bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostate cancer androgen receptor splice variant 7 biomarker study - a multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol
Authors: Clark Emma , Morton Miranda , Sharma Shriya , Fisher Holly , Howel Denise , Walker Jenn , Wood Ruth , Hancock Helen , Maier Rebecca , Marshall John , Bahl Amit , Crabb Simon , Jain Suneil , Pedley Ian , Jones Rob , Staffurth John , Heer Rakesh
Published: April 2023

Introduction

Prostate cancer is the most common male cancer with one in four developing non-curable metastatic disease. Initial treatment responses to hormonal therapies are transient and further management options lie between (1) further hormone therapy or (2) a non-hormonal approach involving additional chemotherapy or molecular radiotherapy (radium-223). There is no clear rationale for choosing between these mechanistically different treatment approaches. The biology of hormone resistance is driven through abnormal androgen receptor activity and we can assay this through a blood test measuring androgen receptor variant 7 (AR-V7) expression in circulating tumour cells. Despite increasing evidence supporting AR-V7’s role as a prognostic marker, the clinical utility of such measures remains unknown in helping personalise treatment decisions.

Methods and design

The VARIANT feasibility trial is a pragmatic design, to be run over 18 months with participants randomised into the intervention arm receiving biomarker (AR-V7) guided clinical treatment and participants randomised into the control arm with conventional standard management (no biomarker guidance). AR-V7 positive participants (likely to be insensitive to further hormone treatment) will receive chemotherapy or in other cases radium-223 (where routinely available). Seventy male ≥18 years old participants with metastatic castrate resistant prostate cancer clinically indicated to proceed to further hormone therapy or chemotherapy, will be recruited from three National Health Service Trusts based in England, Scotland and Wales. The feasibility primary outcome is willingness of patients to be randomised and clinicians to recruit to a biomarker-based treatment strategy, with trial data informing the basis of a definitive and appropriately powered randomised control trial.

Ethics and dissemination

Formal ethics review was undertaken with a favourable opinion, through Wales NRES Committee 2 18/WA/0419. Findings to be disseminated through patient and professional organisations that have expressed their support, media outlets and peer-reviewed journal publication.

Trial registration number

NCT10246848
Duloxetine combined with intra-articular injection versus intra-articular injection alone for pain relief in knee osteoarthritis: a study protocol for a randomised controlled trial
Authors: Li Duo Yi , Han Rong , Zhao Zhi Gang , Luo Fang
Published: April 2023

Introduction

Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain.

Methods

This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24 hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle.

Ethics approval and dissemination

This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.

Trial registration number

ClinicalTrials.gov Identifier:NCT04117893.
Study protocol: evaluation of the 0–5 public health investment in England – a mixed-methods study integrating analyses of national linked administrative data with in-depth case studies
Authors: Harron Katie , Cavallaro Francesca L , Bunting Catherine , Clery Amanda , Kendall Sally , Cassidy Rebecca , Atkins Julie , Saloniki Eirini-Christina , Bedford Helen , Woodman Jenny
Published: April 2023

Introduction

Health visiting is a long-established, nationally implemented programme that works with other services at a local level to improve the health and well-being of children and families. To maximise the impact and efficiency of the health visiting programme, policy-makers and commissioners need robust evidence on the costs and benefits of different levels and types of health visiting, for different families, in different local contexts.

Methods and analysis

This mixed-methods study will analyse individual-level health visiting data for 2018/2019 and 2019/2020 linked with longitudinal data from children’s social care, hospitals and schools to estimate the association of number and type of health visiting contacts with a range of children and maternal outcomes. We will also use aggregate local authority data to estimate the association between local models of health visiting and area-level outcomes. Outcomes will include hospitalisations, breast feeding, vaccination, childhood obesity and maternal mental health. Where possible, outcomes will be valued in monetary terms, and we will compare total costs to total benefits of different health visiting service delivery models. Qualitative case studies and extensive stakeholder input will help explain the quantitative analyses and interpret the results in the context of local policy, practice and circumstance.

Ethics and dissemination

The University College London Research Ethics Committee approved this study (ref 20561/002). Results will be submitted for publication in a peer-reviewed journal and findings will be shared and debated with national policy-makers, commissioners and managers of health visiting services, health visitors and parents.
Development and testing of the QDis-MH checklist for discharge letters from specialised mental healthcare: a stakeholder-centred study
Authors: Biringer Eva , Helgeland J , Hellesen H B , Aβmus Jörg , Hartveit M
Published: April 2023

Background

The ‘discharge letter’ is the mandatory written report sent from specialists in the specialist services to general practitioners (GPs) on patient discharge. Clear recommendations from relevant stakeholders for contents of discharge letters and instruments to measure the quality of discharge letters in mental healthcare are needed. The objectives were to (1) detect which information relevant stakeholders defined as important to include in discharge letters from mental health specialist services, (2) develop a checklist to measure the quality of discharge letters and (3) test the psychometric properties of the checklist.

