bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical evaluation of cell lysis methods for metallodrug studies in cancer cells
Authors: Riisom Mie , Jamieson Stephen M F , Hartinger Christian G 
Published: August 2023

Abstract
Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein content in lysates and in cell uptake studies of the Ru anticancer complex [chlorido(8-oxyquinolinato)(η6-p-cymene)ruthenium(II)] ([Ru(cym)(HQ)Cl]). The physical lysis methods osmosis and sonication were chosen for comparison with chemical lysis with the radioimmunoprecipitation assay (RIPA) buffer. Based on the protein content and the total Ru accumulated in the lysates, the latter determined using inductively coupled plasma–mass spectrometry, RIPA buffer was the most efficient lysis method. Measurements of plastic adsorption blanks revealed that the higher Ru content determined in the RIPA buffer lysis samples may be due a higher amount of Ru extracted from the plastic incubation plates compared with osmosis and sonication. Overall, we found that the choice of lysis method needs to be matched to the information sought and we suggest the least disruptive osmosis method might be the best choice for labile drug–biomolecule adducts. Minimal differences were found for experiments aimed at measuring the overall cell uptake of the Ru complex.
A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice
Authors: Wang Guohao , Jin Shuhan , Liu Jiaqi , Li Xu , Dai Peng , Wang Yuetong , Hou Steven X 
Published: August 2023

ABSTRACT
Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1β with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.
Health Equity and Antibiotic Prescribing in the United States: A Systematic Scoping Review
Authors: Kim Christine , Kabbani Sarah , Dube William C , Neuhauser Melinda , Tsay Sharon , Hersh Adam , Marcelin Jasmine R , Hicks Lauri A 
Published: August 2023

AbstractWe performed a scoping review of articles published from 1 January 2000 to 4 January 2022 to characterize inequities in antibiotic prescribing and use across healthcare settings in the United States to inform antibiotic stewardship interventions and research. We included 34 observational studies, 21 cross-sectional survey studies, 4 intervention studies, and 2 systematic reviews. Most studies (55 of 61 [90%]) described the outpatient setting, 3 articles were from dentistry, 2 were from long-term care, and 1 was from acute care. Differences in antibiotic prescribing were found by patient's race and ethnicity, sex, age, socioeconomic factors, geography, clinician's age and specialty, and healthcare setting, with an emphasis on outpatient settings. Few studies assessed stewardship interventions. Clinicians, antibiotic stewardship experts, and health systems should be aware that prescribing behavior varies according to both clinician- and patient-level markers. Prescribing differences likely represent structural inequities; however, no studies reported underlying drivers of inequities in antibiotic prescribing.
Biosynthesis of gibberellin-related compounds modulates far-red light responses in the liverwort Marchantia polymorpha
Authors: Sun Rui , Okabe Maiko , Miyazaki Sho , Ishida Toshiaki , Mashiguchi Kiyoshi , Inoue Keisuke , Yoshitake Yoshihiro , Yamaoka Shohei , Nishihama Ryuichi , Kawaide Hiroshi , Nakajima Masatoshi , Yamaguchi Shinjiro , Kohchi Takayuki 
Published: August 2023

Abstract
Gibberellins (GAs) are key phytohormones that regulate growth, development, and environmental responses in angiosperms. From an evolutionary perspective, all major steps of GA biosynthesis are conserved among vascular plants, while GA biosynthesis intermediates such as ent-kaurenoic acid (KA) are also produced by bryophytes. Here, we show that in the liverwort Marchantia polymorpha, KA and GA12 are synthesized by evolutionarily conserved enzymes, which are required for developmental responses to far-red light (FR). Under FR-enriched conditions, mutants of various biosynthesis enzymes consistently exhibited altered thallus growth allometry, delayed initiation of gametogenesis, and abnormal morphology of gamete-bearing structures (gametangiophores). By chemical treatments and liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses, we confirmed that these phenotypes were caused by the deficiency of some GA-related compounds derived from KA, but not bioactive GAs from vascular plants. Transcriptome analysis showed that FR enrichment induced the up-regulation of genes related to stress responses and secondary metabolism in M. polymorpha, which was largely dependent on the biosynthesis of GA-related compounds. Due to the lack of canonical GA receptors in bryophytes, we hypothesize that GA-related compounds are commonly synthesized in land plants but were co-opted independently to regulate responses to light quality change in different plant lineages during the past 450 million years of evolution.
What makes police officers resist research and evidence-based policing? Examining the role of organizational and environmental factors
Authors: Kuen Kiseong , Lum Cynthia , Kim Seung Hyun 
Published: August 2023

