bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in the diagnosis and treatment of the malignant adnexal neoplasms of the head and neck
Authors: Wierzbicka Małgorzata , Kraiński Patryk , Bartochowska Anna 
Published: March 2023

Purpose of review
The current review is to present the current knowledge regarding epidemiology, diagnostics, and management of malignant adnexal neoplasms (MANs).

Recent findings
Immunotherapy and gene-related therapies are still being developed as the methods of salvage treatment in advanced and disseminated cases: CACNA1S, ATP2A1, RYR1, and MYLK3, as well as p53 or the JAK/STAT pathways, may be therapeutic targets; the efficiency of talimogene laherparepvec and nivolumab is assessed.

Summary
MANs are rare tumors, but due to the aging of population their incidence is increasing. Their clinical presentation is unspecific, which makes the diagnosis challenging. Histopathological assessment is difficult even for experienced pathologists. Mohs micrographic surgery or wide local excision are recommended to treat primary lesions. Adjuvant radiotherapy may be beneficial in case of insufficient or positive surgical margins, in nodal metastases, in selected types of MANs like sebaceous, trichilemmal, and pilomatrix carcinomas, and as the induction treatment in large tumors located in medically fragile or cosmetically important regions. The role of chemotherapy is not well defined; however, it is recommended in distant metastases. Immunotherapy can improve the prognosis in advanced stage of the disease.
Cardiovascular and Thyroid Late Effects in Pediatric Patients With Hodgkin Lymphoma Treated With ABVD Protocol
Authors: Ali Nesreen , Selim Mustafa , Salah Zeinab , El Nabarawy Nahla M. , Hussein Hany , Sidhom Iman 
Published: March 2023

Background:
Hodgkin lymphoma (HL) survivors are at risk of developing a range of therapy-related complications. The goal of this study is to investigate therapy-related late-effects in HL survivors.

Materials and Methods:
We performed a cross-sectional study on 208 HL survivors who were treated at the National Cancer Institute or at the Children Cancer Hospital Egypt with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy.

Results:
Age at diagnosis ranged from 2.5 to 17.5 with a median of 8.7 years. The cumulative incidence of cardiac toxicity at 5 and 9 years were 18.7%±2.7% and 43.3%±4.4%, respectively. Preexisting cardiac abnormalities, cumulative anthracycline dose, and end of treatment cardiac status are strong predictors of late cardiotoxicity. Hypertension was observed in ~31% of patients. Young age and obesity at the time of treatment are important risk factors for hypertension. Thyroid abnormalities developed with a 5-year cumulative incidence of 2%±1%, whereas at 9 years the cumulative incidence was 27.9%±4.5%. Thyroid dysfunction was observed in 21.2% and thyroid tumors in 1.6% of cases. Subclinical hypothyroidism was the most common thyroid abnormality.

Conclusions:
Cardiotoxicity, hypertension, and thyroid dysfunction are frequent late effects after doxorubicin, bleomycin, vinblastine, and dacarbazine regimen, especially if combined with radiation therapy.
Improvements and Residual Limitations Experienced by Patients with Guillain-Barré Syndrome Undergoing Inpatient Rehabilitation
Authors: Andrews Addison Williams , Bohannon Richard Wallace 
Published: March 2023

ABSTRACT
The purposes of this study were to: 1) describe the level of functional independence of patients with Guillain-Barré Syndrome (GBS) before and after inpatient rehabilitation (IPR), 2) determine whether the level of functional independence increased in each functional domain during IPR, and 3) determine whether independence at the end of IPR differed significantly between domains. Data from patients with GBS discharged from IPR settings in 2019 were obtained from the Uniform Data System for Medical Rehabilitation® database. The primary variables analyzed were paired, dichotomous variables of the number of patients who achieved full independence in the admission and discharge scores for the activities that comprise the domains, subscales, and total of the Functional Independence Measure. All patients admitted to IPR required assistance with at least one if not several domains of function, motor as well as cognitive. By the end of the IPR stay, for each domain of function, significantly more patients were independent (p < 0.0001). Independence at the end of IPR differed significantly between domains (p < 0.0001); more patients achieved independence in the communication (87.5%) and social cognition (74.8%) domains while fewer patients achieved independence in the self-care (35.9%), transfers (34.2%), and locomotion domains (24.7%).
Successful Implementation of Workflow-Embedded Clinical Pathways During the COVID 19 Pandemic
Authors: Wendel Sarah K. , Bookman Kelly , Holmes Molly , Wiler Jennifer L. 
Published: March 2023

