bluuebunny/crossref_metadata_2025 huggingface dataset:
Submarine geohazards on the northwestern continental margin of the South China Sea and their mechanism
Authors: Du Wenbo , Zhu Rongwei , Hu Xiaosan , Gao Hongfang
Published: April 2024

Submarine geohazards significantly threaten human economic activities and essential infrastructure. Based on multi‐beam data and high‐resolution 2D seismic data, two types of submarine geohazards are identified: direct and indirect geohazards on the northwestern continental slope and the Xisha Uplift of the South China Sea (SCS). Direct geohazards include submarine landslides and active faults, while indirect geohazards include buried channels, submarine canyons, pockmarks, volcanoes and magma diapirs. This study comprehensively analyzes geomorphological features, including their characteristics, genesis and distribution. Statistical analysis reveals that the gradient of the Xisha Uplift slope is steeper than the shelf break, making it a more unstable region. However, assessing disaster potential indicates that submarine geohazards at the shelf break pose a greater threat than those at the Xisha Uplift. Many factors, including tectonic activity, sediment supply and relative sea‐level changes, influence submarine geohazards' formation. These hazards do not occur in isolation but often interact with one another. The research results provide a scientific basis for predicting deep‐sea geohazards near the northern continental margin and Xisha Island in the SCS.
Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short‐term and long‐term complications and functional outcomes
Authors: Kanyo Emese C. , Wu Shannon S. , Reddy Chandana A. , Silver Natalie L. , Lamarre Eric D. , Burkey Brian B. , Prendes Brandon L. , Scharpf Joseph , Lorenz Robert R. , Kmiecik Joann , Ku Jamie A.
Published: April 2024

Background

Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary‐fit TEP in the setting of salvage laryngectomy.

Methods

A retrospective, single‐center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short‐term and long‐term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy.

Results

In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes.

Conclusion

Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.
When DNA damage responses meet tumor immunity: From mechanism to therapeutic opportunity
Authors: Pan Dong , Wang Qi , Shen Aihua , Qi Zhihao , Zheng Chunfu , Hu Burong
Published: April 2024

DNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects. This review explores the mechanisms behind DNA damage‐induced antitumor immune responses, the importance of DNA damage in antitumor immunity, and potential therapeutic approaches for cancer immunotherapy targeting DDR. Additionally, we discuss the challenges of combination therapy and strategies for integrating DNA damage‐targeting therapies with current cancer immunotherapy. In summary, this review highlights the critical role of DNA damage in tumor immunology, underscoring the potential of DDR inhibitors as promising therapeutic modalities for cancer treatment.
Prediction of physicochemical and pharmacokinetic properties of botanical constituents by computational models
Authors: Liu Yitong , Lawless Michael , Li Miao , Fairman Kiara , Embry Michelle R. , Mitchell Constance A.
Published: April 2024

Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. This study sought to use computational (i.e., in silico) models, including quantitative structure–activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were investigated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half of these constituents fell into BCS classes I and II at dose levels no greater than 100 mg per day, indicating high permeability and absorption (%Fa > 75%) in the gastrointestinal tract. However, some constituents such as glycosides in ashwagandha and Asian ginseng showed low bioavailability after oral administration due to poor absorption (BCS classes III and IV, %Fa < 40%). These in silico results fill data gaps for botanical constituents and could guide future safety studies. For example, the predicted human plasma concentrations may help select concentrations for in vitro toxicity testing. Additionally, the in silico data could be used in tiered or batteries of assays to assess the safety of botanical products. For example, highly absorbed botanical constituents indicate potential high exposure in the body, which could lead to toxic effects.
Neural graph distance embedding for molecular geometry generation
Authors: Margraf Johannes T.
Published: April 2024

This article introduces neural graph distance embedding (nGDE), a method for generating 3D molecular geometries. Leveraging a graph neural network trained on the OE62 dataset of molecular geometries, nGDE predicts interatomic distances based on molecular graphs. These distances are then used in multidimensional scaling to produce 3D geometries, subsequently refined with standard bioorganic forcefields. The machine learning‐based graph distance introduced herein is found to be an improvement over the conventional shortest path distances used in graph drawing. Comparative analysis with a state‐of‐the‐art distance geometry method demonstrates nGDE's competitive performance, particularly showcasing robustness in handling polycyclic molecules—a challenge for existing methods.
Study on the correlation between retrograde ductus arteriosus flow and right ventricular function evaluated by Z‐score of tricuspid annular plane systolic excursion in fetuses with Ebstein anomaly
Authors: Guo Xianfeng , Li Yilin , Zhao Bowen , He Yihua
Published: April 2024

Purpose

To analyze the influence of RV dysfunction evaluated by Free‐angle M‐mode (FAM) TAPSE Z‐score on retrograde ductus arteriosus flow (RDAF) in fetuses with Ebstein anomaly (EA).

