bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment confidence and patient participation in multidisciplinary tumor conferences: A structural equation modeling approach
Authors: Degenhardt Marie , Ernstmann Nicole , Schellenberger Barbara , Ansmann Lena , Heuser Christian
Published: May 2024

Objective

Multidisciplinary tumor conference (MTC) is a key instrument in multidisciplinary cancer care. In recent years, if and how patient participation in MTC can contribute to a more patient‐centered care have been scientifically discussed. This study aimed to identify determinants of treatment confidence in the context of patient participation in MTC. Therefore, the association among health literacy‐sensitive communication, trust in health‐care providers (HCP), and treatment confidence is examined.

Methods

This study used data from the multicenter, observational study “PINTU” on patient participation in MTC. Data were collected from November 2018 to February 2020. Validated scales for treatment confidence, health literacy‐sensitive communication, and trust in providers were included in the structural equation modeling (SEM) analysis.

Results

A total of 95 patients participated in MTC. The sample compromised n = 80 completed datasets. The SEM fit measures indicated good fit of the proposed model. The analysis showed a positive association between health literacy‐sensitive communication and treatment confidence when adding the mediating effect of trust in providers.

Conclusion

Patient‐centered communication during MTC in combination with a trustful relationship between participating patients and health‐care providers is positively associated with treatment confidence. The results indicated the relevance of a trustful doctor–patient communication and relationship. Trainings for physicians targeting patient‐centered communication could be a promising approach to strengthen patient participation.
Aldehyde dehydrogenase 1 family: A potential molecule target for diseases
Authors: Duan Xiangning , Hu Haoliang , Wang Lingzhi , Chen Linxi
Published: May 2024

Aldehyde dehydrogenase 1 (ALDH1), a crucial aldehyde metabolizing enzyme, has six family members. The ALDH1 family is expressed in various tissues, with a significant presence in the liver. It plays a momentous role in several pathophysiological processes, including aldehyde detoxification, oxidative stress, and lipid peroxidation. Acetaldehyde detoxification is the fundamental function of the ALDH1 family in participating in vital pathological mechanisms. The ALDH1 family can catalyze retinal to retinoic acid (RA) that is a hormone‐signaling molecule and plays a vital role in the development and adult tissues. Furthermore, there is a need for further and broader research on the role of the ALDH1 family as a signaling molecule. The ALDH1 family is widely recognized as a cancer stem cell (CSC) marker and plays a significant role in the proliferation, invasion, metastasis, prognosis, and drug resistance of cancer. The ALDH1 family also participates in other human diseases, such as neurodegenerative diseases, osteoarthritis, diabetes, and atherosclerosis. It can inhibit disease progression by inhibiting/promoting the expression/activity of the ALDH1 family. In this review, we comprehensively analyze the tissue distribution, and functions of the ALDH1 family. Additionally, we review the involvement of the ALDH1 family in diseases, focusing on the underlying pathological mechanisms and briefly talk about the current status and development of ALDH1 family inhibitors. The ALDH1 family presents new possibilities for treating diseases, with both its upstream and downstream pathways serving as promising targets for therapeutic intervention. This offers fresh perspectives for drug development in the field of disease research.
Free intraperitoneal air in infected pancreatic necrosis with intraperitoneal rupture: A rare presentation of a complex diseases
Authors: Kejela Segni , Ager Genet , Gebremariam Meklit Solomon
Published: May 2024

Key Clinical Message

Among the multitude of causes for acute abdomen patients presenting with free intraperitoneal air, one almost never finds infected pancreatic necrosis as one of the culprits. In patients with risk factors for acute pancreatitis presenting with generalized peritonitis with free intraperitoneal air, consideration should be given to this often deadly entity.

Acute pancreatitis is a morbid acute abdominal pathology that has been increasing in incidence in recent years. Most patients have a mild disease and treated medically, while a few proportion require interventional procedures. We present the case of a 39‐year‐old male patient who presented with progressive abdominal pain, vomiting, and yellowish discoloration of the eyes. The abdominal condition progressed to the point where clinical signs became consistent with generalized peritonitis and an x‐ray finding of free intraperitoneal air. The patient underwent exploratory laparotomy with intraoperative findings of intraperitoneal rupture of infected pancreatic necrosis with intraperitoneal purulent collection. He was managed with necrosectomy and discharged improved after intensive care and general ward stay.
Enantioselective Synthesis of Dihydrobenzofurans, Dihydrobenzosulfones, and Dihydroindoles by Merging One‐pot Intramolecular Heck‐Matsuda Reactions from Anilines with Redox‐Relay Process
Authors: Scarpa de Souza Edson Leonardo , Gorbatov Sergei Aleksandrovich , Pierozzi Breno Mendes , Batista Junior João Marcos , Duarte Correia Carlos Roque
Published: May 2024