Background and Objectives:
Clinical pathways have been found effective for improving adherence to evidence-based guidelines, thus providing better patient outcomes. As coronavirus disease-2019 (COVID-19) clinical guidance changed rapidly and evolved, a large hospital system in Colorado established clinical pathways within the electronic health record to guide clinical practice and provide the most up-to-date information to frontline providers.

Methods:
On March 12, 2020, a system-wide multidisciplinary committee of specialists in emergency medicine, hospital medicine, surgery, intensive care, infectious disease, pharmacy, care management, virtual health, informatics, and primary care was recruited to develop clinical guidelines for COVID-19 patient care based on the limited available evidence and consensus. These guidelines were organized into novel noninterruptive digitally embedded pathways in the electronic health record (Epic Systems, Verona, Wisconsin) and made available to nurses and providers at all sites of care. Pathway utilization data were analyzed from March 14 to December 31, 2020. Retrospective pathway utilization was stratified by each care setting and compared with Colorado hospitalization rates. This project was designated as a quality improvement initiative.

Results:
Nine unique pathways were developed, including emergency medicine, ambulatory, inpatient, and surgical care guidelines. Pathway data were analyzed from March 14 to December 31, 2020, and showed that COVID-19 clinical pathways were used 21 099 times. Eighty-one percent of pathway utilization occurred in the emergency department setting, and 92.4% applied embedded testing recommendations. A total of 3474 distinct providers employed these pathways for patient care.

Conclusions:
Noninterruptive digitally embedded clinical care pathways were broadly utilized during the early part of the COVID-19 pandemic in Colorado and influenced care across many care settings. This clinical guidance was most highly utilized in the emergency department setting. This shows an opportunity to leverage noninterruptive technology at the point of care to guide clinical decision-making and practice.
Ultra-High-Resolution Photon-Counting CT Imaging of the Chest
Authors: Remy-Jardin Martine , Hutt Antoine , Flohr Thomas , Faivre Jean-Baptiste , Felloni Paul , Khung Suonita , Remy Jacques 
Published: March 2023

AbstractAfter a decade of preclinical testing, photon-counting computed tomography (PCCT) has now entered daily routine, enabling radiologists to start investigating thoracic disorders in unprecedented conditions. The improved spatial resolution of the ultra-high-resolution (UHR) scanning mode is a major step for the analysis of bronchopulmonary disorders, making abnormalities at the level of small anatomical structures such as secondary pulmonary lobules accessible to radiologists. Distal divisions of pulmonary and systemic vessels also benefit from UHR protocols as alterations of lung microcirculation were previously excluded from confident analysis with energy-integrating detector CT. Although noncontrast chest CT examinations were the initial target of UHR protocols, the clinical value of this mode is also applicable to chest CT angiographic examinations with improved morphological evaluation and higher-quality lung perfusion imaging. The clinical benefits of UHR have been evaluated in initial studies, allowing radiologists to foresee the field of future applications, all combining high diagnostic value and radiation dose reduction. The purpose of this article is to highlight the technological information relevant to daily practice and to review the current clinical applications in the field of chest imaging.
Dosing of convalescent plasma and hyperimmune anti-SARS-CoV-2 immunoglobulins: a phase I/II dose finding study
Authors: Huygens Sammy , Preijers Tim , Swaneveld Francis H. , Budde Ilona Kleine , GeurtsvanKessel Corine H. , Koch Birgit C.P. , Rijnders Bart J.A. 
Published: March 2023