AbstractDespite a growing body of research on police officers’ receptivity or resistance to evidence-based policing (EBP) and research, the mechanisms behind officers’ resistance have received limited attention. To address this gap, we investigate the impact of organizational factors (i.e. organizational justice, supervisor support, cynicism towards organizational change) and environmental factors (i.e. disrespected experience by citizens, citizen animus, crime trends) on shaping officer resistance to EBP and research using survey data from 457 front-line officers from seven police departments in Seoul, South Korea. Our findings reveal that cynicism towards organizational change significantly impacts officer resistance to EBP and research, more so than the impact of officers’ dispositional resistance to change. Furthermore, we find that organizational justice and supervisor support have significant indirect effects on officer resistance to EBP and research through cynicism towards organizational change. These results underscore the importance of improving organizational climates to reduce officer resistance to EBP and research.
Have increased deaths at home during the pandemic returned to pre-pandemic levels? An analysis of publicly available Scottish death registrations
Authors: Savinc J , Atherton I M 
Published: August 2023

Abstract

Background
Deaths at home increased in Scotland at the start of the Coronavirus disease 2019 (COVID-19) pandemic by ~35%. The majority did not involve COVID-19. This has implications for resource allocation and care at the end of life.

Methods
Publicly available weekly death registrations by National Records Scotland (NRS) between 2015 and week 25 of 2023 were summarized by place of death. Linear and logistic regressions of the number and proportion of deaths at home, respectively, between 2015 and 2019, were used to estimate the expected number and proportion of deaths in the period 2020–2023 had the pandemic not happened.

Results and conclusion
The number of deaths at home continues in 2023 at rates similar to the pandemic period and has not reverted to pre-pandemic levels. Had the pre-pandemic trend of growth in deaths at home continued, the number of deaths observed in 2020 would not be observed until 2025–2032. Deaths at home increased across Local Authorities but the scale of the increase varied. The impact of the increased number of deaths at home on quality of care and quality of death is not known and requires further study.
Serious Mental Illness, Glycemic Control, and Neighborhood Factors within an Urban Diabetes Cohort
Authors: Iturralde Esti , Rubinsky Anna D , Nguyen Kim H , Anderson Chelsie , Lyles Courtney R , Mangurian Christina 
Published: August 2023

Abstract

Background and Hypothesis
Serious mental illness (SMI) may compromise diabetes self-management. This study assessed the association between SMI and glycemic control, and explored sociodemographic predictors and geographic clustering of this outcome among patients with and without SMI.

Study Design
We used electronic health record data for adult primary care patients with diabetes from 2 San Francisco health care delivery systems. The primary outcome was poor glycemic control (hemoglobin A1c &gt;9.0%), which was modeled on SMI diagnosis status and sociodemographics. Geospatial analyses examined hotspots of poor glycemic control and neighborhood characteristics.

Study Results
The study included 11 694 participants with diabetes, 21% with comorbid SMI, of whom 22% had a schizophrenia spectrum or bipolar disorder. Median age was 62 years; 52% were female and 79% were Asian, Black, or Hispanic. In adjusted models, having schizophrenia spectrum disorder or bipolar disorder was associated with greater risk for poor glycemic control (vs participants without SMI, adjusted relative risk [aRR] = 1.24; 95% confidence interval, 1.02, 1.49), but having broadly defined SMI was not. People with and without SMI had similar sociodemographic correlates of poor glycemic control including younger versus older age, Hispanic versus non-Hispanic White race/ethnicity, and English versus Chinese language preference. Hotspots for poor glycemic control were found in neighborhoods with more lower-income, Hispanic, and Black residents.

