bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Horizons in Peripheral Artery Disease
Authors: Houghton John S M , Saratzis Athanasios N , Sayers Rob D , Haunton Victoria J 
Published: June 2024

Abstract
Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.
Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie
Authors: Tian Meihui , Sun Weifang , Mao Yinhui , Zhang Yanan , Liu Huan , Tang Yong 
Published: June 2024

Abstract
One of the prevalent chronic inflammatory disorders of the nasal mucosa, allergic rhinitis (AR) has become more widespread in recent years. Acupuncture pterygopalatine ganglion (aPPG) is an emerging alternative therapy that is used to treat AR, but the molecular mechanisms underlying its anti-inflammatory effects are unclear. This work methodically demonstrated the multi-target mechanisms of aPPG in treating AR based on bioinformatics/topology using techniques including text mining, bioinformatics, and network topology, among others. A total of 16 active biomarkers and 108 protein targets related to aPPG treatment of AR were obtained. A total of 345 Gene Ontology terms related to aPPG of AR were identified, and 135 pathways were screened based on Kyoto Encyclopedia of Genes and Genomes analysis. Our study revealed for the first time the multi-targeted mechanism of action of aPPG in the treatment of AR. In animal experiments, aPPG ameliorated rhinitis symptoms in OVA-induced AR rats; decreased serum immunoglobulin E, OVA-sIgE, and substance P levels; elevated serum neuropeptide Y levels; and modulated serum Th1/Th2/Treg/Th17 cytokine expression by a mechanism that may be related to the inhibition of activation of the TLR4/NF-κB/NLRP3 signaling pathway. In vivo animal experiments once again validated the results of the bioinformatics analysis. This study revealed a possible multi-target mechanism of action between aPPG and AR, provided new insights into the potential pathogenesis of AR, and proved that aPPG was a promising complementary alternative therapy for the treatment of AR.
AITeQ: a machine learning framework for Alzheimer’s prediction using a distinctive five-gene signature
Authors: Ahammad Ishtiaque , Lamisa Anika Bushra , Bhattacharjee Arittra , Jamal Tabassum Binte , Arefin Md Shamsul , Chowdhury Zeshan Mahmud , Hossain Mohammad Uzzal , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md 
Published: June 2024

Abstract
Neurodegenerative diseases, such as Alzheimer’s disease, pose a significant global health challenge with their complex etiology and elusive biomarkers. In this study, we developed the Alzheimer’s Identification Tool (AITeQ) using ribonucleic acid-sequencing (RNA-seq), a machine learning (ML) model based on an optimized ensemble algorithm for the identification of Alzheimer’s from RNA-seq data. Analysis of RNA-seq data from several studies identified 87 differentially expressed genes. This was followed by a ML protocol involving feature selection, model training, performance evaluation, and hyperparameter tuning. The feature selection process undertaken in this study, employing a combination of four different methodologies, culminated in the identification of a compact yet impactful set of five genes. Twelve diverse ML models were trained and tested using these five genes (CNKSR1, EPHA2, CLSPN, OLFML3, and TARBP1). Performance metrics, including precision, recall, F1 score, accuracy, Matthew’s correlation coefficient, and receiver operating characteristic area under the curve were assessed for the finally selected model. Overall, the ensemble model consisting of logistic regression, naive Bayes classifier, and support vector machine with optimized hyperparameters was identified as the best and was used to develop AITeQ. AITeQ is available at: https://github.com/ishtiaque-ahammad/AITeQ.
Sensitive and error-tolerant annotation of protein-coding DNA with BATH
Authors: Krause Genevieve R , Shands Walt , Wheeler Travis J 
Published: June 2024

Abstract

Summary
We present BATH, a tool for highly sensitive annotation of protein-coding DNA based on direct alignment of that DNA to a database of protein sequences or profile hidden Markov models (pHMMs). BATH is built on top of the HMMER3 code base, and simplifies the annotation workflow for pHMM-based translated sequence annotation by providing a straightforward input interface and easy-to-interpret output. BATH also introduces novel frameshift-aware algorithms to detect frameshift-inducing nucleotide insertions and deletions (indels). BATH matches the accuracy of HMMER3 for annotation of sequences containing no errors, and produces superior accuracy to all tested tools for annotation of sequences containing nucleotide indels. These results suggest that BATH should be used when high annotation sensitivity is required, particularly when frameshift errors are expected to interrupt protein-coding regions, as is true with long-read sequencing data and in the context of pseudogenes.