AbstractBackgroundDuring the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing neutralizing antibody (Nab) titers following the administration of ConvP or hyperimmune globulins(COVIg).MethodsImmunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination received a range of anti-SARS-CoV-2 antibodies in the form of COVIg or ConvP infusion. The popPK analysis was performed using NONMEM v7.4. Monte Carlo simulations were performed to assess potential COVIg and ConvP dosing regimens for prevention of COVID-19.Results44 patients were enrolled, and data from 42 were used for constructing the popPK model. A two-compartment elimination model with mixed residual error best described the Nab-titers after administration. Inter individual variation was associated to CL (44.3%), V1 (27.3%), and V2 (29.2%). Lean body weight and type of treatment (ConvP/COVIg) were associated with V1 and V2, respectively. Median elimination half-life was 20 days (interquartile-range: 17–25 days). Simulations demonstrated that even monthly infusions of 600ml of the ConvP or COVIg used in this trial would not achieve potentially protective serum antibody levels for >90% of the time. However, as a result of hybrid immunity and/or repeated vaccination plasma donors with extremely high Nab-titers are now readily available, and a >90% target attainment should be possible.ConclusionThe results of this study may inform future intervention studies on the prophylactic and therapeutic use of antiviral antibodies in the form of ConvP or COVIg.
Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma
Authors: Joulia Régis , Puttur Franz , Stölting Helen , Traves William J. , Entwistle Lewis J. , Voitovich Anastasia , Martín Minerva Garcia , Al-Sahaf May , Bonner Katie , Scotney Elizabeth , Molyneaux Philip L. , Hewitt Richard J. , Walker Simone A. , Yates Laura , Saglani Sejal , Lloyd Clare M. 
Published: March 2023

AbstractAllergic asthma generally starts during early life and is linked to substantial tissue remodelling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLS), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MCs) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-Cadherin. Furthermore, spatial transcriptomics of paediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodelling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.
Spatiotemporal mapping of the contractile and adhesive forces sculpting earlyC. elegansembryos
Authors: Yamamoto Kazunori , Ichbiah Sacha , Perez Matthieu , Borrego-Pinto Joana , Delbary Fabrice , Goehring Nate , Turlier Hervé , Charras Guillaume 
Published: March 2023

SummaryEmbryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging due to difficulties in measuring temporal changes in tensions. Here, we characterise the spatiotemporal changes in cellular tensions shaping the early nematode embryo using AFM, live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that calibrates relative inferred tensions temporally using cortical myosin enrichment and absolute tensions using AFM measurements. Applied to embryos within their native shell, we infer a spatiotemporal map of absolute tensions, revealing that ABa, ABp, and EMS compaction is driven by increased tension at free surfaces, while P2’s initial exclusion is due to high tension at intercellular contacts. We uncover a direct and non-affine contribution of cadherins to cell-cell contact tension, comparable to cadherins’ indirect contribution via actomyosin regulation.HighlightsP lineage cells have lower cortical tensions than AB lineage cellsEnrichment of Myosin-II at the cell cortex is a good predictor of cell-medium tension but is not sufficient to determine tension at cell-cell contacts.Myosin-informed tension inference allows determination of the spatiotemporal evolution of all surface tensions within the embryo.ABa, ABp, and EMS compact due to high tensions at their cell-medium interfaces compared to their cell-cell interfaces, while P2is initially excluded due to high cell-cell contact tensions.Cadherins contribute directly in a non-linear way by reducing cell-cell contact tension by nearly 50%.Open AccessFor the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.
STORM imaging buffer with refractive index matched to standard immersion oil
Authors: Lee Youngseop , Lee Yeunho , Lee Minchol , Koo Donghoon , Kim Dongwoo , Lee Kangwon , Kim Jeongmin 
Published: March 2023

