bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between COVID-19 vaccination and menstruation: a state of the science review
Authors: Payne Laura A , Wise Lauren A , Wesselink Amelia K , Wang Siwen , Missmer Stacey A , Edelman Alison
Published: June 2024

Introduction

Menstrual health is a key patient-reported outcome beyond its importance as a general indicator of health and fertility. However, menstrual function was not measured in the clinical trials of COVID-19 vaccines. The purpose of this review was to synthesise the existing literature on the relationship between COVID-19 vaccination and menstrual health outcomes.

Methods

A PubMed search to 31 October 2023 identified a total of 53 publications: 11 prospective cohort studies, 11 retrospective cohort studies or registry-based cohort studies, and 31 cross-sectional or retrospective case–control studies.

Results

Identified studies were generally at moderate-to-high risk of bias due to retrospective design, interviewer bias, and failure to include a non-vaccinated control group. Nonetheless, the bulk of the literature demonstrates that COVID-19 vaccine is associated with temporary changes in menstrual characteristics (cycle length and flow) and menstrual pain. Follicular phase (at the time of vaccination) is associated with greater increases in cycle length. Evidence suggests temporary post-vaccine menstrual changes in adolescents, abnormal vaginal bleeding in postmenopausal individuals, and a potential protective effect of using hormonal contraception.

Conclusions

In this review we found evidence supporting an association between the COVID-19 vaccine and menstrual health outcomes. Given the importance of menstrual function to overall health, we recommend that all future vaccine trials include menstruation as a study outcome. Future vaccine studies should include rigorous assessment of the menstrual cycle as an outcome variable to limit sources of bias, identify biological mechanisms, and elucidate the impact of stress.
Evolutions in care, unmet needs, and research priorities in heart failure
Authors: Halliday Brian P , Ahmed Fozia Z , Beezer Janine , Fuat Ahmet , Ludman Andrew J , Pellicori Pierpaolo , Savage Henry Oluwasefunmi , Taylor Clare J , Cleland John G F
Published: June 2024

The current treatment landscape for heart failure is predominantly stratified using ejection fraction. Established drug combinations and devices such as cardiac resynchronisation therapy are available for heart failure with reduced ejection fraction (HFrEF), but medical options for heart failure with preserved ejection fraction (HFpEF) have, until recently, been lacking.

A major advance in recent years has been the discovery of effective therapies for HFpEF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors and perhaps also the mineralocorticoid receptor antagonist, spironolactone. For patients with atrial fibrillation and heart failure, the benefit of rhythm control with either radiofrequency ablation or medical therapy is uncertain. Targeted therapies for the small proportion of patients with transthyretin cardiac amyloidosis are available, while antifibrotics seem promising for a larger proportion of patients.

For patients with HFrEF, additional treatment options have emerged in the past 10 years. The angiotensin receptor–neprilysin inhibitor (ARNI) combination sacubitril–valsartan and SGLT-2 inhibitors reduce mortality and improve life expectancy in symptomatic patients with HFrEF and at least mildly elevated plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). The oral soluble guanylate cyclase stimulator vericiguat and cardiac myosin activator omecamtiv mecarbil are not yet licensed in the UK but may provide further treatment options, perhaps in more select groups of patients.

Whether all patients with a prior diagnosis of HFrEF who are now in heart failure remission should continue all therapies at maximum tolerated dose indefinitely remains a dilemma. Individualised de-escalation of therapy remains controversial due to the risk of relapse but is occasionally trialled, particularly in patients with a triggering factor such as pregnancy. The ultimate aim is a personalised treatment plan—based on disease phenotype and trajectory—that minimises the risk of relapse and maximises the individual’s quality of life.
High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)
Authors: Moutafi Myrto K , Bates Katherine M , Aung Thazin Nwe , Milian Rolando Garcia , Xirou Vasiliki , Vathiotis Ioannis A , Gavrielatou Niki , Angelakis Athanasios , Schalper Kurt A , Salichos Leonidas , Rimm David L
Published: June 2024

Background

Despite the impressive outcomes with immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC), only a minority of the patients show long-term benefits from ICI. In this study, we used retrospective cohorts of ICI treated patients with NSCLC to discover and validate spatially resolved protein markers associated with resistance to programmed cell death protein-1 (PD-1) axis inhibition.

Methods

Pretreatment samples from 56 patients with NSCLC treated with ICI were collected and analyzed in a tissue microarray (TMA) format in including four different tumor regions per patient using the GeoMx platform for spatially informed transcriptomics. 34 patients had assessable tissue with tumor compartment in all 4 TMA spots, 22 with leukocyte compartment and 12 with CD68 compartment. The patients’ tissue that was not assessable in fourfold redundancy in each compartment was designated as the validation cohort; cytokeratin (CK) (N=22), leukocytes CD45 (N=31), macrophages, CD68 (N=43). The human whole transcriptome, represented by~18,000 individual genes assessed by oligonucleotide-tagged in situ hybridization, was sequenced on the NovaSeq platform to quantify the RNAs present in each region of interest.

