bluuebunny/crossref_metadata_2025 huggingface dataset:
Pleomorphic Sarcoma, an Atypical Conjunctival Tumor
Authors: Ortiz Alvaro , Vázquez Emmanuel , Shields Carol
Published: September 2024

Sarcomas are malignant tumors of connective tissue with a mesodermal origin that, in rare occasions, is presented in conjunctiva; undifferentiated pleomorphic sarcoma represents <1% of orbital tumors. It is characterized by not meeting the histologic, immunohistochemical, ultrastructural, or molecular criteria in the classification proposed by the World Health Organization. The authors present the case of an 82-year-old man, blind due to absolute glaucoma, who consulted for a conjunctival mass of a few months’ evolution. He reported progressive enlargement of the left eye, associated with red eye, conjunctival discharge, and foreign body sensation. The patient was examined by the anterior segment department, which decided to biopsy the lesion due to the biomicroscopic aspect. After the diagnosis of a pleomorphic sarcoma by histopathology and immunohistochemistry, enucleation of the eye was decided.
New targets in spontaneous intracerebral hemorrhage
Authors: Chiang Pu-Tien , Tsai Li-Kai , Tsai Hsin-Hsi
Published: September 2024

Purpose of review

Intracerebral hemorrhage (ICH) is a devastating stroke with limited medical treatments; thus, timely exploration of emerging therapeutic targets is essential. This review focuses on the latest strategies to mitigate secondary brain injury post-ICH other than targeting surgery or hemostasis, addressing a significant gap in clinical practice and highlighting potential improvements in patient outcomes.

Recent findings

Promising therapeutic targets to reduce secondary brain injury following ICH have recently been identified, including attenuation of iron toxicity and inhibition of ferroptosis, enhancement of endogenous resorption of hematoma, and modulation of perihematomal inflammatory responses and edema. Additionally, novel insights suggest the lymphatic system of the brain may potentially play a role in hematoma clearance and edema management. Various experimental and early-phase clinical trials have demonstrated these approaches may potentially offer clinical benefits, though most research remains in the preliminary stages.

Continued research is essential to identify multifaceted treatment strategies for ICH. Clinical translation of these emerging targets could significantly enhance the efficacy of therapeutic interventions and potentially reduce secondary brain damage and improve neurological recovery. Future efforts should focus on large-scale clinical trials to validate these approaches, to pave the way for more effective treatment protocols for spontaneous ICH.
Sensory-motor tuning allows generic features of conspecific acoustic scenes to guide rapid, adaptive, call-timing responses in túngara frogs
Authors: Larter Luke C. , Ryan Michael J.
Published: September 2024

Male frogs court females from within crowded choruses, selecting for mechanisms allowing them to call at favourable times relative to the calls of rivals and background chorus noise. To accomplish this, males must continuously evaluate the fluctuating acoustic scene generated by their competitors for opportune times to call. Túngara frogs produce highly frequency- and amplitude-modulated calls from within dense choruses. We used similarly frequency- and amplitude-modulated playback tones to investigate the sensory basis of their call-timing decisions. Results revealed that different frequencies present throughout this species’ call differed in their degree of call inhibition, and that lower-amplitude tones were less inhibitory. Call-timing decisions were then driven by fluctuations in inhibition arising from underlying frequency- and amplitude-modulation patterns, with tone transitions that produced steeper decreases in inhibition having higher probabilities of triggering calls. Interactions between the varied behavioural sensitivities to different conspecific call frequencies revealed here, and the stereotyped amplitude- and frequency-modulation patterns present in this species’ calls, can explain previously surprising patterns observed in túngara frog choruses. This highlights the importance of understanding the specific sensory drivers underpinning conspecific signalling interactions, and reveals how sensory systems can mediate the interplay between signal perception and production to facilitate adaptive communication strategies.
Rickettsia rickettsiiencodes a secretory lipase that facilitates intracytosolic colonization in host cells
Authors: Sadik Mohammad , Moin Imran , Ullah Saif , Sayeedur Rahman M. , Voss Oliver H.
Published: September 2024

The key cellular processes required for rickettsial obligate intracellular lifestyle, include internalization by phagocytosis, regulation of intracellular trafficking, and evasion of lysosomal destruction to establish an intracytosolic replication niche, remain poorly defined. Recent reports showed that rickettsial phospholipases play an important role in vacuolar escape, but their functions are dispensable depending on the host cell-type. Here, we report the identification of a highly conserved putative lipase containing a Serine hydrolase motif (GXSXG), named RLip (RickettsiaLipase). Our work reveals that RLip expression is cytotoxic to yeast cells, a genetically tractable heterologous model system. We demonstrate that RLip possesses lipase enzymatic activity and show a lipid specificity towards phosphoinositide (PI)(3), PI(3,4,5)P3, and PI(3,4)P2, and to a lesser extent PI(4,5)P2. Further, we found that RLip expression is induced during infection of pathogenicR. rickettsii, while its expression is low or undetectable forR. parkeri(mild-pathogenic) andR. montanensis(non-pathogenic), respectively, during host invasion. Intriguingly, RLip is highly enriched in the cytoplasmic fraction of host cells, however, minimally retained by the rickettsiae themselves, suggesting RLip is synthesized during infection and then secreted into the host cell cytoplasm. Neutralization of RLip activity, by antibody-blocking, significantly abrogatedR. rickettsiiescape from bactericidal phagolysosomal fusion, suggesting RLip plays a critical role in facilitating the intracytosolic colonization of pathogenicR. rickettsii.