AbstractStochastic optical reconstruction microscopy (STORM) provides exceptional super-resolution imaging by sparsely blinking individual dye molecules in thiol-containing media. STORM is now well-established for imaging thin biological specimens, and recent technological advancements have expanded its use to thick tissues. While the use of mounting media with an oil refractive index has been shown to reduce light scattering within tissues and thus greatly improve imaging depth and resolution in optical microscopy, the refractive index of STORM imaging buffers is typically water-like and oil-index (OI) buffers have never been considered for this purpose. In this study, we report a 3-pyridinemethanol-based STORM buffer that matches the refractive index of standard immersion oil. Our OI buffer exhibits similar superior performance in terms of photoswitching of Alexa Flour 647 dye and STORM image quality in fixed cells as conventional STORM buffers, despite having a completely different refractive index. Interestingly, it shows remarkable stability for at least 25 days, and potentially longer, which will enable STORM imaging of a large number of cells on a single prepared slide, as well as larger field-of-view imaging through multiple field stitching. By achieving perfect index matching with oil immersion objectives, OI buffers can produce accurate nanoscale morphology of thin biological specimens, without the need for complex microscope calibrations across sample depth. More importantly, our STORM buffer is expected to play a crucial role in lightsheet STORM applications for thick tissues by reducing light scattering, thereby leading to improved imaging depth and localization performance.
Operant training for highly palatable food alters translating mRNA in nucleus accumbens D2 neurons and reveals a modulatory role ofNeurochondrin
Authors: Montalban Enrica , Giralt Albert , Taing Lieng , Nakamura Yuki , Pelosi Assunta , Brown Mallory , de Pins Benoit , Valjent Emmanuel , Martin Miquel , Nairn Angus C. , Greengard Paul , Flajolet Marc , Hervé Denis , Gambardella Nicolas , Roussarie Jean-Pierre , Girault Jean-Antoine 
Published: March 2023

ABSTRACTBACKGROUNDHighly palatable food triggers behavioral alterations reminiscent of those induced by addictive drugs. These effects involve the reward system and dopamine neurons, which modulate neurons in the nucleus accumbens (NAc). The molecular mechanisms underlying the effects of highly palatable food on feeding behavior are poorly understood.METHODSWe studied the effects of 2-week operant conditioning of mice with standard or isocaloric highly palatable food. We investigated the behavioral effects and dendritic spine modifications in the NAc. We compared the translating mRNA in NAc neurons identified by the type of dopamine receptors they express, depending on the type of food and training. We tested the consequences of invalidation of an abundant downregulated gene, Ncdn (Neurochondrin).RESULTSOperant conditioning for highly palatable food increases motivation for food even in well-fed mice. In control mice, free access to regular or highly palatable food results in increased weight as compared to regular food only. Highly palatable food increases spine density in the NAc. In animals trained for highly palatable food, translating mRNAs are modified in NAc dopamine D2-receptor-expressing neurons, mostly corresponding to striatal projection neurons, but not in those expressing D1-receptors. Knock-out of Ncdn, an abundant down-regulated gene, opposes the conditioning-induced changes in satiety-sensitive feeding behavior and apparent motivation for highly palatable food, suggesting down-regulation may be a compensatory mechanism.CONCLUSIONSOur results emphasize the importance of mRNA alterations D2 striatal projection neurons in the NAc in the behavioral consequences of highly palatable food conditioning and suggest a modulatory contribution of Ncdn downregulation.
Evolution of pollination-induced plasticity of flower longevity
Authors: Xu Kuangyi 
Published: March 2023

