bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Reduced Diameter of the Cochlear Nerve in Long-term Deaf Patients Quantified With Semiautomatic Measurement of Nerve Cross-sectional Area Using 3T MRI Data
Authors: Reimann Katrin , Klose Uwe , Ehrenpfordt Ulrike , Thangavelu Kruthika , Schulze Maximilian
Published: January 2024

Hypothesis:

High-resolution parallel transmit T2 sampling perfection with application optimized contrast using different flip angle evolution sequence with improved edge discrimination and semiautomatic determination of nerve cross-sectional area (CSA) can be used to evaluate nerve degeneration in the inner auditory canal (IAC) in long-term deaf patients.

Background:

In patients with hearing loss, temporal bone MRI is routinely acquired to evaluate the morphology of the nerves within the IAC. Earlier studies have shown that the diameter of the cochlear nerve can be used as prognostic marker for the auditory performance after cochlear implantation in postlingually deaf patients.

Methods:

Eighty-two consecutive MRI scans were analyzed using a semiautomatic tool to measure CSA of cranial nerves in the IAC. Results were correlated with patient history and audiology testing as well as with age and gender.

Results:

There was a significant reduced CSA of the cochlear nerve in ears with moderate-to-profound hearing loss and deafness compared with ears with normal hearing, but no significant difference in ears with mild-to-moderate hearing loss compared with normal hearing. In detail, normal hearing ears had a CSA of 1.23 ± 0.11 mm2, whereas ears with pantonal hearing loss of more than 40 dB had 1.02 ± 0.05 mm2 (P = 0.026). Maximal CSA of the facial nerve was not different among all groups (average, 1.04 mm2 ± 0.03; linear regression, P = 0.001) and stable with age. However, vestibular nerve CSA decreased significantly with age (average, 1.78 ± 0.05 mm2; linear regression, P = 0.128).

Conclusions:

In long-term deaf patients, smaller the diameter of cochlear nerve is the more severe the hearing loss is. The new semiautomatic tool can primarily be used to assess nerve diameter and possibly determine ears with nerve degeneration.
Rhode Island (RI) Women's Breast Cancer Mammography Use Prior to and After Cancer Diagnosis: Linkage of RI Cancer Registry Data With RI All-Payer Claims Database
Authors: Vyas Ami , Kamat Shweta , Oh Junhie
Published: January 2024

Objective:

A limitation of the central cancer registries to examine associations between mammography use and cancer diagnosis is their lack of cancer screening history. To fill this measurement gap, Rhode Island Cancer Registry (RICR) breast cancer (BC) records were linked to Rhode Island-all-payer claims database (RI-APCD) to study Rhode Island (RI) women's regular mammography use and identify its predictors.

Methods:

From the linked 2011-2019 data, we identified 4 study cohorts: (1) women who ever received mammography by Women's Cancer Screening Program (WCSP) and were diagnosed with BC (“WCSP-BC” cohort: n = 149), (2) women diagnosed with BC outside of WCSP (BC-control cohort: n = 4304), (3) women with a history of mammography use at WCSP but no BC diagnosis (n = 6513), and (4) general RI women with no BC diagnosis (n = 15 121). Logistic regressions were conducted to identify predictors of regular mammography use.

Results:

The linkage for RI-APCD and RICR for our study had a high matching rate of 82%. Mammography use prior to BC diagnosis was not different between the WCSP-BC cohort and the BC-control cohort (58% vs 57%). Women in the BC-control cohort who had mammography in 2 years prior to their cancer diagnosis were more likely of being diagnosed at an early-stage disease. Among BC-control group, women with no anxiety/depression or with no preventive examinations were less likely of regular mammography use. Among women with no BC, a lower proportion of women with a history of screening at WCSP had regular mammography use, compared with the general RI women (38% vs 66%).

Conclusion:

RI-APCD data linkage with RICR provides excellent opportunities to examine regular mammography use among RI women and compare their outcomes to the general women population in the state. We identified opportunities for improving their mammography use. A measurement gap in the central cancer registries can be effectively reduced by utilizing statewide claims database.
Spectrum of Thoracic Imaging Findings in the Setting of Substance Abuse
Authors: Gann Lauren S. , Kunin Jeffrey R. , Ebada Mohamed , Walker Christopher M.
Published: January 2024

Substance abuse continues to be prevalent nationwide and can lead to a myriad of chest pathologies. Imaging findings are vast and can include nodules, masses, ground-glass opacities, airspace disease, and cysts. Radiologists with awareness of these manifestations can assist in early identification of disease in situations where information is unable to be obtained from the patient. This review focuses on thoracic imaging findings associated with various forms of substance abuse, which are organized by portal of entry into the thorax: inhalation, ingestion, and injection.
Malignant Peritoneal Mesothelioma Complicating Familial Mediterranean Fever on 18F-FDG PET/CT
Authors: Fayand Antoine , Kerrou Khaldoun , Wendum Dominique , Grateau Gilles , Georgin-Lavialle Sophie
Published: January 2024