Importance

Arthropod-borne rickettsial diseases are on the rise globally, presenting a perilous threat to humans and livestock. However, our inadequate understanding on howRickettsiamanipulates cellular processes, including the evasion of lysosomal destruction, has impaired the development of effective therapeutic interventions.

Here, we identify of a conserved putative lipase containing a Serine hydrolase motif, named RLip (RickettsiaLipase). Our work demonstrates that RLip possesses lipase enzymatic activity and is enriched in the cytoplasm of host cells, while minimally retained by the bacteria itself. Neutralization of RLip activity abrogatedR. rickettsiiescape from bactericidal phagolysosomal fusion. In sum, our data support a mechanism by which pathogenicR. rickettsiiemploys RLip to escape from bactericidal phagolysosomal fusion in order to colonize the host.
Drivers of host-pathogen community assemblies in European forests and urban green spaces
Authors: Sluydts Vincent , Bouilloud Marie , Galan Maxime , Alburkat Hussein , Bordes Anaïs , Bourret Vincent , Colombo Valeria , DeBruyn Luc , Dutra Lara , Eccard Jana , Firozpoor Jasmin , Gallet Romain , Grzybek Maciej , Henttonen Heikki , Jacob Jens , McManus Andrew , Sironen Tarja , Stuart Peter , Tatard Caroline , Roche Benjamin , Leirs Herwig , Charbonnel Nathalie
Published: September 2024

Major advances in the understanding of infectious diseases have been achieved in the last decades. However, the persistence and re-emergence of pathogens continue to raise public and veterinary health concerns, of which the recent COVID-19 pandemic may be one of the most dramatic examples. Understanding the impact of habitat alterations and concomitant biodiversity loss on pathogen transmission and emergence from wildlife remains challenging. Here, we aim to elucidate the interlinkages between biodiversity and rodent-borne diseases at local and European scales. We present recently collected host-pathogen data from 21 temperate forest sites and eight urban green spaces throughout five European countries, environments where rodents are abundant and human/domestic animals – wildlife interactions are likely to occur. 3766 specimens were analyzed during the period from 2020 to 2022 comprising 15 different small mammal species. Different organ tissues of each specimen were screened for bacteria by either 16S rRNA amplicon sequencing or specific PCR. The presence of antibodies to different families of viruses was screened using immunofluorescent assays. A multitude of pathogens of zoonotic potential from several genera includingBartonella, Borrelia, Mycoplasma, Anaplasma, Neoehrlichia, Leptospira, Orthohantavirus and Orthopoxvirus were detected at non-negligible prevalence in 11 different terrestrial mammal species. A shift in host community composition was observed along the anthropization gradient with more urban adapters in more anthropized sites. Pathogen richness increased with an increase in host species diversity, following the “host-diversity begets parasite-diversity” hypothesis. The absence of some vector-transmitted parasites in urban areas suggests a shift in pathogen community along the anthropization gradient. Host species and host intrinsic factors were dominant explanatory variables for endoparasiticMycoplasmaspecies andSarcocystidae, while extrinsic environmental and climatic factors where influential in explaining variations in occurrences of several vector-transmitted pathogens.Apodemus sylvaticusandClethrionomys glareoluswere important connector host species in respectively urban green spaces and temperate forests. Increased host diversity, but not anthropization, correlated with a richer pathogen community. These results ultimately lead to an increased understanding of the complex host-pathogen system at the local landscape that can aid future management decisions and support the public health sector.
Validation of a Difference-in-Differences Investigation Tool (DiD IT) for quantifying local outbreaks
Authors: Morbey Roger , Charlett Andre , Todkill Daniel , Elliot Alex J.
Published: September 2024

The Difference-in-Differences Investigation Tool (‘DiD IT’) is a new tool used to estimate the impact of local threats to public health in England. ‘DiD IT’ is part of a daily all hazards syndromic surveillance service. We present a validation of the ‘DiD IT’ tool, using synthetic injects to assess how well it can estimate small, localised increases in the number of people presenting to health care. Furthermore, we assess how control settings within ‘DiD IT’ affect it’s performance.

‘DiD IT’ was validated across ten different syndromic indicators, chosen to cover a range of data volumes and potential public health threats. Injects were added across different times of year and days of week, including public holidays. Also, different size of injects were created, including some with an impact spread to neighbouring locations or spread over several days. The control settings within ‘DiD IT’ were tested by varying the control location and periods, using, for example a ‘washout period’ or excluding nearest neighbours. Performance was measured by comparing the estimates for excess counts produced by ‘DiD IT’ with the actual synthetic injects added.

