaling graphs to facilitate the development and applications of novel AI models, like LLMs, graph AI, for AI4PHM science discovery, like discovering novel disease pathogenesis, signaling pathways, therapeutic targets, drugs and synergistic cocktails.
Egocentric Perception of Walking Environments using an Interactive Vision-Language System
Authors: Tan Haining , Mihailidis Alex , Laschowski Brokoslaw
Published: December 2024

Large language models can provide a more detailed contextual understanding of a scene beyond what computer vision alone can provide, which have implications for robotics and embodied intelligence. In this study, we developed a novel multimodal vision-language system for egocentric visual perception, with an initial focus on real-world walking environments. We trained a number of state-of-the-art transformer-based vision-language models that use causal language modelling on our custom dataset of 43,055 image-text pairs for few-shot image captioning. We then designed a new speech synthesis model and a user interface to convert the generated image captions into speech for audio feedback to users. Our system also uniquely allows for feedforward user prompts to personalize the generated image captions. Our system is able to generate detailed captions with an average length of 10 words while achieving a high ROUGE-L score of 43.9% and a low word error rate of 28.1% with an end-to-end processing time of 2.2 seconds. Overall, our new multimodal vision-language system can generate accurate and detailed descriptions of natural scenes, which can be further augmented by user prompts. This innovative feature allows our image captions to be personalized to the individual and immediate needs and preferences of the user, thus optimizing the closed-loop interactions between the human and generative AI models for understanding and navigating of real-world environments.
Refugee Healthcare Resilience and Burdens: A 10-year Mixed-Methods Analysis of System Shocks in Canada
Authors: Norrie Eric , Holdbrook Linda , Grewal Rabina , Talavlikar Rachel , Essar Mohammad Yasir , Williamson Tyler , Coakley Annalee , McBrien Kerry , Fabreau Gabriel E.
Published: December 2024

Background

System shocks, including sudden policy changes, refugee surges and pandemics, strain healthcare systems. These shocks compound existing vulnerabilities in refugee healthcare, limiting ability to provide patient care, but can also catalyze resilient adaptations. Investigating how local refugee health systems respond to shocks is critical to understanding resilience.

Methods

We conducted a sequential explanatory mixed-methods study (2011–2020) at a specialized refugee health centre in Alberta, Canada, investigating four health system shocks: IFHP Funding Cuts (2012), Syrian Surge (2015), Yazidi Resettlement (2017), and COVID-19 (2020). We analyzed patient sociodemographic characteristics, health center utilization, and healthcare provider supply, conducting interrupted time series analysis of mean monthly appointments (total, family physicians, specialists and multidisciplinary team) and rates of change. We adapted a Health System Resilience framework to thematically analyze interviews with centre leaders and integrated these findings with quantitative findings to assess resilience and operational burdens.

Findings

From 2011 to 2020, 10,661 refugees from 106 countries attended 107,642 appointments. Mean monthly appointments rose from 455 to 2,208 (3.9-fold, p<0.01). Monthly appointments increased between IFHP and Syrian periods (610.8 to 937.9, p<0.01), but not between Syrian Surge and Yazidi Resettlement (p=0.29). During COVID-19, mean appointments remained stable (1,412.4 to 1,414.0, p=0.11), but additional monthly appointments rose from 6.3 to 110.4 (17.5-fold, p<0.01). Over ten years, mean provider hours increased from 320 to 736 (2.3-fold), and from 59.5 to 871.4 (14.6-fold) for family physicians and multidisciplinary team members. Qualitative analysis revealed resilience capacities but highlighted costs such as burnout, vicarious trauma, and financial strain. Integration showed the centre developed resilience but experienced notable operational burden.

Interpretation

Over a decade, a specialized refugee health centre adapted to successive shocks, transforming into a beacon clinic. It demonstrated resilience through care expansion and innovation, but with notable costs, financially and to health worker wellbeing.

Funding

None
Functional and epitope specific monoclonal antibody discovery directly from immune sera using cryoEM
Authors: Ferguson James A. , Raghavan Sai Sundar Rajan , Peña Alzua Garazi , Bhavsar Disha , Huang Jiachen , Rodriguez Alesandra J. , Torres Jonathan L. , Bottermann Maria , Han Julianna , Krammer Florian , Batista Facundo D. , Ward Andrew B.
Published: December 2024