A 77-year-old man with a personal history of familial Mediterranean fever presented with a slowly enlarging tumefaction of the left abdominal wall and persistent inflammatory syndrome despite good adherence to colchicine. 18F-FDG PET/CT showed a hypermetabolic muscular mass of the abdominal wall along with other hypermetabolic lesions including a peritoneal mass and several subcutaneous soft tissue nodules. CT-guided needle biopsy led to the diagnosis of a muscular localization of a malignant peritoneal mesothelioma, which is an extremely rare complication of familial Mediterranean fever. Six courses of chemotherapy with carboplatin and pemetrexed allowed an almost complete response.
False-Positive Metastatic Bone Disease on FDG PET/CT Due to Multilevel Tophaceous Gout of the Spine
Authors: Drazyk Anna , Loh Han , Bui Chuong , Ding Pei , Mansberg Robert
Published: January 2024

A 74-year-old woman was referred for 18F-FDG PET/CT for the evaluation of incidental CT finding of expansile destruction of left L4/5 facet joint with associated soft tissue mass concerning for a metastatic deposit. The FDG PET/CT revealed variable abnormally increased FDG activity involving multiple facet joints in all regions of the spine with corresponding expansile “punched-out” lytic lesions with sclerotic rims and overhanging margins on CT, raising the possibility of inflammatory polyarthropathy, including gout, as a differential diagnosis. Dual-energy CT of lumbar spine and CT-guided biopsy and culture of the left L4/5 facet joint demonstrated the presence of urate crystal deposition with no evidence of malignancy or infection, confirming the diagnosis of multilevel tophaceous gout of the spine.
FDG-Avid Periprosthetic Particle Disease Mimicking Osteosarcoma Recurrence
Authors: Dong Ziqian , Guo Ziyu , Guan Meichao , Zhang Yingjie , Xie Peng
Published: January 2024

A 24-year-old man with a history of osteosarcoma presented with swelling in his right thigh for more than 1 year. 18F-FDG PET/CT demonstrated increased FDG uptake in multiple juxtacortical masses around the prosthesis, which highly suggested the possibility of osteosarcoma recurrence. A biopsy was performed, and the pathology confirmed the diagnosis of particle disease. The current case indicates that particle disease should be considered when interpreting the PET/CT images with high FDG uptake around the prosthesis.
Intracranial Phosphaturic Mesenchymal Tumor Detected by 68Ga-DOTATATE PET/CT
Authors: Shi Qinwen , Cheng Junjun , Zhang Yue , Su Minggang
Published: January 2024

A 68Ga-DOTATATE PET/CT scan was conducted to locate the causative tumor responsible for suspected tumor-induced osteomalacia in a 56-year-old woman. The PET/CT images showed a focus in the right occipital region. Subsequent MRI showed an extra-axial nodule in the right occipital region, mimicking a meningioma. Although rare, an intracranial phosphaturic mesenchymal tumor was still suspected because of the typical clinical settings. Finally, phosphaturic mesenchymal tumor was confirmed by the postoperative pathology.
Comparison of Lugano Criteria Versus RECIL and PERCIST as Prognostic Factors in Diffuse Large B-Cell Lymphoma
Authors: Tang Pan , Cui Futao , Jiang Chong , Zhou Yushan , Su Minggang , Tian Rong
Published: January 2024

Objective

This study aimed to compare the criteria of the Lugano, RECIL, and PERCIST for prognosis in patients with diffuse large B-cell lymphoma.

Patients and Methods

We retrospectively evaluated 335 patients with diffuse large B-cell lymphoma. All patients underwent baseline 18F-FDG PET/CT. Among them, 252 and 213 patients underwent interim PET/CT (I-PET/CT) and end-of-treatment PET/CT (EoT-PET/CT), respectively. Scans were interpreted by 2 nuclear medicine physicians using Lugano, RECIL, and PERCIST. RECIL and PERCIST were compared with Lugano for predicting progression-free survival (PFS) and overall survival (OS).

Results

All 3 response criteria could be used to predict PFS and OS. In I-PET/CT, the concordance index of Lugano in predicting PFS and OS was higher than that of RECIL (both P = 0.043) or PERCIST (P = 0.008 and P = 0.034, respectively). In EoT-PET/CT, the concordance index of Lugano for predicting PFS and OS was similar to RECIL and not significantly different from PERCIST (P = 0.597 and P = 0.231, respectively).

Conclusions

For I-PET/CT, using the Lugano criteria is more accurate than RECIL or PERCIST in predicting PFS and OS. However, for EoT-PET/CT, the PERCIST criteria are minimally better.
AI-enabled Left Atrial Volumetry in Cardiac CT Scans Improves CHARGE-AF and Outperforms NT-ProBNP for Prediction of Atrial Fibrillation in Asymptomatic Individuals: Multi-Ethnic Study of Atherosclerosis
Authors: Naghavi Morteza , Yankelevitz David , Reeves Anthony P. , Budoff Matthew J. , Li Dong , Atlas Kyle C. , Zhang Chenyu , Atlas Thomas L. , Lirette Seth , Wasserthal Jakob , Henschke Claudia , Defilippi Christopher , Heckbert Susan R. , Greenland Philip
Published: January 2024

Background

Coronary artery calcium (CAC) scans contain actionable information beyond CAC scores that is not currently reported.