Methods

We used a stepwise multimethod stakeholder-centred approach. Group interviews with GPs, mental health specialists and patient representatives defined 68 information items with 10 consensus-based thematic headings relevant to include in high-quality discharge letters. Information items rated as highly important by GPs (n=50) were included in the Quality of Discharge information-Mental Health (QDis-MH) checklist. The 26-item checklist was tested by GPs (n=18) and experts in healthcare improvement or health services research (n=15). Psychometric properties were assessed using estimates of intrascale consistency and linear mixed effects models. Inter-rater and test–retest reliability were assessed using Gwet’s agreement coefficient (Gwet’s AC1) and intraclass correlation coefficients.

Results

The QDis-MH checklist had satisfactory intrascale consistency. Inter-rater reliability was poor to moderate, and test–retest reliability was moderate. In descriptive analyses, mean checklist scores were higher in the category of discharge letters defined as ‘good’ than in ‘medium’ or ’poor’ letters, but differences did not reach statistical significance.

Conclusions

GPs, mental health specialists and patient representatives defined 26 information items relevant to include in discharge letters in mental healthcare. The QDis-MH checklist is valid and feasible. However, when using the checklist, raters should be trained and the number of raters kept to a minimum due to questionable inter-rater reliability.
Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort
Authors: Stoltze Ulrik Kristoffer , Hildonen Mathis , Hansen Thomas Van Overeem , Foss-Skiftesvik Jon , Byrjalsen Anna , Lundsgaard Malene , Pignata Laura , Grønskov Karen , Tumer Zeynep , Schmiegelow Kjeld , Brok Jesper Sune , Wadt Karin A W
Published: April 2023

Background

Studies suggest that Wilms tumours (WT) are caused by underlying genetic (5%–10%) and epigenetic (2%–29%) mechanisms, yet studies covering both aspects are sparse.

Methods

We performed prospective whole-genome sequencing of germline DNA in Danish children diagnosed with WT from 2016 to 2021, and linked genotypes to deep phenotypes.

Results

Of 24 patients (58% female), 3 (13%, all female) harboured pathogenic germline variants in WT risk genes (FBXW7, WT1andREST). Only one patient had a family history of WT (3 cases), segregating with theRESTvariant. Epigenetic testing revealed one (4%) additional patient (female) with uniparental disomy of chromosome 11 and Beckwith-Wiedemann syndrome (BWS). We observed a tendency of higher methylation of the BWS-related imprinting centre 1 in patients with WT than in healthy controls. Three patients (13%, all female) with bilateral tumours and/or features of BWS had higher birth weights (4780 g vs 3575 g; p=0.002). We observed more patients with macrosomia (>4250 g, n=5, all female) than expected (OR 9.98 (95% CI 2.56 to 34.66)). Genes involved in early kidney development were enriched in our constrained gene analysis, including both known (WT1,FBXW7) and candidate (CTNND1, FRMD4A) WT predisposition genes. WT predisposing variants, BWS and/or macrosomia (n=8, all female) were more common in female patients than male patients (p=0.01).

Conclusion

We find that most females (57%) and 33% of all patients with WT had either a genetic or another indicator of WT predisposition. This emphasises the need for scrutiny when diagnosing patients with WT, as early detection of underlying predisposition may impact treatment, follow-up and genetic counselling.
Endovascular intervention for the treatment of epistaxis: cone beam CT review of anatomy, collateral, and treatment implications/efficacy
Authors: Hoover Madeline , Berwanger Robert , Scott John A , DeNardo Andrew , Amuluru Krishna , Payner Troy , Kulwin Charles , Raz Eytan , Gibson Daniel , Sahlein Daniel H
Published: April 2023

Epistaxis is common, impacting more than half the population, and can require procedural intervention in approximately 10% of cases. With an aging population and increasing use of antiplatelets and anticoagulants, severe epistaxis is likely to increase in frequency significantly over the next two decades. Sphenopalatine artery embolization is rapidly becoming the most common type of procedural intervention. The efficacy of endovascular embolization is dependent on a refined understanding of the anatomy and collateral physiology of this circulation as well as the impact of temporizing measures such as nasal packing and inflation of a nasal balloon. Likewise, safety is dependent on a detailed appreciation of collateralization with the internal carotid artery and ophthalmic artery. Cone beam CT imaging has the resolution to enable a clear visualization of the anatomy and collateral circulation associated with the arterial supply to the nasal cavity, in addition to assisting with hemorrhage localization. We present a review of epistaxis treatment, a detailed description of anatomic and physiologic considerations informed by cone beam CT imaging, and a proposed protocol for sphenopalatine embolization for which there is currently no standard.
A Quantitative Evaluation Method for Communication Impact of Sporting Events Based on SIR Dynamic Diffusion Model
Authors: Li Fangni , Du Siyuan
Published: April 2023

The quantitative evaluation for communicable events has been a significant demand in digital society management. This paper takes the 2022 Winter Olympic Games as the object and proposes a quantitative evaluation method for the communication impact of sporting events based on the SIR dynamic diffusion model. Specifically, this study combinesa long short-term memory (LSTM) neural network, wavelet packet decomposition, and other techniques to propose a digital evaluation approach for the quantification of communication impact. Among these, the transfer probability is quantified and calculated by the user node reputation value algorithm. In the experimental simulation, the effects of different mechanisms of joining consensus nodes and blockchain on the propagation probability in the model are discussed, respectively. Some simulation experiments are conducted on the real-world scenes of social networks, and the simulation results show that the number of nodes spreading false information is reduced by 9.89% compared with baseline methods. Finally, a sports event communication effect evaluation index system was constructed, and the data characteristics of indicators at all levels were analyzed to preliminarily predict the communication effect, after which the fuzzy hierarchical comprehensive evaluation method, combined with the expert survey method, was used to empirically evaluate, and test the communication effect of its events.
Parametrically Excited Nonlinear Pneumatic Artificial Muscle Under Hard Excitation: A Theoretical and Experimental Investigation
Authors: Kalita Bhaben , Dwivedy Santosha K.
Published: April 2023