Antibodies are crucial therapeutics, comprising a significant portion of approved drugs due to their safety and clinical efficacy. Traditional antibody discovery methods are labor-intensive, limiting scalability and high-throughput analysis. Here, we improved upon our streamlined approach combining structural analysis and bioinformatics to infer heavy and light chain sequences from electron potential maps of serum-derived polyclonal antibodies (pAbs) bound to antigens. Using ModelAngelo, an automated structure-building tool, we accelerated pAb sequence determination and identified sequence matches in B cell repertoires via ModelAngelo derived Hidden Markov Models (HMMs) associated with pAb structures. Benchmarking against results from a non-human primate HIV vaccine trial, our pipeline reduced analysis time from weeks to under a day with higher precision. Validation with murine immune sera from influenza vaccination revealed multiple protective antibodies. This workflow enhances antibody discovery, enabling faster, more accurate mapping of polyclonal responses with broad applications in vaccine development and therapeutic antibody discovery.
Spatially-resolved molecular sex differences at single cell resolution in the adult human hypothalamus
Authors: Mulvey Bernard , Wang Yi , Divecha Heena R. , Bach Svitlana V. , Montgomery Kelsey D. , Cinquemani Sophia , Chandra Atharv , Du Yufeng , Miller Ryan A. , Kleinman Joel E. , Page Stephanie C. , Hyde Thomas M. , Martinowich Keri , Hicks Stephanie C. , Hansen Kasper D. , Maynard Kristen R.
Published: December 2024

The hypothalamus contains multiple regions, including the ventromedial hypothalamus (VMH) and arcuate (ARC), which are responsible for sex-differentiated functions such as endocrine signaling, metabolism, and reproductive behaviors. While molecular, anatomic, and sex-differentiated features of rodent hypothalamus are well-established, much less is known about these regions in humans. Here we provide a spatially-resolved single cell atlas of sex-differentially expressed (sex-DE) genes in human VMH and ARC. We identify neuronal populations governing hypothalamus-specific functions, define their spatial distributions, and show increased retinoid pathway gene expression compared to rodents. Within VMH and ARC, we find correlated autosomal expression differences localized toESR1/TAC3-expressing andCRHR2-expressing neurons, and extensive sex-DE of genes linked to sex-biased disorders including autism, depression, and schizophrenia. Our molecular mapping of disease associations to hypothalamic cell types with established roles in sex-divergent physiology and behavior provides insights into mechanistic bases of sex bias in neurodevelopmental and neuropsychiatric disorders.
Pooled overexpression screening identifies PIPPI as a novel microprotein involved in the ER stress response
Authors: Lafranchi Lorenzo , Spinner Anna , Hornisch Maximilian , Schlesinger Dörte , Luzon Carmen Navarro , Brinkenstråhle Linus , Shao Rui , Piazza Ilaria , Elsässer Simon J
Published: December 2024

Microproteins encoded by short open reading frames (sORFs) of less than 100 codons have been predicted to constitute a substantial fraction of the eukaryotic proteome. However, relevance and roles of the majority of microproteins remain undefined because only a small fraction of these intriguing cellular players have been in-depth characterized so far. Here we use pooled overexpression screens with a library of 11’338 sORFs to overcome the challenge of elucidating which of the thousands of putative translated sORFs are biologically functional. As a proof-of-concept, we performed a phenotypic screen to identify sORFs protecting cells from treatment with the nucleotide analogue 6-thioguanine. With this approach, we identified two cytoprotective microproteins: altDDIT3 and PIPPI. PIPPI is encoded as part of the LC16a core duplicon/Morpheus gene cluster, a highly duplicated region of the human genome, which is undergoing rapid positive selection in primates. Our data show that PIPPI interacts with proteins of the endoplasmic reticulum, including protein disulfide isomerase ERp44. Besides providing mechanistic insights on a new microprotein, this study highlights the power of using pooled overexpression screens to identify functional microproteins.
mTOR signaling governs the formation of epithelial apical projection via S6K1-RhoA and aPKC-Lgl2 axes
Authors: Sen Sumit , Ghosh Prithwish , Mukherjee Sudipta , Prabhu Shreedha , Khurana Ginni , Pinto Clyde Savio , Gupta Kirti , Venkatramani Ravindra , Sonawane Mahendra
Published: December 2024

In metazoans, epithelia perform functions of absorption, diffusion, and secretion. The actin-based apical projections on the epithelial cells, contribute to these functions and are formed via cell-autonomous mechanisms that control cell polarity, intracellular transport, and the cytoskeleton. However, the cues that function upstream of these cell-autonomous regulators remain poorly known. Using microridges on zebrafish epithelial cells as a paradigm, we show that mTOR, a metabolic sensor, regulates the formation of apical projections. Mechanistically, mTORC1 controls the RhoA-ROCK activity via S6K1 to prevent the overactivation of Non-muscle Myosin II (NMII) to restrict microridge elongation. Furthermore, genetic, biochemical, and molecular dynamics simulation analyses reveal that mTORC2 regulates microridge pattern by modulating the activity of aPKC via its differential phosphorylation at two conserved sites. We propose that mTOR integrates the developmental and/or metabolic status of epithelial cells with cell autonomously acting RhoA and aPKC to regulate tissue wide formation of apical projections.
Cell volume regulates terminal differentiation of cultured human epidermal keratinocytes
Authors: Zijl Sebastiaan , Hiratsuka Toru , Mobasseri Atefeh , Ebrahimkutty Mirsana , Börmel Mandy , Garcia-Manyes Sergi , Watt Fiona M.
Published: December 2024