Methods

We have applied artificial intelligence-enabled automated cardiac chambers volumetry to CAC scans (AI-CAC), taking on average 21 seconds per CAC scan, to 5535 asymptomatic individuals (52.2% women, ages 45-84) that were previously obtained for CAC scoring in the baseline examination (2000-2002) of the Multi-Ethnic Study of Atherosclerosis (MESA). We used the 5-year outcomes data for incident atrial fibrillation (AF) and compared the time-dependent AUC of AI-CAC LA volume with known predictors of AF, the CHARGE-AF Risk Score and NT-proBNP (BNP). The mean follow-up time to an AF event was 2.9±1.4 years.

Results

At 1,2,3,4, and 5 years follow-up 36, 77, 123, 182, and 236 cases of AF were identified, respectively. The AUC for AI-CAC LA volume was significantly higher than CHARGE-AF or BNP at year 1 (0.836, 0.742, 0.742), year 2 (0.842, 0.807,0.772), and year 3 (0.811, 0.785, 0.745) (p<0.02), but similar for year 4 (0.785, 0.769, 0.725) and year 5 (0.781, 0.767, 0.734) respectively (p>0.05). AI-CAC LA volume significantly improved the continuous Net Reclassification Index for prediction of AF over years 1-5 when added to CAC score (0.74, 0.49, 0.53, 0.39, 0.44), CHARGE-AF Risk Score (0.60, 0.28, 0.32, 0.19, 0.24), and BNP (0.68, 0.44, 0.42, 0.30, 0.37) respectively (p<0.01).

Conclusion

AI-CAC LA volume enabled prediction of AF as early as one year and significantly improved on risk classification of CHARGE-AF Risk Score and BNP.
Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis
Authors: Costa Gonçalo , Resende Bernardo , Oliveiros Bárbara , Gonçalves Lino , Teixeira Rogério
Published: January 2024

Background

Unfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, current guidelines do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterisation laboratory.

Methods

Between June and July 2023, we systematically searched PubMed, Embase and Cochrane databases for studies comparing UFH pretreatments in patients with STEMI. A random-effects meta-analysis and meta-regression analyses were performed.

Results

Fourteen studies were included, of which four were randomised clinical trials (RCTs). A total of 76446 patients were included: 31238 in the pretreatment group and 39208 in the control group. Our meta-analysis revealed a lower all-cause mortality for the pretreatment strategy when compared with the control group, albeit with high heterogeneity (pooled odds ratio (OR) = 0.61, 95% confidence interval (CI) [0.49 - 0.76],P< 0.01; I² = 77%); lower in-hospital cardiogenic shock (pooled OR = 0.68, 95% CI [0.58, 0.78],P< 0.21; I² = 27%) and a higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI [1.47, 1.91],P< 0.01; I² = 79%). In terms of major bleeding, the UFH pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI [0.73, 0.99],P= 0.40; I² = 4%).

Conclusions

Our study suggests that UFH pretreatment in patients with STEMI undergoing primary PCI was associated to reduced all-cause mortality, cardiogenic shock, enhancing reperfusion rates, whilst diminishing major bleeding events.
Single-Cell Local Stress Analysis in Tumoroids
Authors: Rodrigues de Mercado Rick , Beslmüller Klara , Vorselen Daan , Danen Erik H.J. , Schmidt Thomas
Published: January 2024

The reciprocal interplay between cancer cells and their local environment, mediated by mechanical forces, necessitates a deeper experimental understanding. This requires precise quantitative measurements of cellular forces within the intricate three-dimensional context of the extracellular matrix. While methods such as traction-force microscopy and micropillar-array technology have effectively reported on cellular forces in two-dimensional cell culture, extending these techniques to three dimensions has proven exceedingly challenging. In the current study, we introduced a novel approach utilizing soft, elastic hydrogel microparticles, resembling the size of cells, to serve as specific and sensitive traction probes in three-dimensional cell culture of collagen-embedded tumoroids. Our methodology relies on high-resolution detection of microparticle deformations. These deformations are translated into spatially resolved traction fields, reaching a spatial resolution down to 1 µm and thereby detecting traction forces as low as 30 Pa. By integrating this high-resolution traction analysis with three-dimensional cell segmentation, we reconstructed the traction fields originating from individual cells. Our methodology enables us to explore the relationships between cellular characteristics, extracellular traction fields, and cellular responses. We observed that cellular stresses ranged from 10 to 100 Pa, integrating to cellular forces from 0.1 to 100 nN, which correlated with the localization of the cells actin skeleton, and the interaction area that cells developed towards the microparticles. Interestingly, the interaction of cells with inert microparticles appeared to be governed by contact mechanics resembling that of two soft spheres. The methodology presented here not only addresses the challenges of extending traditional stress-probe techniques to three dimensions, but also opens a strategy for the study of specific interactions between cells and the local tumoroid environment in a strive to further understand cell-matrix reciprocity in tissue.

