bluuebunny/crossref_metadata_2025 huggingface dataset:
Aucubin alleviates methotrexate‐induced enteritis in rats by inducing autophagy
Authors: Yang Tongao , Lang Wuying , Zhao Yun , Yang Yahan , Liu Hongli , Li Sufen , Li Xianglong , Zhang Shuangqi , Zhang Haihua
Published: August 2023

One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti‐inflammation, anti‐apoptosis and anti‐oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX‐induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX‐induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D‐lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved‐caspase 1, IL‐18 and IL‐1β. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy‐related markers microtubule‐associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX‐induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX‐induced enteritis. However, 3‐methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX‐induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX‐resulted enteritis.
Crisis communication for public organizations: Examining Pakistan Railways' use of information technology and social media for image repair
Authors: Kamboh Shafiq Ahmad , Ittefaq Muhammad , Jin Yan
Published: August 2023

This study examines the induction of information technology and the use of image‐repair focused crisis response strategies on social media by Pakistan Railways amid a recent crisis. A mix‐method based content analysis (i.e., qualitative and quantitative) to investigate whether and if so, how Pakistan Railways used Benoit's suggested image restoration strategies on social media to repair its image among customers and in print media. Our results show that Pakistan Railways predominantly used reducing the offensiveness of event (40%), followed by corrective action (34.6%), evasion of responsibility (10.6%), denial (8%) and mortification (6.4%) strategies, respectively. In addition, the use of image‐repair focused crisis response strategies significantly varied by social media platform. An analysis of the publics' emotions found in their online comments reveals that, during the course of the organizational crisis communication, negative public emotions gradually subsided into ambivalent ones; and contrary to a highly negative newspaper coverage tone in the beginning of the crisis, the introduction of the Twitter handle has associated with more positive media coverage afterward. Theoretical and practical implications, especially the need for advancing social‐mediated crisis response effectiveness in developing countries, are discussed.
Meaning‐making within inclusion: Exploring parents, teachers and students lay theories of ADHD and their implications for inclusive practice
Authors: Carr‐Fanning Kate
Published: August 2023

This paper explores the Lay Theories of ADHD of stakeholders (teacher, parent and student) in an Irish context. Academic theories of difference have and continue to evolve, moving from medicalisation, through more socially oriented ideas, to more current trend around neurodivergence. However, inclusion as a process is socially negotiated within classrooms and the wider community. An understanding of stakeholders' lay theories or their beliefs about ADHD (e.g., what causes it and how to respond) gives us insights into this process. This paper draws on findings from a multi‐case study (N = 15) that explored the lay theories of 17 parents, 15 students (7–18 year; Mean = 12.8; SD = 3.09), and 12 teachers (4 primary and 8 secondary) affected by ADHD in mainstream schools. Participants took part in a semi‐structured interview. A data‐driven Thematic Analysis identified three themes: what is ADHD, do they have control, and medication. Each stakeholder group held distinctly different views, which created considerable confusion. Findings are discussed in terms the need for the education of key stakeholders, and what those educational initiatives might include, as well as for the role of collaboration within the process of inclusion.
The valuation of ecosystems services in the Inner Mongolia Autonomous Region of China
Authors: Fan Yu , Wu Qiong , Jia Changgeng , Liu Xingzhuo , Li Sihui , Ji Jiayang , Zheng Yun , Song Youtao
Published: August 2023

The valuation of ecosystem services is a powerful strategy on measuring the relations between natural resources and human capitals, to achieve the goal of protecting and promoting the positive contribution of nature. Gross Ecosystem Product (GEP) is a series of statistics that incorporates the monetary value of ecosystem services, which turns the ecological data comparable to GDP. As a case study of the relationship between ecosystem services and economic development, this work focused on the Inner Mongolia Autonomous Region (IMAR) in the northern part of China, with 12 main cities including 104 districts and counties in the highest latitude. The GEP was calculated at the municipal level using 30 m‐resolution remote sensing image data and a framework tailored to the specific economic and ecological conditions of IMAR. The results showed that the distribution of GEP in IMAR at the municipal level in 2020 ranged from 10.4 billion to 1920.7 billion RMB Yuan, with an overall value of 3.85 trillion RMB Yuan, and that the ratio of GEP to GDP was 1.17. Among various GEP components, the value of ecosystem regulating services took an essential part as 75.7%. Basically, the spatial distribution of GEP was diverse. The cities with the highest GEP values were Hulunbeir, Xilin Gol League, and Chifeng, The GEP hotspots are mainly distributed in the Hulunbuir region. Based on the dual analysis of GEP and GDP, there is still high room for improvement in most cities in the IMAR region. The GEP and GDP in IMAR can be enhanced through carbon trading, water rights and grassland tourism industry, which is conducive to the sustainable development of environment and economy in IMAR.
Structural, rheological, and gelling characteristics of starch‐based materials in context to 3D food printing applications in precision nutrition
Authors: Wu Huanqi , Sang Shangyuan , Weng Peifang , Pan Daodong , Wu Zufang , Yang Junsi , Liu Lingyi , Farag Mohamed A. , Xiao Jianbo , Liu Lianliang
Published: August 2023