Results

54,000 gene variables were generated per case, from them 25,740 were analyzed after removing targets with expression lower than a prespecified frequency. Cox proportional-hazards model analysis was performed for overall and progression-free survival (OS, PFS, respectively). After identifying genes significantly associated with limited survival benefit (HR>1)/progression per spot per patient, we used the intersection of them across the four TMA spots per patient. This resulted in a list of 12 genes in the tumor-cell compartment (RPL13A, GNL3, FAM83A, CYBA, ACSL4, SLC25A6, EPAS1, RPL5, APOL1, HSPD1, RPS4Y1, ADI1). RPL13A, GNL3in tumor-cell compartment were also significantly associated with OS and PFS, respectively, in the validation cohort (CK: HR, 2.48; p=0.02 and HR, 5.33; p=0.04). In CD45 compartment, secreted frizzled-related protein 2, was associated with OS in the discovery cohort but not in the validation cohort. Similarly, in the CD68 compartmentARHGAPand PNN interacting serine and arginine rich protein were significantly associated with PFS and OS, respectively, in the majority but not all four spots per patient.

Conclusion

This work highlightsRPL13AandGNL3as potential indicative biomarkers of resistance to PD-1 axis blockade that might help to improve precision immunotherapy strategies for lung cancer.
Exploring compact stellar structures in Finsler–Randers geometry with the Barthel connection
Authors: Praveen J. , Narasimhamurthy S. K. , Yashwanth B. R.
Published: June 2024

This study introduces a pioneering approach to analyzing compact stars through Finslerian geometry, which has not been previously explored in this context. By employing the Barthel connection within Finsler–Randers spaces, the research derives a novel metric for compact stars, utilizing the unique geometric nature of spacetime inherent in Finslerian geometry. This offers a fresh perspective on understanding the structure of these stars, departing from the traditional Riemannian geometry commonly used in astrophysics. Specifically, the investigation delves into the Randers metric within Finslerian geometry to investigate the dynamics of these celestial bodies. It defines a component of Randers space, denoted as $$\eta (r)=a+\frac{br^{2}}{R^{2}}$$

η

(
r
)

=
a
+

b

r
2

R
2

, where a and b are constants, r represents radial distance, and R signifies the observed radius of the star. The research focuses on developing metric potentials within the Finslerian framework, enabling a comprehensive comparative analysis of their regularity. By leveraging the unique physical properties of compact stars, the study determines the values of constants “a” and “b,” as well as those associated with metric potentials. Through an analysis of four distinct compact stars, the research provides valuable insights into various physical attributes based on estimated data. Furthermore, the investigation explores thermodynamic quantities derived within the Finslerian framework, contributing to the characterization of these compact stars. The study emphasizes the stability inherent in the configuration of compact stars under Finsler space geometry, indicating the potential applicability of Finsler geometry in understanding and characterizing celestial bodies in astrophysics.
Sentiment Analysis-Based Automatic Stress and Emotion Recognition using Weighted Fused Fusion-Based Cascaded DTCN with Attention Mechanism from EEG Signal
Authors: Kathole Atul B. , Lonare Savita , Dharmale Gulbakshee , Katti Jayashree , Vhatkar Kapil , Kimbahune Vinod V.
Published: June 2024

When loaded with difficulties in fulfilling daily requirements, a lot of people in today’s world experience an emotional pressure known as stress. Stress that lasts for a short duration of time has more advantages as they are good for mental health. But, the persistence of stress for a long duration of time may lead to serious health impacts in individuals, such as high blood pressure, cardiovascular disease, stroke and so on. Long-term stress, if unidentified and not treated, may also result in personality disorder, depression and anxiety. The initial detection of stress has become more important to prevent the health issues that arise due to stress. Detection of stress based on brain signals for analysing the emotion in humans leads to accurate detection outcomes. Using EEG-based detection systems and disease, disability and disorders can be identified from the brain by utilising the brain waves. Sentiment Analysis (SA) is helpful in identifying the emotions and mental stress in the human brain. So, a system to accurately and precisely detect depression in human based on their emotion through the utilisation of SA is of high necessity. The development of a reliable and precise Emotion and Stress Recognition (ESR) system in order to detect depression in real-time using deep learning techniques with the aid of Electroencephalography (EEG) signal-based SA is carried out in this paper. The essentials needed for performing stress and emotion detection are gathered initially from benchmark databases. Next, the pre-processing procedures, like the removal of artifacts from the gathered EEG signal, are carried out on the implemented model. The extraction of the spectral attributes is carried out from the pre- processed. The extracted spectral features are considered the first set of features. Then, with the aid of a Conditional Variational Autoencoder (CVA), the deep features are extracted from the pre-processed signals forming a second set of features. The weights are optimised using the Adaptive Egret Swarm Optimisation Algorithm (AESOA) so that the weighted fused features are obtained from these two sets of extracted features. Then, a Cascaded Deep Temporal Convolution Network with Attention Mechanism (CDTCN-AM) is used to recognise stress and emotion. The validation of the results from the developed stress and emotion recognition approach is carried out against traditional models in order to showcase the effectiveness of the suggested approach.
Noncommutative of Klein–Gordon and Schrödinger equations in the background of the improved Hua plus modified Eckart potential model in 3D-(R/NR)NCQS symmetries: Spectrum and thermodynamic properties
Authors: Maireche Abdelmadjid
Published: June 2024