Here, we present a novel methodology that permits the measurement of quantitative surface stresses on small, inert, elastic, deformable microparticles. Our approach tackles the involved task of mapping local three-dimensional stress fields within tissue. Our methodology was successfully applied to analyze local stresses within a tumor spheroid. We foresee that our research represents a significant advancement toward comprehending the intricate dynamics of cell-matrix reciprocity within tissue.
BaYaka mothers balance childcare and subsistence tasks during collaborative foraging in Congo Basin
Authors: Visine Amandine E. S. , Boyette Adam H. , Ouamba Yann Reische , Lew-Levy Sheina , Sarma Mallika , Jang Haneul
Published: January 2024

Across cultures, mothers face trade-offs between childcare and other labor. In hunter-gatherer societies, mothers face this choice on a daily basis when deciding either to take infants on foraging trips or to leave them with caregivers in the village. Yet, it remains unclear how the presence of infants in foraging groups constrains mothers’ mobility during foraging. Here, we present GPS, energy expenditure and food returns data of 359 foraging trips of 23 BaYaka mothers in the Republic of the Congo. We find that mothers spent more time on out-of-village foraging activities when they took infants along, compared to when they left infants behind. However, infant presence in foraging groups does not affect mothers’ travel distance, travel range, energy expenditure or food returns. Regardless of infant presence, women travel longer and further in a larger area when foraging in groups, compared to when foraging alone, especially in groups with more adults, females and both kin and non-kin. Our results suggest that BaYaka mothers develop ways to accommodate childcare with foraging activities by combining individual-level and group-level behavioural strategies. Our study highlights that group foraging may allow mothers with infants to maintain high mobility, which may have been a key to human range expansion.
Activation of HIF2 leads to vascular remodeling and inflammation, coronary thrombosis and arterial dilation, recapitulating cardiac involvement of Kawasaki disease
Authors: Escobar B , Menendez-Montes I , Albendea-Gomez T , Mendoza-Tamajón S , Castro-Mecinas R , Diaz-Diaz C , Palacios B , Ruiz-Cabello J , Jimenez-Borreguero LJ , Cid MC , Takahashi K , Martin-Puig S
Published: January 2024

Background

global deletion ofVhlleads to vascular defects and early lethality, precluding the study of VHL/HIF signaling during coronary formation and homeostasis. Hypoxia pathway has been associated with cardiovascular diseases involving inflammation and vascular remodeling like atherosclerosis, but its role in Kawasaki Disease (KD) remains unknown. Coronary dilatation and vessel rupture are the most serious complications of KD, while the molecular mechanisms underlying these cardiac events remain poorly understood. Here we aim to determine the function of VHL/HIF pathway in the development of cardiovascular defects and its role in KD.

Methods

We generated a new mouse model to genetically hyperactivate hypoxia pathway in progenitors contributing to coronary vessels and cardiac fibroblasts (Vhl/Wt1). We characterized the model by means of echocardiography, magnetic resonance imaging, histological analysis and molecular approaches. Human cardiac tissue from KD individuals suffering fatal coronary aneurysm were screened for HIF signaling and inflammatory markers by immunohistochemistry.

Results

conditionalVhlKO do not undergo developmental abnormalities but displays cardiomegaly and epicardial vascular defects, with cardiac hypertrophy and progressive coronary diameter increase, as well as pericardial hemorrhage and systemic inflammation early after birth. Histological characterization reveals inflammation of coronary arteries, vascular remodeling with elastin breaks and dilatation, increased perivascular fibrosis and smooth muscle cells death, together with high incidence of intracoronary thrombus formation. In addition, the mutants display vascular calcification and severe cardiac inflammation and interstitial hemorrhages, dying suddenly between 15-20 weeks of age due to vessel rupture. Simultaneous elimination of HIF2 and VHL prevents the cardiovascular abnormalities displayed by single cVhlKO, highlighting the essential role of HIF2 in coronary instability and vascular inflammation. Histological characterization of human cardiac samples shows positive signal for HIF1 and specially HIF2, in the coronary lesions and its surroundings in regions with high inflammatory infiltration, confirming the activation of hypoxia signaling in KD patients with cardiovascular complications.

Conclusions

Our data demonstrate the importance of HIF2 signaling in the development of coronary inflammation and vascular remodeling and provide new evidences connecting low oxygen tensions with cardiovascular lesions occurring during the onset of the most severe cases of KD. Furthermore, theVhl/Wt1 mouse generated recapitulates cardiac features of KD with critical heart complications, providing a new platform to uncover unknown aspects of KD pathogenesis.
GeneSelectR: An R Package Workflow for Enhanced Feature Selection from RNA Sequencing Data
Authors: Zhakparov Damir , Moriarty Kathleen , Roqueiro Damian , Baerenfaller Katja
Published: January 2024

Motivation

High-dimensional Bulk RNA sequencing (RNAseq) datasets pose a considerable challenge in identifying biologically relevant features for downstream analyses and data mining efforts. The standard approach involves differential gene expression (DGE) analysis, but its effectiveness can be limited depending on the data due to its univariate nature. In complex datasets, an alternative approach involves employing a variety of machine learning (ML) tools, which attempt to understand non-linear relationships between features and focus on generalizability rather than statistical significance. This approach will result in the generation of multiple feature lists, which might exhibit similarities in terms of classification performance metrics. Therefore, there is an urgent need for a cohesive workflow that seamlessly integrates robust feature selection using diverse ML methods while also evaluating the biological relevance of the resulting feature lists. This combined approach would enable the prioritization of the best-performing list, considering both sets of criteria.