Conclusions
Poor diabetes control was significantly related to having a schizophrenia spectrum or bipolar disorder, and to sociodemographic factors and neighborhood. Community-based mental health clinics in hotspots could be targets for implementation of diabetes management services.
Anti-inflammatory and antioxidative effects of elderberry diet in the rat model of seizure: a behavioral and histological investigation on the hippocampus
Authors: Bayat Amir-Hossein , Eskandari Neda , Sani Mojtaba , Fotouhi Farid , Shenasandeh Zahra , Saeidikhoo Sara , Rohani Razieh , Sabbagh Alvani Mohammadamin , Mafi Balani Mohammadreza , Eskandarian Boroujeni Mahdi , Abdollahifar Mohammad-Amin , Tajari Faezeh , Aliaghaei Abbas , Hassani Moghaddam Meysam 
Published: August 2023

Abstract
The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the Seizure + EB group, EB powder was added to the rats’ routine diet for eight consecutive weeks. The study included several behavioral tests, immunohistopathology, Voronoi tessellation (to estimate the spatial distribution of cells in the hippocampus), and Sholl analysis. The results in the Seizure + EB group showed an improvement in the behavioral aspects of the study, a reduction in astrogliosis, astrocyte process length, number of branches, and intersections distal to the soma in the hippocampus of rats compared to controls. Further analysis showed that EB diet increased nuclear factor-like 2 expression and decreased caspase-3 expression in the hippocampus in the Seizure + EB group. In addition, EB protected hippocampal pyramidal neurons from PTZ toxicity and improved the spatial distribution of hippocampal neurons in the pyramidal layer and dentate gyrus. The results of the present study suggest that EB can be considered a potent modifier of astrocyte reactivation and inflammatory responses.
The putative protein kinase Stk36 is essential for ciliogenesis and CSF flow by associating with Ulk4
Authors: Zhang Hongye , Yang Meimei , Zhang Jianhua , Li Li , Guan Tianyuan , Liu Jiaxin , Gong Xuanwei , Yang Fan , Shen Sanbing , Liu Min , Han Yongfeng 
Published: August 2023

AbstractMotile cilia lining on the ependymal cells are crucial for cerebrospinal fluid (CSF) flow and its dysfunction is often associated with hydrocephalus. Unc51‐like‐kinase 4 (Ulk4) was previously linked to CSF flow and motile ciliogenesis in mice, as the hypomorph mutant of Ulk4 (Ulk4tm1a/tm1a) developed hydrocephalic phenotype resulted from defective ciliogenesis and disturbed ciliary motility, while the underling mechanism is largely obscure. Here, we report that serine/threonine kinase 36 (STK36), a paralog of ULK4, directly interacts with ULK4 and this was demonstrated by yeast two‐hybrid (Y2H) in yeast and coimmunoprecipitation (co‐IP) assays in HEK293T cells, respectively. The interaction region was confined to their respective N‐terminal kinase domain. The hypomorph mutant of Stk36 (Stk36tmE4−/−) also developed progressive hydrocephalus postnatally and dysfunctional CSF flow, with multiple defects of motile cilia, including reduced ciliary number, disorganized ciliary orientation, defected axonemal structure and inconsistent base body (BB) orientation. Stk36tmE4−/− also disturbed the expression of Foxj1 transcription factor and a range of other ciliogenesis‐related genes. All these morphological changes, motile cilia defects and transcriptional dysregulation in the Stk36tmE4−/− are practically copied from that in Ulk4tm1a/tm1a mice. Taken together, we conclude that both Stk36 and Ulk4 are crucial for CSF flow, they cooperate by direct binding with their kinase domain to regulate the Foxj1 transcription factor pathways for ciliogenesis and cilia function, not limited to CSF flow. The underlying molecular mechanism probably conserved in evolution and could be extended to other metazoans.
Cholesterol metabolism in T‐cell aging: Accomplices or victims
Authors: Hu Cexun , Wu Hongliang , Zhu Qun , Cao Na , Wang Hui 
Published: August 2023