Availability and implementation
The software is available at https://github.com/TravisWheelerLab/BATH.
Bootstrap test procedure for variance components in nonlinear mixed effects models in the presence of nuisance parameters and a singular Fisher information matrix
Authors: Guédon T , Baey C , Kuhn E 
Published: June 2024

Summary
We examine the problem of variance component testing in general mixed effects models using the likelihood ratio test. We account for the presence of nuisance parameters, ie, the fact that some untested variances might also be equal to zero. Two main issues arise in this context, leading to a nonregular setting. First, under the null hypothesis, the true parameter value lies on the boundary of the parameter space. Moreover, due to the presence of nuisance parameters, the exact locations of these boundary points are not known, which prevents the use of classical asymptotic theory of maximum likelihood estimation. Then, in the specific context of nonlinear mixed effects models, the Fisher information matrix is singular at the true parameter value. We address these two points by proposing a shrunk parametric bootstrap procedure, which is straightforward to apply even for nonlinear models. We show that the procedure is consistent, solving both the boundary and the singularity issues, and we provide a verifiable criterion for the applicability of our theoretical results. We show through a simulation study that, compared to the asymptotic approach, our procedure has a better small sample performance and is more robust to the presence of nuisance parameters. A real data application on bird growth rates is also provided.
Cytokeratin 17 expression is commonly observed in keratinocytic skin tumours and controls tissue homeostasis impacting human papillomavirus protein expression
Authors: Hasche Daniel , Hufbauer Martin , Braspenning-Wesch Ilona , Stephan Sonja , Silling Steffi , Schmidt Gabriele , Krieg Stephan , Kreuter Alexander , Akgül Baki 
Published: June 2024

Abstract

Background
The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas other keratins are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas, where ultraviolet irradiation and infection with cutaneous human papillomaviruses are important cofactors. It was previously reported that K17 is upregulated in papillomavirus (PV)-induced benign skin lesions in mice and induces an immunological status that is beneficial for tumour growth.

Objectives
In order to investigate whether K17 upregulation is induced by PVs, we analysed K17 levels in skin tumour specimens of different animal models and humans.

Methods
Various immunofluorescence stainings were performed to identify K17 expression as well as levels of E-cadherin, vimentin and CD271. Tissues were further analysed by polymerase chain reaction (PCR), quantitative (q)PCR and enzyme-linked immunosorbent assay to control for PV activity. K17 knockdown cells were generated and effects on viral life cycle were investigated by infection assays, qPCR and Western blotting.

Results
We showed that K17 is commonly expressed in skin tumours and that its presence is not directly linked to viral oncoprotein expression. Rather, K17 expression seems to be a marker of epithelial differentiation and its absence in tumour tissue is associated with an epithelial-to-mesenchymal transition. We further demonstrated that the absence of K17 in skin tumours increases markers of cancer stem-like cells and negatively affects viral protein synthesis.

Conclusions
Collectively, our data indicate that K17 expression is a common feature in skin tumorigenesis. While K17 is not primarily targeted by PV oncoproteins, our in vivo and in vitro data suggest that it is an important regulator of epithelial differentiation and thus may play a role in controlling viral protein synthesis.
Intrarenal pressure with hand-pump or pressurized-bag irrigation: randomized clinical trial at retrograde intrarenal surgery
Authors: Croghan Stefanie M , O’Meara Sorcha , Cunnane Eoghan M , Purtill Helen , Walsh Michael T , O’Brien Fergal J , Manecksha Rustom P , McGuire Barry B , Breen Kieran J , Davis Niall F 
Published: June 2024

Abstract

Background
The aim was to ascertain the impact of irrigation technique on human intrarenal pressure during retrograde intrarenal surgery.