Starch‐based materials have viscoelasticity, viscous film‐forming, dough pseudoplasticity, and rheological properties, which possess the structural characteristics (crystal structure, double helix structure, and layered structure) suitable for three‐dimensional (3D) food printing inks. 3D food printing technology has significant advantages in customizing personalized and precise nutrition, expanding the range of ingredients, designing unique food appearances, and simplifying the food supply chain. Precision nutrition aims to consider individual nutritional needs and individual differences, which include special food product design and personalized precise nutrition, thus expanding future food resources, then simplifying the food supply chain, and attracting extensive attention in food industry. Different types of starch‐based materials with different structures and rheological properties meet different 3D food printing technology requirements. Starch‐based materials suitable for 3D food printing technology can accurately deliver and release active substances or drugs. These active substances or drugs have certain regulatory effects on the gut microbiome and diabetes, so as to maintain personalized and accurate nutrition.
Origins of thirstiness sensation and current food solutions
Authors: Picó‐Munyoz Ruth , Tárrega Amparo , Laguna Laura
Published: August 2023

The sensation of thirstiness is the desire to drink water. In certain situations, the ingestion of liquid water can be restricted. As a result, thirstiness is not relieved, resulting in an uncomfortable and distressing situation. The present review describes thirstiness and hydration, the food products and beverages that cause thirstiness, and the beverages and food products currently available to quench thirstiness in individuals with restricted access to liquid ingestion. It also discusses how to measure the effectiveness of calming thirstiness. To diminish thirstiness distress, different alternatives to liquids are proposed. Individuals with swallowing disorders are given thickened water, individuals with restricted water ingestion are given ice cubes or ice popsicles of different flavors, and sportspeople are given energy gels. However, current beverage solutions seem not to relieve thirst fully, although some stimuli like iced water, flavors (especially lemon and mint), or acids seem to work better than plain stimuli and could be added to existing products. Therefore, there is still a need to incorporate these strategies into beverage and food formulations and to test their effectiveness.
Rapid detection of synthetic cannabinoid receptor agonists impregnated into paper by attenuated total reflectance Fourier transform infrared spectroscopy
Authors: Coombs Thomas , Abdelkader Amor , Tang Leung , Al‐Jumeily Dhiya , Assi Sulaf
Published: August 2023

The last few years have witnessed the change in the modalities of smuggling of synthetic cannabinoid receptor agonists (SCRAs) by impregnating them in mail envelopes and fast parcels. Considering the aforementioned scenario, it is important to develop a portable technique to identifying SCRAs through packages. The purpose of this research was to detect SCRAs impregnated into substrates of paper using attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy. Three SCRAs that included 5F‐PB‐22, AB‐FUBINACA and AKB‐48 were purchased from Sigma Aldrich. The three SCRAs and four cutting agents were impregnated into paper of variable thickness at four concentrations (10, 15, 20, and 25 mg/mL). Spectra were collected over the wavenumber range of 650–4000 cm−1 using ATR‐FTIR spectroscopy and were exported to Matlab 2020b where data analysis was applied. The FTIR spectral data was able to show the three SCRAs could be detected on paper using ATR‐FTIR spectroscopy and quantitatively modeled using the partial least squares regression algorithm. Principal component analysis showed separate clustering for the compounds that crystallized (5F‐PB‐22, AB‐FUBINACA and caffeine) onto the papers surface from those impregnated into the bulk of the paper (AKB‐48 and procaine) with the latter situated near blank papers in score plots. In summary, ATR‐FTIR spectroscopy has proven to be a successful non‐destructive technique in detecting and quantifying a selection of SCRAs impregnated into paper.
Introduction of QScript real‐time prescription monitoring system was associated with a fall in pregabalin poisoning presentations to a clinical toxicology unit
Authors: Holford Amanda , Martin Christopher , Staib Andrew , Harris Keith , Isoardi Katherine Z
Published: August 2023

Objective

To investigate the impact of QScript implementation on pregabalin‐related poisoning presentations to the ED.

Methods

This is a retrospective review of pregabalin‐related poisoning presentations to a tertiary Australian ED in the 4 years prior to, and 1 year following the introduction of QScript real‐time prescription monitoring system.

Results

Pregabalin‐related poisoning presentations fell by 28% from an average of 98 presentations annually over the 4 years prior to QScript implementation to 71 in 2022. The severity of poisonings was similar over the periods.