‘DiD IT’ was able to provide a positive estimate in 99.8% of trials, with a mean absolute error of 1.5. However, confidence intervals for the central estimate could not be produced in 42.5% of trials. Furthermore, the 95% confidence intervals for the central estimates only included the actual inject count within 62.8% of the intervals. Unsurprising, mean errors were slightly higher when synthetic injects were not concentrated in one location on one day but were spread across neighbouring areas or days. Selecting longer control periods and using more locations as controls tended to lower the errors slightly. Including a washout period or excluding neighbouring locations from the controls did not improve performance.

We have shown that ‘DiD IT’ is accurate for assessing the impact of local incidents but that further work is needed to improve the how the uncertainty of these estimates are communicated to users.
Evaluation of Potentially Toxic Elements in Soil and Potential Ecological Risks Generated by Environmental Liabilities in Tacna, Peru
Authors: Cáceda César Julio , Maraza Gisela , de Lourdes Fora Gabriela , Farfan Diana Galeska , Obando Edwin , Chiampo Fulvia , Carpio Milena
Published: September 2024

Environmental liabilities continue to pose an unresolved concern for administrators due to their high potential for ecosystem contamination. This research focuses on assessing the content of potentially toxic elements, the degree of contamination, and potential ecological risks in abandoned mining areas that formerly exploited sulfur and copper. The results showed elevated concentrations of Arsenic (1,102 mg/Kg), Cadmium (271 mg/Kg), Lead (15,961 mg/Kg). The presence of flora, fauna activity, rivers, and rural communities near the mining sites was observed, indicating significant environmental risks. The evaluated mining environmental liabilities (MELs) lack direct responsible parties, thus requiring the Peruvian government to assume remediation responsibilities. To date, no mitigation actions have been taken, primarily due to the absence of a situational diagnosis. Concerning contamination indices, such as the Geoaccumulation Index, Contamination Degree, Pollution Load Index, Contamination Load Coefficient, and Potential Ecological Risk Index, all areas exhibited some form of contamination, indicating high environmental risks. A preliminary risk assessment associated with the presence of mining environmental liabilities has been conducted, marking this research as the first of its kind in the southern region of Peru. This assessment provides administrators with crucial information to establish priorities for implementing remediation plans aimed at reducing pollutant loads. The findings underscore the urgent need for comprehensive contamination assessments and the development of effective management practices, including the implementation of a monitoring program to safeguard soils affected by mining activities. Additionally, it is essential to design various technological strategies to restore degraded ecosystems, thereby protecting rivers, agricultural zones, and nearby rural communities.
Comparison of the Ecological Footprints of administering Salbutamol by Metered-Dose Inhaler and by Nebulization in Emergency Treatment of Acute Asthma
Authors: Berthelot Simon , Ménard Jean-François , Bélanger-Chabot Guillaume , Garcia Gabriela Arias , Mantovani Diego , Simard Chantale , Guertin Jason R. , Marx Tania , Bluteau Ariane
Published: September 2024

Background

The scientific evidence indicates little or no difference in the effectiveness or cost of using of metered-dose inhalers (MDIs) versus nebulization to treat acute asthma in the emergency department (ED). However, the use of MDIs raises questions of environmental impact. The objective of this study was to compare the carbon footprint of salbutamol administered by MDI versus nebulization.

Methods

Applying a life cycle assessment methodology, we quantified the resources extracted and pollutants emitted by each therapeutic option, from the factory production of medication and equipment to disposal by incineration. Each piece of inventory data was then translated into CO2-equivalent emissions (CO2eq) using the IPCC2021/GWP100 method. Results were estimated for the administration of 1 and 3 treatments of 800 µg of salbutamol by MDI and 5 mg by nebulization (standard doses for adults and children ≥ 24 kg) and compared to the use of a subcompact car.

Results

One and three ED-administered treatments with salbutamol emit respectively 1.9 and 4.0 kg of CO2eq via MDI versus 0.9 and 1.0 kg via nebulization, which corresponds to 5.5 km and 11.6 km and to 2.7 km and 2.8 km traveled in a subcompact car. Each series of 8 inhalations from an MDI releases 1.1 kg of CO2eq due to emission of the hydrofluoroalkane propellent.

Interpretation

Considering the absence or minimal difference in clinical effectiveness, this study suggests that nebulization may be a more eco-efficient administration route than MDIs in the emergency treatment of asthma.

Trail registration

N/A

TAKE-HOME POINTS

Study question

What is the ecological footprint of metered-dose inhalers compared to nebulization for administering salbutamol when treating a patient with acute asthma in the emergency department?

Results

Nebulization was found to have half the carbon footprint of 1 MDI administration and one quarter of 3 MDI administrations.