A one‐pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open‐flask conditions. This process combines the in situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecular Heck‐Matsuda reaction linked to a redox relay process to provide the final products as the dimethyl acetals. These Heck products were smoothly converted into the corresponding primary alcohols or esters. The robustness and the efficiency of the protocol are demonstrated by the synthesis of 24 enantioenriched dihydrobenzofurans, dihydrobenzosulfones, and dihydroindoles in overall yields up to 78 % in enantiomeric ratios up to 99 : 1 by a sequential 5‐step protocol.
Photo‐ and Stress‐Induced Bending of (E)‐1,2‐Bis(pyridinium‐4‐yl)ethene Dinitrate Crystals
Authors: Kusumoto Sotaro , Wakabayashi Kaede , Rakumitsu Kenta , Harrowfield Jack , Kim Yang , Koide Yoshihiro
Published: May 2024

We report on the elastic and photodynamic properties of (E)‐1,2‐bis(pyridinium‐4‐yl)ethene dinitrate [H2Ebpe](NO3)2, whose needle‐like crystals can be reversibly deformed by applying external mechanical stress. The macro‐scale mechanical properties of [H2Ebpe](NO3)2 crystals were quantified by a three‐point bending test, which gave a stress‐strain curve with an elastic modulus of 1.18 GPa, and its values are lower than those of other flexible elastic organic crystals. It can also be reversibly bent through the [2+2] cycloaddition reaction of the olefin moiety, depending on the direction of UV irradiation.
Multicolor Anti‐counterfeiting Strategy and Synchronous High Capacity Storage Based on Acidochromic Organic Fluorescent Materials
Authors: Fang Ying , Luan Jun‐Yu , Liu Li‐Hao , Huang Ying‐Qing , Luo Yi‐Ning , Wang Kun‐Peng , Chen Shaojin , Hu Hai‐Yu , Hu Zhi‐Qiang
Published: May 2024

Comprehensive Summary

Many industries are plagued by economic losses and product failures caused by counterfeit goods. Therefore, advanced anti‐counterfeiting techniques are continuously needed. In this study, we constructed a series of acid‐base sensitive cyclic chalcone dyes A—F by modifying different electron‐donating groups. Differences in acid sensitivity of different structures are well rationalised by NMR and theoretical calculations. Aniline is difficult to protonate than fatty amines, so there is a difference in fluorescence. Hiding and anti‐counterfeiting of information is achieved by this phenomenon. Powder X and Y are the anti‐counterfeit fluorescent powder containing montmorillonite and cyclic chalcone, which have orange fluorescence and the very similar appearance. However, under the influence of acid the Powder X containing triphenylamine modified cyclic chalcone shows red shifted fluorescence and Powder Y containing morpholino and diethylamino groups modified cyclic chalcone shows blue shifted fluorescence. Therefore, the anti‐counterfeiting strategy based on cyclic chalcone is not only limited to UV‐irradiated fluorescence development, but also has more colorization and pattern variations with the aid of acid developer. Data encryption and decryption of numbers, English alphabets and Chinese characters have been realized using A—F, which have great potential for practical applications.
Chiral Isothiourea‐Catalyzed Acylative Dynamic Kinetic Resolution of 3‐Hydroxyphthalides for Enantioselective Synthesis of Phthalidyl Esters
Authors: Hao Zeyang , Lin Wei , Yuan Zi‐Qi , Zhang Wei , Li Xin
Published: May 2024

Comprehensive Summary

Phthalides serve as core structures pervasive in a wide array of natural products and drug molecules, which display a diverse array of biological activities. We report herein a highly efficient dynamic kinetic resolution of 3‐hydroxyphthalides by chiral isothioureas (ITUs) catalyzed asymmetric acylation, facilitating the effective synthesis of a variety of chiral phthalidyl esters with good yields and enantioselectivities. Notably, this reaction features mild reaction conditions, expansive substrate scope as well as good functional group compatibility. In addition, the practicality of this method is underscored by the large‐scale synthesis, reduced catalyst loading experiment and the synthesis of the chiral phthalidyl ester prodrug.
Safety of ultra‐low contrast coronary angiography in patients with acute kidney injury
Authors: Rozenbaum Zach , Chang Mailing Flores , Wiley Jose , Gholam Ali , Irimpen Anand , Alsaad Ali A.
Published: May 2024

Background

Ultra‐low contrast administration during coronary angiography has been previously shown to be feasible and safe among patients with stable chronic kidney disease. In the present study, we investigate the safety of ultra‐low contrast coronary angiography in patients with pre‐existing acute kidney injury (AKI).

Methods

The study was a retrospective single‐center evaluation of hospitalized patients who had AKI and required coronary angiography. Ultra‐low contrast use was defined as ≤18 mL of contrast media.

Results

The cohort consisted of a case series of eight inpatients with AKI who required coronary angiography. The mean age was 57 (±16) years and half were females. All patients had chronic kidney disease with a mean baseline estimated glomerular filtration rate of 34 (±17) mL/min/1.73 m2. The mean creatinine before angiography was 3 (±1) mg/dL and volume of contrast administered was 14 (±4) mL. One patient had a 0.1 mg/dL increase in creatinine during admission, and no patients had further AKI up to 1‐week postprocedure.