Methods

A retrospective cohort study of 30 EA and 60 normal fetuses were enrolled. The EA group was divided into two groups: with RDAF (EA‐RDAF group) and without RDAF (EA‐NRDAF group). FAM was used to measure TAPSE of EA and normal fetuses, and Z‐scores were calculated. The differences of FAM‐TAPSE Z‐score, gestational week (GW), maternal age (MA), and mitral valve‐tricuspid valve distance (MTD) between three groups were compared. The correlation and binary logistic regression between FAM‐TAPSE Z‐score, GW, MA, MTD, and RDAF were analyzed.

Results

FAM‐TAPSE Z‐score was significantly lower in EA‐RDAF group compared to other groups (p < 0.05). FAM‐TAPSE Z‐score, GW, and MA were negatively correlated with RDAF (p < 0.05), but no correlation was found between TR, MDT, and RDAF (p > 0.05). Multivariate logistic regression showed that FAM‐TAPSE Z‐score was an independent influencing factor for RDAF (OR = 0.102, p < 0.05).

Conclusion

RV dysfunction is an independent factor leading to RDAF in EA fetus, which provides a feasible theoretical basis for further study on improvement of RV function through intrauterine treatment to delay and prevent the RDAF, to avoid death cycle and improve live‐birth rate.
Utility of the cerebro‐placental‐uterine ratio in predicting composite adverse perinatal outcomes in pregestational diabetes: A prospective cohort study
Authors: Agaoglu Zahid , Tanacan Atakan , Ipek Goksun , Peker Ayca , Ozturk Agaoglu Merve , Bastemur Ayse Gulcin , Kara Ozgur , Sahin Dilek
Published: April 2024

Purpose

To examine the cerebro‐placental‐uterine ratio (CPUR) in pregnant women with pregestational diabetes and determine its role in predicting adverse prenatal outcomes.

Methods

This prospective, cohort study conducted at a tertiary hospital included 65 patients with pregestational diabetes (25 with type1 diabetes, 40 with type2 diabetes) and 130 low‐risk patients in the control group. The cerebroplacental (CPR) ratio and the CPUR were calculated. Composite adverse perinatal outcome (CAPO) is defined as the presence of any of the following: (1) Neonatal intensive care unit (NICU) admission, (2) Apgar at 5 min <7, and (3) umbilical cord arterial pH <7.10. The relationship of CPR and CPUR with CAPO was investigated.

Results

CPR and CPUR were significantly lower in the pregestational diabetes group than in the control group. The NICU admission was higher in the case group. In receiver operating characteristic analyses, the optimal cut‐off value of CPUR was 1.46 (AUC = 0.72, p = 0.003, 80% sensitivity, and 69% specificity) to predict CAPO and the optimal cut‐off value of CPUR was 1.50 for NICU admission (AUC = 0.70, p = 0.013, 77% sensitivity, and 66% specificity).

Conclusion

Low CPUR values were found to be associated with adverse perinatal outcomes in women with pregestational diabetes. With the increasing number of studies, CPUR is expected to be utilized more widely in routine obstetric practice.
On the value of meta‐research for early career researchers: A commentary
Authors: Fabiano Nicholas , Gupta Arnav , Fiedorowicz Jess G. , Solmi Marco
Published: April 2024

Meta‐research, also known as “research on research” is a field of study that investigates the methods, reporting, reproducibility, evaluation, and incentives along the research continuum. Meta‐research literacy is imperative to ensure high quality, transparent and reproducible primary data or meta‐research products. In this commentary, we propose that early career researchers should be trained in meta‐research as a foundation to develop a deeper understanding of the research process and ability to appraise the research literature and design high‐quality original studies, irrespective of their chosen field of study. We discuss the importance of meta‐research and open science from the perspective of an early career trainee, highlighting essential areas for growth and obstacles one may encounter.
From molecules to visuals: Empowering drug discovery and development with mass spectrometry imaging
Authors: Chen Bingming , Vavrek Marissa , Cancilla Mark T.
Published: April 2024