AbstractAging has a significant impact on the function and metabolism of T cells. Cholesterol, the most important sterol in mammals, is known as the “gold of the body” because it maintains membrane fluidity, rigidity, and signal transduction while also serving as a precursor of oxysterols, bile acids, and steroid hormones. Cholesterol homeostasis is primarily controlled by uptake, biosynthesis, efflux, and regulatory mechanisms. Previous studies have suggested that there are reciprocal interactions between cholesterol metabolism and T lymphocytes. Here, we will summarize the most recent advances in the effects of cholesterol and its derivatives on T‐cell aging. We will furthermore discuss interventions that might be used to help older individuals with immune deficiencies or diminishing immune competence.
The Warburg effect drives cachectic states in patients with pancreatobiliary adenocarcinoma
Authors: Li Qiuju , Zhang Dapeng , Sui Xiaojun , Song Tao , Hu Lijuan , Xu Xiaoqing , Wang Ximo , Wang Feng 
Published: August 2023

AbstractWe have studied whether the Warburg effect (uncontrolled glycolysis) in pancreatobiliary adenocarcinoma triggers cachexia in the patient. After 74 pancreatobiliary adenocarcinomas were removed by surgery, their glucose transporter‐1 and four glycolytic enzymes were quantified using Western blotting. Based on the resulting data, the adenocarcinomas were equally divided into a group of low glycolysis (LG) and a group of high glycolysis (HG). Energy homeostasis was assessed in these cancer patients and in 74 non‐cancer controls, using serum albumin and C‐reactive protein and morphometrical analysis of abdominal skeletal muscle and fat on computed tomography scans. Some removed adenocarcinomas were transplanted in nude mice to see their impacts on host energy homeostasis. Separately, nude mice carrying tumor grafts of MiaPaCa‐2 pancreatic adenocarcinoma cells were treated with the glycolytic inhibitor 3‐bromopyruvate and with emodin that inhibited glycolysis by decreasing hypoxia‐inducible factor‐1α. Adenocarcinomas in both group LG and group HG impaired energy homeostasis in the cancer patients, compared to the non‐cancer reference. The impaired energy homeostasis induced by the adenocarcinomas in group HG was more pronounced than that by the adenocarcinomas in group LG. When original adenocarcinomas were grown in nude mice, their glycolytic abilities determined the levels of hepatic gluconeogenesis, skeletal muscle proteolysis, adipose‐tissue lipolysis, and weight loss in the mice. When MiaPaCa‐2 cells were grown as tumors in nude mice, 3‐bromopyruvate and emodin decreased tumor‐induced glycolysis and cachexia, with the best effects being seen when the drugs were administered in combination. In conclusion, the Warburg effect in pancreatobiliary adenocarcinoma triggers cancer cachexia.
Cuproptosis enhances docetaxel chemosensitivity by inhibiting autophagy via the DLAT/mTOR pathway in prostate cancer
Authors: Wen Hongzhuang , Qu Changbao , Wang Zhu , Gao Haitao , Liu Wuyao , Wang Hu , Sun Hao , Gu Junfei , Yang Zhan , Wang Xiaolu 
Published: August 2023

AbstractCuproptosis, a newly discovered programmed cell death induced by copper ions, is associated with the progression and drug resistance of various tumors. Docetaxel plays a vital role as a first‐line chemotherapeutic agent for advanced prostate cancer; however, most patients end up with prostate cancer progression because of inherent or acquired resistance. Herein, we examined the role of cuproptosis in the chemotherapeutic resistance of prostate cancer to docetaxel. We treated prostate cancer cell lines with elesclomol–CuCl2, as well as with docetaxel. We performed analyses of CCK8, colony formation tests, cell cycle flow assay, transmission electron microscopy, and mTOR signaling in treated cells, and treated a xenograft prostate cancer model with elesclomol–CuCl2 and docetaxel in vivo, and performed immunohistochemistry and Western blotting analysis in treated tumors. We found that elesclomol–CuCl2 could promote cell death and enhance chemosensitivity to docetaxel. Elesclomol–CuCl2 induced cell death and inhibited the growth of prostate cancer cells relying on copper ions‐induced cuproptosis, not elesclomol. In addition, dihydrolipoamide S‐acetyltransferase (DLAT) was involved in cuproptosis‐enhanced drug sensitivity to docetaxel. Mechanistically, upregulated DLAT by cuproptosis inhibited autophagy, promoted G2/M phase retention of cells, and enhanced the sensitivity to docetaxel chemotherapy in vitro and in vivo via the mTOR signaling pathway. Our findings demonstrated that the cuproptosis‐regulated DLAT/mTOR pathway inhibited autophagy and promoted cells in G2/M phase retention, thus enhancing the chemosensitivity to docetaxel. This discovery may provide an effective therapeutic option for treating advanced prostate cancer by inhibiting the chemotherapeutic resistance to docetaxel.
Improving Operating Room Efficiency Through Reducing First Start Delays in an Academic Center
Authors: Singh Dylan , Cai Lawrence , Watt Dominique , Scoggins Elise , Wald Samuel , Nazerali Rahim 
Published: August 2023