Methods
A parallel randomized trial recruited patients across three hospital sites. Patients undergoing retrograde intrarenal surgery for renal stone treatment with an 11/13-Fr ureteral access sheath were allocated randomly to 100 mmHg pressurized-bag (PB) or manual hand-pump (HP) irrigation. The primary outcome was mean procedural intrarenal pressure. Secondary outcomes included maximum intrarenal pressure, variance, visualization, HP force of usage, procedure duration, stone clearance, and clinical outcomes. Live intrarenal pressure monitoring was performed using a COMETTMII pressure guidewire, deployed cystoscopically to the renal pelvis. The operating team was blinded to the intrarenal pressure.

Results
Thirty-eight patients were randomized between July and November 2023 (trial closure). The final analysis included 34 patients (PB 16; HP 18). Compared with PB irrigation, HP irrigation resulted in significantly higher mean intrarenal pressure (mean(s.d.) 62.29(27.45) versus 38.16(16.84) mmHg; 95% c.i. for difference in means (MD) 7.97 to 40.29 mmHg; P = 0.005) and maximum intrarenal pressure (192.71(106.23) versus 68.04(24.16) mmHg; 95% c.i. for MD 70.76 to 178.59 mmHg; P &lt; 0.001), along with greater variance in intrarenal pressure (log transformed) (6.23(1.59) versus 4.60(1.30); 95% c.i. for MD 0.62 to 2.66; P = 0.001). Surgeon satisfaction with procedural vision reported on a scale of 10 was higher with PB compared with HP irrigation (mean(s.d.) 8.75(0.58) versus 6.28(1.27); 95% c.i. for MD 1.79 to 3.16; P &lt; 0.001). Subjective HP usage force did not correlate significantly with transmitted intrarenal pressure (Pearson R = −0.15, P = 0.57). One patient (HP arm) developed urosepsis.

Conclusion
Manual HP irrigation resulted in higher and more fluctuant intrarenal pressure trace (with inferior visual clarity) than 100-mmHg PB irrigation.

Registration number
osf.io/jmg2h (https://osf.io/).
Effect of vitamin E δ-tocotrienol and aspirin on Wnt signaling in human colon cancer stem cells and in adenoma development in APCmin/+ mice
Authors: Husain Kazim , Coppola Domenico , Yang Chung S , Malafa Mokenge P 
Published: June 2024

Abstract
In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of adenoma formation in APCmin/+ mice. We found that knockdown of the adenomatous polyposis coli (APC) gene led to subsequent activation of Wnt signaling in colon epithelial cells (NCM460-APCsiRNA) and induction of β-catenin and its downstream target proteins c-MYC, cyclin D1, and survivin. When aspirin and DT3 were combined, cell growth and survival were inhibited and apoptosis was induced in colon epithelial cells and CCSCs. However, DT3 and/or aspirin had little or no effect on the control of normal colon epithelial cells (NCM460-NCsiRNA). The induction of apoptosis was directly related to the activation of caspase 8 and cleavage of BH3-interacting-domain (BID) to truncated BID. In addition, DT3- and/or aspirin-induced apoptosis was associated with cleaved Poly (ADP-ribose) polymerase (PARP), elevated levels of cytosolic cytochrome c and BAX, and depletion of antiapoptotic protein BCl-2 in CCSCs. The combination of aspirin and DT3 inhibited the self-renewal capacity, Wnt/β-catenin receptor activity, and expression of β-catenin and its downstream targets c-MYC, cyclin D1, and survivin in CCSCs. We also found that treatment with DT3 alone or combined with aspirin significantly inhibited intestinal adenoma formation and Wnt/β-catenin signaling and induced apoptosis, compared with vehicle, in APCmin/+ mice. Our study demonstrated a rationale for further investigation of the combination of DT3 and aspirin for colorectal cancer prevention and therapy.
Variability of morphology–performance relationships under acute exposure to different temperatures in 3 strains of zebrafish
Authors: Miller Christina L , Dugand Robert , McGuigan Katrina 
Published: June 2024