Conclusions

The introduction of QScript was associated with a reduction in pregabalin‐related poisoning presentations.
Transgastric versus transrectal: Which access route is the best for NOTES gallbladder‐preserving gallstone therapy?
Authors: Ullah Saif , Zhang Ji Yu , Liu Dan , Zhao Li Xia , Liu Bing Rong
Published: August 2023

Objectives

To compare the effectiveness and safety of transgastric and transrectal pure natural orifice transluminal endoscopic surgery (NOTES) for cholecystolithotomy.

Methods

This was a single‐center retrospective comparative study of consecutive patients who underwent pure NOTES for either transrectal or transgastric gallbladder‐preserving cholecystolithotomy between September 2017 and April 2020. Patients with symptomatic cholelithiasis were assigned for transrectal or transgastric NOTES based on the patients’ choice. Treatment success, postoperative pain, peritonitis, time to resume normal diet, and duration of hospitalization were compared.

Results

The technical success rate was 100%. Forty‐eight patients underwent successful NOTES cholecystolithotomy via the transrectal (n = 26) or transgastric route (n = 22). One (3.8%) patient in the transrectal NOTES group experienced postoperative abdominal pain compared to 6 (27.3%) in the transgastric NOTES group (P = 0.04). Fever and bile peritonitis developed in one (3.8%) patient in the transrectal NOTES group versus 8 (36.4%) in the transgastric NOTES group (P = 0.005). A postoperative fluid diet was commenced at 6 h with the transrectal approach versus on day 3 for the transgastric NOTES group. The mean postoperative hospitalization for transrectal and transgastric NOTES groups was 4.5 days versus 7 days (P = 0.001). Three patients in the transgastric NOTES group developed postoperative gastric fistula.

Conclusions

Transrectal NOTES has advantages over transgastric NOTES, including preserved spatial orientation, relatively easier removal of specimens, early food intake, shorter hospitalization, fewer postoperative complications and less pain. Multicenter clinical trials with long‐term follow‐up are needed to confirm the safety and efficacy of both approaches.
The role of miRNAs carried by extracellular vesicles in type 2 diabetes and its complications
Authors: Chao Yining , Gu Tianwei , Zhang Zhou , Wu Tianyu , Wang Jin , Bi Yan
Published: August 2023

Diabetes poses severe global public health problems and places heavy burdens on the medical and economic systems of society. Type 2 diabetes (T2D) accounts for 90% of these cases. Diabetes also often accompanies serious complications that threaten multiple organs such as the brain, eyes, kidneys, and the cardiovascular system. MicroRNAs (miRNAs) carried by extracellular vesicles (EV‐miRNAs) are considered to mediate cross‐organ and cross‐cellular communication and have a vital role in the pathophysiology of T2D. They also offer promising sources of diabetes‐related biomarkers and serve as effective therapeutic targets. Here, we briefly reviewed studies of EV‐miRNAs in T2D and related complications. Specially, we innovatively explore the targeting nature of miRNA action due to the target specificity of vesicle binding, aiding mechanism understanding as well as the detection and treatment of diseases.
Renal angiomyolipoma: Beyond size criteria for predicting rupture
Authors: McQueen Simon , Combes Alexander , Benz David
Published: August 2023

Introduction

Renal angiomyolipomas (AMLs) are vascular tumours that while histologically benign, carry a risk of rupture and potentially life‐threatening haemorrhage. Selective arterial embolisation (SAE) has been demonstrated as effective treatment; however, given most tumours are asymptomatic, the challenge facing the radiologist is selection of which AML should undergo treatment. This study considers presence and size of intratumoural aneurysm, to advance the readers treatment decision‐making beyond historical size criteria.

Methods

Retrospective cohort analysis of all SAE‐treated AML at a quaternary‐level institution in the last 10 years was completed independently by two radiologists. Computerised tomography (CT) and angiographic imaging were reviewed to evaluate tumour size, presence of intratumoural aneurysm and aneurysm size. Univariant and multivariant statistical analyses were used to identify predictors of spontaneous rupture and haemorrhage.

Results

Twenty‐seven renal AML underwent SAE. Five tumours had presented with haemorrhage. Twenty‐two were asymptomatic or without CT/angiographic detectable haemorrhage. There was no statistically significant size difference between ruptured (mean 7.8 cm, range 6.1–12.0 cm) and unruptured AML (7.5 cm, 3.3–21.7 cm) in the study population. Eighty percent of ruptured AML and 27% of unruptured AML contained at least one intratumoural aneurysm (P‐value < 0.05). Mean aneurysm size in ruptured AMLs was 5.4 mm, versus 4.6 mm among unruptured AML (P‐value > 0.05).