The impact of deformation space on the physical characteristics of diverse physics systems has been thoroughly investigated in research papers. In this work, we study the deformed Klein–Gordon equation (DKGE) in the three-dimensional relativistic non-commutative quantum space (3D-RNCQS) regime by using the improved Hua plus modified Eckart potential (IHPMEP) model. For this consideration, the DKGE in the 3D-RNCQS regime is solved using the standard perturbation theory and the well-known Bopp’s shifts method with the Greene–Aldrich approximation to the centrifugal barrier. The new relativistic energy equation and eigenfunction for the IHPMEP in the presence of deformation space-space for the heterogeneous (CO, HF, and NO) and homogeneous (N2, H2, and Li2) diatomic molecules are obtained to be sensitive to the atomic quantum numbers ([Formula: see text] and [Formula: see text]), the mixed potential depths ([Formula: see text], and [Formula: see text]), the inverse of the screening parameter [Formula: see text], and non-commutativity parameters ([Formula: see text], [Formula: see text], and [Formula: see text]). Analysis is performed on the non-relativistic limit of new energy spectra. By appropriately adjusting the combined potential parameters, we analyze the obtained new bound state eigenvalues of the DKGE and deformed Schrödinger equation with the IHPMEP in 3D-NCQS symmetries and obtain the new modified Eckart potential, the modified Hua potential, the modified Morse potential, and the modified Pöschl–Teller potential. Within the framework of the 3D-NRNCQS regime, the homogeneous and heterogeneous composite systems under IHPMEP models are examined. A thorough investigation is carried out into the impact of space-space deformation on the thermal parameters of the IHPMEP, including the partition function, mean energy, free energy, specific heat, and entropy. This work is of a fundamental absorbability nature and pedagogical interest in atomic and molecular physics.
Training with a Visual-Haptic Simulator for Trocar Insertion
Authors: Hassun Andres , Kho Kimberly , Williams-Brown M. Yvette , Fey Ann Majewicz
Published: June 2024

Trocar insertion is a critical first step of all minimally invasive surgery; however, it also carries a high risk for errors. Studies suggest that entry errors are the most common complication in laparoscopic surgery with 4% of errors leading to patient fatality. Surgeon error due to excessive force is often the cause for entry errors; however, adequate training has been shown to reduce the risk of these surgical errors. In practice, institutions lack widespread and relatively inexpensive means to train surgeons for trocar entry that does not involve patient risk. In our prior work, we presented a simple Stewart platform haptic device with a numerical model to simulate key force characteristics of trocar insertion. Evaluation in our first study was limited to device characterization. In this paper, we present a more robust haptic mechanism with higher fidelity linear actuators, an increased workspace, and tissue visualization to accompany haptic cues. We also present a novel upper module that allows for a sudden drop of the trocar after the final puncture event to create a more realistic simulation. We performed a user study with eight novices to investigate how well the device and visualization train users in the trocar insertion procedure. By the end of the experiment, subjects using the device had a normalized error reduction of roughly 85% on average, relative to themselves. This device shows potential for widespread training of trocar insertion, possibly leading to fewer complications and deaths following the procedure. Finally, our upper module also represents an innovative addition for traditional admittance-type haptic device designs, not typically capable of accurately representing motion in free space.
Exploring Plant-Derived Bioactive Compounds in Olea Europaea L. Leaves as Potent Inhibitors of PTP-1B Using an In silico Approach
Authors: Deshpande N. Shridhar , Wagh Shrutesh , Sharma Abhishek Prakash , Ramesh Amgoth , Mahindra  , Lavanya  , Moksha B. S. , Divyashree  , Disha  , Dixit Sheshagiri R. , Singh Deepshikha , Bidye Durgesh Paresh , Revanasiddappa B. C.
Published: June 2024

In this study, we focus on exploring the medicinal potential of Olea Europaea L., a commonly used plant with diverse indigenous medicinal applications. The main aim is to identify promising phytoconstituents from Olea Europaea L. leaves that can act as inhibitors for the PTP-1B target, utilizing an in silico approach. The phytoconstituents were sourced from the IMMPAT database, and molecular docking was employed to assess their binding affinities. The docking results revealed that rutin (−10.05 kcal/mol) and quercetin (−8.28 kcal/mol) displayed the highest binding scores against PTP-1B, outperforming reference compounds. Furthermore, MM-GBSA calculations indicated favorable free binding energy. To ensure stability, 200 ns Molecular Dynamics simulations were conducted on the 2QBS-Rutin complex. The results revealed that the 2QBS-Rutin complex showed stable conformation throughout the simulation, maintaining consistency with RMSD values below 1 Å. This study highlights rutin and quercetin as promising phytoconstituents from Olea Europaea L. leaves, demonstrating potent-binding affinities against PTP-1B inhibitors.
Adopting a systems engineering approach to a feasibility study of a sidings development at the Midsomer Norton railway station
Authors: Ekici Üsame
Published: June 2024