Interpretation

Implementing low-emission treatment protocols for acute asthma should be one of many avenues to explore to achieve net-zero greenhouse gas emissions in healthcare services.
Simultaneous Profiling of the Blood and Gut T and B Cell Repertoires in Crohn’s Disease and Symptomatic Controls Illustrates Tissue-specific Alterations in the Immune Repertoire of Crohn’s Disease Patients
Authors: Mahdy Aya K. H. , Schöpfel Valentina , Huppertz-Hauss Gert , Perminow Gøri , Tran Florian , Bang Corinna , Hov Johannes Roksund , Bengtson May-Bente , Ricanek Petr , Opheim Randi , Aabrekk Tone Bergene , Detlie Trond Espen , Kristensen Vendel A. , Poyet Mathilde , Høivik Marte Lie , Franke Andre , ElAbd Hesham
Published: September 2024

Crohn’sdisease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have shown that the T cell repertoire of CD patients harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. To profile the immunological signature of CD at a high-resolution we simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa for 27 treatment-naïve CD patients and 27 age-matched symptomatic controls. Regardless of disease, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of CD patients relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells in the blood repertoire, an expansion ofTRAV29/DV5-TRAJ5+clonotypes and a significant depletion of multipleIGHV3-33-IGHJ4+andIGHV3-33-IGHJ6+clonotypes in the blood and gut IGH repertoire of CD patients. In conclusion, our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues.
Harnessing multi-output machine learning approach and dynamical observables from network structure to optimize COVID-19 intervention strategies
Authors: Alves Caroline L. , Kuhnert Katharina , Rodrigues Francisco Aparecido , Moeckel Michael
Published: September 2024

The COVID-19 pandemic has necessitated the development of accurate models to predict disease dynamics and guide public health interventions. This study leverages the COVASIM agent-based model to simulate 1331 scenarios of COVID-19 transmission across various social settings, focusing on the school, community, and work contact layers. We extracted complex network measures from these simulations and applied deep learning algorithms to predict key epidemiological outcomes, such as infected, severe, and critical cases. Our approach achieved an R2 value exceeding 95%, demonstrating the model’s robust predictive capability. Additionally, we identified optimal intervention strategies using spline interpolation, revealing the critical roles of community and workplace interventions in minimizing the pandemic’s impact. The findings underscore the value of integrating network analytics with deep learning to streamline epidemic modeling, reduce computational costs, and enhance public health decision-making. This research offers a novel framework for effectively managing infectious disease outbreaks through targeted, data-driven interventions.
Optimizing UK Biobank Cloud Based Research Analysis Platform to Fine Map Coronary Artery Disease Loci in Whole Genome Sequencing Data
Authors: Sng Letitia M.F. , Kaphle Anubhav , O’Brien Mitchell J. , Hosking Brendan , Reguant Roc , Verjans Johan , Jain Yatish , Twine Natalie A. , Bauer Denis C.
Published: September 2024

We conducted the first comprehensive association analysis of a coronary artery disease (CAD) cohort within the recently released UK Biobank (UKB) whole genome sequencing dataset. We employed fine mapping tool PolyFun and pinpointrs10757274 as the most likely causal SNV within the 9p21.3 CAD risk locus. Notably, we show that machine-learning (ML) approaches, REGENIE and VariantSpark, exhibited greater sensitivity compared to traditional single-SNV logistic regression, uncoveringrs28451064 a known risk locus in 21q22.11. Our findings underscore the utility of leveraging advanced computational techniques and cloud-based resources for mega-biobank analyses. Aligning with the paradigm shift of bringing compute to data, we demonstrate a 44% cost reduction and 94% speedup through compute architecture optimisation on UK Biobank’s Research Analysis Platform using our RAPpoet approach. We discuss three considerations for researchers implementing novel workflows for datasets hosted on cloud-platforms, to pave the way for harnessing mega-biobank-sized data through scalable, cost-effective cloud computing solutions.
Lipid Fingerprinting by MALDI Biotyper Sirius Instrument Fails to Differentiate the Three Subspecies of theMycobacterium abscessusComplex
Authors: Yoshida Mitsunori , Fukano Hanako , Yahara Koji , Nakano Satoshi , Komine Takeshi , Suzuki Masato , Fujinaga Azumi , Dohke Kohei , Hoshino Yoshihiko
Published: September 2024

The number of patients suffering fromMycobacterium abscessuscomplex (MABC) pulmonary diseases is steadily increasing. MABC consists of three subspecies, and it is recommended that the three subspecies be distinguished because of their differing macrolide susceptibilities. Unfortunately, current methods are inefficient due to their high cost, complexity, and time requirements. The third-generation Bruker MALDI Biotyper (MBT) Sirius has the capability to detect phospholipids and glycolipids using negative-ion mode. Mycobacterial cell walls are rich in lipids, and if lipid structure diversity can serve as species-specific fingerprints, this method may provide an alternative for microbial identification. This study aimed to examine the accuracy of discriminating between the three MABC subspecies by lipid profiling. Our best model failed to differentiate the three subspecies. Even in the two-dimensional space of the most significant peaks,M. abscessusandM. massiliensecould not be separated. The agreement rate between lipid fingerprint-based and WGS-based identification was, at most, 47.2% for negative-ion mode. Even after applying recent machine learning algorithms to detect variables and create predictive models, accuracy remained at 50%. Our results suggest that using lipid fingerprinting alone to differentiate the three MABC subspecies is currently inadequate. Further advancements and standardization of MALDI-TOF MS-based methods are necessary for the routine differentiation of MABC subspecies in clinical settings.
Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor
Authors: He Shenghong , West Timothy O , Plazas Fernando R , Wehmeyer Laura , Pogosyan Alek , Deli Alceste , Wiest Christoph , Herz Damian M , Simpson Thomas , Andrade Pablo , Baig Fahd , Hart Michael G , Morgante Francesca , FitzGerald James J. , Barbe Michael T , Visser-Vandewalle Veerle , Green Alexander L , Pereira Erlick A , Cagnan Hayriye , Tan Huiling
Published: September 2024

Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the central nervous system, including cerebellar, motor cortex, or peripheral nerves, have also been developed for treating ET, but the clinical outcomes remain inconsistent. Existing studies suggest that pathology in ET may emerge from multiple cortical and subcortical areas, but its exact mechanisms remain unclear. By simultaneously capturing neural activities from motor cortices and thalami, and hand tremor signals recorded via accelerometers in fifteen human subjects who have undergone lead implantations for DBS, we systematically characterized the efferent and afferent cortico-thalamic tremor networks. Through the comparisons of these network characteristics and tremor amplitude between DBS OFF and ON conditions, we further investigated the associations between different tremor network characteristics and the magnitude of DBS effect. Our findings implicate the thalamus, specifically the contralateral hemisphere, as the primary generator of tremor in ET, with a significant contribution of the ipsilateral hemisphere as well. Although there is no direct correlation between the cortico-tremor connectivity and tremor power or reduced tremor by DBS, the strength of connectivity from the motor cortex to the thalamus and vice versa at tremor frequency predicts baseline tremor power and effect of DBS. Interestingly, there is no correlation between these two connectivity pathways themselves, suggesting that, independent of the subcortical pathway, the motor cortex appears to play a relatively distinct role, possibly mediated through an afferent/feedback loop in the propagation of tremor. DBS has a greater clinical effect in those with stronger cortico-thalamo-tremor connectivity involving the contralateral thalamus, which is also associated with bigger and more stable tremor measured with an accelerometer. Interestingly, stronger cross-hemisphere coupling between left and right thalami is associated with more unstable tremor. Together this study provides important insights into a better understanding of the cortico-thalamic tremor generating network and its implication for the development of patient-specific therapeutic approaches for ET.
Fusion of middle ear optical coherence tomography and computed tomography in three ears
Authors: Wang Junzhe , Couvreur Floor , Farrell Joshua D. , Ghedia Reshma , Shoman Nael , Morris David P , Adamson Robert B.A.
Published: September 2024

Importance

Middle ear OCT imaging in patients has not previously been directly compared to a standard of care clinical 3D imaging technology such as CT. This represents the first such comparison and provides new insight into OCT’s capabilities, strengths and limitations.

Objective

To qualitatively compare the capabilities of middle ear OCT to CT in normal and pathological ears on representative slices in co-registered OCT and CT datasets.

Design, Setting, and Participants

One normal middle ear, one ear affected by traumatic injury and one ear with cholesteatoma were imaged with both OCT and high-resolution clinical temporal bone CT. Participants were drawn from the patient population of a tertiary otology clinic. CT and OCT images were aligned using rigid co-registration with manual landmark selection.

Main Outcomes and Measures

Images were analyzed qualitatively for field of view, resolution, shadowing, artefacts, soft tissue and bony tissue contrast and presentation of diagnostically important features.

Results

In the three imaged ears, OCT was capable of visualizing many of the important features indicative of middle ear pathology. When compared to CT, OCT was found to exhibit a limited field of view (FOV) largely confined to the mesotympanum and subject to shadowing from bony structures. However, OCT could resolve soft tissue features that were not readily apparent in the CT images, to have a higher resolution than CT and to provide excellent anatomical fidelity with CT which allowed OCT images to be accurately co-registered with CT images.

Conclusions and Relevance

The results support a role for middle ear OCT in otological diagnostics. While OCT is not capable of replacing CT due to its limited FOV and inability to image through thick bony tissues, it can visualize many signs of pathology including some soft tissue features that are difficult to visualize with CT. Given OCT’s ability to image in real-time, its compatibility with in-office imaging and its lack of ionizing radiation, it may, despite its limitations compared to CT, be an appealing imaging modality for many applications in middle ear diagnostics.

Key Points

Question (1 sentence)

What are the strengths and limitations of middle ear optical coherence tomography (OCT) imaging compared to computed tomography (CT) in real-world clinical imaging scenarios?

Finding (1-2 sentence)

OCT and CT imaging produce complementary diagnostic information with CT offering unobstructed images of bony anatomy and OCT providing the ability to visualize soft tissue.

Meaning (1 sentence)

OCT, CT and fused OCT/CT imaging can each provide useful, complementary diagnostic information in clinical otology.
Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women
Authors: Ansah Emmanuel Owusu , Kyei Foster , Opoku Caleb Frimpong , Danquah Andrews , Fosu Kwadwo , Agyenim Emmanuel Boateng , Agyirifo Daniel Sakyi
Published: September 2024