Conclusion

The presence of intratumoural aneurysm is a useful predictor for AMLs that are at risk of spontaneous rupture and haemorrhage. Intratumoural aneurysm should therefore be considered when selecting patients to undergo SAE.
Knockdown of BUB1 inhibits tumor necrosis factor‐α‐induced proliferation and migration of rheumatoid arthritis synovial fibroblasts by regulating PI3K/Akt pathway
Authors: He Qian , Jia Lanlan , Wang Xiaowan , Feng Dandan , Mao Tongjun
Published: August 2023

Background

Rheumatoid arthritis (RA) is a common disease with joint cartilage destruction. BUB1 Mitotic Checkpoint Serine/Threonine Kinase (BUB1) is abnormally expressed in synovial tissues of RA patients, but its effect on RA remains unclear. In this study, we explored the role of BUB1 in RA.

Methods

An RA cell model was constructed by treating MH7A cells with tumor necrosis factor‐α (TNF‐α). The levels of BUB1, GAPDH, phosphorylated phosphatidylinositol 3 kinase (p‐PI3K)/PI3K, and phosphorylated serine/threonine kinase (p‐Akt)/Akt in MH7A cells were examined by Western blot. The MH7A cell proliferation was examined by colony formation assay. Wound healing assay and transwell assay were carried out to detect MH7A cell migration and invasion. The mRNA levels of proinflammatory cytokines were assessed by quantitative reverse transcription polymerase chain reaction.

Results

The results showed that knockdown BUB1 inhibited TNF‐α‐induced MH7A cell proliferation, migration, and invasion. Silencing BUB1 repressed the PI3K/Akt pathway in TNF‐α‐induced MH7A cells. We also found that the TNF‐α‐induced MH7A cell proliferation, migration, and invasion were repressed by si‐BUB1 transfection, whereas these effects were attenuated by 740Y‐P (an activator of the PI3K pathway) co‐treatment. Knockdown of BUB1 reduced the expression of the proinflammatory cytokines.

Conclusion

Knockdown BUB1 repressed TNF‐α‐induced MH7A cell proliferation, migration and invasion through the PI3K/Akt pathway.
To read or to listen? Does disclosure delivery mode impact investors' reactions to managers' tone language?
Authors: Elliott W. Brooke , Loftus Serena , Winn Amanda
Published: August 2023

We examine how disclosure delivery mode—oral versus written—influences investors' reactions to managers' tone language. We hypothesize that listening to disclosures, relative to reading them, causes managers' qualitative word choices to have a greater impact on investors' judgments. We theorize that this effect occurs because oral delivery mode promotes heuristic processing and qualitative tone language is an easy‐to‐process disclosure element. The results from an experiment in a conference call setting are consistent with our hypothesis and suggest a boundary condition. Specifically, the interaction of mode and tone language is significant in a setting where heuristic processing is likely (good earnings news) but not in a setting where investors are likely to scrutinize the disclosure (bad earnings news). Our results inform investors about the potential consequences of how they consume disclosures. Specifically, we show that investors are more susceptible to managers' tone language when listening to disclosures containing good news than when reading them.
Estimating clade‐specific diversification rates and palaeodiversity dynamics from reconstructed phylogenies
Authors: Mazet Nathan , Morlon Hélène , Fabre Pierre‐Henri , Condamine Fabien L.
Published: August 2023

Understanding palaeodiversity dynamics through time and space is a central goal of macroevolution. Estimating palaeodiversity dynamics has been historically addressed with fossil data because it directly reflects the past variations of biodiversity. Unfortunately, some groups or regions lack a good fossil record, and dated phylogenies can be useful to estimate diversification dynamics. Recent methodological developments have unlocked the possibility to investigate palaeodiversity dynamics by using phylogenetic birth‐death models with non‐homogeneous rates through time and across clades. One of them seems particularly promising to detect clades whose diversity has declined through time. However, empirical applications of the method have been hampered by the lack of a robust, accessible implementation of the whole procedure, therefore requiring users to conduct all the steps of the analysis by hand in a time‐consuming and error‐prone way.

Here we propose an automation of Morlon et al. (2011) clade‐shift model with additional features accounting for recent developments, and we implement it in the R package RPANDA. We also test the approach with simulations focusing on its ability to detect shifts of diversification and to infer palaeodiversity dynamics. Finally, we illustrate the automation by investigating the palaeodiversity dynamics of Cetacea, Vangidae, Parnassiinae and Cycadales.

Simulations showed that we accurately detected shifts of diversification although false shift detections were higher for time‐dependent diversification models with extinction. The median global error of palaeodiversity dynamics estimated with the automated model is low, showing that the method can capture diversity declines. We detected shifts of diversification for three of the four empirical examples considered (Cetacea, Parnassiinae and Cycadales). Our analyses unveil a waxing‐and‐waning pattern due to a phase of negative net diversification rate embedded in the trees after isolating recent radiations.