Over the past three decades, mass spectrometry imaging (MSI) has emerged as a valuable tool for the spatial localization of drugs and metabolites directly from tissue surfaces without the need for labels. MSI offers molecular specificity, making it increasingly popular in the pharmaceutical industry compared to conventional imaging techniques like quantitative whole‐body autoradiography (QWBA) and immunohistochemistry, which are unable to distinguish parent drugs from metabolites. Across the industry, there has been a consistent uptake in the utilization of MSI to investigate drug and metabolite distribution patterns, and the integration of MSI with omics technologies in preclinical investigations. To continue the further adoption of MSI in drug discovery and development, we believe there are two key areas that need to be addressed. First, there is a need for accurate quantification of analytes from MSI distribution studies. Second, there is a need for increased interactions with regulatory agencies for guidance on the utility and incorporation of MSI techniques in regulatory filings. Ongoing efforts are being made to address these areas, and it is hoped that MSI will gain broader utilization within the industry, thereby becoming a critical ingredient in driving drug discovery and development.
Effects of intermittent fasting on periodontal inflammation and subgingival microbiota
Authors: Lira‐Junior Ronaldo , Aogáin Micheál Mac , Crncalo Eva , Ekberg Neda Rajamand , Chotirmall Sanjay H. , Pettersson Sven , Gustafsson Anders , Brismar Kerstin , Bostanci Nagihan
Published: April 2024

Background

Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long‐term intermittent fasting on periodontal health and the subgingival microbiota.

Methods

This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n = 14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6 months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing.

Results

After 6 months of intermittent fasting, weight, body mass index, C‐reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p < 0.05). Moreover, significant reductions were observed in bleeding on probing (p = 0.01) and the presence of shallow periodontal pockets after fasting (p < 0.001), while no significant change was seen in plaque index (p = 0.14). While we did not observe significant changes in α‐ or β‐diversity of the subgingival microbiota related to dietary intervention (p > 0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4–5 mm compared to those with <60% reduction (bad responders).

Conclusion

Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.
Structural and functional properties of whey protein isolate–inulin conjugates prepared with ultrasound or wet heating method
Authors: Qin Yu‐Qing , Fan Yan‐Ge , Ren Jing‐Nan , Wang Liu‐Yan , Han Nan‐Feng , Fan Gang
Published: April 2024

BACKGROUND

Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI–polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI–inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined.

RESULTS

In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), new C–N bonds were formed in Fourier‐transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h.

CONCLUSION

This study revealed that WPI–inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.
A 4.7‐inch 650 PPI AMQLED display prepared by direct photolithography
Authors: Zhang Di , Li Zhuo , Lu Shaoyong , Li Dong , Chen Zhuo , Li Yanzhao , Li Xinguo , Xu Xiaoguang
Published: April 2024

In this work, a highly efficient photosensitive quantum dot (QD) system was designed. The optimized photosensitive QD system had high photoluminescence quantum yield and colloidal stability. By direct photolithography, RGB pixel arrays with a single sub‐pixel size of 39 μm × 5 μm were successfully prepared. Further, the full‐color QLED device was realized. There were no residual QD emission peaks from neighboring sub‐pixels observed in the electroluminescence spectra. Experience on the full‐color QLED device guided the successful preparation of a 4.7‐inch 650 PPI active matrix QLED prototype. The active matrix QLED prototype could display clear and complete pictures. The color gamut reached 85% of the BT2020 standard. This is the first active matrix QLED prototype prepared with a record‐high resolution by direct photolithography, which promoted the development of QLED display technology.
Using the Moral Injury and Distress Scale to identify clinically meaningful moral injury
Authors: Maguen Shira , Griffin Brandon J. , Pietrzak Robert H. , McLean Carmen P. , Hamblen Jessica L. , Norman Sonya B.
Published: April 2024