Conclusions

The current data suggest that ultra‐low contrast coronary angiography can be safely performed in patients with pre‐existing AKI The study should be viewed as hypothesis‐generating due to its small sample size. A larger cohort is required to validate the results.
Chitosan as Support Material for Metal‐Organic Framework based Catalysts
Authors: Jabbour Christia R. , Schnabl Kordula B. , Yan Haoxiang , O'Beirn Naoise N. , Dorresteijn Joren M. , Meirer Florian , Mandemaker Laurens D. B. , Weckhuysen Bert M.
Published: May 2024

Turning waste into valuable products is one of the main challenges of the chemical industry. In this work, chitosan (CS), an abundant, low‐cost, and non‐toxic biopolymer derived from chitin, was reshaped into beads of ~3 mm. Their suitability as a support material for active phase catalyst materials was tested for a zirconium‐based Metal‐Organic Framework (MOF) with incorporated Pt, namely UiO‐67‐Pt. Its incorporation was investigated via two procedures: a one‐pot synthesis (OPS) and a post‐synthetic functionalization (PSF) synthesis method. Scanning electron microscopy (SEM) images show good UiO‐67‐Pt dispersion throughout the CS beads for the one‐pot synthesized material (UiO‐67‐Pt‐OPS@CS). However, this uniform dispersion was not observed for the post‐synthetically functionalized material (UiO‐67‐Pt‐PSF@CS). The success of the implementation of UiO‐67‐Pt was evaluated with ultraviolet‐visible and infrared spectroscopy for both composite materials. Thermogravimetric analysis (TGA) reveals higher thermal stabilities for UiO‐67‐Pt‐OPS@CS composite beads in comparison to pure CS beads, but not for UiO‐67‐Pt‐PSF@CS. The study provides valuable insights into the potential of chitosan as a green, bead‐shaped support material for MOFs, offering flexibility in their incorporation through different synthesis routes. It further contributes to the broader goal of the sustainable and eco‐friendly design of a new generation of catalysts made from waste materials, which will be the topic of future studies.
Adaptable Self‐Assembly of a PEG Dendrimer‐Coiled Coil Conjugate
Authors: Lee Young‐joo , Jung You‐jin , Lim Yong‐beom
Published: May 2024

Self‐assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self‐assembly has demonstrated several advantageous features for smart materials. Here, we demonstrate that an α‐helical coiled coil conjugated with a dendrimer can adapt to spatial restriction due to the strong steric repulsion between dendrimer chains. The adaptable transformation of a tetrameric coiled coil to a trimeric coiled coil can be confirmed using analytical ultracentrifugation upon conjugation of the dendrimer to the coiled coil‐forming building block. Interestingly, circular dichroism spectroscopy analysis of the dendrimer conjugate revealed an unconventional trend: the multimerization of the coiled coil is inversely dependent on concentration. This result implies that the spatial crowding between the bulky dendritic chains is significantly stronger than that between linear chains, thereby affecting the overall assembly process. We further illustrated the application potential by decorating the surface of gold nanorods (AuNRs) with the adaptable coiled coil. The dendrimer‐coiled coil peptide conjugate can be utilized to fabricate organic‐inorganic nanohybrids with enhanced colloidal and thermal stabilities. This study demonstrates that the coiled coil can engage in the adaptable mode of self‐assembly with the potential to form dynamic peptide‐based materials.
Mirikizumab Exposure–Response Relationships in Patients with Moderately‐to‐Severely Active Ulcerative Colitis in Randomized Phase II and III Studies
Authors: Friedrich Stuart , Chua Laiyi , Adams David H. , Crandall Wallace , Zhang Xin Cindy
Published: May 2024

Mirikizumab is a humanized anti‐interleukin‐23p19 monoclonal antibody being developed for ulcerative colitis (UC) and Crohn's disease. We characterized the relationship of mirikizumab systemic exposure with efficacy and safety end points in patients with UC using phase II (NCT02589665) and III (NCT03518086, NCT03524092) trial data. Exposure–response models were developed for clinical remission, clinical response, endoscopic remission, and change in modified Mayo score following induction (50–1,000 mg i.v. every 4 weeks) and maintenance (200 mg s.c. every 4 or 12 weeks) treatment. These models evaluated observed and pharmacokinetic model‐predicted mirikizumab exposures as the exposure measure. Key safety event rates were compared across mirikizumab exposure quartiles in the phase III trial. Mirikizumab efficacy in patients with UC showed an apparent positive association with systemic exposure following both induction and maintenance. However, further analysis found this relationship to be overstated by the presence of confounding factors that were not among the tested patient covariates. While prior biologic experience and baseline disease severity showed statistically significant influences on estimated placebo effect, no patient factors affected the mirikizumab effect parameters in any of the phase III exposure–response models. There was no apparent mirikizumab concentration relationship with any adverse event of special interest. When the phase II and III data and confounding are considered together, efficacy was unlikely to be strongly affected by variation in exposures across individual patients at the phase III dose. Together with the previously demonstrated mirikizumab exposure insensitivity to patient factors, these findings indicate that mirikizumab dose adjustment to patient characteristics is not required.
Social and occupational profile of mediators in Portugal: Evidence and challenges
Authors: Silva Ana Maria Costa e , Guiomar Patrícia , Neves Tiago
Published: May 2024