Our work makes it possible to easily apply non‐homogeneous models of diversification in which rates can vary through time and across clades to reconstruct palaeodiversity dynamics. By doing so, we detected palaeodiversity declines among three of the four groups tested, highlighting that such periods of negative net diversification might be common. We discuss the extent to which this approach might provide reliable estimates of extinction rates, and we provide guidelines for users.
Mapping spatial patterning of Bronze Age towers in Oman according to water flow accumulation
Authors: Nathan Smiti , Harrower Michael J.
Published: August 2023

Water played an undeniably significant role in the origins of complex societies across the Near East, but political complexity in regions like Southeast Arabia diverges dramatically from the more well‐known histories of Egypt, the Levant and Mesopotamia. Through quantitative analysis, this paper investigates spatial associations between water availability and Umm an‐Nar towers in Adh Dhahirah Governorate of Oman. We hypothesise that ancient Umm an‐Nar people targeted high water flow accumulation areas for major settlements with towers. Our results lead us to reject the null hypothesis of no spatial association between tower settlements and water and help clarify the role of water in the rise of complex polities.
Associations between cardiorespiratory fitness and lifestyle‐related factors with DNA methylation‐based ageing clocks in older men: WASEDA'S Health Study
Authors: Kawamura Takuji , Radak Zsolt , Tabata Hiroki , Akiyama Hiroshi , Nakamura Nobuhiro , Kawakami Ryoko , Ito Tomoko , Usui Chiyoko , Jokai Matyas , Torma Ferenc , Kim Hyeon‐Ki , Miyachi Motohiko , Torii Suguru , Suzuki Katsuhiko , Ishii Kaori , Sakamoto Shizuo , Oka Koichiro , Higuchi Mitsuru , Muraoka Isao , McGreevy Kristen M. , Horvath Steve , Tanisawa Kumpei
Published: August 2023

DNA methylation‐based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age‐adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65–72 years were used to appraise first‐ (i.e., DNAmHorvath and DNAmHannum) and second‐ (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2/kg at VT) and peak oxygen uptake (VO2/kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2/kg at VT and VO2/kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle‐related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men.
A mobile integrated health program for the management of undifferentiated acute complaints in older adults is safe and feasible
Authors: O'Connor Laurel , Reznek Martin , Hall Michael , Inzerillo Julie , Broach John P. , Boudreaux Edwin
Published: August 2023

Background

Poor care access and lack of proper triage of medical complaints leads to inappropriate use of acute care resources. Mobile integrated health (MIH) programs may offer a solution by providing adaptable on‐demand care. There is little information describing programs that manage undifferentiated complaints in the community. The objective of this study was to assess the safety and feasibility of an MIH program that responds to the community to manage medical complaints in older adults.

Methods

This was a prospective observational study examining a pilot MIH program. Seven ambulatory clinics and their affiliated patients aged 65 and older were oriented to the program and invited to use its services. Visit and follow‐up data for all patients who underwent an MIH visit were abstracted, along with 30‐day follow‐up information. All demographic data and outcomes were reported descriptively.

Results

In 21 months, 153 MIH visits were completed, involving 91 patients (mean age 81 years, 60.4% female). The most common chief complaints were generalized weakness (28.8%) and shortness of breath (18.9%). Electrocardiogram (57.5%) and point‐of‐care bloodwork (34.6%) were the most common diagnostic tests performed. Sixteen visits (10.4%) were followed by an emergency department (ED) visit within 72 h. In 11 encounters, the patient was referred to the ED; in five cases, the ED visit was unforeseen. Fifteen patients (9.8%) were admitted to the hospital after an MIH visit. There were two deaths within 30 days following an index visit.

Conclusions

An MIH program designed to address the acute complaints of community‐dwelling older adults was feasible and safe, with low rates of unforeseen emergency services utilizations. MIH programs have valuable diagnostic and therapeutic capabilities and may serve to help triage the acute medical needs of patients. Further study is required to validate the efficacy and cost‐effectiveness of MIH programs.
Clinical and psychosocial outcomes by sex among individuals prescribed buprenorphine‐naloxone (BUP‐NX) or extended‐release naltrexone (XR‐NTX) for opioid use disorder
Authors: Paschen‐Wolff Margaret , Greenfield Shelly F. , Kathryn McHugh R. , Burlew Kathleen , Pavlicova Martina , Choo Tse‐Hwei , Barbosa‐Leiker Celestina , Ruglass Lesia M. , Mennenga Sarah , Rotrosen John , Nunes Edward V. , Campbell Aimee N. C.
Published: August 2023

Background and Objectives

Limited research has explored sex differences in opioid use disorder medication (MOUD) treatment outcomes. The purpose of this study was to examine MOUD initiation onto buprenorphine‐naloxone (BUP‐NX) versus extended‐release naltrexone (XR‐NTX) by sex, and sex differences in clinical and psychosocial outcomes.

