bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
Authors: Sagawa Tamotsu , Sato Yasushi , Hirakawa Masahiro , Hamaguchi Kyoko , Tamura Fumito , Nagashima Hiroyuki , Fujikawa Koshi , Okamoto Koichi , Kawano Yutaka , Sogabe Masahiro , Miyamoto Hiroshi , Takayama Tetsuji 
Published: June 2023

BackgroundTreatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in KRAS and NRAS in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis.Case presentationA 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. RAS in the ctDNA was assessed during treatment. The RAS status changed from wild type to mutant type, back to wild type, and again to mutant type (NRAS/KRAS codon 61) during the course of treatment.ConclusionIn this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in KRAS and NRAS in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy.
Pain sensitivity differs between dog breeds but not in the way veterinarians believe
Authors: Caddiell Rachel M. P. , Cunningham Rachael M. , White Philip A. , Lascelles B. Duncan X. , Gruen Margaret E. 
Published: June 2023

BackgroundVeterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivity thresholds differ across a set of dog breeds and, if so, whether veterinarians’ pain sensitivity ratings explain these differences or whether these ratings are attributed to behavioral characteristics.MethodsPain sensitivity thresholds [using quantitative sensory testing (QST) methods] and canine behaviors (using owner questionnaires and emotional reactivity tests) were prospectively measured across selected dog breeds. Adult, healthy dogs from 10 dog breeds/breed types were recruited, representing breeds subjectively rated by veterinarians as high (chihuahua, German shepherd, Maltese, Siberian husky), average (border collie, Boston terrier, Jack Russell terrier), or low (golden retriever, pitbull, Labrador retriever) pain sensitivity. A final sample of 149 dogs was included in statistical analyses.ResultsVeterinarians’ pain sensitivity ratings provided a minimal explanation for pain sensitivity thresholds measured using QST in dogs; however, dog breeds did differ in their pain sensitivity thresholds across the QST methods evaluated. Breed differences were observed for some aspects of emotional reactivity tests; however, these behavioral differences did not explain the differences in pain sensitivity thresholds found. Veterinarians’ pain sensitivity ratings were positively associated with dog approach scores for the disgruntled stranger test suggesting that the way dogs greet strangers may be a factor influencing veterinarians’ ratings of pain sensitivity across dog breeds.Conclusions and clinical relevanceOverall, these findings highlight a need to investigate biological mechanisms that may explain breed differences in pain sensitivity because this may inform pain management recommendations. Further, future research should focus on when and how these breed-specific pain sensitivity beliefs developed in veterinarians, as veterinarians’ beliefs could impact the recognition and treatment of pain for canine patients.
Long-term follow-up in common variable immunodeficiency: the pediatric-onset and adult-onset landscape
Authors: Carrabba Maria , Salvi Marco , Baselli Lucia Augusta , Serafino Serena , Zarantonello Marina , Trombetta Elena , Pietrogrande Maria Cristina , Fabio Giovanna , Dellepiane Rosa Maria 
Published: June 2023

IntroductionThe primary aim of this study is to investigate the evolution of the clinical and laboratory characteristics during the time in a longitudinal cohort of pediatric-onset and adult-onset Common Variable Immunodeficiency (CVID) patients in order to identify early predictive features of the disease and immune dysregulation complications.MethodsThis is a retrospective-prospective monocentric longitudinal study spanning from 1984 to the end of 2021. The data of pediatric-onset vs. adult-onset patients have been compared for immunological features and for infectious and non-infectious complications assessed at diagnosis and follow-up.ResultsSeventy-three CVID patients have been enrolled, with a mean of 10.0 years (SD ± 8.17) of prospective follow-up. At diagnosis, infections were observed in 89.0% of patients and immune dysregulation in 42.5% of patients. At diagnosis, 38.6% of pediatric-onset and 20.7% of adult-onset patients presented with only infections. Polyclonal lymphoid proliferation (62.1%) and autoimmunity (51.7%) were more prevalent in the adult-onset than in the pediatric-onset group (polyclonal lymphoid proliferation 52.3% and autoimmunity 31.8%, respectively). Enteropathy was present in 9.1% of pediatric-onset and 17.2% of adult-onset patients. The prevalence of polyclonal lymphoid proliferation increased during follow-up more in pediatric-onset patients (diagnosis 52.3%—follow-up 72.7%) than in adult-onset patients (diagnosis 62.1%—follow-up 72.7%). The cumulative risk to develop immune dysregulation increases according to the time of disease and the time of diagnostic delay. At the same age, pediatric-onset patients have roughly double the risk of having a complication due to immune dysregulation than adult-onset patients, and it increases with diagnostic delay. The analysis of lymphocyte subsets in the pediatric-onset group showed that CD21 low B cells at diagnosis may be a reliable prognostic marker for the development of immune dysregulation during follow-up, as the ROC curve analysis showed (AUC = 0.796). In the adult-onset group, the percentage of transitional B cells measured at diagnosis showed a significant accuracy (ROC AUC = 0.625) in identifying patients at risk of developing immune dysregulation.DiscussionThe longitudinal evaluation of lymphocyte subsets combined with clinical phenotype can improve the prediction of lymphoid proliferation and allow experts to achieve early detection and better management of such complex disorder.
Improving localization accuracy for non-invasive automated early left ventricular origin localization approach
Authors: Zhou Shijie , Wang Raymond , Seagren Avery , Emmert Noah , Warren James W. , MacInnis Paul J. , AbdelWahab Amir , Sapp John L. 
Published: June 2023