Blood lipids are associated with breast cancer. An increasing number of reports have attempted to explore the genetic connection between blood lipids and the risk of developing breast cancer. However, observational studies can be affected by confounding factors and reverse causation, which can compromise the reliability of the findings. We used univariate and multivariable two-sample mendelian randomization to explore the causal association between blood lipids and breast cancer. Summary-level data for lipid traits were obtained from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N= 10,603, 58.5% of women). For breast cancer, we leveraged summary statistics from the most comprehensive Genome-wide Association Studies (GWAS) on breast cancer consisting of 18,034 cases and 22,104 controls of women of African ancestry. Our analysis suggests that genetically predicted triglycerides had a potential protective effect on breast carcinoma (OR = 0.73, 95% CI = 0.56, 0.95, FDR = 0.001). We found no evidence that genetically elevated levels of TC, HDL, and LDL may be associated with the risk of breast cancer TC (OR = 1.04; 95% CI, 0.93, 1.18;FDR= 0.029); HDL (OR = 1.29, 95% CI = 0.93, 1.79, FDR = 0.008); LDL (OR = 1.04, 95% CI = 0.90, 1.20, FDR = 0.036). Multivariate mendelian randomization analysis, which adjusted for the effects of TG, TC, LDL, and HDL, attenuated the observation of TG and breast cancer and also found no relationship between TC, HDL, LDL, and breast cancers. Furthermore, there was no evidence for a causal association between lipid traits and breast cancer subtypes. Our findings were robust in several sensitivity analyses. This study provides strong evidence that circulating TG may be associated with a decreased risk of breast cancer, while TC, LDL and HDL may not be related to the risk of breast cancer among African women.
Awareness about the risk of hearing loss after ototoxic treatments in Swiss childhood cancer survivors
Authors: Jörger Philippa , Nigg Carina , Žarković Maša , Sommer Grit , Kompis Martin , Michel Gisela , Ansari Marc , Waespe Nicolas , Kuehni Claudia E.
Published: September 2024

Objectives

The International Guideline Harmonization Group recommends childhood cancer survivors (CCS) exposed to ototoxic treatments be aware of the risk of hearing loss. We assessed awareness among adult CCS.

Methods

We identified adults diagnosed with cancer <20 years who received ototoxic treatments through the Swiss Childhood Cancer Registry (ChCR) and invited them to the HEAR-study. Participants completed a questionnaire and underwent pure-tone audiometry. Cancer and treatment data came from the ChCR. We used logistic regression to explore factors influencing awareness.

Results

105 of 424 invited CCS participated (25%). 57% did not remember receiving information on hearing loss prior to the study. CCS who remembered being informed were more likely diagnosed after 1995 (OR: 4.5, 95% CI: 1.3-15.4), reported hearing problems (10.9, 2.6-45.1) and other late effects (4.1, 1.3-13.2), and treated with platinum chemotherapy only (10.8, 2.2-53.2) versus cranial radiotherapy only. 44% of participants presented clinically relevant hearing loss.

Conclusions

Over half of CCS exposed to ototoxic treatments were unaware of their risk of hearing loss.

Practice Implications

Educating CCS about potential late effects of ototoxic treatments is important to allow early diagnosis and treatment, especially for those who had cancer longer ago and those exposed to cranial radiation.

Highlights

Half of CCS exposed to ototoxic treatment were unaware of the risk of hearing loss

CCS treated before 1995 were less aware about the risk of hearing loss

Information provision is key to effective monitoring and early intervention
Integrating Kolmogorov-Arnold Networks with Ordinary Differential Equations for Efficient, Interpretable and Robust Deep Learning: A Case Study in the Epidemiology of Infectious Diseases
Authors: Ma Kexin , Lu Xu , Bragazzi Nicola Luigi , Tang Biao
Published: September 2024

In this study, we extend the universal differential equation (UDE) framework by integrating Kolmogorov-Arnold Network (KAN) with ordinary differential equations (ODEs), herein referred to as KAN-UDE models, to achieve efficient and interpretable deep learning for complex systems. Our case study centers on the epidemiology of emerging infectious diseases. We develop an efficient algorithm to train our proposed KAN-UDE models using time series data generated by traditional SIR models. Compared to the UDE based on multi-layer perceptrons (MLPs), training KAN-UDE models shows significantly improves fitting performance in terms of the accuracy, as evidenced by a rapid and substantial reduction in the loss. Additionally, using KAN, we accurately reconstruct the nonlinear functions represented by neural networks in the KAN-UDE models across four distinct models with varying incidence rates, which is robustness in terms of using a subset of time series data to train the model. This approach enables an interpretable learning process, as KAN-UDE models were reconstructed to fully mechanistic models (RMMs). While KAN-UDE models perform well in short-term prediction when trained on a subset of the data, they exhibit lower robustness and accuracy when real-world data randomness is considered. In contrast, RMMs predict epidemic trends robustly and with high accuracy over much longer time windows (i.e., long-term prediction), as KAN precisely reconstructs the mechanistic functions despite data randomness. This highlights the importance of interpretable learning in reconstructing the mechanistic forms of complex functions. Although our validation focused on the transmission dynamics of emerging infectious diseases, the promising results suggest that KAN-UDEs have broad applicability across various fields.
Longitudinal Monitoring of Glioblastoma Small Extracellular Vesicle Evolution Using a Nanodiagnostic to Detect Emergence of Glioma Stem Cells Driving Recurrent Disease
Authors: Zhang Zhen , Lobb Richard J , Tooney Paul , Wang Jing , Lane Rebecca , Zhou Quan , Niu Xueming , Faulkner Sam , Day Bryan W , Puttick Simon , Rose Stephen , Fay Mike , Trau Matt
Published: September 2024