It is planned to reopen Midsomer Norton railway station, which is a station on the Somerset & Dorset Heritage Railway Line, to traffic. As a first step, Midsomer Norton will be a terminus, and it is proposed to build sidings and a depot for the trains that terminate there. However, a ground investigation is essential before commencing construction of the sidings and the depot, as this is a vital part of any civil engineering process. The behaviour of the ground must be known in order for a structure to be supported by it; therefore, data from the ground investigation are used as reference for any kind of structure development. This study covers a site investigation that includes a desk study, walkover survey, sampling and laboratory testing in order to ascertain the feasibility of a suitable design. Moisture content testing, liquid limit and plastic limit tests, standard compaction testing, shear vane tests, and triaxial compression tests were carried out to determine the soil characteristics and to analyse the soil behaviour. A strong recommendation was made to follow a systems engineering approach in the construction phase, as well as in the design stage. The dependability of the system is ensured by the good use of V – process of systems engineering.
Quantum Speed-Ups for String Synchronizing Sets, Longest Common Substring, and
k
-mismatch Matching
Authors: Jin Ce , Nogler Jakob
Published: June 2024

Longest common substring (LCS)
is an important text processing problem, which has recently been investigated in the quantum query model. The decision version of this problem,
LCS with threshold

\(d\)

, asks whether two length-

\(n\)

input strings have a common substring of length

\(d\)

. The two extreme cases,

\(d=1\)

and

\(d=n\)

, correspond, respectively to Element Distinctness and Unstructured Search, two fundamental problems in quantum query complexity. However, the intermediate case

\(1\ll d\ll n\)

was not fully understood. We show that the complexity of LCS with threshold

\(d\)

smoothly interpolates between the two extreme cases up to

\(n^{o(1)}\)

factors:

—

LCS with threshold

\(d\)

has a quantum algorithm in

\(n^{2/3+o(1)}/d^{1/6}\)

query complexity and time complexity, and requires at least

\(\Omega(n^{2/3}/d^{1/6})\)

quantum query complexity.

Our result improves upon previous upper bounds

\(\widetilde{O}(\min\{n/d^{1/2},n^{2/3}\})\)

(Le Gall and Seddighin ITCS 2022, Akmal and Jin SODA 2022), and answers an open question of Akmal and Jin. Our main technical contribution is a quantum speed-up of the powerful
String Synchronizing Set
technique introduced by Kempa and Kociumaka (STOC 2019). It consistently samples

\(n/\tau^{1-o(1)}\)

synchronizing positions in the string depending on their length-

\(\Theta(\tau)\)

contexts, and each synchronizing position can be reported by a quantum algorithm in

\(\widetilde{O}(\tau^{1/2+o(1)})\)

time. Our quantum string synchronizing set also yields a near-optimal LCE data structure in the quantum setting. As another application of our quantum string synchronizing set, we study the

\(k\)

-mismatch Matching
problem, which asks if the pattern has an occurrence in the text with at most

\(k\)

Hamming mismatches. Using a structural result of Charalampopoulos et al. (FOCS 2020), we obtain:

—

\(k\)

-mismatch matching has a quantum algorithm with

\(k^{3/4}n^{1/2+o(1)}\)

query complexity and

\(\widetilde{O}(kn^{1/2})\)

time complexity. We also observe a non-matching quantum query lower bound of

\(\Omega(\sqrt{kn})\)

.
Regulatory Mechanisms of Aging Through the Nutritional and Metabolic Control of Amino Acid Signaling in Model Organisms
Authors: Obata Fumiaki , Miura Masayuki
Published: June 2024

Life activities are supported by the intricate metabolic network that is fueled by nutrients. Nutritional and genetic studies in model organisms have determined that dietary restriction and certain mutations in the insulin signaling pathway lead to lifespan extension. Subsequently, the detailed mechanisms of aging as well as various nutrient signaling pathways and their relationships have been investigated in a wide range of organisms, from yeast to mammals. This review summarizes the roles of nutritional and metabolic signaling in aging and lifespan with a focus on amino acids, the building blocks of organisms. We discuss how lifespan is affected by the sensing, transduction, and metabolism of specific amino acids and consider the influences of life stage, sex, and genetic background on the nutritional control of aging. Our goal is to enhance our understanding of how nutrients affect aging and thus contribute to the biology of aging and lifespan.
Regulation of Bacterial Growth and Behavior by Host Plant
Authors: Nakagami Satoru , Wang Zhe , Han Xiaowei , Tsuda Kenichi
Published: June 2024

Plants are associated with diverse bacteria in nature. Some bacteria are pathogens that decrease plant fitness, and others are beneficial bacteria that promote plant growth and stress resistance. Emerging evidence also suggests that plant-associated commensal bacteria collectively contribute to plant health and are essential for plant survival in nature. Bacteria with different characteristics simultaneously colonize plant tissues. Thus, plants need to accommodate bacteria that provide service to the host plants, but they need to defend against pathogens at the same time. How do plants achieve this? In this review, we summarize how plants use physical barriers, control common goods such as water and nutrients, and produce antibacterial molecules to regulate bacterial growth and behavior. Furthermore, we highlight that plants use specialized metabolites that support or inhibit specific bacteria, thereby selectively recruiting plant-associated bacterial communities and regulating their function. We also raise important questions that need to be addressed to improve our understanding of plant–bacteria interactions.
The Greening of One Health: Plants, Pathogens, and the Environment
Authors: Scholthof Karen-Beth G.
Published: June 2024