In this work, a single degree of freedom system consisting of a mass and a Pneumatic Artificial Muscle subjected to time-varying pressure inside the muscle is considered. The system is subjected to hard excitation and the governing equation of motion is found to be that of a nonlinear forced and parametrically excited system under super- and sub-harmonic resonance conditions. The solution of the nonlinear governing equation of motion is obtained using the method of multiple scales. The time and frequency response, phase portraits, and basin of attraction are plotted to study the system response along with the stability and bifurcations. Further, the different muscle parameters are evaluated by performing experiments which are further used for numerically evaluating the system response using the theoretically obtained closed form equations. The responses obtained from the experiments are found to be in good agreement with those obtained from the method of multiple scales. With the help of examples, the procedure to obtain the safe operating range of different system parameters is illustrated.
Classification of doubly periodic untwisted (p,q)-weaves by their crossing number and matrices
Authors: Fukuda Mizuki , Kotani Motoko , Mahmoudi Sonia
Published: April 2023

A weave is the lift to the thickened Euclidean plane of a particular type of quadrivalent planar connected graph with an over or under crossing information to each vertex and such that the lifted components are non-intersecting simple open curves. In this paper, we introduce a formal topological definition of weaves as three-dimensional entangled structures and characterize the equivalence classes of doubly periodic untwisted [Formula: see text]-weaves by introducing a new invariant, called crossing matrix. Finally, we suggest a combinatorial approach to classify this specific class of weaves by their crossing number.
Synthesis and aggregation-induced emission properties of α-perimidinyl 3-pyrrolyl BODIPY
Authors: Chauhan Pinky , Behera Kanhu Charan , Ravikanth Mangalampalli
Published: April 2023

A new dye called the [Formula: see text]-perimidinyl 3-pyrrolyl BODIPY(PPyBODIPY) was synthesized readily by treating [Formula: see text]-formyl 3-pyrrolyl BODIPY with 1,8-diamino naphthalene in ethanol at reflux. The PPyBODIPY was thoroughly characterized and studied by HR-MS, 1D & 2D NMR, absorption, fluorescence and DFT/TDDFT techniques. The PPyBODIPY absorbs strongly in the 500-600 nm region and emits weakly in the region of 550–650 nm with low quantum yield. DFT optimized structure of PPyBODIPY revealed that the 3-pyrrolyl BODIPY unit was almost planar and the perimidinyl moiety was oriented at 78.88[Formula: see text] relative to appended pyrrole of 3-pyrrolyl BODIPY unit. The photophysical studies revealed that the PPyBODIPY acts as AIEgen and showed aggregation-induced emission behavior in a 60% H2O-THF mixture.
Osmium ester-hinged chlorin dimers
Authors: Chaudhri Nivedita , Dorazio Sarina J. , Samankumara Lalith P. , Daddario Pedro , Head Michelle L. , Zeller Matthias , Brückner Christian
Published: April 2023

A bis(dihydroxychlorin) osmate ester is formed as a side product in the osmylation of meso-tetraphenylporphyrin. The product can also be formed in good yield along well-known reaction pathways of osmate esters by treatment of the monomeric chlorin diol osmate ester bispyridine complex with acid. The dimer was spectroscopically characterized. The free base dimer can be metalated with zinc(II). The bis([dihydroxychlorinato]zinc) osmate ester dimer was spectroscopically and structurally characterized, showing its clamshell architecture with a 42[Formula: see text] angle between the mean planes of the two metallochlorin chromophores and a 9.11 Å zinc-to-zinc separation. Upon reaction with dimethylaminopyridine (DMAP), the clamshell structure pivots around the osmium center and arranges the two chromophores, each zinc center coordinated to DMAP, in maximum separation from each other, as shown by structural analysis. Preliminary1H NMR titration data are presented that show the bis-zinc clamshell structure to form a 1:1 supramolecular complex with diethylenetriamine (DETA), expressing a three-point recognition motive: the terminal amine functionalities coordinate to the zinc ions in each half-shell, thus bridging both chromophores, and the central amine functionality was deduced to be H-bonded to the osmium oxo group pointing toward the inside of the host. The UV-vis spectroscopic response upon DETA binding shows greater complexity in the interaction at higher ligand:host ratios, suggesting multiple binding modes. A similarly complex binding situation is also observed for the interactions of the chlorin osmate ester monomer with DETA.
Toward Understanding the Design of Intertwined Human–Computer Integrations
Authors: Mueller Florian ‘Floyd’ , Semertzidis Nathan , Andres Josh , Marshall Joe , Benford Steve , Li Xiang , Matjeka Louise , Mehta Yash
Published: April 2023