Methods

Using data from a 24‐week open‐label comparative effectiveness trial of BUP‐NX or XR‐NTX, this study examined MOUD initiation (i.e., receiving a minimum one XR‐NTX injection or first BUP‐NX dose) and 24‐week self‐report outcomes. We used regression models to estimate the probability of MOUD initiation failure among the intent‐to‐treat sample (N = 570), and the main and interaction effects of sex on outcomes of interest among the subsample of participants who successfully initiated MOUD (n = 474).

Results

In the intent‐to‐treat sample, the odds of treatment initiation failure were not significantly different by sex. In the subsample of successful MOUD initiates, the effect of treatment on employment at week 24 was significantly moderated by sex (p = .003); odds of employment were not significantly different among males by MOUD type; females randomized to XR‐NTX versus BUP‐NX had 4.63 times greater odds of employment (p < .001). Males had significantly lower odds of past 30‐day exchanging sex for drugs versus females (adjusted odds ratios [aOR] = 0.10, p = .004), controlling for treatment and baseline outcomes.

Discussion and Conclusions

Further research should explore how to integrate employment support into OUD treatment to improve patient outcomes, particularly among women.

Scientific Significance

The current study addressed gaps in the literature by examining sex differences in MOUD initiation and diverse treatment outcomes in a large, national sample.
Evaluating the substance use disorder treatment gap in the United States, 2016−2019: A population health observational study
Authors: Sahker Ethan , Pro George , Poudyal Hemant , Furukawa Toshi A.
Published: August 2023

Background and Objectives

Only 10% of Americans with substance use disorders (SUDs) receive treatment with insufficient treatment access and screening practices proposed and potential contributing factors.

Methods

This retrospective cross‐sectional study used National Survey on Drug Use and Health (NSDUH) data to assess individuals with SUDs receiving treatment between 2016 and 2019 (survey n = 12,111; weighted n = 12,394,214). Demographic, access, and screening characteristics were investigated as predictors of treatment receipt using time‐series logistic regression analyses to test trends and assessed treatment receipt odds, controlling for demographic and treatment characteristics.

Results

For those with past‐year SUDs, 13.0% reported receiving past‐year SUD treatment (survey n = 1605; weighted n = 1,612,154). The SUD treatment receipt rate remained statistically stable from 2016 to 2019, with a nonsignificant treatment receipt trend declining from 14% to 12%. Treatment changes were notable among Native Americans (+53.80%), Pacific Islanders (+94.10%), multiracial (−59.96%), ages 65+ (−70.18%), and ages 12−17 (−50.70%). In the regression model, race, sex, age, insurance status, and receiving mental health treatment were associated with SUD treatment receipt.

Discussion and Conclusions

The treatment gap remains substantial and stable. Annually, about 87% of Americans with SUDs are not receiving the treatment they need. Asian Americans were less likely and those attending general mental health services were more likely to receive treatment.

Scientific Significance

We present an updated SUD treatment gap evaluation, and identify access and screening characteristics associated with SUD treatment receipt. Policymakers, clinicians, and researchers must continue improving access and identification of those in need of care.
Epistemic Injustice and the Electoral Connection
Authors: Pottle Justin
Published: August 2023

This article argues office seekers’ messaging gives rise to a distinct and underappreciated epistemic form of political inequality. Electoral incentives push representatives to orient their rhetoric toward appealing to strategically valuable constituencies, yielding flows of elite cues that disproportionately reflect those groups’ perspectives. When inequalities in strategic value overlap with other inequalities of social power, politicians’ messaging strategies exacerbate the epistemic marginalization of disadvantaged citizens by denying them equal influence on the frames and understandings circulated in mainstream debate. This dynamic is best understood as a democratically perverse form of epistemic injustice distinct from but mutually reinforcing with citizens’ unequal influence on political outcomes. Moreover, I show how such inequalities distort otherwise epistemically salutary mechanisms of electoral accountability and undermine the quality of representative decision‐making. I conclude by suggesting hypotheses for testing electoral reform's potential to mitigate these discursive consequences.
Bilateral Conflict: An Experimental Study of Strategic Effectiveness and Equilibrium
Authors: Holt Charles A. , Palfrey Thomas R.
Published: August 2023

Bilateral conflict involves an attacker with several alternative attack methods and a defender who can take various actions to better respond to different types of attack. These situations have wide applicability to political, legal, and economic disputes, but they are particularly challenging to study empirically because the payoffs are unknown. Moreover, each party has an incentive to behave unpredictably, so theoretical predictions are stochastic. This article reports results of an experiment where the details of the environment are tightly controlled. The results sharply contradict the Nash equilibrium predictions about how the two parties’ choice frequencies change in response to the relative effectiveness of alternative attack strategies. In contrast, nonparametric quantal response equilibrium predictions match the observed treatment effects. Estimation of the experimentally controlled payoff parameters across treatments accurately recovers the true values of those parameters with the logit quantal response equilibrium model but not with the Nash equilibrium model.
AnEAACIreview: Go green in health care and research. Practical suggestions for sustainability in clinical practice, laboratories, and scientific meetings
Authors: Pali‐Schöll Isabella , Hermuth‐Kleinschmidt Kerstin , Dramburg Stephanie , Agache Ioana , Mayerhofer Hanna , Jensen‐Jarolim Erika , Goshua Anna , Nadeau Kari C.
Published: August 2023