One Health has an aspirational goal of ensuring the health of humans, animals, plants, and the environment through transdisciplinary, collaborative research. At its essence, One Health addresses the human clash with Nature by formulating strategies to repair and restore a (globally) perturbed ecosystem. A more nuanced evaluation of humankind's impact on the environment (Nature, Earth, Gaia) would fully intercalate plants, plant pathogens, and beneficial plant microbes into One Health. Here, several examples point out how plants and plant microbes are keystones of One Health. Meaningful cross-pollination between plant, animal, and human health practitioners can drive discovery and application of innovative tools to address the many complex problems within the One Health framework.
Engineering a One Health Super Wheat
Authors: Ayala Francisco M. , Hernández-Sánchez Itzell Eurídice , Chodasiewicz Monika , Wulff Brande B.H. , Svačina Radim
Published: June 2024

Wheat is the predominant crop worldwide, contributing approximately 20% of protein and calories to the human diet. However, the yield potential of wheat faces limitations due to pests, diseases, and abiotic stresses. Although conventional breeding has improved desirable traits, the use of modern transgenesis technologies has been limited in wheat in comparison to other crops such as maize and soybean. Recent advances in wheat gene cloning and transformation technology now enable the development of a super wheat consistent with the One Health goals of sustainability, food security, and environmental stewardship. This variety combines traits to enhance pest and disease resistance, elevate grain nutritional value, and improve resilience to climate change. In this review, we explore ways to leverage current technologies to combine and transform useful traits into wheat. We also address the requirements of breeders and legal considerations such as patents and regulatory issues.
Boric Acid for the Treatment of Vaginitis: New Possibilities Using an Old Anti‐Infective Agent: A Systematic Review
Authors: Lærkeholm Müller Matilde , Damsted Petersen Christina , Saunte Ditte Marie L.
Published: June 2024

Introduction. Increasing microbial resistance to conventional pharmaceuticals calls for nonpharmaceutical treatments of vaginitis. This systematic review summarizes the efficacy of the antiseptic agent boric acid (BA) as a treatment option for microbial vaginitis in comparison to conventional therapies and proposes clinical recommendations. Materials and Methods. PubMed and Embase were searched for “boric acid” and “microbial vaginitis.” A protocol was registered on PROSPERO (CRD42020160146). Inclusion criteria included clinical trials, observational and interventional studies, including case series/reports. Exclusion criteria included in vitro and animal studies, non‐English language, and no BA treatment outcome. Primary outcomes included microbial, clinical, and complete cure. Secondary outcomes included adverse events, relapse/reinfection rates, evidence levels, microorganisms, treatment regimens, and follow‐up time. Data were extracted to a predefined Excel sheet. Results. Of 195 identified unique articles, 54 were retrieved and 41 met our inclusion criteria. Heterogeneity precluded the conduction of a meta‐analysis. Conclusion. An average cure rate of 76% was found for vulvovaginal candidiasis BA treatment. Recurrent bacterial vaginosis was controlled with BA and 5‐nitroimidazole with promising results. Maintenance BA was equal to maintenance oral itraconazole therapy in vulvovaginal candidiasis and bacterial vaginosis in a retrospective study. Prolonged BA monotherapy cured three of six recurrent Trichomonas infections. Adverse events (7.3%) were typically mild and temporary. Based on our findings and the rising antimicrobial therapy resistance, we suggest intravaginal BA 600 mg/day for 2 weeks for (recurrent) vulvovaginal candidiasis and 600 mg/day for 2‐3 weeks for recurrent bacterial vaginosis. Rare resistant Trichomonas infections can be treated with BA 600 mg × 2/day for months and in combination with oral antimicrobials. We suggest a maintenance regimen of BA 600 mg × 2/week for recurrent vulvovaginal candidiasis. In case of resistant bacterial vaginosis, we suggest BA 600 mg × 2‐3/week. Data on maintenance therapy and BA treatment of bacterial vaginosis and trichomoniasis are however limited.
High Technical Success Rate of Endoscopic Balloon Dilatation Reduces Surgical Requirement for Patients With Stricturing Crohn’s Disease
Authors: Lim Emily , Thai Maxter , An Yoon-Kyo , Hendy Peter , Alchlaihawi Mahmoud , Leong Rupert , Connor Susan , Ng Watson , Gu Bonita , Thin Lena , Sparrow Miles , Gilmore Robert , Taylor Kirstin , Sallis Olivia , Andrews Jane M. , Daker Charlotte , Gearry Richard B. , Wark Gabrielle , Ghaly Simon , Begun Matt , Krishnaprasad Krupa , Wu Tianhong , Ruddick-Collins Leonie , Schreiber Veronika , Okano Satomi , Radford-Smith Graham , Schulberg Julien , van Langenberg Daniel , Begun Jakob
Published: June 2024

Background: Endoscopic balloon dilatation (EBD) is an alternative therapy to avoid or delay surgery in stricturing Crohn’s disease (CD); however, certain factors determining outcomes remain poorly defined, and conflicting evidence exists in current studies. In one of the largest cohorts to date, we assess outcomes following EBD for stricturing CD for both anastomotic and de novo strictures.

Methods: A retrospective cohort study of CD patients undergoing EBD was conducted at 12 hospitals across Australia and New Zealand. Local databases were used to identify cases from February 1999 to November 2019. Data from patient endoscopy reports and medical records were used to determine patient medical details and EBD outcomes. Multivariable analysis was undertaken to identify factors associated with technical and long‐term success.