Human–computer integration is an HCI trend in which computational machines can have agency, i.e., take control. Our work focuses on a particular form of integration in which the user and the computational machine share agency over the user's body, that is, can simultaneously (in contrast to a traditional turn-taking approach) control the user's body. The result is a user experience where the agency of the user and the computational machine is so intertwined that it is often no more discernable who contributed what to what extent; we call this “intertwined integration”. Due to the recency of advanced technologies enabling intertwined integration systems, we find that little understanding and documented design knowledge exist. To begin constructing such an understanding, we use three case studies to propose two key dimensions (“awareness of machine's agency” and “alignment of machine's agency”) to articulate a design space for intertwined integration systems. We differentiate four roles that computational machines can assume in this design space (angel, butler, influencer, and adversary). Based on our craft knowledge gained through designing such intertwined integration systems, we discuss strategies to help designers create future systems. Ultimately, we aim at advancing the HCI field's emerging understanding of sharing agency.
A Chisel Framework for Flexible Design Space Exploration through a Functional Approach
Authors: Ferres Bruno , Muller Olivier , Rousseau Frédéric
Published: April 2023

As the need for efficient digital circuits is ever growing in the industry, the design of such systems remains daunting, requiring both expertise and time. In an attempt to close the gap between software development and hardware design, powerful features such as functional and object-oriented programming have been used to define new languages, known as Hardware Construction Languages. In this article, we investigate the usage of such languages—more precisely, of Chisel—in the context of Design Space Exploration, and propose a novel design methodology to build custom and adaptable design flows. We apply an innovative functional approach to define flexible strategies for design space exploration, based on the composition of basic exploration steps, and provide a library of basic strategies along with a proof-of-concept framework—which we believe to be the first Chisel-based DSE framework. This framework fully integrates within the ecosystem of Chisel to allow users to define their DSE processes in the same framework (and language) they use to describe their designs. We demonstrate our methodology through several use cases, illustrating how our functional approach makes it possible to consider various metrics of interest when building exploration processes—in particular, we provide a
quality of service
-driven exploration example.

The methodology presented in this work makes use of designers’ expertise to reduce the time required for hardware design, in particular for Design Space Exploration, and its application should ease digital design and enhance hardware developers’ productivity.
Compositional Safe Approximation of Response Time Probability Density Function of Complex Workflows
Authors: Carnevali Laura , Paolieri Marco , Reali Riccardo , Vicario Enrico
Published: April 2023

We evaluate a stochastic upper bound on the response time Probability Density Function (PDF) of complex workflows through an efficient and accurate compositional approach. Workflows consist of activities having generally distributed stochastic durations with bounded supports, composed through sequence, choice/merge, and balanced/unbalanced split/join operators, possibly breaking the structure of well-formed nesting. Workflows are specified using a formalism defined in terms of Stochastic Time Petri Nets that permits decomposition into a hierarchy of subworkflows with positively correlated response times, guaranteeing that a stochastically larger end-to-end response time PDF is obtained when intermediate results are approximated by stochastically larger PDFs and when dependencies are simplified by replicating activities appearing in multiple subworkflows. In particular, an accurate stochastically larger PDF is obtained by combining shifted truncated Exponential terms with positive or negative rates. Experiments are performed on sets of manually and randomly generated models with increasing complexity, illustrating under which conditions different decomposition heuristics work well in terms of accuracy and complexity and showing that the proposed approach outperforms simulation having the same execution time.
Robust Multi-task Learning-based Korean POS Tagging to Overcome Word Spacing Errors
Authors: Park Cheoneum , Kim Juae
Published: April 2023

End-to-end neural network-based approaches have recently demonstrated significant improvements in natural language processing (NLP). However, in the NLP application such as assistant systems, NLP components are still processed to extract results using a pipeline paradigm. The pipeline-based concept has issues with error propagation. In Korean, morphological analysis and part-of-speech (POS) tagging step, incorrectly analyzing POS tags for a sentence containing spacing errors negatively affects other modules behind the POS module. Hence, we present a multi-task learning-based POS tagging neural model for Korean with word spacing challenges. When we apply this model to the Korean morphological analysis and POS tagging, we get findings that are robust to word spacing errors. We adopt syllable-level input and output formats, as well as a simple structure for ELECTRA and RNN-CRF models for multi-task learning, and we achieve a good performance 98.30 of F1, better than previous studies on the Sejong corpus test set.
CRISPR-Based Biosensing Strategies: Technical Development and Application Prospects
Authors: Tian Tian , Zhou Xiaoming
Published: April 2023

Biosensing based on CRISPR-Cas systems is a young but rapidly evolving technology. The unprecedented properties of the CRISPR-Cas system provide an innovative tool for developing new-generation biosensing strategies. To date, a series of nucleic acid and non-nucleic acid detection methods have been developed based on the CRISPR platform. In this review, we first introduce the core biochemical properties underpinning the development of CRISPR bioassays, such as diverse reaction temperatures, programmability in design, high reaction efficiency, and recognition specificity, and highlight recent efforts to improve these parameters. We then introduce the technical developments, including how to improve sensitivity and quantification capabilities, develop multiplex assays, achieve convenient one-pot assays, create advanced sensors, and extend the applications of detection. Finally, we analyze obstacles to the commercial application of CRISPR detection technology and explore development opportunities and directions.
The Design and Application of DNA-Editing Enzymes as Base Editors
Authors: Rallapalli Kartik L. , Komor Alexis C.
Published: April 2023