Despite the proliferation of moral injury studies, a remaining gap is distinguishing moral injury from normative distress following exposure to potentially morally injurious events (PMIEs). Our goal was to leverage mental health and functional measures to identify clinically meaningful and functionally impairing moral injury using the Moral Injury and Distress Scale (MIDS). Participants who endorsed PMIE exposure (N = 645) were drawn from a population‐based sample of military veterans, health care workers, and first responders. Using signal detection methods, we identified the optimally efficient MIDS score for detecting clinically significant posttraumatic stress and depressive symptom severity, trauma‐related guilt, and functional impairment. The most efficient cut scores across outcomes converged between 24 and 27. We recommend a cut score of 27 given that roughly 70% of participants who screened positive on the MIDS at this threshold reported clinically significant mental health symptoms, and approximately 50% reported severe trauma‐related guilt and/or functional impairment. Overall, 10.2% of respondents exposed to a PMIE screened positive for moral injury at this threshold, particularly those who identified as a member of a minoritized racial or ethnic group (17.9%) relative to those who identified as White, non‐Hispanic (8.0%), aOR = 2.52, 95% CI [1.45, 4.42]. This is the first known study to establish a cut score indicative of clinically meaningful and impairing moral injury. Such scores may enhance clinicians’ abilities to conduct measurement‐based moral injury care by enabling them to identify individuals at risk of negative outcomes and better understand risk and protective factors for moral injury.
Doppler Ultrasound of the Renal Vasculature
Authors: Gunabushanam Gowthaman , Chaubal Rajas , Scoutt Leslie M.
Published: April 2024

Ultrasound is the first‐line imaging modality used in patients with suspected renovascular disease. Common indications include renovascular hypertension and unexplained renal dysfunction. We review the ultrasound imaging findings of various pathologies involving the renal vessels, including the renal arteries (atherosclerotic stenosis, fibromuscular dysplasia, dissection, arteriovenous fistula, and aneurysm) and veins (tumor and bland thrombus as well as vascular compression syndromes). The current role of renal artery stent placement for atherosclerotic stenosis is also discussed.
Questions a patient with moderate to severe atopic dermatitis would like to be asked: Data from a qualitative study conducted by anthropologists
Authors: Nicogossian Judith , Héas Stéphane , Thénié Claire , Noel Margaux , Misery Laurent , Barbarot Sebastien , Martin Juchat Fabienne
Published: April 2024

Background

A considerable number of patients with moderate to severe atopic dermatitis (AD) are undertreated and have inadequate control of their symptoms leading to a hight patient dissatisfaction during their care. The VECUDA study composed of VECU and DA for french word lived and atopic dermatitis was conducted by anthropologists in cooperation with dermatologists, aimed to better understand the complexity of the care pathway and the physician‐patient relationship by questioning patients with moderate to severe AD.

Objectives

The aim was to identify patient's needs and to propose concrete ways of improving the doctor‐patient relationship by focusing on the narrative of their affects. Co‐designed easy‐to‐use tools were proposed by these patients.

Methods

The exploratory qualitative study involved 24 patients with moderate‐to‐severe AD. The study was conducted in two stages: a codesign phase with four patients, and a deepening phase with all patients (24), supported by a multidisciplinary scientific committee. During group interviews, conducted using creativity tools, patients' stories related to their experiences of the disease and its management were collected.

Results

By studying the patients' affect stories, researchers were able to identify the needs of patients who might be 1. emotional (better consideration of their experiences); 2. informational (more information about their disease and treatments); 3. participatory (being involved in their care: therapeutic alliance). Mechanisms of therapeutic dissatisfaction and satisfaction were mapped into vicious and virtuous circles. Patients also offered concrete and easy‐to‐use tools. We are presenting here the grid of questions these patients would like to be asked during their doctor's appointment: the Doctor‐Facing Questions Grid that these patients would like to be asked during a consultation.

Conclusions

By facilitating the identification of patients' needs/expectations, these tools would help guide the clinician's discussion and management in a few questions. The VECUDA study confirms the value of considering patients' perspective as a lever for improving the doctor‐patient relationship.
Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Cancer
Authors: Hondorp Brian , Punjabi Nihal , Macias David , Liu Yuan , Frank Ethan , Kim Paul D. , Inman Jared C.
Published: April 2024

Objective

To enhance understanding in patterns of discordance between clinical and pathological T and N staging in multiple sites of head and neck squamous cell cancer.

Methods

A retrospective cohort of 580 newly diagnosed and surgically treated head and neck squamous cell carcinoma patients from a single institution over a 10‐year period are presented. Clinical and pathologic staging are compared.

Results

Notably, 33% of cases had staging discordance. Overall Cohen's kappa agreement was κ = 0.55 (moderate agreement). Highly discordant site stages with κ < 0.45 included: T2 oral cavity, T2 oropharynx, T3 larynx, and N1 lymph node. T2‐4 oral cavity cancers were often overstaged, and more than one‐third of T3 larynx cancers were understaged. Highly concordant site stages with κ>0.65 included: T1 larynx, T4 oropharynx, N0 lymph node, and N3 lymph node.