Abstract
Locomotion is thermally sensitive in ectotherms and therefore it is typically expressed differently among thermally heterogenous environments. Locomotion is a complex function, and whereas physiological and behavioral traits that influence locomotor performance may respond to thermal variation throughout life, other contributing traits, like body shape, may have more restricted responses. How morphology affects locomotor performance under variable temperature conditions is unknown. Here, we investigated 3 genetically distinct strains of zebrafish, Danio rerio (AB, WIK, and Tu) with a shared multi-generational history at 28 °C. After rearing fish at 28 °C, we measured prolonged swimming speed (Ucrit) at each of 6 temperatures (between 16 °C and 34 °C). Speed was strongly positively correlated among temperatures, resulting in most among individual variation being temperature-independent (i.e., fish were relatively fast or slow across all temperatures). However, we also detected significant variation along 2 axes reflecting temperature-dependent variation. Although strains differed in mean swimming performance, within strain (among-individual) patterns of speed variation were markedly consistent. Body shape and size explained significant variation among individuals in both temperature-independent and temperature-dependent axes of swimming speed variation. Notably, morphological traits that were most strongly associated with temperature-independent performance variation (i.e., faster–slower) differed from those associated with temperature-dependent (i.e., hotter–colder) variation. Further, there were significant differences among strains in both the direction and strength of association for specific morphological traits. Our results suggest that thermally heterogenous environments could have complex effects on the evolution of traits that contribute to whole organism performance traits.
Disentangling the value equation: a step forward in value-based healthcare
Authors: García-Lorenzo Borja , Alayo Itxaso , Arrospide Arantzazu , Gorostiza Ania , Fullaondo Ane ,   VOICE Study Group, Zas Susana Castelo , Baena Patricia Cobos , Camiña Inés Gallego , Narbaiza Begoña Izaguirre , Mallabiabarrena Gaizka , Ustarroz-Aguirre Iker , Rigabert Alina , Balzi William , Maltoni Roberta , Massa Ilaria , López Isabel Álvarez , Lobera Sara Arévalo , Esteban Mónica , Calleja Marta Fernández , Mediavilla Jenifer Gómez , Fernández Manuela , del Oro Hitar Manuel , del Carmen Ortega Torres María , Ferrandez María Consuelo Sanz , Sánchez Luís Manso , Balazote Pablo Serrano , Rodríguez Carolina Varela , Campone Mario , Lann Sophie Le , Vercauter Piet , Tournoy Kurt , Borges Marina , Oliveira Ana Sofía , Soares Marta , Lerma Iratxe Vázquez , Irazabal Izaskun Artola , de Larrinoa Santamaría Aitor Fernandez , Capanaga Andere Frias , Elorduy Eduardo Vicario , Acaiturri-Ayesta Teresa , Gómez-Inhiesto Elisa , Danesi Valentina , Gentili Nicola , Roncadori Andrea , Alarz Fátima Hermoso , Iraola Karmele Imaz , Adam Valerie , De Rijck Helene , Everaert Ellen , Barreira Esmeralda , Medeiros Pedro , Barros Emanuel 
Published: June 2024

Abstract

Background
The value equation of value-based healthcare (VBHC) as a single figure remains ambiguous, closer to a theoretical framework than a useful tool for decision making. The challenge lies in the way patient-centred outcomes (PCOs) might be combined to produce a single value of the numerator. This paper aims to estimate the weights of PCOs to provide a single figure in the numerator, which ultimately will allow a VBHC figure to be reached.