DNA-editing enzymes perform chemical reactions on DNA nucleobases. These reactions can change the genetic identity of the modified base or modulate gene expression. Interest in DNA-editing enzymes has burgeoned in recent years due to the advent of clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) systems, which can be used to direct their DNA-editing activity to specific genomic loci of interest. In this review, we showcase DNA-editing enzymes that have been repurposed or redesigned and developed into programmable base editors. These include deaminases, glycosylases, methyltransferases, and demethylases. We highlight the astounding degree to which these enzymes have been redesigned, evolved, and refined and present these collective engineering efforts as a paragon for future efforts to repurpose and engineer other families of enzymes. Collectively, base editors derived from these DNA-editing enzymes facilitate programmable point mutation introduction and gene expression modulation by targeted chemical modification of nucleobases.
Padlock Probe–Based Targeted In Situ Sequencing: Overview of Methods and Applications
Authors: Magoulopoulou Anastasia , Salas Sergio Marco , Tiklová Katarína , Samuelsson Erik Reinhold , Hilscher Markus M. , Nilsson Mats
Published: April 2023

Elucidating spatiotemporal changes in gene expression has been an essential goal in studies of health, development, and disease. In the emerging field of spatially resolved transcriptomics, gene expression profiles are acquired with the tissue architecture maintained, sometimes at cellular resolution. This has allowed for the development of spatial cell atlases, studies of cell–cell interactions, and in situ cell typing. In this review, we focus on padlock probe–based in situ sequencing, which is a targeted spatially resolved transcriptomic method. We summarize recent methodological and computational tool developments and discuss key applications. We also discuss compatibility with other methods and integration with multiomic platforms for future applications.
Throat Swab Culture Positivity and Antibiotic Resistance Profiles in Children 2–5 Years of Age Suspected of Bacterial Tonsillitis at Hargeisa Group of Hospitals, Somaliland: A Cross-Sectional Study
Authors: Darod Hamda Hussein , Melese Addisu , Kibret Mulugeta , Mulu Wondemagegn
Published: April 2023

Introduction. Tonsillitis is the third most frequently diagnosed infection in the pediatric age and is associated with significant morbidity and loss of school attendance. Throat swab cultures are useful for the confirmation of children with a clinically suspected tonsillitis. However, Somaliland is one of the underdeveloped countries with a low standard of sanitation and poor health seeking culture. Treatment of tonsillitis with antibiotics is irrational and not empirical. This study determined the bacterial throat swab culture positivity and antibiotic resistance profiles of the bacterial isolates among children 2–5 years of age with suspicion of tonsillitis at Hargeisa Group of Hospital, Somaliland. Materials and Methods. A cross-sectional study was conducted from March to July 2020. A total of 374 children from 2 to 5 years of age suspicion of tonsillitis was included using a convenient sampling method. Throat swabs were collected, and bacterial isolation and identification were done using standard bacteriological procedures. Antimicrobial susceptibility testing was done using the disk diffusion method. Data on demographic variables and clinical profiles were collected using structured questionnaires. Logistic regression analysis was computed to identify factors associated with bacterial tonsillitis. Results. Overall, 120 (32.1%) (95% CI 27.4–36.8%) of children were positive for bacterial throat cultures. Of these, 23 (19.2%) were mixed bacterial isolates. The most frequent bacterial isolates were beta-hemolytic streptococci 78 (55%), Staphylococcus aureus 42 (29%), and Streptococcus pneumoniae 10 (7%). Isolates revealed 83.3–100% rate of resistance to ampicillin. Beta-hemolytic streptococci isolates were 94.9% resistant to ampicillin. S. aureus was resistant to clarithromycin (38%) while S. pneumoniae isolates were 100% resistant to ampicillin. History of tonsillitis (AOR = 0.12; 95% CI = 0.06–0.21), difficulty in swallowing (AOR = 6.99; 95% CI = 3.56–13.73), and attending schools (AOR = 2.98; 95% CI = 1.64–5.42) were found to be associated with positive throat culture. Conclusions. Resistance to ampicillin and MDR among beta-hemolytic streptococci and other isolates of throat colonizers in children with clinically suspected of bacterial tonsillitis are major concerns in Hargeisa, Somaliland. Therefore, treatments of cases are recommended to be guided by regular culture and antimicrobial susceptibility testing to prevent complications of tonsillitis and associated antibiotic resistance.
Oxidative Changes in Ten Vegetable Oils Caused by the Deep-Frying Process of Potato
Authors: Yılmaz Birsen , Şahin Teslime Özge , Ağagündüz Duygu
Published: April 2023

Deep-fried foods are among the foods that are increasing in popularity both in the food industry and in domestic applications. While these foods stand out due to their sensory properties, oxidative alterations in frying oils cause concern. This study analysed the thermo-oxidative alterations that occur during deep frying with 10 commonly used culinary oils. Deep frying processes (180 ± 5°C) were carried out with a total of one liter of each type of oil and 100-g potatoes at every turn (sliced into 1 cm