Mediators have gained visibility in the national and international context because of the relevance of their intervention in light of current social challenges. However, the professional profile of mediators is not consolidated, and its recognition has been slow and ambiguous. The diversity of the initial basic training of mediators and the diversity of training available in mediation are two contributing factors to this lack of recognition. The objectives of this article are to characterize the professional profile of Portuguese mediators, to understand their stance regarding the introduction of a bachelor's in mediation in Portuguese higher education, and contribute to the debate about the consolidation and formal recognition of these professionals. Inspired by theoretical and empirical reflections and studies that discuss the possibility of creating a bachelor's in mediation as a strategy to standardize and consolidate mediation and the professional profile of mediators, we present, in this article, a quantitative and qualitative descriptive analysis of the socio‐occupational situation of 175 mediators in Portugal. Most respondents agree that a bachelor's in mediation may contribute to the recognition of the area and the quality of the mediators' work. However, the advantages of multidisciplinary initial basic training and the lack of employability in the area of mediation are two factors that may call into question the relevance of creating this degree. Given the results, it is important to reflect on the nature and modalities of training in mediation, namely at the bachelor level, in order to contribute to the professional recognition of mediators.
Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species
Authors: Wang Chaowen , Zeng Wenjing , Wang Li , Xiong Xiaowei , Chen Sheng , Huang Qianqian , Zeng Guohua , Huang Qiren
Published: May 2024

Asprosin (ASP) is a newly‐identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP‐deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP‐deficiency significantly alleviated the high‐fat diet‐induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator‐activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP‐deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF‐κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl‐CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.
Impact of parenthood on eating pathology in young adults
Authors: Meier K. , Apon L. C. , Van Hoeken D. , Van Eeden A. E. , Hoek H. W. , Oldehinkel A. J.
Published: May 2024

Objective

Few studies investigated parenthood as a predictor of eating pathology in young adulthood. We studied the association between parenthood, in the first year after becoming a parent and beyond, and eating pathology. Furthermore, we examined whether moving in together with a partner affected this association.

Method

This study used data of four measurement waves from TRAILS (Tracking Adolescents' Individual Lives Survey), a Dutch community cohort study (N = 2229) from preadolescence into young adulthood. The Eating Disorder Diagnostic Scale (EDDS), a measure to assess eating pathology, was assessed at ages 22, 26, and 29. Risk for eating disorder was assessed at age 19. Pregnant participants were excluded.

Results

Parenthood was not associated with an increase of eating pathology in the first year after becoming a parent and beyond. Instead, parents were more likely to report being free from eating pathology symptoms compared to childless individuals (OR 2.07, 95% CI: 1.11–3.84). Among those who reported experiencing at least one eating problem, parenthood was not associated with the number of eating problems. Moving in together with a partner did not alter the association between parenthood and eating problems and neither did this association differ between males and females.

Discussion

Parenthood in young adulthood was associated with a decreased risk of having eating pathology.

Public Significance Statement

In this longitudinal study among young adults, parenthood was not associated with the development of eating pathology.
Thermal–Hydraulic Performance of Flat‐Plate Solar Collector Plant Using Different Heat‐Transfer Fluids
Authors: Guo Yingying , Mo Zhelong , Zhang Ruichao , Wang Dengjia , Fan Jianhua
Published: May 2024

The physical parameters such as density, specific heat capacity, and viscosity of the heat‐transfer fluid have an important influence on the performance of the solar collector system. If the physical parameters of heat‐transfer fluids are studied as constant physical properties, it will be difficult to reflect the influence of heat‐transfer fluids on the performance of the solar collector system. In this study, expressions are fitted for the physical parameters of heat‐transfer fluids and a coupled thermal–hydraulic performance model of the solar collector system is established. The coupled model is validated through performance‐testing experiments on the system and is used to investigate the impact of heat‐transfer fluid types and concentrations on the performance of the system under various solar radiation intensities, ambient temperatures, inlet temperatures, and flow rates. In the results, it is shown that in the case of anti‐freezing, a 50% volume concentration of ethylene glycol is more suitable for the heat‐collecting system. When selecting the heat‐transfer fluid, the heat‐transfer fluid with a lower concentration should be selected as far as possible while ensuring the freezing point. In the results of this study, a certain reference for the selection of the heat‐transfer fluid can be provided.
Experimental and theoretical research on the temperature evolution law of overcurrent fault wires
Authors: Huo Yan , Xu Xueyan , Li Yang , Li Ruonan , Yu Zhijin , Wang Weifeng
Published: May 2024