Conclusion

There exists a quantifiable and, in certain sites, clinically relevant pattern of discordance between clinical and pathologic staging. Tumor board multidisciplinary evaluation can highlight these discrepancies and aide in limiting effects on treatment decisions. However, discordant staging can affect the interpretation and application of prognostication, treatment, and data accuracy. Further investigation is warranted to improve clinical staging accuracy in areas of highest discordance.

Level of Evidence

3 Laryngoscope, 134:4284–4291, 2024
Demographic Representation in Clinical Research Relative to a Cochlear Implant Patient Population
Authors: Nix Evan P. , Davis Amanda G. , Brown Kevin D. , Panoncillo Stephanie G. , Thompson Nicholas J. , Overton Andrea B. , Dedmon Matthew M. , Dillon Margaret T.
Published: April 2024

Objectives

Research samples that are representative of patient populations are needed to ensure the generalizability of study findings. The primary aim was to assess the efficacy of a study design and recruitment strategy in obtaining a participant sample that was representative of the broader cochlear implant (CI) patient population at the CI center. A secondary aim was to review whether the CI recipient population was representative of the state population.

Methods

Demographic variables were compared for a research participant sample (n = 79) and the CI patient population (n = 338). The participant sample was recruited from the CI patient population. The study design included visits that were at the same location and frequency as the recommended clinical follow‐up intervals. The demographics for the combined group (participant sample and patient population) were then compared to the reported demographics for the population in North Carolina.

Results

There were no significant differences between the participant sample and patient population for biological sex, age at implantation, racial distribution, socioeconomic position, degree of urbanization, or drive time to the CI center (p ≥ 0.086). The combined CI recipient population was significantly different from the North Carolina population for the distributions of race, ethnicity, and degree of urbanization (p < 0.001).

Conclusion

The study design and recruitment strategy allowed for recruitment of a participant sample that was representative of the CI patient population. Disparities in access to cochlear implantation persist, as supported by the significant differences in the combined CI recipient population and the population for our state.

Level of Evidence

3 Laryngoscope, 134:4101–4110, 2024
A simple and rapid method for measuring total free sulfides in marine sediments
Authors: Cranford Peter J.
Published: April 2024

The quantitatively most important process by which organic matter in marine sediments is mineralized is performed by sulfate‐reducing bacteria, resulting in the accumulation of total dissolved (free) sulfide (S2− = H2S + HS− + S2−) in porewater. S2− is toxic to benthic animals and vascular plants and measurements serve as a proxy for the deleterious effects of organic enrichment on benthic habitat, biodiversity, and ecosystem function. Methodologies for measuring S2− in water have been pursued for at least a century, and standard approaches employ colorimetry (methylene blue and iodometric titration) and potentiometry. These standard methods require between 1 and 200 mL of porewater, which can be laborious to obtain. The ion‐selective electrode method is widely employed as a practical approach for sediment S2− analysis but lacks analytical robustness and is highly prone to measurement biases that misinform research and environmental management decisions. A technically simple method is described, based on direct UV spectrophotometry, for the near real‐time field analysis of small porewater samples. The procedure prevents known measurement biases associated with particulate sulfide interference, S2− volatilization and oxidation, and represents a practical approach for monitoring organic enrichment and classifying benthic ecological quality status. Porewater concentrations between 200 and 15,000 μmol L−1 can be measured and instrument calibration is highly stable. The method has the capacity to rapidly process and analyze sediment samples at low cost, which helps resolve the problem of chronic under‐sampling associated with the use of traditional S2− methods.
A review on polymers in ocular drug delivery systems
Authors: Bisen Amol C. , Biswas Arpon , Dubey Ayush , Sanap Sachin N. , Agrawal Sristi , Yadav Karan S. , Singh Vaishali , Rawat Priyanka , Sagar Sudhanshu , Mugale Madhav N. , Bhatta Rabi S.
Published: April 2024