Results: A total of 273 patients with stricturing CD were identified (48% female; 49.6% Montreal L3 disease). Of 695 EBD procedures (355 anastomotic, 340 de novo strictures), the majority (80.1% of strictures with identified length) was performed on short strictures (< 4 cm). Technical success, defined as the ability to traverse the stricture with a colonoscope after dilation, was achieved in 577 (83%) of endoscopic procedures, with success more likely with de novo strictures compared with anastomotic strictures (aOR: 3.21, P = 0.010). A significantly higher failure rate was noted with long strictures (aOR: 0.09, P < 0.001). A total of 74 patients (27%) required surgery within 5 years with stricture length, the only significant factor associated with increased surgery risk (aHR: 2.37, P < 0.01).

Conclusion: EBD is a highly effective and safe procedure in both de novo and anastomotic strictures < 4 cm that can prevent or delay the need for surgical treatment.
A Ductile Fracture Phase Field Model Based on Strain Rate‐Dependent Fracture Toughness
Authors: Shi Qianyu , Wang Zhijian , Tang Hui , Mu Libo , Zhao He
Published: June 2024

The numerical simulation of ductile fracture failure plays an important role in the evaluation of the integrity of engineering structures with the development of computing science and technology. As a competitive approach to predict fractures, the phase field model has been developed for about two decades to deal with a variety of crack growth problems. Rate‐dependent fracture is an important research interest, and some studies have begun to focus on using phase field method to predict rate‐dependent fracture. Such as coupling viscous material constitutive with phase field or defining a rate‐dependent fracture toughness within the framework of phase field models. In this paper, a ductile fracture phase field model based on strain rate‐dependent fracture toughness is presented to describe the rate‐dependent mechanical response in elastoplastic materials such as metallic alloys. The fracture toughness is defined as a power function of the plastic strain rates, which can make a more flexible control of the rate‐dependent behavior of ductile fracture compared with the existing phase field methods. Additionally, a total energy density threshold is introduced to ensure a real stress‐strain response of elastoplastic materials prior to crack growth. Several numerical examples are conducted to illustrate the effectiveness of this model.
Effects of Predrying and Spontaneous Fermentation Treatments on Nib Acidification, Fermentation Quality, and Flavour Attributes of Ghanaian Cocoa (Theobroma cacao) Beans
Authors: Haruna Lukeman , Abano Ernest E. , Teye Ernest , Tukwarlba Isaac , Yeboah Wilson , Agyei Kesse J. , Lukeman Mary
Published: June 2024

Cocoa bean acidification, fermentation, and flavour quality are intricately shaped by pulp preconditioning and fermentation treatments. This study investigates the impact of predrying and subsequent fermentation on key parameters such as pH, titratable acidity, fermentation quality (% purity), fermentation index (FI), and overall flavour quality (global quality (GQ)) of cocoa beans. Extended predrying periods and fermentation durations demonstrated a significant enhancement in bean acidification, reflected in the rise of nib pH (6.61–7.33) and the decline in nib acidity (0.023–0.013 meg NaOH/100 g). Notably, the cut test underscored the substantial improvement in % purity, reaching 75.6–99.7% for beans predried at 2–8 hours followed by a 6‐day of fermentation. FI increased significantly from 1.026 to a peak of 1.067, followed by a decline to 0.098 in the control, 6 hours, and 8 hours of predried beans, respectively. Sensory evaluation showed substantial improvement in the GQ (40.1–44.6) of beans predried at 2–8 hours and fermented for 6 days, compared to the control (38.3). In addition, a significantly higher preference was shown for cocoa liquor made from the beans predried for 4‐6 hours and fermented for 6 days. Principal component analysis clustered samples according to the predrying time, fermentation duration, and quality parameters measured. Optimal conditions for enhanced nib acidification, fermentation quality, and flavour attributes were identified at 6‐hour predrying and 6‐day fermentation using the response surface methodology. The study highlights the potential of predrying as a pulp preconditioning technique for enhancing fermentative and final bean quality.
Hyperparameter Optimization of the Machine Learning Model for Distillation Processes
Authors: Oh Kwang Cheol , Kwon Hyukwon , Park Sun Yong , Kim Seok Jun , Kim Junghwan , Kim DaeHyun
Published: June 2024

This study was conducted to enhance the efficiency of chemical process systems and address the limitations of conventional methods through hyperparameter optimization. Chemical processes are inherently continuous and nonlinear, making stable operation challenging. The efficiency of processes often varies significantly with the operator’s level of expertise, as most tasks rely on experience. To move beyond the constraints of traditional simulation approaches, a new machine learning‐based simulation model was developed. This model utilizes a recurrent neural network (RNN) algorithm, which is ideal for analyzing time‐series data from chemical process systems, presenting new possibilities for applications in systems with special chemical reactions or those that are continuous and complex. Hyperparameters were optimized using a grid search method, and optimal results were confirmed when the model was applied to an actual distillation process system. By proposing a methodology that utilizes machine learning for the optimization of chemical process systems, this research contributes to solving new problems that were previously unaddressed. Based on these results, the study demonstrates that a machine learning simulation model can be effectively applied to continuous chemical process systems. This application enables the derivation of unique hyperparameters tailored to the specificities of a limited control volume system.
Development of a Synthesized Gene Unique to Lumpy Skin Disease Virus and Its Application in Serological Differentiation of Naturally Infected from Vaccinated Cattle with Attenuated Goat Pox Vaccine
Authors: Yuan Xinwei , Zhang Haoyun , Wang Yu , Wu Di , Shirani Ihsanullah , Chen Yingyu , Chen Jianguo , Chen Xi , Zhang Lei , Chen Huanchun , Hu Changmin , Guo Aizhen
Published: June 2024