To investigate the problems of overload and excessive thermal insulation associated with building electrical fires caused by wires, a theoretical model of wire heat transfer is established, and the pyrolysis and combustion phenomena of the insulation layer are analyzed. The results showed that the temperature evolution of the wire underwent three stages: constant temperature, insulation heating, and high‐temperature pyrolysis. The insulation layer experiences bulging, exhausting, carbonization, dripping, and burning in sequence, and insulation layer dripping requires at least 160 A of current. As the current increases, the temperature increase rate of the wire increases gradually, and the fusing time of the wire gradually decreases. Under the same current, 160°C is the turning point at which the temperature increases. The temperature increase rate of the copper wire is greater than that of the aluminum alloy wire, and the temperature increase rate of the bare wire is greater than that of the insulated wire. The fusing time of an aluminum alloy wire is less than that of a copper wire, and the fusing time of a bare wire is less than that of an insulated wire. The research results provide theoretical guidance for the prevention and investigation of building electrical fires.
Exploring neural tracking of acoustic and linguistic speech representations in individuals with post‐stroke aphasia
Authors: Kries Jill , De Clercq Pieter , Gillis Marlies , Vanthornhout Jonas , Lemmens Robin , Francart Tom , Vandermosten Maaike
Published: May 2024

Aphasia is a communication disorder that affects processing of language at different levels (e.g., acoustic, phonological, semantic). Recording brain activity via Electroencephalography while people listen to a continuous story allows to analyze brain responses to acoustic and linguistic properties of speech. When the neural activity aligns with these speech properties, it is referred to as neural tracking. Even though measuring neural tracking of speech may present an interesting approach to studying aphasia in an ecologically valid way, it has not yet been investigated in individuals with stroke‐induced aphasia. Here, we explored processing of acoustic and linguistic speech representations in individuals with aphasia in the chronic phase after stroke and age‐matched healthy controls. We found decreased neural tracking of acoustic speech representations (envelope and envelope onsets) in individuals with aphasia. In addition, word surprisal displayed decreased amplitudes in individuals with aphasia around 195 ms over frontal electrodes, although this effect was not corrected for multiple comparisons. These results show that there is potential to capture language processing impairments in individuals with aphasia by measuring neural tracking of continuous speech. However, more research is needed to validate these results. Nonetheless, this exploratory study shows that neural tracking of naturalistic, continuous speech presents a powerful approach to studying aphasia.
Information and vaccine hesitancy: The role of broadband Internet
Authors: Amaral‐Garcia Sofia , Nardotto Mattia , Propper Carol , Valletti Tommaso
Published: May 2024

We examine the effect of Internet diffusion on the uptake of an important public health intervention: the measles, mumps and rubella (MMR) vaccine. We study England between 2000 and 2011 when Internet diffusion spread rapidly and there was a high profile medical article (falsely) linking the MMR vaccine to autism. OLS estimates suggest Internet diffusion led to an increase in vaccination rates. This result is reversed after allowing for endogeneity of Internet access. The effect of Internet diffusion is sizable. A one standard deviation increase in Internet penetration led to around a 20% decrease in vaccination rates. Localities characterized by higher proportions of high skilled individuals and lower deprivation levels had a larger response to Internet diffusion. These findings are consistent with higher skilled and less‐deprived parents responding faster to false information that the vaccine could lead to autism.
Do time preferences predict diabetes outcomes? A combined survey and register‐based study
Authors: Madsen Kristoffer Panduro , Kjær Trine
Published: May 2024

Identifying determinants of heterogeneity in health outcomes continues to be a focus in the health economic literature. In this study, we analyze whether time preferences predict health outcomes in individuals with type 1 diabetes (T1D) who use insulin pump therapy to manage their condition. We collect data on time preferences using a hypothetical matching task and estimate aggregate as well as individual‐level discounting parameters using the exponential, hyperbolic, and quasi‐hyperbolic discounting models. These parameters are then regressed against essential diabetes‐related health outcomes obtained from registries and medical records, including glycemic control, kidney function, BMI, and number of hospital contacts. Our analyses indicate that all three discounting models fit the data equally well. Except for hospital contacts, we find robust evidence that impatience, as reflected by higher discounting, predicts worse health outcomes. Additionally, present bias is associated with worse kidney function. Our findings suggest that time preferences can explain some of the heterogeneity in health among individuals with T1D and call for increased attention on the role of time preferences in the design of disease management programs for individuals with chronic conditions.
Value of Assessing 1‐Hydroxymidazolam in Drug‐Drug Interaction Studies with Midazolam as a Substrate of Cytochrome P450 3A
Authors: Magliocca Massimo , Berger Benjamin , Lemoine Vincent , Kaufmann Priska , Dingemanse Jasper
Published: May 2024

The purpose of this overview was to perform an exploratory analysis of in‐house drug‐drug interaction (DDI) studies conducted with investigational drugs and oral midazolam to assess the value of measuring 1‐OH‐midazolam (1‐OHM) in such studies. The perpetrator effect of the investigational drugs on cytochrome P450 3A (CYP3A) was assessed by analyzing both midazolam and 1‐OHM in plasma and evaluating their pharmacokinetic parameters. Given the almost exclusive metabolism of the parent drug by CYP3A to the main metabolite 1‐OHM, an increase in midazolam and a decrease in 1‐OHM exposure in the case of CYP3A inhibition caused by a perpetrator drug would be expected. The opposite would be anticipated in the case of CYP3A induction. For this analysis, the perpetrator potential of eight different investigational drugs was incorporated. Among the 10 studies included, the identified CYP3A inhibitors (n = 4) and inducers (n = 1) were classified based on the data generated with midazolam per se, with 1‐OHM levels not contributing to the interpretation of the data as they did not corroborate the findings of the parent compound. Therefore, it was concluded that continued analysis of 1‐OHM in plasma may be questionable as it does not add value to the interpretation of the results when performing CYP3A DDI studies with an investigational drug as a perpetrator.
Gender and work–life balance: Results of a national survey of pediatric hospitalists
Authors: Kim Juliann L. , Forster Catherine S. , Allan Jessica M. , Schondelmeyer Amanda , Ruch‐Ross Holly , Barone Lauren , Fromme H. Barrett
Published: May 2024