∗

1 cm

∗

6 cm pieces). The process was carried out keeping the conditions constant for all oils and was repeated 10 times consecutively for all oils. The malondialdehyde and peroxide values of vegetable ghee (VG) were found to be 0.669 nmol/g and 21.0 mEqO2/kg, respectively, and were higher than those of other oils. Extra virgin olive oil (EVOO) (232.23) had the highest iodine value, while hazelnut oil (HO) (27.92) had the lowest value. While total polar compounds were within legal limits in all oils, they were higher (17%–23%) in EVOO, palm oil (PO), VG, and refined olive pomace oil than in other oils (17%–23%). As a result of this study, the thermo-oxidative changes in frying made with sunflower oil types are less than those of other oils, and the oxidative product/polar compound levels, which have adverse effects on health, are close to the legal limit in some oils (PO, VG, refined olive pomace, and corn oil).
Monitoring Spike Potential and Abrupt Impedance Rise with Concomitant Temperature/Contact Force Change for Timely Detection of the Occurrence of “Silent” or “Nonaudible” Steam Pop
Authors: Di Chengye , Wang Qun , Wu Yanxi , Li Longyu , Lin Wenhua
Published: April 2023

Aim. Steam pop (SP) during radiofrequency catheter ablation (RFCA) for pulmonary vein isolation (PVI) may cause cardiac perforation, which may require drainage and emergent thoracotomy or even lead to death. Data investigating the timely detection of the occurrence of “silent” or “nonaudible” SP events are limited. Methods and Results. A total of 516 consecutive atrial fibrillation (AF) patients who underwent index PVI were included in this retrospective observational study. The duration, power, impedance, temperature, and contact force (CF) of RFCA were continually monitored and recorded throughout the procedure. A total of 15 (2.9%) audible SP events occurred in 14 patients; 2 of the patients developed pericardial tamponade, 1 patient underwent drainage, and 1 patient underwent emergent thoracotomy. The time from RFCA initiation to the occurrence of audible SP was 19.4 ± 6.9 s. Abrupt temperature change occurred in 13 (86.7%) of the 15 SP events, of which 8 (53.3%) exhibited an abrupt temperature rise of 2.3 ± 1.0°C, 5 (33.3%) exhibited an abrupt temperature drop of 2.3 ± 1.3°C, and 2 (13.3%) exhibited no discernible temperature change. Conclusions. In conclusion, simultaneously recorded spike potentials and abrupt impedance rise with concomitant temperature and/or CF change could be a feasible method for the timely detection of the occurrence of audible, “silent,” or “nonaudible” SP events, particularly in regions where the risk of perforation may be of concern.
The Roles and Mechanisms of Gut Microbiota in Food Allergy
Authors: Cheng Yiwen , Liu Xia , Chen Feng , Rolnik Benjamin M. , Chleilat Faye , Ling Zongxin , Snyder Michael P. , Zhou Xin
Published: April 2023

Recent research reveals that the increasing prevalence of food allergies (FA) is due in part to changes in the commensal microbiome. Studies in humans have shown that compared with healthy controls, individuals have distinct gut microbiomes during the onset and progression of FA. Mechanistic studies have established that the gut microbiota can affect the growth of immune tolerance to food antigens by modifying regulatory T cell differentiation, regulating basophil populations, and enhancing intestinal barrier function. New therapeutic and preventive approaches to altering the gut microbiota using diet adjustments, probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and Chinese medicine have been developed towards FA. Herein, we summarized the latest evidence on the gut microbiota profiles and functions associated with FA, oral tolerance mechanisms, and gut microbiota-targeted therapeutic strategies for FA.
Data from Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riuye , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: April 2023

AbstractPurpose:
To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation.
Patients and Methods:
Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.
Results:
Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9–17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60–1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15–1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events.
Conclusions:
An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.
Supplementary Figures 1-2, Tables 1-3 from βII-Tubulin and βIII-Tubulin Mediate Sensitivity to Peloruside A and Laulimalide, but not Paclitaxel or Vinblastine, in Human Ovarian Carcinoma Cells
Authors: Kanakkanthara Arun , Northcote Peter T. , Miller John H.
Published: April 2023

PDF file - 1.6MB
Supplementary Figure 1 from [18F]-FLT Positron Emission Tomography Can Be Used to Image the Response of Sensitive Tumors to PI3-Kinase Inhibition with the Novel Agent GDC-0941
Authors: Cawthorne Christopher , Burrows Natalie , Gieling Roben G. , Morrow Christopher J. , Forster Duncan , Gregory Jamil , Radigois Marc , Smigova Alison , Babur Muhammad , Simpson Kathryn , Hodgkinson Cassandra , Brown Gavin , McMahon Adam , Dive Caroline , Hiscock Duncan , Wilson Ian , Williams Kaye J.
Published: April 2023

PDF file - 74 KB, GDC-0941 inhibits hypoxic signaling in drug sensitive U87 tumors.
Supplementary Table 1 from Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma
Authors: Knutson Sarah K. , Kawano Satoshi , Minoshima Yukinori , Warholic Natalie M. , Huang Kuan-Chun , Xiao Yonghong , Kadowaki Tadashi , Uesugi Mai , Kuznetsov Galina , Kumar Namita , Wigle Tim J. , Klaus Christine R. , Allain Christina J. , Raimondi Alejandra , Waters Nigel J. , Smith Jesse J. , Porter-Scott Margaret , Chesworth Richard , Moyer Mikel P. , Copeland Robert A. , Richon Victoria M. , Uenaka Toshimitsu , Pollock Roy M. , Kuntz Kevin W. , Yokoi Akira , Keilhack Heike
Published: April 2023