Results

We introduce GeneSelectR, an open-source R package that innovatively combines ML and bioinformatic data mining approaches for enhanced feature selection. With GeneSelectR, features can be selected from a normalized RNAseq dataset with a variety of ML methods and user-defined parameters. This is followed by an assessment of their biological relevance with Gene Ontology (GO) enrichment analysis, along with a semantic similarity analysis of the resulting GO terms. Additionally, similarity coefficients and fractions of the GO terms of interest are calculated. With this, GeneSelectR optimizes ML performance and rigorously assesses the biological relevance of the various lists, offering a means to prioritize feature lists with regard to the biological question. When applied to the TCGA-BRCA dataset, the GeneSelectR workflow generated several feature lists using different ML methods and a DGE analysis. By leveraging the various functions in GeneSelectR, the different lists could be evaluated based on both ML performance and biological relevance. This comprehensive evaluation facilitated the selection of the best-performing list, which exhibited both strong machine learning performance and high relevance to the biological question while maintaining a manageable number of highly specific features.

Availability

The package is available on CRAN. To install it, run: install.packages(‘GeneSelectR’)

Contact

dzhakparov@gmail.com

Supplementary information

Supplementary data are available atBioinformaticsonline.
Genetic characterisation of candidate ecdysteroid kinases inDrosophila melanogaster
Authors: Scanlan Jack L. , Robin Charles
Published: January 2024

Ecdysteroids are major hormones in insects and control moulting, growth, reproduction, physiology, and behaviour. The biosynthesis of ecdysteroids such as 20-hydroxyecdysone (20E) from dietary sterols is well characterised, but ecdysteroid catabolism is poorly understood. Ecdysteroid kinases (EcKs) mediate the reversible phosphorylation of ecdysteroids, which has been implicated in ecdysteroid recycling during embryogenesis and reproduction in various insects. However, to date only two EcK-encoding genes have been identified, in the silkwormBombyx moriand the mosquitoAnopheles gambiae. Previously, we identified two ecdysteroid kinase-like (EcKL) genes—Wallflower(Wall) andPinkman(pkm)—in the model fruit flyDrosophila melanogasterthat are orthologs of the ecdysteroid 22-kinase geneBmEc22K. Here, using gene knockdown, knockout and misexpression, we exploreWallandpkm’s possible functions and genetically test the hypothesis that they encode EcKs.Wallandpkmnull mutants are viable and fertile, suggesting they are not essential for development or reproduction, whereas phenotypes arising from RNAi and somatic CRISPR appear to derive from off-target effects or other artefacts. However, misexpression ofWallresults in dramatic phenotypes, including developmental arrest, and defects in trachea, cuticle and pigmentation.Wallmisexpression fails to phenocopy irreversible ecdysteroid catabolism through misexpression ofCyp18a1, suggesting Wall does not directly inactivate 20E. Additionally,Wallmisexpression phenotypes are not attenuated inCyp18a1mutants, strongly suggesting Wall is not an ecdysteroid 26-kinase. We hypothesise that the substrate of Wall in this misexpression experiment and possibly generally is an unknown, atypical ecdysteroid that plays essential roles inDrosophiladevelopment, and may highlight aspects of insect endocrinology that are as-yet uncharacterised. We also provide preliminary evidence thatCG5644encodes an ecdysteroid 22-kinase conserved across Diptera.
On the lipid dependence of bacterial mechanosensitive channel gating in situ
Authors: Britt Madolyn , Sawasato Katsuhiro , Moller Elissa , Kidd Gerald , Bogdanov Mikhail , Sukharev Sergei
Published: January 2024

For bacterial mechanosensitive channels acting as turgor-adjusting osmolyte release valves, membrane tension is the primary stimulus driving opening transitions. Because tension is transmitted through the surrounding lipid bilayer, it is possible that the presence or absence of different lipid species may influence the function of these channels. In this work, we characterize the lipid dependence of chromosome-encoded MscS and MscL in E. coli strains with genetically altered lipid composition. We use two previously generated strains that lack one or two major lipid species (PE, PG, or CL) and engineer a third strain that is highly enriched in CL due to the presence of hyperactive cardiolipin synthase ClsA. We characterize the functional behavior of these channels using patch-clamp and quantify the relative tension midpoints, closing rates, inactivation depth, and the rate of recovery back to the closed state. We also measure the osmotic survival of lipid-deficient strains, which characterizes the functional consequences of lipid-mediated channel function at the cell level. We find that the opening and closing behavior of MscS and MscL tolerate the absence of specific lipid species remarkably well. The lack of cardiolipin (CL), however, reduces the active MscS population relative to MscL and decreases the closing rate, slightly increasing the propensity of MscS toward inactivation and slowing the recovery process. The data points to the robustness of the osmolyte release system and the importance of cardiolipin for the adaptive behavior of MscS.
Maternal histone methyltransferases antagonistically regulate monoallelic expression inC. elegans
Authors: Sands Bryan , Yun Soo R. , Oshima Junko , Mendenhall Alexander R.
Published: January 2024

Undefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This sort of random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematodeCaenorhabditis elegansto study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7ZIP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT-catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.
Gelatinous matrix, an original strategy to cope with oligotrophy in Nassellaria (Radiolaria)
Authors: Llopis Monferrer Natalia , Romac Sarah , Laget Manon , Nakamura Yasuhide , Biard Tristan , Sandin Miguel M.
Published: January 2024

Radiolaria are heterotrophic protists abundant in the world’s oceans playing important roles in biogeochemical cycles. Some species host photosynthetic algae also contributing to primary production. Such mixotrophic behaviour is believed to explain their ecological success in oligotrophic waters, notably Collodaria, exclusively mixotrophic radiolarians within a gelatinous matrix. Yet, our understanding of Radiolaria ecology is limited to direct observations, as they have so far withstood reproduction in culture and their genomes are unexplored. Sampling oligotrophic California Current communities revealed an abundant, rarely observed population of Nassellaria of the genusPhlebarachnium, characterized to live within a gelatinous matrix along with other Radiolaria. Phylogenetic reconstruction of the ribosomal DNA suggests that these distantly related lineages within Nassellaria independently developed the ability to produce a gelatinous matrix ∼150 million years ago. By matching physical samples with their genetic signature, we identified these rarely observed organisms in global metabarcoding datasets, revealing strong biogeographic affinity to oligotrophic water masses. Global ocean co-occurrence networks showed that Radiolaria with a gelatinous matrix have a distinct biogeography compared to those without the matrix. Results suggest that the gelatinous matrix is an adaptation to oligotrophic waters, but further research is needed to evaluate similarities between the gelatinous matrices across different Radiolaria groups. This strategy could increase the effective volume to weight ratio favoring prey capture and create a favorable microenvironment for symbionts, enhancing ecological success in nutrient-depleted waters. This study advances our understanding of eukaryotic diversity evolution, emphasizing specific advantages of certain adaptations, specifically when evolution occurs independently across lineages.
Individual bioenergetic capacity as a potential source of resilience to Alzheimer’s disease
Authors: Arnold Matthias , Buyukozkan Mustafa , Doraiswamy P. Murali , Nho Kwangsik , Wu Tong , Gudnason Vilmundur , Launer Lenore J. , Wang-Sattler Rui , Adamski Jerzy ,   The Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium, De Jager Philip L. , Ertekin-Taner Nilüfer , Bennett David A. , Saykin Andrew J. , Peters Annette , Suhre Karsten , Kaddurah-Daouk Rima , Kastenmüller Gabi , Krumsiek Jan
Published: January 2024

Impaired glucose uptake in the brain is one of the earliest presymptomatic manifestations of Alzheimer’s disease (AD). The absence of symptoms for extended periods of time suggests that compensatory metabolic mechanisms can provide resilience. Here, we introduce the concept of a systemic ‘bioenergetic capacity’ as the innate ability to maintain energy homeostasis under pathological conditions, potentially serving as such a compensatory mechanism. We argue that fasting blood acylcarnitine profiles provide an approximate peripheral measure for this capacity that mirrors bioenergetic dysregulation in the brain. Using unsupervised subgroup identification, we show that fasting serum acylcarnitine profiles of participants from the AD Neuroimaging Initiative yields bioenergetically distinct subgroups with significant differences in AD biomarker profiles and cognitive function. To assess the potential clinical relevance of this finding, we examined factors that may offer diagnostic and therapeutic opportunities. First, we identified a genotype affecting the bioenergetic capacity which was linked to succinylcarnitine metabolism and significantly modulated the rate of future cognitive decline. Second, a potentially modifiable influence of beta-oxidation efficiency seemed to decelerate bioenergetic aging and disease progression. Our findings, which are supported by data from more than 9,000 individuals, suggest that interventions tailored to enhance energetic health and to slow bioenergetic aging could mitigate the risk of symptomatic AD, especially in individuals with specific mitochondrial genotypes.
An Empty Scoping Review of Emergency Department to School Transition for Youth with Mental Health Concerns
Authors: Smith Lora Henderson , Warren Emily , Hendrickson Natalie , Joshua Kate
Published: January 2024

The number of youth Emergency Department (ED) visits due to mental health concerns has been steadily increasing with a large number of youth being referred from school. Despite the increase in ED visits, there has not been an increase in the number of students who are actually admitted to the hospital. Further, youth referred from school are more likely to be discharged from the ED. Given the unique relationship between school and ED referrals and the large number of youth who do not require hospitalization, this study sought to understand how schools are supporting students who return to school after an ED visit. We conducted a scoping review to identify programs and practices to support ED to school transition. Two reviewers screened 907 manuscripts, but none of the manuscripts met the inclusion criteria. We discuss the importance of supporting students returning to school from the ED and draw from the literature on hospital to school transition to make recommendations for educators.
WITHDRAWN: Prompt Engineering GPT-4 to Answer Patient Inquiries: A Real-Time Implementation in the Electronic Health Record across Provider Clinics
Authors: Afshar Majid , Gao Yanjun , Wills Graham , Wang Jason , Churpek Matthew M , Westenberger Christa J , Kunstman David T , Gordon Joel E , Liao Frank J , Patterson Brian
Published: January 2024