In medicine, difficulty integrating work and home can lead to decreased job satisfaction, diminished well‐being, and increased turnover. Understanding the experience of pediatric hospitalists can provide insights into building a stable, long‐term workforce. We aim to examine gender differences in work–life balance and parental leave for physicians practicing Pediatric Hospital Medicine.

Methods

This was a cross‐sectional survey study of 1096 pediatric hospitalists. Responses were collected via an online survey platform and summarized using descriptive statistics, including frequency distributions and measures of central tendency. A multivariable logistic regression was used to examine associated variables and work–life balance satisfaction. We analyzed free responses on parental leave to provide nuance to quantitative survey data.

Results

Five hundred and sixty‐five respondents (52% response rate) completed the survey with 71% women. 343 (62%) prioritize work–life balance in career decision‐making. Women report taking on more household responsibilities than their partners (41.4% vs. 8.4%; p < .001) including a larger percentage of caregiving and domestic tasks. Female gender and performing <50% caregiving were associated with decreased work–life balance satisfaction; performing <50% domestic tasks increased satisfaction. Median parental leaves were 4 weeks, with men taking significantly shorter leaves (3.5 vs. 6 weeks; p < .001) and more “paid back” time off.

Conclusion

Work–life balance is an important factor in career decisions for men and women. Women perceive carrying a larger load at home. Qualitative results suggest that parental leave may be inadequate in length and salary support for men and women. This study adds insights into work–life integration in PHM.
Cost‐Effectiveness and Budget Impact Analysis of the Implementation of Differentiated Service Delivery Models for HIV Treatment in Mozambique: a Modelling Study
Authors: Moiana Uetela Dorlim Antonio , Zimmermann Marita , Chicumbe Sérgio , Gudo Eduardo Samo , Barnabas Ruanne , Uetela Onei Andre , Dinis Aneth , Augusto Orvalho , Gaveta Sandra , Couto Aleny , Gaspar Irénio , Macul Hélder , Hughes James P. , Gimbel Sarah , Sherr Kenneth
Published: May 2024

Introduction

In 2018, the Mozambique Ministry of Health launched guidelines for implementing differentiated service delivery models (DSDMs) to optimize HIV service delivery, improve retention in care, and ultimately reduce HIV‐associated mortality. The models were fast‐track, 3‐month antiretrovirals dispensing, community antiretroviral therapy groups, adherence clubs, family approach and three one‐stop shop models: adolescent‐friendly health services, maternal and child health, and tuberculosis. We conducted a cost‐effectiveness analysis and budget impact analysis to compare these models to conventional services.

Methods

We constructed a decision tree model based on the percentage of enrolment in each model and the probability of the outcome (12‐month retention in treatment) for each year of the study period—three for the cost‐effectiveness analysis (2019–2021) and three for the budget impact analysis (2022–2024). Costs for these analyses were primarily estimated per client‐year from the health system perspective. A secondary cost‐effectiveness analysis was conducted from the societal perspective. Budget impact analysis costs included antiretrovirals, laboratory tests and service provision interactions. Cost‐effectiveness analysis additionally included start‐up, training and clients’ opportunity costs. Effectiveness was estimated using an uncontrolled interrupted time series analysis comparing the outcome before and after the implementation of the differentiated models. A one‐way sensitivity analysis was conducted to identify drivers of uncertainty.

Results

After implementation of the DSDMs, there was a mean increase of 14.9 percentage points (95% CI: 12.2, 17.8) in 12‐month retention, from 47.6% (95% CI, 44.9–50.2) to 62.5% (95% CI, 60.9–64.1). The mean cost difference comparing DSDMs and conventional care was US$ –6 million (173,391,277 vs. 179,461,668) and –32.5 million (394,705,618 vs. 433,232,289) from the health system and the societal perspective, respectively. Therefore, DSDMs dominated conventional care. Results were most sensitive to conventional care interaction costs in the one‐way sensitivity analysis. For a population of 1.5 million, the base‐case 3‐year financial costs associated with the DSDMs was US$550 million, compared with US$564 million for conventional care.

Conclusions

DSDMs were less expensive and more effective in retaining clients 12 months after antiretroviral therapy initiation and were estimated to save approximately US$14 million for the health system from 2022 to 2024.
Determining the minimally clinically important difference for the pediatric liver transplant quality of life questionnaire
Authors: Kortbeek Simone , Johara Fatema T. , Kwan Karina , John Tomisin , Ng Vicky L.
Published: May 2024

Purpose

The Pediatric Liver Transplant Quality of Life (PeLTQL) questionnaire is a disease‐specific patient reported outcome measure for pediatric liver transplant (LT) recipients. To‐date, threshold values above which a change in PeLTQL score is considered meaningful to patients are unavailable. This study proposes the first values for the minimally clinically important difference (MCID) for the PeLTQL.