PDF file - 25K, Table S1: LCC Values for EPZ-6438 for WSU-DLCL2 Human Lymphoma Cells Dosed Either Continuously or After Compound Washout.
Supplementary Figure 4 from Nedd8-Activating Enzyme Inhibitor MLN4924 Provides Synergy with Mitomycin C through Interactions with ATR, BRCA1/BRCA2, and Chromatin Dynamics Pathways
Authors: Garcia Khristofer , Blank Jonathan L. , Bouck David C. , Liu Xiaozhen J. , Sappal Darshan S. , Hather Greg , Cosmopoulos Katherine , Thomas Michael P. , Kuranda Mike , Pickard Michael D. , Liu Ray , Bandi Syamala , Smith Peter G. , Lightcap Eric S.
Published: April 2023

PDF file - 145KB, Comparison of the Degree of Interaction between MLN4924 and 14 Different Agents as Measured by Nonlinear Blending Values.
Supplementary Figure 4 from Blockade of mTOR Signaling via Rapamycin Combined with Immunotherapy Augments Antiglioma Cytotoxic and Memory T-Cell Functions
Authors: Mineharu Yohei , Kamran Neha , Lowenstein Pedro R. , Castro Maria G.
Published: April 2023

Supplementary Figure 4: Rapamycin enhances therapeutic efficacy of anti-GBM DC vaccine
Supplementary Materials and Methods, Supplementary Tables 1 through 3, and Supplementary Figures 1 through 8 from Tunicamycin Potentiates Cisplatin Anticancer Efficacy through the DPAGT1/Akt/ABCG2 Pathway in Mouse Xenograft Models of Human Hepatocellular Carcinoma
Authors: Hou Helei , Sun Hefen , Lu Ping , Ge Chao , Zhang Lixing , Li Hong , Zhao Fangyu , Tian Hua , Zhang Lin , Chen Taoyang , Yao Ming , Li Jinjun
Published: April 2023

PDF - 922KB, Supplementary Materials and Methods. Supplementary Table S1: Drugs and chemical reagents. Supplementary Table S2: Primers used for Real-time PCR and other sequences. Supplementary Table S3: Antibodies used in this study. Supplementary Figure S1. The expression of ABCG2 was correlated with drug resistance of HCC. Supplementary Figure S2. TM inhibited ABCG2 expression in both HCC and other tumor cell lines. Supplementary Figure S3. Glycosylation inhibitors influenced SP of HCC cells. Supplementary Fig. S4 TM inhibited ABCG2 and p-Akt expression in CD133+/- MHCC-97L cells nude mouse models. Supplementary Figure S5. The anti-tumor effect of chemotherapeutic drugs combined with TM in PLC/PRF/5 cells was evaluated by Western blotting. Supplementary Figure S6. TM enhanced the therapeutic effect of CDDP through Akt-ABCG2 pathway in vivo. Supplementary Figure S6. TM inhibited the glycosylation of EGFR and blocked its downstream signalling. Supplementary Figure S8. The combination treatment effect of sorafenib and TM was evaluated in HCC cell lines.
Supplementary Figure 2 from Biochemical Assays for the Discovery of TDP1 Inhibitors
Authors: Marchand Christophe , Huang Shar-yin N. , Dexheimer Thomas S. , Lea Wendy A. , Mott Bryan T. , Chergui Adel , Naumova Alena , Stephen Andrew G. , Rosenthal Andrew S. , Rai Ganesha , Murai Junko , Gao Rui , Maloney David J. , Jadhav Ajit , Jorgensen William L. , Simeonov Anton , Pommier Yves
Published: April 2023

PDF - 188K, Suface Plasmon Resonance (SPR) profiles binding for JLT048 and NCGC00183674 to recombinant TDP1 bound to the surface.
Supplementary Tables 4 and 5 from Rationale and Preclinical Efficacy of a Novel Anti-EMP2 Antibody for the Treatment of Invasive Breast Cancer
Authors: Fu Maoyong , Maresh Erin L. , Helguera Gustavo F. , Kiyohara Meagan , Qin Yu , Ashki Negin , Daniels-Wells Tracy R. , Aziz Najib , Gordon Lynn K. , Braun Jonathan , Elshimali Yahya , Soslow Robert A. , Penichet Manuel L. , Goodglick Lee , Wadehra Madhuri
Published: April 2023

PDF - 64K, Supplementary Table 4. Evaluation of EMP2 IgG1 toxicity compared to control IgG following 7 weeks of treatment delivered systemically IP. Supplementary Table 5. Evaluation of EMP2 IgG1 toxicity compared to control IgG following systemic IP treatment of up to 40mg/kg.
Supplementary Figure 3 from Antiproliferative Effects of Continued Mitogen-Activated Protein Kinase Pathway Inhibition following Acquired Resistance to BRAF and/or MEK Inhibition in Melanoma
Authors: Carlino Matteo S. , Gowrishankar Kavitha , Saunders Catherine A.B. , Pupo Gulietta M. , Snoyman Stephanie , Zhang Xu Dong , Saw Robyn , Becker Therese M. , Kefford Richard F. , Long Georgina V. , Rizos Helen
Published: April 2023