Assessing therapeutic response in glioblastoma (GBM) is a major factor limiting the clinical development of new and effective therapies. The intracranial location limits serial biopsies, and only provides an intermittent view of the tumor molecular profile from the initial resection. Liquid biopsy techniques, specifically small extracellular vesicle (sEV) analysis, have the potential to overcome these limitations by providing a window into the brain using peripheral blood. To address the need for monitoring tumor evolution and therapeutic resistance, we developed a GBM biomarker panel (ATP1B2, EAAT2, CD24, CD44, CD133 and EGFR) for multiplexed profiling of sEVs using an advanced GBM Extracellular vesicle Monitoring Phenotypic Analyzer Chip (GEMPAC). We successfully tracked patient response to treatment by monitoring changes in glioma stem cell markers on circulating sEVs. We propose that these results provide a strong rationale for using GBM sEVs as a serial monitoring tool in the future clinical management of GBM patients.
WITHDRAWN: Comprehensive Analysis of Theoretical Models and Frameworks for Investigating Determinants of Breast Cancer Screening Participation: A Scoping Review
Authors: Zheng Dandan , Sriyuktasuth Aurawamon , Lekdamrongkul Pichitra
Published: September 2024

Withdrawal Statement

“The authors have withdrawn this manuscript because of erroneous data, with potential implications of academic misconduct. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.”
Climate Adaptation and Genetic Differentiation in the Mosquito SpeciesCulex tarsalis
Authors: Liao Yunfei , Islam Touhid , Noorai Rooksana , Streich Jared , Saski Christopher , Cohnstaedt Lee W. , Cooper Elizabeth A.
Published: September 2024

The increasing prevalence of vector-borne diseases around the world highlights the pressing need for an in-depth exploration of the genetic and environmental factors that shape the adaptability and widespread distribution of mosquito populations. This research focuses onCulex tarsalis, a principal vector for various viral diseases including West Nile Virus (WNV). Through the development of a new reference genome and the examination of Restriction-Site Associated DNA sequencing (RAD-seq) data from over 300 individuals and 28 locations, we demonstrate that variables such as temperature, evaporation rates, and the density of vegetation significantly impact the genetic makeup ofCx. tarsalispopulations. Among the alleles most strongly associated with environmental factors is a nonsynonymous mutation in a key gene related to circadian rhythms. These results offer new insights into the mechanisms of spread and adaptation in a key North American vector species, which is poised to become a growing health threat to both humans and animals in the face of ongoing climate change.
Dynamics of microglia-glioblastoma crosstalk at the far infiltration zone
Authors: Nebeling Felix C. , Fuhrmann Falko , Mittag Manuel , Musacchio Fabrizio , Gockel Nala E. , Friker Lea L. , Leonardelli Sonia , Filser Severin , Deli A , Stork Miriam , Bano Daniele , Pietsch Torsten , Parrinello Simona , Hoelzel Michael , Herrlinger Ulrich , Salomoni Paolo , Fuhrmann Martin
Published: September 2024

The interaction of glioblastoma (GB) and microglia is critical due to its implications for tumor progression, immune response modulation, and potential therapeutic strategies. However, the role of microglia in GB pathogenesis remains unclear, especially regarding the in vivo dynamics of their interplay. Performing three-photon imaging in an autochthonous, immunocompetent mouse GB model, we examined tumor/microglia dynamics within previously inaccessible regions at the GB far infiltration zone in the corpus callosum. Initially, microglia increased tissue surveillance upon encountering GB-cells in sparsely infiltrated areas. In contrast, when GB-cell density increased, microglia reduced surveillance, suggesting a biphasic response to tumor invasion. Additionally, microglia were not uniformly attracted to infiltrating GB-cells; only a subset moved directionally toward them within a defined spatial range. This study provides insight into the heterogeneity of the immune response to tumor invasion and the dynamics of microglia-GB interactions in vivo.
Camera Paths, Modeling, and Image Processing Tools for ArtiaX
Authors: Ermel Utz H. , Moser Deborah , Roth Pauline , Arctaedius Gunnar , Wehrheim Maren , Scheffer Margot P. , Frangakis Achilleas S.
Published: September 2024

The enhancement of biomolecular image analysis and data interpretation is significantly improved through the application of advanced visualization techniques. Numerous visualization packages are currently available, spanning a broad spectrum of applications. Recently, we have extended the capabilities of UCSF ChimeraX to address the specific demands of cryo-electron tomography. Here, we introduce the evolution of our existing plugin, ArtiaX, designed to generate models that facilitate particle selection, define camera recording paths, and execute particle selection routines. In particular, diverse models can be generated and populated with putative particle positions and orientations. A specifically tailored coarse grained algorithm was developed to rectify overlaps, as encountered in template matching, employing a rapid and efficient approach. In addition, models can be used to drive the camera position, thereby simplifying the process of movie creation. The plugin incorporates fundamental image filtering options for the on-the-fly analysis of tomographic data and also provides compatibility of particle lists with RELION-5 star files. Collectively, this update of ArtiaX comprehensively encompasses essential tools for the analysis and visualization of electron tomograms. It retains its hallmark attributes of speed, reliability, and user-friendliness, fostering seamless human-machine interaction.
GRAS Family Transcription Factor Binding Behaviors in Sorghum bicolor, Oyrza, and Maize
Authors: Gladman Nicholas , Kumari Sunita , Fahey Audrey , Regulski Michael , Ware Doreen
Published: September 2024