Background: We previously developed a non-invasive approach to localize the site of early left ventricular activation origin in real time using 12-lead ECG, and to project the predicted site onto a generic LV endocardial surface using the smallest angle between two vectors algorithm (SA).Objectives: To improve the localization accuracy of the non-invasive approach by utilizing the K-nearest neighbors algorithm (KNN) to reduce projection errors.Methods: Two datasets were used. Dataset #1 had 1012 LV endocardial pacing sites with known coordinates on the generic LV surface and corresponding ECGs, while dataset #2 included 25 clinically-identified VT exit sites and corresponding ECGs. The non-invasive approach used “population” regression coefficients to predict the target coordinates of a pacing site or VT exit site from the initial 120-m QRS integrals of the pacing site/VT ECG. The predicted site coordinates were then projected onto the generic LV surface using either the KNN or SA projection algorithm.Results: The non-invasive approach using the KNN had a significantly lower mean localization error than the SA in both dataset #1 (9.4 vs. 12.5 mm, p &lt; 0.05) and dataset #2 (7.2 vs. 9.5 mm, p &lt; 0.05). The bootstrap method with 1,000 trials confirmed that using KNN had significantly higher predictive accuracy than using the SA in the bootstrap assessment with the left-out sample (p &lt; 0.05).Conclusion: The KNN significantly reduces the projection error and improves the localization accuracy of the non-invasive approach, which shows promise as a tool to identify the site of origin of ventricular arrhythmia in non-invasive clinical modalities.
The relationship between underage initiation of selling sex and depression among female sex workers in Eswatini
Authors: Grosso Ashley , Fielding-Miller Rebecca , Matse Sindy , Sithole Bhekie , Baral Stefan 
Published: June 2023

BackgroundMinors who sell sex are likely to have complex mental health needs that may persist into adulthood. This topic is understudied in sub-Saharan Africa. This study hypothesized that adult female sex workers in Eswatini who started selling sex as minors have a higher prevalence of depression than those who started as adults. We also examined correlates of depression and underage initiation of selling sex, including stigma and condom-related behaviors.MethodsFrom October–December 2014, women aged 18 or older who sold sex in the past 12 months in Eswatini were recruited through venue-based sampling. Participants completed a survey including the 9-item Patient Health Questionnaire (PHQ-9) and a question about the age at which they first sold sex for money. T-tests, χ2 tests and multivariable logistic regression were used to assess associations.ResultsOverall, 43.1% of participants (332/770) had probable depression, and 16.6% (128/770) started selling sex as minors under the age of 18. Over half (55.5%, 71/128) of those who started selling sex as minors had depression. This was significantly higher than the 40.7% (261/642) prevalence of depression among participants who started selling sex as adults (p = 0.002). After adjusting for confounders, female sex workers who started selling sex as minors had higher odds of depression than those who started as adults (adjusted odds ratio [aOR] 1.70, 95% confidence interval 1.11–2.60).ConclusionResults highlight the need for trauma-informed and adolescent-friendly mental health services in settings free of stigma toward female sex workers in Eswatini.
Making tacit knowledge explicit through objects: a qualitative study of the translation of resilience into practice
Authors: Lyng Hilda Bø , Haraldseid-Driftland Cecilie , Guise Veslemøy , Ree Eline , Dombestein Heidi , Fagerdal Birte , Wæhle Hilde Valen , Wiig Siri 
Published: June 2023