Amid the escalating prevalence of eye diseases and the intricate nature of the eye as a crucial target organ for drug delivery, researchers face significant challenges in developing delivery systems tailored specifically for ocular complications. Addressing the gaps in the current conventional ocular drug delivery system (ODDS) is crucial and this can be achieved by incorporating polymers while designing newer ODDS. This review aims to offer a concise overview of the diverse polymers utilized in the development of ODDS, designed to address various eye conditions and disorders, enhance treatment outcomes, and ensure patient adherence. Introducing the anatomy of the eye and different ocular routes of administration, alongside the barriers encountered, this review presents polymer‐based ODDS, renowned for their unique properties facilitating the engineering of specialized devices for enhanced drug delivery. Further discussions delve into the applications of polymers in ophthalmology. Emphasis is placed on emerging polymer‐based technologies available in the market for treating ocular diseases, underscoring their potential for revolutionizing ocular healthcare. The review also addresses challenges in translating these advancements into clinical practice, while highlighting the versatility of polymers in treating diverse eye diseases and disorders through customizable properties and sustained drug delivery.
Cellular senescence in cancer: molecular mechanisms and therapeutic targets
Authors: Jin Ping , Duan Xirui , Li Lei , Zhou Ping , Zou Cheng‐Gang , Xie Ke
Published: April 2024

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor‐promoting effect of senescence is mainly elicited by a senescence‐associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A “one‐two‐punch” therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field.
To commit or not? The impact of online reviews on retailers' price commitment strategy in competing supply chains
Authors: Cai Zigong , Liang Lunhai
Published: April 2024

Online reviews can effectively mitigate consumers' uncertainty about product valuations, thus affecting firms' pricing decisions. This paper develops a two‐period game model to investigate the impacts of online reviews on the retailer's price commitment strategies in two competing supply chains, each consisting of one manufacturer and one retailer. In the first period, the retailers strategically set prices and decide whether to commit to prices for their products. In the second period, the retailers adjust product prices in response to online reviews, if they choose not to commit to a price. We show that the retailers' price commitment strategies depend on consumers' perceived uncertainty about product valuations, the information value of online reviews and the unit misfit cost. Interestingly, the retailers can benefit from the information value of online reviews by implementing flexible pricing strategies. Furthermore, if the information value of online reviews is sufficiently high, both retailers will choose not to commit to a price in equilibrium. However, if the information value of online reviews is relatively low, the equilibrium in price commitment is asymmetric, that is, the retailer A commits to a price and its competitor chooses not to commit.
Beyond dopamine: Novel strategies for schizophrenia treatment
Authors: Dudzik Paulina , Lustyk Klaudia , Pytka Karolina
Published: April 2024

Despite extensive research efforts aimed at discovering novel antipsychotic compounds, a satisfactory pharmacological strategy for schizophrenia treatment remains elusive. All the currently available drugs act by modulating dopaminergic neurotransmission, leading to insufficient management of the negative and cognitive symptoms of the disorder. Due to these challenges, several attempts have been made to design agents with innovative, non‐dopaminergic mechanisms of action. Consequently, a number of promising compounds are currently progressing through phases 2 and 3 of clinical trials. This review aims to examine the rationale behind the most promising of these strategies while simultaneously providing a comprehensive survey of study results. We describe the versatility behind the cholinergic neurotransmission modulation through the activation of M1 and M4 receptors, exemplified by the prospective drug candidate KarXT. Our discussion extends to the innovative approach of activating TAAR1 receptors via ulotaront, along with the promising outcomes of iclepertin, a GlyT‐1 inhibitor with the potential to become the first treatment option for cognitive impairment associated with schizophrenia. Finally, we evaluate the 5‐HT2A antagonist paradigm, assessing two recently developed serotonergic agents, pimavanserin and roluperidone. We present the latest advancements in developing novel solutions to the complex challenges posed by schizophrenia, offering an additional perspective on the diverse investigated drug candidates.
Global well‐posedness of the 3D hydrostatic magnetohydrodynamics equations
Authors: Du Lili , Li Dan
Published: April 2024

In this paper, the three‐dimensional hydrostatic magnetohydrodynamic (HMHD) equations are considered on a thin domain. We showed the global existence and uniqueness (regularity) of strong solutions to the three‐dimensional incompressible HMHD equations without any small assumption on the initial data. More precisely, there exists a unique strong solution globally in time for any given
‐smooth initial data.
Blow‐up criterion for the modified compressible Navier–Stokes equations with density‐dependent viscosity
Authors: Hagverdiyev Ali , Novruzov Emil
Published: April 2024

The dynamical behavior of one‐dimensional compressible Navier–Stokes equation with density‐dependent viscosity coefficient is considered. A new sufficient condition under which the solution blows up is established.
On special curves in Lie groups with Myller configuration
Authors: İşbilir Zehra , Doğan Yazıcı Bahar , Tosun Murat
Published: April 2024