Withdrawal Statement

The authors have withdrawn their manuscript owing to needing additional internal review. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Management of Intraductal Papilloma Using Vacuum Assisted Breast Surgery (VABB/VAE):- A Single Institute Study
Authors: Khandelwal Rohan , Sharma Pooja , Desai Dev , Mohanty Sambit
Published: January 2024

Intraductal Papilloma has a higher upgradation rate despite being a benign tumor and warrants an immediate excision. Surgical removal is the gold standard but carries poor cosmetic results and requires general anesthesia. Ultrasound-guided Vacuum Assisted Excision (US-VAE) was used to treat 47 patients after due ethical permissions. 32 patients went US-VAE under local anesthesia and all patients were happy with the cosmetic outcome. The excision was done as a daycare procedure in all patients except indicated by the Anesthetist. Requirements of post-procedure analgesia were also minimal and only 3 patients required prolonged analgesia. The advantages of VABB-guided surgery are faster recovery, scarless procedure, and local anesthesia, thus making it an ideal OPD and daycare procedure for Intraductal Papilloma Excision.

Introduction

Intraductal papilloma, although benign, has a high upgradation rate to malignant breast cancer. Surgical excision is necessary, but the rate of complications is high. Ultrasound-guided vacuum-assisted excision (US-VAE) is a new technique derived from the VABB biopsy method that can give better cosmetic results as well as fewer surgical complications.

Objectives

Understanding the utility of US-VAE in the diagnosis and treatment of intraductal papillomas of the breast.

Methodology

With permission from the Ethics Board and consent of the patients, records of 47 patients were recruited to undergo the US-VAE procedure. USG was used to stage the tumor with Mammography and CNB as needed and patients with single duct or adjacent duct lesions were included while the rest, including patients with malignant changes, were excluded. The Bard VABB biopsy machine and the 7G probe were used by highly trained breast surgeons to perform the procedure.

Results

Of the 47 patients included, 32 patients under local anesthesia were operated while others were under general anesthesia according to the preference of the patient and the level of apprehension. The patients received oral paracetamol as the only painkiller for 5 days. Only 3 patients required prolonged analgesics. 7 patients had prolonged bruising (lasting more than one week), which was the most common complication. All patients (100%) were happy with the cosmetic result after the procedure.

Conclusions

The advantages of VABB-guided surgery are faster recovery, scarless procedure, and the ability to perform the surgery under local anesthesia, making it an OPD and daycare procedure.
Bayesian evidence for the neural dissociation between finger and hand imitation skills
Authors: Rosenzopf Hannah , Röhrig Lisa , Goldenberg Georg , Karnath Hans-Otto
Published: January 2024

Introduction

For limb apraxia ‒ a heterogeneous disorder of higher motor cognition following stroke ‒ an enduring debate has arisen regarding the existence of dissociating neural correlates for finger and hand gestures in the left hemisphere. We re-assessed this question asking whether previous attempts analysing pooled samples of patients with deficits in only one and patients with deficits in both imitation types might have led to systematically biased results.

Methods

We conducted frequentist and Bayesian, voxelwise and regionwise lesion symptom mappings on a pooled sample (N=96) and subsamples containing only shared and only isolated hand and finger imitation deficits and respective controls.

Results

Anatomical analyses on the isolated sample reinforced a cortical dissociation of finger deficits (located more anteriorly) and hand deficits (located more posteriorly). The presence of patients with shared deficits did indeed dilute associations that appeared stronger in the respective isolated samples. Also, brain regions truly associated with hand imitation deficits showed a positive bias for finger imitation deficits, when the sample contained patients with shared deficits. In addition, our frequentist parameters uncovered that some of our Bayesian evidence supported reverse associations (damage protecting from rather than increasing the deficit).

Discussion

Joint analyses of patients with shared and isolated imitation deficits do indeed lead to biases, which may explain why some previous studies have failed to detect the actual neural dissociation between hand and finger imitation deficits.
The inherent fragility of collective proliferative control
Authors: Caldwell Michael G. , Lander Arthur D.
Published: January 2024

Tissues achieve and maintain their sizes through active feedback, whereby cells collectively regulate proliferation and differentiation so as to facilitate homeostasis and the ability to respond to disturbances. One of the best understood feedback mechanisms—renewal control—achieves remarkable feats of robustness in determining and maintaining desired sizes. Yet in a variety of biologically relevant situations, we show that stochastic effects should cause rare but catastrophic failures of renewal control. We define the circumstances under which this occurs and raise the possibility such events account for important non-genetic steps in the development of cancer. We further suggest that the spontaneous stochastic reversal of these events could explain cases of cancer normalization or dormancy following treatment. Indeed, we show that the kinetics of post-treatment recurrence for many cancers are often better fit by a model of stochastic re-emergence due to loss of collective proliferative control, than by deterministic models of cancer relapse.
Transport Cocktails for Cancer Therapeutics
Authors: Kavousanakis Michail E. , Bhatavdekar Omkar , Bastiaannet Remco , Kevrekidis Yannis , Sofou Stavroula
Published: January 2024