IntroductionIt is common practice to use objects to bridge disciplines and develop shared understanding across knowledge boundaries. Objects for knowledge mediation provide a point of reference which allows for the translation of abstract concepts into more externalized representations. This study reports from an intervention that introduced an unfamiliar resilience perspective in healthcare, through the use of a resilience in healthcare (RiH) learning tool. The aim of this paper is to explore how a RiH learning tool may be used as an object for introduction and translation of a new perspective across different healthcare settings.MethodsThis study is based on empirical observational data, collected throughout an intervention to test a RiH learning tool, developed as part of the Resilience in Healthcare (RiH) program. The intervention took place between September 2022 and January 2023. The intervention was tested in 20 different healthcare units, including hospitals, nursing homes and home care services. A total of 15 workshops were carried out, including 39-41 participants in each workshop round. Throughout the intervention, data was gathered in all 15 workshops at the different organizational sites. Observation notes from each workshop make up the data set for this study. The data was analyzed using an inductive thematic analysis approach.Results and conclusionThe RiH learning tool served as different forms of objects during the introduction of the unfamiliar resilience perspective for healthcare professionals. It provided a means to develop shared reflection, understanding, focus, and language for the different disciplines and settings involved. The resilience tool acted as a boundary object for the development of shared understanding and language, as an epistemic object for the development of shared focus and as an activity object within the shared reflection sessions. Enabling factors for the internalization of the unfamiliar resilience perspective were to provide active facilitation of the workshops, repeated explanation of unfamiliar concepts, provide relatedness to own context, and promote psychological safety in the workshops. Overall, observations from the testing of the RiH learning tool showed how these different objects were crucial in making tacit knowledge explicit, which is key to improve service quality and promote learning processes in healthcare.
Comparative toxicity assessment of glyphosate and two commercial formulations in the planarian Dugesia japonica
Authors: Fuselier S. Grace , Ireland Danielle , Fu Nicholas , Rabeler Christina , Collins Eva-Maria S. 
Published: June 2023

Introduction: Glyphosate is a widely used, non-selective herbicide. Glyphosate and glyphosate-based herbicides (GBHs) are considered safe for non-target organisms and environmentally benign at currently allowed environmental exposure levels. However, their increased use in recent years has triggered questions about possible adverse outcomes due to low dose chronic exposure in animals and humans. While the toxicity of GBHs has primarily been attributed to glyphosate, other largely unstudied components of GBHs may be inherently toxic or could act synergistically with glyphosate. Thus, comparative studies of glyphosate and GBHs are needed to parse out their respective toxicity.Methods: We performed such a comparative screen using pure glyphosate and two popular GBHs at the same glyphosate acid equivalent concentrations in the freshwater planarian Dugesia japonica. This planarian has been shown to be a useful model for both ecotoxicology and neurotoxicity/developmental neurotoxicity studies. Effects on morphology and various behavioral readouts were obtained using an automated screening platform, with assessments on day 7 and day 12 of exposure. Adult and regenerating planarians were screened to allow for detection of developmentally selective effects.Results: Both GBHs were more toxic than pure glyphosate. While pure glyphosate induced lethality at 1 mM and no other effects, both GBHs induced lethality at 316 μM and sublethal behavioral effects starting at 31.6 μM in adult planarians. These data suggest that glyphosate alone is not responsible for the observed toxicity of the GBHs. Because these two GBHs also include other active ingredients, namely diquat dibromide and pelargonic acid, respectively, we tested whether these compounds were responsible for the observed effects. Screening of the equivalent concentrations of pure diquat dibromide and pure pelargonic acid revealed that the toxicity of either GBH could not be explained by the active ingredients alone.Discussion: Because all compounds induced toxicity at concentrations above allowed exposure levels, our data indicates that glyphosate/GBH exposure is not an ecotoxicological concern for D. japonica planarians. Developmentally selective effects were not observed for all compounds. Together, these data demonstrate the usefulness of high throughput screening in D. japonica planarians for assessing various types of toxicity, especially for comparative studies of several chemicals across different developmental stages.
Shepherds View of Large Carnivore Recovery in the Pyrenees, Spain
Authors: Ballarín José , García-Serrano Alicia , Herrero Juan , Reiné Ramón 
Published: June 2023

The studied farms are small family businesses, and so, in more than half of the cases, their continuity is not guaranteed. Livestock management is typical of a mountain system, in which the animals graze throughout the year in cultivated fields, sown meadows, forests near the farms, and mountain pastures during the three summer months. The herds always have the constant surveillance of a shepherd. Farmers consider the current infrastructure present in mountain grasslands insufficient to facilitate the management and care of their herd. Their activity conflicts with various species of wildlife, such as the wild boar, Sus scrofa, roe deer, Capreolus capreolus, or griffon vulture, Gyps fulvus, and large carnivores such as the brown bear, Ursus arctos, or the grey wolf Canis lupus, despite all of them taking preventive measures to defend their herds from predators. The most widely used prevention measures are the presence of mastiff dogs, Canis lupus familiaris, next to the herds and the use of electric fencing to lock up livestock at night. Farmers reject the presence of bears and wolves in their area, considering it a real threat to the continuity of their economic activity, which presents a high degree of vulnerability.
Assessment of Penetrability for Different Endodontic Irrigation Activating Techniques Using Cone-Beam Computed Tomography and Periapical Digital Radiography—An In Vitro Study
Authors: Abdelhafeez Manal M. , Alharbi Afnan S. , Srivastava Swati , Abdelaziz Rehab , Eldwakhly Elzahraa , Almohareb Rahaf A. , Algahtani Fahda N. , Soliman Mai 
Published: June 2023