Health care professionals (HCPs) and researchers in the health care sector dedicate their professional life to maintaining and optimizing the health of their patients. To achieve this, significant amounts of resources are used and currently it is estimated that the health care sector contributes to more than 4% of net greenhouse gas (GHG) emissions. GHG emissions adversely impact planetary health and consequently human health, as the two are intricately linked. There are many factors of health care that contribute to these emissions. Hospitals and research labs also use high amounts of consumables which require large amounts of raw materials and energy to produce. They are further responsible for polluting the environment via disposal of plastics, drug products, and other chemicals. To maintain and develop state‐of‐the‐art best practices and treatments, medical experts exchange and update their knowledge on methods and technologies in the respective fields at highly specialized scientific meetings. These meetings necessitate thousands of attendants traveling around the globe. Therefore, while the goal of HCPs is to care for the individual, current practices have an enormous (indirect) impact on the health of the patients by their negative environmental impacts. There is an urgent need for HCPs and researchers to mitigate these detrimental effects. The installation of a sustainability‐manager at health care facilities and research organizations to implement sustainable practices while still providing quality health care is desirable. Increased use of telemedicine, virtual/hybrid conferences and green chemistry have recently been observed. The benefits of these practices need to be evaluated and implemented as appropriate. With this manuscript, we aim to increase the awareness about the negative impacts of the health care system (including health care research) on planetary and human health. We suggest some easy and highly impactful steps and encourage health care professionals and research scientists of all hierarchical levels to immediately implement them in their professional as well as private life to counteract the health care sector's detrimental effects on the environment.
A study of the pharmacokinetics and pharmacodynamics of oxytocin at elective caesarean delivery
Authors: Monks D. T. , Singh P. M. , Kagan L. , Palanisamy A.
Published: August 2023

Oxytocin is widely used to prevent atonic postpartum haemorrhage after caesarean delivery. Initial treatment failure rates are high and inadequate dosing may contribute. Excessive doses, however, are associated with serious adverse effects. The pharmacokinetic data from this context are sparse and there is a lack of data in the immediate postpartum minutes after an initiating bolus. The pharmacodynamic data from this context are exclusively from dose‐effect studies, with some suggesting that higher doses of oxytocin are required to provide adequate uterine tone in obese compared with non‐obese women. We aimed to perform a pharmacokinetic and pharmacodynamic study that would facilitate more precise weight‐based oxytocin dosing. We measured arterial oxytocin concentration, uterine tone and haemodynamic parameters in 25 women in the first 40 min after exogenous oxytocin administration at elective caesarean delivery. Serum oxytocin concentrations varied considerably between individuals. We constructed a one‐compartment pharmacokinetic model of exogenous oxytocin deposition, after its administration with an initiating bolus and a maintenance infusion, at elective caesarean delivery. Body weight was evaluated as a potential covariate but was not included in the model due to lack of statistically significant reduction in the objective function. We calculated the volume of distribution and clearance (mean [coefficient of variation]) as 156.1 l [18%] and 83 ml.s−1 [32%] but found no within‐individual correlation between serum oxytocin concentration and uterine tone or haemodynamic parameters. In conclusion, we observed a large variation in serum oxytocin concentrations between individuals receiving similar doses of oxytocin and were unable to establish weight‐based dosing of exogenous oxytocin at caesarean delivery. Our findings suggest that future studies on oxytocin pharmacokinetics would need large sample sizes. In the absence of such data, oxytocin dosing should continue to be guided by uterine tone assessments and adjusted according to a strategy based on the best evidence from dose‐effect studies.
Caudal autotomy among populations of the lizard Sceloporus variabilis (Squamata: Phrynosomatidae) in contrasting environments
Authors: García‐Rosales Aaron , Cruz‐Elizalde Raciel , Ramírez‐Bautista Aurelio , Hernández‐Camacho Norma
Published: August 2023

Caudal autotomy is a behaviour in lizards that favours survival but brings with it some associated costs, mainly loss of energy, which is related to the position of the breaking point. Moreover, the frequency of tail loss can vary at different levels, between sexes, populations, seasons and at an intra‐ and inter‐population level. In this study, we analysed the breaking position of the tails in individuals and frequencies of tail loss between years, sexes, seasons and populations of the lizard Sceloporus variabilis that inhabit contrasting environments. The results showed a low frequency of tail loss at the ends (distal and proximal) of this organ (except for individuals from the xeric scrubland population) and there was a higher proportion of complete than incomplete tails in lizards for all analysed populations. Also, there was no variation in the frequency of tail loss among populations, sexes (except in one population), years or seasons. A higher proportion of organisms with complete tails suggests that this organ is an important element for these lizards. In addition, the lack of variation in the frequency of tail loss may indicate a similar behaviour such as escape from predators among the groups analysed.
Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation: A retrospective cohort study
Authors: Schagen Maaike R. , Ulu Asiye Nur , Francke Marith I. , van de Wetering Jacqueline , van Buren Marleen C. , Schoenmakers Sam , Matic Maja , van Schaik Ron H. N. , Hesselink Dennis A. , de Winter Brenda C. M.
Published: August 2023

Aims

Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole‐blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model.