Lumpy skin disease (LSD) is an important infectious disease caused by lumpy skin disease virus (LSDV) in bovine. LSDV, sheep pox virus (SPPV), and goat pox virus (GTPV) from the same genus Capripoxvirus (CaPV) of the Poxviridae family exhibit a nucleotide sequence similarity of up to 97%. Therefore, attenuated vaccines of GTPV and SPPV are often used to vaccinate cattle against LSD. However, available serological testing methods cannot accurately differentiate cattle vaccinated with GTPV from those infected with LSDV, posing a significant risk for disease spread. In this study, we developed a synthesized gene unique to LSDV as a differential antigen to detect serum antibodies specific to LSDV and differentiate naturally infected from vaccinated animals (DIVA). We used it for an in‐house indirect enzyme‐linked immunosorbent assay (iELISA), and no cross‐reaction with positive sera for bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitis virus (IBRV), Mycobacterium bovis (M. Tb), Pasteurella multocida (P. multocida), and Mycoplasma bovis (M. bovis). The cut‐off value (S/P%) was 30% for in‐house iELISA. The corresponding diagnostic specificity was 100% (95% CI: 88.43–100), and the diagnostic sensitivity was 93.3% (95% CI: 77.93–99.18). The intra‐assay coefficient of variation (CV) ranged from 1.08% to 4.11%, and the interassay CV was 0.00%–8.90%. Furthermore, 200 clinical serum samples were examined, in the vaccinated herd, there were no positive samples (0/141) indicating the strong differentiation ability of this method. On the other hand, in the infected herds, the overall positivity was 33.90% (20/59) (95% CI: 22.08–47.39). In summary, a valuable synthesized protein unique to LSDV was developed and showed a promising application in an iELISA with high specificity and sensitivity in differentiating cattle infected with LSDV from those vaccinated with GTPV.
The Relationship between High‐Intensity Physical Activity and Traumatic Dental Injury among Young Adults in South Korea
Authors: Son Ji-Young , Han Dong-Hun
Published: June 2024

Background and Aim. High‐intensity physical activities have become increasingly popular in recent times. However, they are associated with an elevated risk of unintentional traumatic dental injury. Therefore, the aim of this study is to evaluate the correlation between high‐intensity physical activity and traumatic dental injury due to exercise in young adults. Materials and Methods. This study analyzed data collected from the 5th National Health and Nutrition Examination Survey (KNHANES V:2010−2012). The total number of participants in the 5th KNAHANES was 5,383 young adults aged 19–39 years, selected from 25,534 participants. Logistic regression analysis was performed using socioeconomic status (sex, age, education level, and income), physical activity intensity (vigorous and moderate), frequency of vigorous and moderate physical activity (days per week), and traumatic dental injuries due to exercise. Results. A total of 5,383 participants were included in the analysis. High‐intensity exercisers had a statistically different association with traumatic dental injuries due to exercise. In all models, high‐intensity exercisers had more traumatic dental injuries than moderate‐intensity exercisers, and participants who exercised vigorously 4 or more days per week had a significantly higher prevalence experience of traumatic dental injuries. Among adults in their 20s, men, college attendees, and those with higher incomes, the prevalence of exercising vigorously 4 or more days per week was higher. Conclusions. Among young adults, a higher frequency of high‐intensity physical activity was associated with a higher prevalence experience of traumatic tooth injury due to exercise compared with no physical activity.
Abstract A006: Delineating functional drivers of esophageal adenocarcinoma to identify synthetic lethal interactions
Authors: Milne Julia V , Mustafa Ebtihal , Fujihara Kenji , Kusnadi Eric , Trigos Anna , Thio Niko , Pechlivanis Maree , Cabalag Carlos , Gulati Twishi , Simpson Kaylene , Duong Cuong , Furic Luc , Phillips Wayne , Clemons Nicholas
Published: June 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR007) of the Conference Program/Proceedings.

Citation Format: Julia V Milne, Ebtihal Mustafa, Kenji Fujihara, Eric Kusnadi, Anna Trigos, Niko Thio, Maree Pechlivanis, Carlos Cabalag, Twishi Gulati, Kaylene Simpson, Cuong Duong, Luc Furic, Wayne Phillips, Nicholas Clemons. Delineating functional drivers of esophageal adenocarcinoma to identify synthetic lethal interactions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A006.
Abstract B005: Regulation of replication-induced PARP1/PARP2 activation by base excision repair: Implications for PARP and PARG inhibitor resistance
Authors: Ibrahim Md , Khan Md Maruf , Roos Wynand P. , Al-Rahaleh Rasha Q. , Hayat Faisal , Migaud Marie E. , Sobol Robert W.
Published: June 2024