The elimination of necrotic and inflamed pulp tissue, dentin debris, and microorganisms is essential for the success of endodontic treatment. However, the root canal’s complexity has led to incomplete cleaning and disinfection. This study aims to compare the efficacy of the penetrability of three different irrigation activating techniques to the apical third of the root canal. Sixty sound single-rooted human mandibular premolars are prepared with rotary instrumentation under continuous sodium hypochlorite irrigation. Three irrigation activation techniques are utilized: group 1 (n = 20), conventional needle irrigation (CN); group 2 (n = 20), side-vented endodontic needle irrigation (EN); and group 3 (n = 20), manual activation irrigation with gutta-percha cone (MA). The penetrability is assessed with the aid of a radiopaque irrigation solution using digital radiography in conjunction with cone-beam computed tomographic (CBCT) measurements. Data are analyzed using a statistical package for social sciences (SPSS), using multiple comparisons to compare the baseline and test values. One-way analysis of variance with post hoc analysis (Tukey honestly significant difference) is performed to detect the statistically significant differences between groups. Manual activation (MA) shows effective delivery of the irrigant into full WL, followed by endodontic needle (EN) and conventional (CN) methods of activation (p < 0.001). The results of the present study show that maximum penetrability of the irrigant is observed with manual activation (MA) using a gutta cone in comparison with the conventional needle (CN).
Expression of EPL1 from Trichoderma atroviride in Arabidopsis Confers Resistance to Bacterial and Fungal Pathogens
Authors: Rojas Moreno Mónica Montserrat , González-Pérez Enrique , Rodríguez-Hernandez Aida Araceli , Ortega-Amaro María Azucena , Becerra-Flora Alicia , Serrano Mario , Jiménez-Bremont Juan Francisco 
Published: June 2023

During plant interaction with beneficial microorganisms, fungi secrete a battery of elicitors that trigger plant defenses against pathogenic microorganisms. Among the elicitor molecules secreted by Trichoderma are cerato-platanin proteins, such as EPL1, from Trichoderma atroviride. In this study, Arabidopsis thaliana plants that express the TaEPL1 gene were challenged with phytopathogens to evaluate whether expression of EPL1 confers increased resistance to the bacterial pathogen Pseudomonas syringae and the necrotrophic fungus Botrytis cinerea. Infection assays showed that Arabidopsis EPL1-2, EPL1-3, EPL1-4 expressing lines were more resistant to both pathogens in comparison to WT plants. After Pseudomonas syringae infection, there were reduced disease symptoms (e.g., small chlorotic spots) and low bacterial titers in the three 35S::TaEPL1 expression lines. Similarly; 35S::TaEPL1 expression lines were more resistant to Botrytis cinerea infection, showing smaller lesion size in comparison to WT. Interestingly, an increase in ROS levels was detected in 35S::TaEPL1 expression lines when compared to WT. A higher expression of SA- and JA-response genes occurred in the 35S::TaEPL1 lines, which could explain the resistance of these EPL1 expression lines to both pathogens. We propose that EPL1 is an excellent elicitor, which can be used to generate crops with improved resistance to broad-spectrum diseases.
Attention-Based Fusion of Ultrashort Voice Utterances and Depth Videos for Multimodal Person Identification
Authors: Moufidi Abderrazzaq , Rousseau David , Rasti Pejman 
Published: June 2023

Multimodal deep learning, in the context of biometrics, encounters significant challenges due to the dependence on long speech utterances and RGB images, which are often impractical in certain situations. This paper presents a novel solution addressing these issues by leveraging ultrashort voice utterances and depth videos of the lip for person identification. The proposed method utilizes an amalgamation of residual neural networks to encode depth videos and a Time Delay Neural Network architecture to encode voice signals. In an effort to fuse information from these different modalities, we integrate self-attention and engineer a noise-resistant model that effectively manages diverse types of noise. Through rigorous testing on a benchmark dataset, our approach exhibits superior performance over existing methods, resulting in an average improvement of 10%. This method is notably efficient for scenarios where extended utterances and RGB images are unfeasible or unattainable. Furthermore, its potential extends to various multimodal applications beyond just person identification.