Beyond biological cell heterogeneity, evidenced by different resistances to therapeutics, “delivery heterogeneity” crucially limits treatment efficacy for advanced solid tumors: variations in therapeutic drug delivery to different tumor areas (perivascular, perinecrotic) leading to nonuniform drug concentrations/doses and to unsuccessful treatment (cancer cell kill). Short-range (40-80 µm), high energy (1-5 MeV) alpha-particles successfully address the biological heterogeneity: the double-strand DNA breaks they cause make them impervious to cell resistance mechanisms. Multiresponsive nanocarriers and/or engineered antibody-drug-conjugates are elegant approaches to delivering such alpha-particle emitters. Delivery heterogeneity, however, remains a challenge in established (i.e. large, vascularized) tumors. Remarkably, delivery properties enabling efficacy at the cell scale (targeting selectivity, affinity, cell drug uptake) may act against spatial delivery uniformity at the tumor scale (binding-site barrier effect1). We have previously demonstrated, in different mouse models, that spatial delivery uniformity, key to the effective killing of solid tumors, can be achieved utilizing combinations of different, distinct delivery carriers of the same emitter, but with different, complementary delivery properties, “leaving no cancer cell behind”. We build first principles reaction-transport models (quantitatively informed by experiments) that explain the “geographically complementary” behaviors of such carrier cocktails, and help optimally design these cocktails and their delivery protocols.
Exploring phenotypic diversity: a comparative analysis of cichlid convergence
Authors: Leal-Cardín Mariana , Bracamonte Seraina E. , Aldegunde Javier , Hudson Alan , Magalhaes Isabel S. , Ornelas-García Claudia Patricia , Barluenga Marta
Published: January 2024

Convergent evolution of similar phenotypes suggests some predictability in the evolutionary trajectories of organisms, due to strong and repeated selective pressures, and/or developmental constraints. In adaptive radiations, particularly in cichlid fish radiations, convergent phenotypes are commonly found within and across geographical settings. There are some main axes of cichlid morphological diversification. Recurrent changes in body patterns reveal adaption to alternative habitats, and modifications of the trophic apparatus respond to the exploitation of different food resources. Here we compare two Neotropical cichlid assemblages, the Mexican desert cichlid, and the Nicaraguan Midas cichlid, with similar polymorphic body and trophic apparatus patterns despite their independent evolution and evaluate morphological and gene expression convergence and divergence. We found a single morphological axis of differentiation in pharyngeal jaws with equivalent papilliform and molariform morphotypes in both cichlid radiations. In contrast, we found two different axes of differentiation in the shape of the body, defining two alternative limnetic body patterns. Genetic differences between morphotypes seem to be specific to each radiation, with no clear patterns of convergence.
Brain-phenotype predictions can survive across diverse real-world data
Authors: Adkinson Brendan D. , Rosenblatt Matthew , Dadashkarimi Javid , Tejavibulya Link , Jiang Rongtao , Noble Stephanie , Scheinost Dustin
Published: January 2024

Recent work suggests that machine learning models predicting psychiatric treatment outcomes based on clinical data may fail when applied to unharmonized samples. Neuroimaging predictive models offer the opportunity to incorporate neurobiological information, which may be more robust to dataset shifts. Yet, among the minority of neuroimaging studies that undertake any form of external validation, there is a notable lack of attention to generalization across dataset-specific idiosyncrasies. Research settings, by design, remove the between-site variations that real-world and, eventually, clinical applications demand. Here, we rigorously test the ability of a range of predictive models to generalize across three diverse, unharmonized samples: the Philadelphia Neurodevelopmental Cohort (n=1291), the Healthy Brain Network (n=1110), and the Human Connectome Project in Development (n=428). These datasets have high inter-dataset heterogeneity, encompassing substantial variations in age distribution, sex, racial and ethnic minority representation, recruitment geography, clinical symptom burdens, fMRI tasks, sequences, and behavioral measures. We demonstrate that reproducible and generalizable brain-behavior associations can be realized across diverse dataset features with sample sizes in the hundreds. Results indicate the potential of functional connectivity-based predictive models to be robust despite substantial inter-dataset variability. Notably, for the HCPD and HBN datasets, the best predictions were not from training and testing in the same dataset (i.e., cross-validation) but across datasets. This result suggests that training on diverse data may improve prediction in specific cases. Overall, this work provides a critical foundation for future work evaluating the generalizability of neuroimaging predictive models in real-world scenarios and clinical settings.
Systemic SARS-CoV-2-specific antibody responses to infection and to COVID-19 and BCG vaccination
Authors: Claus Juana , ten Doesschate Thijs , Taks Esther , Debisarun Priya , Smits Gaby , van Binnendijk Rob , van der Klis Fiona , Verhagen Lilly M. , de Jonge Marien I. , Bonten Marc J.M. , Netea Mihai G. , van de Wijgert Janneke H. H. M.
Published: January 2024

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomized to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/ml, 955.0 IU/ml, and 2290.9 IU/ml for one, two, and three immune events, respectively (p<0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10concentrations were significantly associated with infection severity, and anti-S1 log10concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with Long COVID or long-term loss of smell/taste.