Differentiation of cultured human epidermal stem cells is regulated by interactions with the underlying substrate. Whereas differentiation is typically stimulated when keratinocytes are prevented from spreading, we previously identified two micron-scale topographical substrates that regulate differentiation of spread cells. On one substrate (S1), individual cells interact with small circular topographies, and differentiation is stimulated; on the other (S2), cells interact with larger triangular topographies, and differentiation is inhibited. By scanning electron microscopy we visualised substrate interactions at higher resolution than previously and using live cell imaging we established that induction of the differentiation marker involucrin did not involve transient cell rounding on S1. Bulk gene expression profiling did not reveal any differences between cells on S1 and S2 prior to the selective upregulation of differentiation markers at 12h on S1 and cell stiffness was lower on both S1 and S2 than on flat substrates. Nevertheless, cells on S2 differed from cells on flat and S1 substrates because they exhibited reduced cell volume, prompting us to explore whether cell volume could regulate differentiation independent of culture substrate. Treatment with polyethylene glycol (PEG) reduced cell volume and inhibited differentiation regardless of whether keratinocytes were seeded on flat, S1 or S2 substrates, micropatterned islands or in suspension. Conversely, treatment with deionised water increased cell volume and stimulated differentiation of substrate adherent keratinocytes. On flat substrates treatment with the Ca2+chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid acetoxymethyl ester or an inhibitor of the water channel aquaporin 3 blocked induction of differentiaton by deionised water, whereas the gadolinium3+, a stretch-activated calcium channel blocker, did not. Our studies identify a new mechanism by which keratinocyte-niche interactions regulate initiation of differentiation.
Magnetic ground state and excitations in the mixed
3d−4d
quasi-one-dimensional spin-chain oxide
Sr3NiRhO6
Authors: Jain A. , Adroja D. T. , Rayaprol S. , Hillier A. D. , Kockelmann W. , Yusuf S. M. , Sampathkumaran E. V.
Published: December 2024

Entanglement of spin and orbital degrees of freedom, via relativistic spin-orbit coupling, in 4d transition metal oxides can give rise to a variety of unique quantum phases. A previous study of mixed 3d−4d quasi-1D spin-chain oxide Sr3NiRhO6 using the magnetization measurements by Mohapatra [] revealed a partially disordered antiferromagnetic structure below 50 K. We here report the magnetic ground state and spin-wave excitations in Sr3NiRhO6 using muon spin rotation and relaxation (μSR), and neutron (elastic and inelastic) scattering techniques. Our neutron diffraction study reveals that in the magnetic structure of Sr3NiRhO6 Rh4+ and Ni2+ spins are aligned ferromagnetically in a spin chain, with moments along the crystallographic c axis. However, spin chains are coupled antiferromanetically in the ab plane. μSR reveals the presence of oscillations in the asymmetry-time spectra below 50 K, supporting the long-range magnetically ordered ground state. Our inelastic neutron scattering study reveals gapped quasi-1D magnetic excitations with a large ratio of gap to exchange interaction. The observed spin-wave spectrum could be well fitted with a ferromagnetic isotropic exchange model (with J=3.7 meV) and single ion anisotropy (D=10 meV) on the Ni2+ site. The magnetic excitations survive up to 85 K, well above the magnetic ordering temperature of ∼50 K, also indicating a quasi-1D nature of the magnetic interactions in

Sr

3

NiRhO

6

.

Published by the American Physical Society
2024
Spin coherence in strongly coupled spin baths in quasi-two-dimensional layers
Authors: Schätzle Philip , Ghassemizadeh Reyhaneh , Urban Daniel F. , Wellens Thomas , Knittel Peter , Reiter Florentin , Jeske Jan , Hahn Walter
Published: December 2024

We investigate the spin-coherence decay of NV− spins interacting with the strongly coupled bath of nitrogen defects in diamond layers. For thin diamond layers, we demonstrate that the spin-coherence times exceed those of bulk diamond, thus allowing to surpass the limit imposed by high-defect concentrations in bulk. We show that the stretched-exponential parameter for the short-time spin-coherence decay is governed by the hyperfine interaction in the bath, thereby constraining random-noise models. We introduce a method based on the cluster-correlation expansion applied to strongly interacting bath partitions instead of individual spins. Our results facilitate material development for quantum-technology devices.

Published by the American Physical Society
2024