ABSTRACT

Background:
Delays in operating room (OR) first-case start times can cause additional costs for hospitals, healthcare team frustration and delay in patient care. Here, a novel process improvement strategy to improving first-case start times is presented.

Methods:
First case in room start times were recorded for ORs at an academic medical center. Three interventions—automatic preoperative orders, dot phrases to permit re-creation of unavailable consent forms, and improved H&P linking to the surgical encounter—were implemented to target documentation-related delays. Monthly percentages of first-case on-time starts (FCOTS) and time saved were compared with the “preintervention” time period, and total cost savings were estimated.

Results:
During the first 3-months after implementation of the interventions, the percentage of FCOTS improved from an average of 36.7%–52.7%. Total time savings across all ORs over the same time period was found to be 55.63 hours, which is estimated to have saved a total of $121,834.52 over the 3-month interventional period.

Conclusions:
By implementing multiple quality improvement interventions, delays to first start in room OR cases can be meaningfully reduced. Quality improvement protocols targeted toward root causes of OR delays can be a significant driver to reduce healthcare costs.
All-night spectral and microstate EEG analysis in patients with Recurrent Isolated Sleep Paralysis (RISP)
Authors: Černý Filip , Piorecká Václava , Kliková Monika , Kopřivová Jana , Bušková Jitka , Piorecký Marek 
Published: August 2023

AbstractThe pathophysiology of recurrent isolated sleep paralysis (RISP) has yet to be fully clarified. Very little research has been performed on electroencephalographic (EEG) signatures outside RISP episodes. This study aimed to investigate whether sleep is disturbed even without the occurrence of a RISP episode and in a stage different than conventional REM sleep. 17 RISP patients and 17 control subjects underwent two consecutive full-night video-polysomnography recordings. Spectral analysis was performed on all sleep stages in the delta, theta, and alpha band. EEG microstate (MS) analysis was performed on the NREM 3 phase due to the overall high correlation of subject template maps with canonical templates. Spectral analysis showed a significantly higher power of theta band activity in REM and NREM 2 sleep stages in RISP patients. The observed rise was also apparent in other sleep stages. Conversely, alpha power showed a downward trend in RISP patients’ deep sleep. MS maps similar to canonical topographies were obtained indicating the preservation of prototypical EEG generators in RISP patients. RISP patients showed significant differences in the temporal dynamics of MS, expressed by different transitions between MS C and D and between MS A and B. Both spectral analysis and MS characteristics showed abnormalities in the sleep of non-episodic RISP subjects. Our findings suggest that in order to understand the neurobiological background of RISP, there is a need to extend the analyses beyond REM-related processes and highlight the value of EEG microstate dynamics as promising functional biomarkers of RISP.Significance StatementWe focused on tracking electrophysiological traces of RISP (a REM parasomnia) beyond REM sleep of subjects clinically diagnosed with RISP outside of RISP episodes. We observed a rise of theta band activity in NREM 2 sleep of RISP patients. This may point to a larger dysregulation of sleep mechanism making the person more prone to sudden awakenings in the upcoming REM sleep. Theta band differences were further observed in REM sleep. We additionally utilized the EEG MS methodology on deep sleep to investigate differences in dominant brain topographies. Though dominant brain topographies are consistent with canonical MS, RISP patients show significantly different transitioning between sleep-related topographies suggesting a difference in their sleep regulation mechanisms.