AbstractIn many plants, pollen deposition or removal can lead to early flower senescence, while flowers will live longer when pollination is excluded, and the strength of this pollination-induced plasticity of flower longevity varies across populations. This study builds models to investigate the evolution of the plasticity of flower longevity through group and individual selection under stochastic pollination environments. Generally, stronger plasticity evolves when female and male fitness accrual rates are higher and more volatile, and the evolution of plasticity is also strongly affected by daily maintenance cost of flowers relative to construction costs. Group selection only selects for plasticity in the female function (i.e., ovule fertilization) but not in the male function (i.e., pollen removal), and plasticity is optimal in maximizing fitness only when saved resources through plasticity greatly enhance individual fitness. Plasticity is more likely to evolve under individual selection, but under the same pollination environment, any combination of the plasticity in female and male functions that adds up to a certain overall strength of plasticity can be evolutionarily stable. Given the fact that plasticity in the male function is rare in hermaphroditic populations, the plasticity of flower longevity may evolve mainly through group selection instead of individual selection.
The Role of Reproductive Periodicity in Dispersal Among Hydrothermal Vents and its Implications for Regional Connectivity and Conservation
Authors: Brunner Otis , Methou Pierre , Mitarai Satoshi 
Published: March 2023

AbstractConnectivity among isolated habitat patches via planktonic larval dispersal is crucial for maintaining the regional diversity of hydrothermal vents. Despite, increasing sophistication of techniques for simulating dispersal, limited information on biological and behavioural traits of vent-associated species has unknown affects on the applicability of these methods for conservation. Here we focus on the role of periodic reproduction on dispersal among hydrothermal vents, as periodic spawning has increasingly been observed in a variety of taxa. For generalizeability, we simulate the dispersal of larvae under treatments of periodic and aperiodic release timing at various depths, with a consistant but variable planktonic larval duration. Our results show a highly variable effect of periodicity on the characteristics and distribution of dispersal, which are heavily modified by the dispersal depth and source location. The capacity for reproductive periodicity to impact the among-site dispersal warrents further investigation into its prevelance and timing among vent-associated fauna.
Direct prediction of Homologous Recombination Deficiency from routine histology in ten different tumor types with attention-based Multiple Instance Learning: a development and validation study
Authors: Lavinia Loeffler Chiara Maria , El Nahhas Omar S.M. , Muti Hannah Sophie , Seibel Tobias , Cifci Didem , Treeck Marko van , Gustav Marco , Carrero Zunamys I. , Gaisa Nadine T. , Lehmann Kjong-Van , Leary Alexandra , Selenica Pier , Reis-Filho Jorge S. , Bruechle Nadina Ortiz , Kather Jakob Nikolas 
Published: March 2023

AbstractBackgroundHomologous Recombination Deficiency (HRD) is a pan-cancer predictive biomarker that identifies patients who benefit from therapy with PARP inhibitors (PARPi). However, testing for HRD is highly complex. Here, we investigated whether Deep Learning can predict HRD status solely based on routine Hematoxylin & Eosin (H&E) histology images in ten cancer types.MethodsWe developed a fully automated deep learning pipeline with attention-weighted multiple instance learning (attMIL) to predict HRD status from histology images. A combined genomic scar HRD score, which integrated loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) was calculated from whole genome sequencing data for n=4,565 patients from two independent cohorts. The primary statistical endpoint was the Area Under the Receiver Operating Characteristic curve (AUROC) for the prediction of genomic scar HRD with a clinically used cutoff value.ResultsWe found that HRD status is predictable in tumors of the endometrium, pancreas and lung, reaching cross-validated AUROCs of 0.79, 0.58 and 0.66. Predictions generalized well to an external cohort with AUROCs of 0.93, 0.81 and 0.73 respectively. Additionally, an HRD classifier trained on breast cancer yielded an AUROC of 0.78 in internal validation and was able to predict HRD in endometrial, prostate and pancreatic cancer with AUROCs of 0.87, 0.84 and 0.67 indicating a shared HRD-like phenotype is across tumor entities.ConclusionIn this study, we show that HRD is directly predictable from H&E slides using attMIL within and across ten different tumor types.