In this study, we determine a new type comprehensive frame, which is called the generalized Frenet‐type frame in three‐dimensional Lie groups with Myller configurations, and it includes several special and classical type frames for Euclidean 3‐space and three‐dimensional Lie groups. After constructing this new comprehensive frame, we obtain derivative formulas with the help of the Lie curvature. In addition, we define some special type curves. The geometry of versor fields along a curve with Frenet‐type frame in three‐dimensional Lie groups with Myller configurations is a generalization of the usual theory of curves. Since this particular relationship, the osculating‐type and rectifying‐type curves with Frenet‐type frame in three‐dimensional Lie groups with Myller configurations include some special cases for osculating and rectifying curves in different spaces.
Polarization control parameters evolution of genetic algorithm‐based 2 µm Tm‐doped fiber laser
Authors: Liu Guangmiao , Wang Yibo , Xian Anhua , Wu Kun , Yin Xuejian , Yao Tianchen , Zhu Qiang , Kang Hui , Zheng Fangfang , Qi Liwen , Zhou Wei , Wang Haotian , Wang Fei , Shen Deyuan
Published: April 2024

In this paper, we explored the different performances of the evolution of polarization control parameters under algorithm optimization in one‐dimensional, two‐dimensional, and three‐dimensional parameter space. We found that the genetic algorithm (GA) operation has a typical converging trend as the epoch increasing of groups in ultra‐fast pulse generation. The corresponding deviations were calculated to be 10.8%, 11.2%, and 5.0%, respectively, which is different from the traversal algorithm operation. The typical noise‐like pulse state was effectively automatically searched at different length cavities, with center wavelengths of 1973, 1988.7, and 2002.7 nm, repetition rate of 9.4, 10.4, and 5.4 MHz, and typical spike duration of ~224 fs. Our research shows the effectiveness of the GA in searching and controlling the ultrashort pulse output of a 2‐µm thulium‐doped fiber laser.
Hedonic hunger, eating behavior, and food reward and preferences 1 year after initial weight loss by diet or bariatric surgery
Authors: Aukan Marthe Isaksen , Finlayson Graham , Martins Catia
Published: April 2024

Objective

The objective of this study was to investigate changes in hedonic hunger, eating behavior, and food reward and preferences at 1‐year (1Y) follow‐up after an initial weight loss (WL) induced by a 10‐week, very low‐energy diet alone (controls) or in combination with bariatric surgery.

Methods

Patients scheduled for sleeve gastrectomy or Roux‐en‐Y gastric bypass and controls were recruited. Body weight/composition, hedonic hunger (Power of Food Scale), eating behavior traits (Dutch Eating Behavior Questionnaire and Three‐Factor Eating Questionnaire), and food reward and preferences (computerized behavioral task) were measured at baseline, 11 weeks, and 1Y follow‐up.

Results

Changes in anthropometric variables were comparable across groups in the initial phase (week 11), and hedonic hunger decreased overall. The bariatric‐surgery groups continued to lose body weight and fat mass, whereas weight regain was seen in controls at 1Y follow‐up. Decreases in emotional eating, hunger, disinhibition, and food reward and increases in dietary restraint were seen at 1Y follow‐up in the bariatric‐surgery groups only.

Conclusions

Continued WL with bariatric surgery is paralleled by favorable changes in eating behavior and food reward and preferences. By contrast, controls experienced weight regain at 1Y follow‐up and no changes in eating behavior. These striking differences are likely to be important in the long‐term WL management of individuals with severe obesity.
The political economy of fiscal transfers: The case of Ethiopia
Authors: Yimenu Bizuneh
Published: April 2024

This article examines the political economy of fiscal transfers in Ethiopia. Utilising an original data set spanning 1995–2020, as well as interviews and document analyses, the article illustrates how different factors interact to shape the distribution of grants. Statistical analysis indicates that population size is critical in determining regional grant shares. However, the analyses reveal a pattern of ethno‐regional favouritism in grant distributions during the early stages of Ethiopian federalism. During that period, opaque and centralised decision‐making processes, coupled with the dominant influence of the Tigray People's Liberation Front in the federal government, resulted in grant distribution deviating from principles of fiscal equity. Over time, this evolved into more fluid forms of negotiation influenced by intra‐party competition, dynamics of bargaining between the central and regional authorities, and regional assertiveness, collectively shaping the allocation of grants alongside the grant formula. The analysis highlights how economically and politically marginalised regions are disadvantaged, especially when their population is small. The absence of an independent grant agency means that political considerations continue to affect seemingly formula‐driven allocations. The Ethiopian case underscores how intra‐party bargaining and alignment along ethnic and regional lines undermine the effectiveness of formula‐based grant allocations in the absence of an independent and empowered grant agency.
Evaluating the optimum abrasive water jet machinability for CARALL composites with various fiber orientations
Authors: Altin Karataş Meltem , Motorcu Ali Riza , Ekici Ergün
Published: April 2024