Identifying non-coding regions that control gene expression has become an essential aspect of understanding gene regulatory networks that can play a role in crop improvements such as crop manipulation, stress response, and plant evolution. Transcription Factor (TF)-binding approaches can provide additional valuable insights and targets for reverse genetic approaches such as EMS-induced or natural SNP variant screens or CRISPR editing techniques (e.g. promoter bashing). Here, we present the first ever DAP-seq profiles of three GRAS family TFs (SHR, SCL23, and SCL3) in the cropSorghum bicolor,Oryza sativa japonica, andZea mays. The binding behaviors of the three GRAS TFs display unique and shared gene targets and categories of previously characterized DNA-binding motifs as well as novel sequences that could potentially be GRAS family-specific recognition motifs. Additional transcriptomic and chromatin accessibility data further facilitates the identification of root-specific GRAS regulatory targets corresponding to previous studies. These results provide unique insights into the GRAS family of TFs and novel regulatory targets for further molecular characterization.
scParadise: Tunable highly accurate multi-task cell type annotation and surface protein abundance prediction
Authors: Chechekhina Elizaveta , Tkachuk Vsevolod , Chechekhin Vadim
Published: September 2024

scRNA-seq is revolutionizing biomedical research by revealing tissue architecture, cellular composition, and functional interactions. However, accurate cell type annotation remains a challenge, particularly for rare cell types, with existing automated methods often falling short. Multimodal data, combining mRNA expression and protein markers, improves deep cellular analysis and make functional characterization of complex tissues more accurate. However, it is costly and complex to obtain. We presentscParadise, a cutting-edge Python framework featuring three tools:scAdamfor multi-level cell annotation,scEvefor surface protein prediction, andscNoahfor benchmarking. scAdam surpasses current methods in annotating rare cell types and ensures consistent results across diverse datasets, while scEve enhances clustering and cell type separation. With scNoah’s advanced metrics, scParadise offers a powerful, fast, and reliable solution for single-cell analysis, setting a new standard in scRNA-seq data processing.
Ancient polyploidy and low rate of chromosome loss explain the high chromosome numbers of homosporous ferns
Authors: Li Zheng , Kinosian Sylvia P. , Zhan Shing H. , Barker M. S.
Published: September 2024

A longstanding question in plant evolution is why ferns have many more chromosomes than angiosperms. The leading hypothesis proposes that ferns have ancient polyploidy without chromosome loss or gene deletion to explain the high chromosome numbers of ferns. Here, we test this hypothesis by estimating ancient polyploidy frequency, chromosome evolution, protein evolution in meiosis genes, and patterns of gene retention in ferns. We found similar rates of paleopolyploidy in ferns and angiosperms from independent phylogenomic and chromosome number evolution analyses, but lower rates of chromosome loss in ferns. We found elevated evolutionary rates in meiosis genes in angiosperms, but not in ferns. Finally, we found some evidence of parallel and biased gene retention in ferns, but this was comparatively weak to patterns in angiosperms. This work provides genomic evidence supporting a decades-old hypothesis on fern genome evolution and provides a foundation for future work on plant genome structure.
in vitroanalysis of a competitive inhibition model for T7 RNA polymerase biosensors
Authors: Delaney Ryan , Lamb Katherine A. , Irvin Olivia M. , Baumer Zachary T. , Whitehead Timothy A.
Published: September 2024

T7 RNA polymerase (T7 RNAP) biosensors, in which T7 RNAP transcribes some reporter gene or signal in response to external stimuli, have wide applications in synthetic biology and metabolic engineering. We adapted a biochemical reaction network model and used anin vitrotranscription assay to determine network parameters for different T7 RNAP constructs. Under conditions where template DNA is limiting, the EC50values of native and engineered T7 RNAPs ranged from 33 nM (29 -37 95% c.i.) to 570 nM (258 -714 95% c.i.) (wild-type T7 RNAP). The measured EC50values were largely insensitive to free magnesium, pH, or other buffer conditions. Many biosensor configurations use a split RNAP construct, where the C-terminal (CT7) and N-terminal T7 (NT7) are fused to proximity induced dimerization modules. We used proteolysis and ion exchange chromatography to prepare a CT7 (80 kDa) product. The impact of free CT7 on T7 RNAP transcriptional activity was well described by a competitive inhibition model, with an inhibitory constant KI= 24 nM (22-26 95% c.i.) of the sensor. These model parameters will be useful for forward modeling and design of T7 RNAP-based genetic circuits.

Highlights

EC50values for natural and engineered T7 RNAPs measured in vitro

C-terminal T7 RNAP is a competitive inhibitor of full-length T7 RNAP

The inhibition constant of C-terminal T7 RNAP is lower than the EC50of T7 RNAP