Methods

In this retrospective cohort study, anchor and distribution‐based methods were used to estimate the MCID for the PeLTQL. Questionnaires completed between March 2013, and July 2022 were included if data from two sequential visits were available. An internal anchor question was used for anchor‐based determination of the MCID. A final MCID estimate was ascertained from triangulation of all methods.

Results

PeLTQL data from 65 LT recipients (26 [40%] male, 17 [42%] biliary atresia, median age at LT 3.08 years [interquartile range 0.99–7.30]), and their caregivers were included for analysis. Median patient age at time of baseline PeLTQL completion was 13.84 (10.90–15.86) years. The MCID for self‐PeLTQL total scores ranged from 4.53 to 8.46, and from 4.47 to 8.85 for proxy responses. By triangulation, the MCID of the PeLTQL total score was 6.45 and 6.78 for self and proxy responses respectively.

Conclusion

A change in PeLTQL score of 6.5 or more points suggests a change in health status that is meaningful to the patient, providing the clinical team an opportunity to engage the patient's voice in reassessing current health status and management strategies.
Spurious signals identification in Brillouin light scattering spectrum
Authors: Pang Si‐Min , Lv Yan‐Pei , Zhang Jun
Published: May 2024

Brillouin light scattering (BLS) is the inelastic scattering of light from elementary excitations with periodic density modulation. The characteristics of non‐contact, high sensitivity, and high resolution in energy, wavevector, time, space, and phase make the BLS spectrometer widely used in investigating many intriguing physical phenomena, including the acoustic phonon confinement effects, Bose‐Einstein condensation (BEC), supercurrent, and soliton formation. Generally, the quick and correct assignment of the signals in the BLS spectra is a prerequisite for further investigations. Herein, we experimentally identify the high‐order spurious signals in the BLS spectra, which make the interpretation of the spectra difficult. The additional signals are demonstrated to originate from the laser and the temperature‐controlled laser filter used for laser filtering. Our results would contribute to the rapid assignment of the signals from the sample after excluding the spurious signals reported here. Moreover, the series of high‐order modes spaced by the free spectral range can serve as a weak broadband light source, which has great potential for investigating the optical responses of materials.
Patient‐reported outcome measures in surgical patients with upper gastrointestinal cancers: A qualitative interview study
Authors: Cass Samuel H. , Williams Loretta A. , Rajaram Ravi , Hirata Yuki , Rice David , Tzeng Ching‐Wei D. , Katz Matthew H. G. , Badgwell Brian D. , Wang Xin Shelley , Ikoma Naruhiko
Published: May 2024

Background and Objectives

Patients with pancreatic and gastroesophageal (PGE) cancers experience high symptom burden, but patient experience throughout multimodality treatment remains unclear. We aimed to delineate the experience and symptom burden of patients throughout their perioperative course.

Methods

Qualitative interviews were performed with 17 surgical patients with PGE cancer. Interview transcripts were analyzed and symptoms were ranked by frequency. An expert panel assessed the relevance of these symptom inventory items.

Results

Of the 17 patients included, 35% (n = 6) underwent gastrectomy, 30% (n = 5) underwent esophagectomy, and 35% (n = 6) underwent pancreatectomy; 76% (n = 13) received neoadjuvant systemic chemotherapy and/or chemoradiation. Overall, 32 symptoms were reported, and 19 were reported by over 20% of patients. An expert panel rated nine symptoms to be relevant or very relevant to PGE surgical patients. These symptoms (difficulty swallowing, heartburn/reflux, diarrhea, constipation, flushing/sweating, stomach feeling full, malaise, dizziness, or feeling cold) were added to the core MD Anderson Symptom Inventory (MDASI) if they were commonly reported or reached a threshold relevancy score.

Conclusions

In this qualitative study, we developed a provisional symptom inventory for patients undergoing surgery for PGE cancer. This symptom inventory module of the MDASI for PGE surgical patients will be psychometrically tested for validity and reliability.
The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy
Authors: Carpenter Elizabeth L. , Van Decar Spencer G. , McCarthy Patrick M. , Valdera Franklin A. , Adams Alexandra M. , O'Shea Anne E. , Smolinsky Todd , Thomas Katryna , Clifton Guy T. , Newhook Timothy E. , Peoples George E. , Nelson Daniel W. , Vreeland Timothy J.
Published: May 2024

Background

The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection.

Methods

The 2019 National Cancer Database was queried for patients with non‐metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down‐staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan–Meier method and log‐rank test were used to estimate the cumulative survival.

Results

After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99).