Carbon Fiber Reinforced Aluminum Laminated (CARALL) composites are widely used in aircraft structures due to their ability to be produced in different shapes with desired properties and their high impact resistance properties. As with other layered composite materials, processing of CARALL composites by conventional manufacturing methods results in many damage mechanisms such as fiber breakage, deformation in the hole region, stress concentration, resin‐fiber separation and microcracks. One of the modern manufacturing methods, Abrasive Water Jet (AWJ), is a processing method in which the material is removed by abrasion and almost any material can be cut without thermal degradation. There are no experimental studies in the literature on the drilling of CARALL composites by modern manufacturing methods. The aim of this study is to investigate the impact of machining parameters on the output variables (kerf taper angle (K), roundness error (Re) and material removal rate (MRR)) as well as the effect of fiber orientation on the drilling of CARALL composites with different fiber orientations on an AWJ machine. PROMETHEE‐GAIA weighted by Entropy Weighting Method were used to ascertain the optimum levels of control factors. CARALL composites with different fiber orientations were drilled with an 8 mm diameter AWJ with three different water pressures, three different nozzle feed rates. With PROMETHEE‐GAIA multi‐criteria optimization method, the optimum levels of the factors that provide both minimum Re and K values and maximum MRR value were obtained with twill woven material, 1680 mm/min feed rate and 1680 bar water pressure.

Highlights

CARALL composite materials with two different fiber orientations (twill weave and UD) were used.

CARALL composite materials were drilled at different machining parameters.

Abrasive water jet was used in drilling experiments.

Optimum drilling parameters were determined to achieve minimum roundness error, minimum kerf angle and maximum material removal rate.

PROMETHEE‐GAIA was used as a multi‐criteria decision‐making method.
Three‐phase interfacial design in BaTiO3/rGO/polyetherimide composite enabling enhanced dielectric, thermal and mechanical properties
Authors: Zhang Pengtu , Yuan Shiling , Song Xinwang , Tang Junsong , Lin Qilang , Liu Xiaoyun , Zhuang Qixin , Mi Puke , Zuo Peiyuan
Published: April 2024

As core components in electric/electronic fields, dielectric materials have recently received ever‐increasing interests. Among them, polymer‐based dielectric composites have drawn ever‐increasing attentions due to their high‐temperature resistance and excellent processibility. However, state‐of‐art studies mostly focus on the modification of single‐phase filler, while the heterogeneous three phase interactions between fillers and polymer matrix are rarely studied. To fill this gap, in this study, a novel strategy of interfacial design and structural construction of three‐phase BaTiO3/rGO/polymer nanocomposites have been promoted to simultaneously build interfacial barriers between adjacent rGO nanosheets and to enhance the interfacial polarization of rGO nanosheets for improved dielectric, thermal and mechanical properties. The dielectric constant of 0.6 wt% BT/ARGO/PEI reached 644@1 kHz with a dielectric loss of only 0.218, while these values for 0.5 wt% ARGO/PEI composites are 471 and 0.489, respectively. Meanwhile, the breakdown strength almost doubled (from 48 kV·mm−1 to 87 kV·mm−1) upon the addition of BaTiO3 (BT) nanoparticles. Moreover, the introduced BT nanoparticles significantly enhanced the intermolecular frictions between different materials and contributed largely to promoted mechanical and thermal properties. We therefore speculate this work establishes a strong foundation for fabricating three heterogeneous‐phase high dielectric polymer materials with excellent dielectric, thermal and mechanical properties.

Highlights

Graphene oxide was modified by APTES and reduced by L‐Ascorbic Acid.

Three‐phase BT/ARGO/PEI composites showed enhanced dielectric properties.

The incorporated BT nanoparticles reduced the dielectric loss.

The thermal and mechanical properties of BT/ARGO/PEI composites are optimized.

Interfacial interactions between different phase of materials are studied.