Methods

Data of pregnant women using a twice‐daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness‐of‐fit plots, visual predictive checks and a bootstrap analysis.

Results

A total of 260 whole‐blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance.

Conclusions

Tacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole‐blood tacrolimus predose concentrations during pregnancy, increasing the dose is required.
Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide administration in healthy participants
Authors: Holze Friederike , Erne Livio , Duthaler Urs , Liechti Matthias E.
Published: August 2023

Aims

Lysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic–pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing.

Methods

The present study characterized the pharmacokinetics, pharmacokinetic–pharmacodynamic relationship and urinary recovery of LSD at doses of 85 and 170 μg administered orally in 28 healthy participants. The plasma concentrations and subjective effects of LSD were continuously evaluated over a period of 24 h. Urine was collected during 3 time intervals (0–8, 8–16 and 16–24 h after LSD administration). Pharmacokinetic parameters were determined using compartmental modelling. Concentration–subjective effect relationships were described using pharmacokinetic–pharmacodynamic modelling.

Results

Mean (95% confidence interval) maximal LSD concentrations were 1.8 ng/mL (1.6–2.0) and 3.4 ng/mL (3.0–3.8) after the administration of 85 and 170 μg LSD, respectively. Maximal concentrations were achieved on average after 1.7 h. Elimination half‐lives were 3.7 h (3.4–4.1) and 4.0 h (3.6–4.4), for 85 and 170 μg LSD, respectively. Only 1% of the administered dose was recovered from urine unchanged within the first 24 h, 16% was eliminated as 2‐oxo‐3‐hydroxy‐LSD. Urinary recovery was dose proportional. Mean (±standard deviation) durations of subjective effects were 9.3 ± 3.2 and 11 ± 3.7 h, and maximal effects (any drug effects) were 77 ± 18% and 87 ± 13% after 85 and 170 μg of LSD, respectively.

Conclusion

The present novel study validates previous findings. LSD exhibited dose‐proportional pharmacokinetics and first‐order elimination kinetics and dose‐dependent duration and intensity of subjective effects. LSD is extensively metabolized and shows dose‐proportional urinary recovery.
Effect of lemborexant on pharmacokinetics of clozapine: A potential drug–drug interaction mediated by time‐dependent inhibition of CYP3A4
Authors: Watanabe Kenya , Misaka Shingen , Kanno‐Nozaki Keiko , Chiyoda Takaaki , Suzuki Yuhei , Sato Akiko , Suto Takahiro , Kuroda Junko , Shimomura Kenju , Miura Itaru , Yabe Hirooki
Published: August 2023

Clozapine (CLZ) is extensively used for treatment‐resistant schizophrenia (TRS) with caution to avoid serious adverse events such as agranulocytosis and drug–drug interactions (DDIs). In the current report, we present a case of a 35‐year‐old male non‐smoking TRS patient whose steady‐state plasma trough concentrations (Ctrough) of CLZ and its active metabolite, N‐desmethylclozapine (NDMC), were significantly increased after initiating oral administration of lemborexant (LEM), a dual orexin receptor antagonist, for the treatment of insomnia. The patient experienced oversedation with sleepiness and fatigue while maintaining high levels of Ctrough of CLZ. The increased concentrations of CLZ returned to normal ranges after the discontinuation of LEM dosing, implying a pharmacokinetic DDI between CLZ and LEM. To gain insight into possible mechanisms, we performed in vitro assays of CYP1A2‐ and CYP3A4‐mediated CLZ metabolism by measuring the formations of NDMC and clozapine N‐oxide (CNO). In accordance with previous studies, the incubation of CLZ with each enzyme resulted in the production of both metabolites. LEM had only a weak inhibitory effect on CYP1A2‐ and CYP3A4‐mediated CLZ metabolism. However, the preincubation of LEM with CYP3A4 in the presence of NADPH showed a significant enhancement of inhibitory effects on CLZ metabolism with IC50 values for the formations of CNO and NDMC of 2.8 μM and 4.1 μM, respectively, suggesting that LEM exerts as a potent time‐dependent inhibitor for CYP3A4. Taken together, the results of the current study indicate that co‐medication of CLZ with LEM may lead to increase in exposure to CLZ and risks of CLZ‐related adverse events.