Methods
A cohort of patients diagnosed with breast cancer (n = 690) with a 6-month follow-up recruited in 2019–20 across six European hospitals was used. Patient-reported outcomes (PROs), clinical-related outcomes (CROs), and clinical and socio-demographic variables were collected. The numerator was defined as a composite indicator of the PCOs (CI-PCO), and regression analysis was applied to estimate their weights and consequently arrive at a single figure.

Results
Pain showed as the highest weight followed by physical functioning, emotional functioning, and ability to work, and then by a symptom, either arm or breast. PCOs weights were robust to sensitivity analysis. The CI-PCO value was found to be more informative than the health-related quality of life (HRQoL) value.

Conclusions
To the best of our knowledge, this is the first research to combine the PCOs proposed by ICHOM to provide a single figure in the numerator of the value equation. This figure shows a step forward in VBHC to reach a holistic benchmarking across healthcare centres and a value-based payment. This research might also be applied in other medical conditions as a methodological pathway.
Prevalence of Cefixime-Resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021–2022
Authors: Chow Eric P F , Stevens Kerrie , De Petra Vesna , Chen Marcus Y , Bradshaw Catriona S , Sherry Norelle L , Barbee Lindley A , Vodstrcil Lenka A , Aguirre Ivette , Seib Kate L , Maddaford Kate , Williamson Deborah A , Howden Benjamin P , Fairley Christopher K 
Published: June 2024

Abstract
While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176), and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was highest among women (16.4%, 10/61), followed by men who have sex with women (6.4%, 7/109) and men who have sex with men (5.8%, 57/982). The prevalence of cefixime-resistant N gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; thus, cefixime treatment would have limited benefits in Australia.
Four-bar Geometry is Shared among Ecologically DivergentFish Species
Authors: Camarillo H , Burress E D , Muñoz M M 
Published: June 2024

Synopsis
Understanding the factors that influence morphological evolution is a major goal in biology. One such factor is the ability to acquire and process prey. Prey hardness and evasiveness are important properties that can impact evolution of the jaws. Similar diets and biomechanical systems have repeatedly evolved among fish lineages, providing an opportunity to test for shared patterns of evolution across distantly related organisms. Four-bar linkages are structures often used by animals to transmit force and motion during feeding and that provide an excellent system to understand the impact of diet on morphological and biomechanical evolution. Here, we tested how diet influences the evolutionary dynamics of the oral four-bar linkage system in wrasses (Family: Labridae) and cichlids (Family: Cichlidae). We found that shifts in prey hardness/evasiveness are associated with limited modifications in four-bar geometry across these two distantly related fish lineages. Wrasse and cichlid four-bar systems largely exhibit many-to-one mapping in response to dietary shifts. Across two iconic adaptive radiations of fish, an optimal four-bar geometry has largely been co-opted for different dietary functions during their extensive ecological diversification. Given the exceptional jaw diversity of both lineages, many-to-one mapping of morphology to mechanical properties may be a core feature of fish adaptive radiation.
Digital Therapy for Negative Consumption Experiences: The Impact of Emotional and Rational Reviews on Review Writers
Authors: Wu Alisa Yinghao , Morwitz Vicki G 
Published: June 2024

Abstract
This research tests a solution for consumers to recover faster from negative experiences. We identify this solution by examining how the manner in which review writers express their emotions and rational thoughts in their reviews causally influences review writers. The results of five studies (field data and experiments) show that, similar to writing about traumatic life events, when review writers express both emotional and rational aspects in reviews about negative consumption experiences, they feel better afterwards (i.e., they recover affectively), and are more likely to purchase again (i.e., they recover cognitively). We further examine why writing integrated reviews has positive effects on review writers by collecting biophysiological response data, which provide support for an account related to affective recovery, and by analyzing thought listing data, which provide support for an account related to cognitive recovery. This research shows that writing online reviews can serve as a digital therapy tool that helps consumers recover from negative experiences.