Acquired poly (ADP-ribose) polymerases (PARP)-inhibitor (PARPi) and/or poly (ADP-ribose) glycohydrolase (PARG)-inhibitor (PARGi) resistance in BRCA1/2-defective tumors is common, emphasizing the need for identifying new targets. Protein poly ADP-ribosylation (PARylation) is a posttranslational modification of proteins catalyzed by PARP to form poly-(APD-ribose) (PAR) chains on itself and chromatin-associated proteins in response to DNA damage. Our study reveals that PARylation occurs in a replication-, PARP1-, and PARP2-dependent manner even in undamaged cells. Using proximity labeling, specifically Split-TurboID, we found that replication-dependent PARylation recruits the base excision repair (BER) factors XRCC1, POLB, APTX, and LIG3. These factors, in turn, suppress further PARylation. The BER factors XRCC1, POLB, APTX, or LIG3 promote PARPi and PARGi resistance as loss of these replication-associated BER (R-BER) factors re-sensitizes cancer cells to these inhibitors. Of interest, BRCA1 and BRCA2 localize with R-BER factors in undamaged cells. Lastly, XRCC1, POLB, APTX, and LIG3 depletion activate the S-phase checkpoint kinase CHK1, and targeting either this kinase or ATR under these conditions overcomes PARGi resistance in glioblastoma and ovarian cancer cells. In conclusion, our data highlight the crucial role of R-BER in protecting the cell during S-phase and propose a potential intervention strategy for resistant tumors.

Citation Format: Md Ibrahim, Md Maruf Khan, Wynand P. Roos, Rasha Q. Al-Rahaleh, Faisal Hayat, Marie E. Migaud, Robert W. Sobol. Regulation of replication-induced PARP1/PARP2 activation by base excision repair: Implications for PARP and PARG inhibitor resistance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B005.
Abstract B019: Stearoyl-CoA desaturase is a synthetic lethal target in SMAD4-deficient cancers
Authors: Lu Alvin Z. , Fenoglio Silvia , Wu Hsin-Jung , Chen Yingnan P.
Published: June 2024

Mothers against decapentaplegic homolog 4, or SMAD4, is a member of the SMAD family of transcription factors that mediate TGF-β signal transduction. SMAD4 loss of function mutation or deletion is found in about 30% of PDAC and 15% of COAD and EAC patients, and it is associated with their poor prognosis. Over the past two decades, its tumor suppressor role has been elucidated, and the loss of SMAD4 is sufficient to promote tumorigenesis in multiple GEM models. To identify novel therapeutic vulnerabilities for SMAD4-deficient cancers, a CRISPR dropout screening approach was employed in SMAD4 isogenic PDAC models. We identified stearoyl-CoA desaturase, SCD, as a synthetic lethal target in SMAD4-deficient context. SCD is critical for de novo lipid biogenesis and catalyzes the rate-limiting step in the production of monounsaturated fatty acid. Genetic and pharmacologic studies in vitro confirmed this synthetic lethal relationship. Additionally, drug-anchored CRISPR dropout screening and RNA expression profiling demonstrated that accumulation of saturated fatty acid in response to SCD inhibition drives cytotoxicity in SMAD4-deficient cells. Mouse studies with CRISPR-based knockout of SCD and a well-characterized SCD inhibitor (A939572) demonstrated anti-tumor efficacy in SMAD4-mutant xenograft models. However, compared to genetic KO of SCD the pharmacological inhibitor was less effective at inhibiting tumor proliferation in vivo. Together, these data identify SCD as a selective vulnerability in SMAD4-mutant cancers.

Citation Format: Alvin Z. Lu, Silvia Fenoglio, Hsin-Jung Wu, Yingnan P. Chen. Stearoyl-CoA desaturase is a synthetic lethal target in SMAD4-deficient cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B019.
Abstract B028: Expression of NOTCH1 in head and neck tumours at selected hospitals in Ghana
Authors: Barnes Precious , Saahene Roland Osei
Published: June 2024

Head and neck tumors (HNT) are of paranasal sinuses origin (the salivary glands and the upper aerodigestive tract). It constitutes the sixth most common tumors. Studies have shown that, factors such as tobacco and alcohol intake and viral infections may increase the relative risk to the tumor. Notch1 pathways are frequently altered in many tumors, however, the clinical significance of NOTCH1dysregulation in head and neck tumors is poorly understood. METHOD: The aim of this study was to investigate the expression NOTCH1 in head and neck tumor and also to elucidate the various anatomical pattern of the head and neck tumors in selected hospitals in Ghana. NOTCH1 expression were analyzed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on tissue samples from a consecutive series of head and neck tumor patients resections over a four-year period. RESULTS: The percentage of low expression of Notch1 were 71.4% in the malignant tissue (n=98) and 76.9% (n=52) in the benign tissue. The anatomical site with high of low expression of the NOTCH1 was found in oral cavity (37.1%) followed by respiratory (27.1%) followed by mandible (14.3%). CONCLUSION: There were low expression of NOTCH1 in head and neck tumour tissues suggesting that NOTCH1may be a tumor suppressor gene. We further propose that, NOTCH1 offers a potential tool as a target molecule in the development of therapies for head and neck tumors.

Citation Format: Precious Barnes, Roland Osei Saahene. Expression of NOTCH1 in head and neck tumours at selected hospitals in Ghana [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B028.