PDF file - 1073K, BRAF inhibition does not reduce the proliferation of wild-type BRAF melanoma cells.
Supplementary Table 1 from Mechanism of Differentiation-Enhanced Photodynamic Therapy for Cancer: Upregulation of Coproporphyrinogen Oxidase by C/EBP Transcription Factors
Authors: Anand Sanjay , Hasan Tayyaba , Maytin Edward V.
Published: April 2023

PDF file - 64K, Oligo sequences.
Supplementary Figure 1 from Preclinical Characterization of AMG 330, a CD3/CD33-Bispecific T-Cell–Engaging Antibody with Potential for Treatment of Acute Myelogenous Leukemia
Authors: Friedrich Matthias , Henn Anja , Raum Tobias , Bajtus Monika , Matthes Katja , Hendrich Larissa , Wahl Joachim , Hoffmann Patrick , Kischel Roman , Kvesic Majk , Slootstra Jerry W. , Baeuerle Patrick A. , Kufer Peter , Rattel Benno
Published: April 2023

PDF file - 83KB, Supplementary Figure S1. Characteristics of purified AMG 330.
Supplementary Figure Legends from New Insights into PARP Inhibitors' Effect on Cell Cycle and Homology-Directed DNA Damage Repair
Authors: Jelinic Petar , Levine Douglas A.
Published: April 2023

PDF - 51K, Legends for Supplementary Figures.
Supplementary Table 5 from Selective Activity of the Histone Deacetylase Inhibitor AR-42 against Leukemia Stem Cells: A Novel Potential Strategy in Acute Myelogenous Leukemia
Authors: Guzman Monica L. , Yang Neng , Sharma Krishan K. , Balys Marlene , Corbett Cheryl A. , Jordan Craig T. , Becker Michael W. , Steidl Ulrich , Abdel-Wahab Omar , Levine Ross L. , Marcucci Guido , Roboz Gail J. , Hassane Duane C.
Published: April 2023

PDF - 306K, Differentially expressed genes upon AR-42 treatment.
Supplementary Figure 1 from Characterization of the Novel and Specific PI3Kα Inhibitor NVP-BYL719 and Development of the Patient Stratification Strategy for Clinical Trials
Authors: Fritsch Christine , Huang Alan , Chatenay-Rivauday Christian , Schnell Christian , Reddy Anupama , Liu Manway , Kauffmann Audrey , Guthy Daniel , Erdmann Dirk , De Pover Alain , Furet Pascal , Gao Hui , Ferretti Stephane , Wang Youzhen , Trappe Joerg , Brachmann Saskia M. , Maira Sauveur-Michel , Wilson Christopher , Boehm Markus , Garcia-Echeverria Carlos , Chene Patrick , Wiesmann Marion , Cozens Robert , Lehar Joseph , Schlegel Robert , Caravatti Giorgio , Hofmann Francesco , Sellers William R.
Published: April 2023

PDF - 37K, NVP-BYL719 was tested at 10 different concentrations (from 0.5 nmol/L to 10 μmol/L in 1 third dilution steps) against CLK2 (A) and LRRK2 (B). SelectScreenTM Kinase Profiling Service uses XLfit from IDBS to determine the IC50 values (IC50 CLK2=621 nmol/L; IC50 LRRK2=3'220 nmol/L). The dose response curve is curve fit to model number 205 (sigmoidal dose-response model).
Supplementary Figure 4 from Expression of Leukemia-Associated Fusion Proteins Increases Sensitivity to Histone Deacetylase Inhibitor–Induced DNA Damage and Apoptosis
Authors: Petruccelli Luca A. , Pettersson Filippa , del Rincón Sonia V. , Guilbert Cynthia , Licht Jonathan D. , Miller Wilson H.
Published: April 2023

PDF file - 842K, PLZF-RARα and vorinostat induce a G2-M arrest in PLZFRARβ3 cells.
Supplementary Figure 2 from Inhibition of Akt Reverses the Acquired Resistance to Sorafenib by Switching Protective Autophagy to Autophagic Cell Death in Hepatocellular Carcinoma
Authors: Zhai Bo , Hu Fengli , Jiang Xian , Xu Jun , Zhao Dali , Liu Bing , Pan Shangha , Dong Xuesong , Tan Gang , Wei Zheng , Qiao Haiquan , Jiang Hongchi , Sun Xueying
Published: April 2023

PDF file - 224K, Supplementary Fig. S2.Sorafenib activates the Akt pathway independent of PP2A in hepatocellular carcinoma cells.
Supplementary Methods and Figure Legends from Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner
Authors: Cerezo Michaël , Tichet Mélanie , Abbe Patricia , Ohanna Mickaël , Lehraiki Abdelali , Rouaud Florian , Allegra Maryline , Giacchero Damien , Bahadoran Philippe , Bertolotto Corine , Tartare-Deckert Sophie , Ballotti Robert , Rocchi Stéphane
Published: April 2023

PDF - 69K, Supplemental methods and supplemental figure legend.