Conclusion

Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.
Ultra‐Narrow Linewidth Polariton Lasing in Optically Trapped Bose‐Einstein Condensates at Room Temperature
Authors: Wang Yaqi , Zhou Binru , Zhang Xingfei , Zheng Huying , Wang Runchen , Dong Junxing , Wang Lisheng , Zhang Yunwei , Li Zhicong , Zhang Yiyun , Yi Xiaoyan , Wang Junxi , Li Jinmin , Zhu Hai
Published: May 2024

Polariton lasing via Bose‐Einstein condensation (BEC) provides a peculiar method to achieve low threshold coherent light sources. Until now, the cryogenic operating temperature required for polariton lasers has hampered the development of polaritonics. Here, a novel approach is first reported to realize the ultra‐narrow linewidth polariton lasing under quasi‐3D quantum confinement at room‐temperature (RT). The potential trap landscape is constructed by ring‐shaped optical excitation, wherein the continuum polariton dispersion is modulated into discrete simple harmonic oscillator (SHO) states. The coherent condensation lasing of trapped polaritons occurs beyond the threshold power. Benefiting from the horizontal quantum confinement, the trapped polariton lasing exhibits an ultra‐narrow linewidth (0.7 meV) and excellent quality factor (Q = 3510). Moreover, the second‐order quantum coherence properties of trapped polariton condensation are determined to reveal the quantum phase transition of Bosonic system. The results offer a feasible route for realizing a low‐threshold ultra‐narrow linewidth polariton laser at RT, which significantly facilitates the fabrication of polariton laser and switches on opportunities for future applications.
Giant Optical Nonlinear Response up to 60th‐Order Induced by the Ytterbium Energy Relay Mediated Photon Avalanches
Authors: Wang Chenyi , Wen Zizhao , Pu Rui , Zhan Qiuqiang
Published: May 2024

The exploration of photon avalanching (PA) luminescence in different lanthanide emitters has profound implications in plentiful frontier applications. However, studies for universal mechanisms at the nanoscale to exhibit giant nonlinear responses in various avalanching emitters are limited. Here, record‐breaking nonlinear responses up to 60th‐order in high‐lying emitting levels of various emitters at room temperature are generated by proposing a universal mechanism named energy relay‐mediated photon avalanche (enrePA). By harnessing energy from the avalanching nano‐engine through the energy relay of Yb3+ ions, the brightness of blue emissions from Tm3+ and Ho3+ can be enhanced with giant optical nonlinearity up to 60th and 38th order, respectively. Further incorporating gadolinium‐based systems, more emitters (Tb3+, Eu3+, Dy3+, Nd3+) can be activated with extreme optical nonlinearities up to 48th‐order. By expanding PA into the full‐spectrum range, the enrePA mechanism opens exciting avenues for flexible and high‐efficiency PA modulation in multilayer nanostructures, enabling the applicability of PA in more technologies such as super‐resolution imaging, lithography, and optical detection.
A weak theory of building blocks
Authors: Murwanashyaka Juvenal
Published: May 2024

We apply the mereological concept of parthood to the coding of finite sequences. We propose a first‐order theory in which coding finite sequences is intuitive and transparent. We compare this theory with Robinson arithmetic, adjunctive set theory and weak theories of finite strings and finite trees using interpretability.
Fisetin induces G2/M phase arrest and caspase‐mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC
Authors: Yadav Monika , Kandhari Kushal , Mathan Sivapar V. , Ali Mansoor , Singh Rana P.
Published: May 2024

The anticancer potential and associated mechanisms of flavonoid fisetin are yet to be fully investigated on human head and neck squamous cell carcinoma (HNSCC). In the present study, fisetin (25‐75 µM for 24–48 h) dose‐dependently inhibited growth and induced death in HNSCC Cal33 and UM‐SCC‐22B cells, without showing any death in normal cells. Fisetin (25–50 µM) induced G2/M phase arrest via decrease in Cdc25C, CDK1, cyclin B1 expression, and an increase in p53(S15). A concentration‐dependent increase in fisetin‐induced DNA damage and apoptosis in HNSCC cells was authenticated by comet assay, gamma‐H2A.X(S139) phosphorylation, and marked cleavage of PARP protein. Interestingly, fisetin‐induced cell death occurred independently of p53 and reactive oxygen species production. The activation of JNK and inhibition of PI3K/Akt, ERK1/2, EGFR, and STAT‐3 signaling were identified. Further, fisetin‐induced apoptosis was mediated, in part, via p21Cip1 and p27Kip1 cleavage by caspase, which was reversed by z‐VAD‐FMK, a pan‐caspase inhibitor. Subsequently, fisetin was also found to induce autophagy; nevertheless, autophagy attenuation exaggerated apoptosis. Oral fisetin (50 mg/kg body weight) treatment to establish Cal33 xenograft in mice for 19 days showed 73% inhibition in tumor volume (p < 0.01) along with a decrease in Ki67‐positive cells and an increase in cleaved caspase‐3 level in tumors. Consistent with the effect of 50 µM fisetin in vitro, the protein levels of p21Cip1 and P27Kip1 were also decreased by fisetin in tumors. Together, these findings showed strong anticancer efficacy of fisetin against HNSCC with downregulation of EGFR‐Akt/ERK1/2‐STAT‐3 pathway and activation of JNK/c‐Jun, caspases and caspase‐mediated cleavage of p21Cip1 and p27Kip1.