bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers
Authors: Gibson Lucy L. , Abdelnour Carla , Chong Joyce , Ballard Clive , Aarsland Dag 
Published: June 2023

Purpose of review
Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges.

Recent findings
Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future.

Summary

In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.
A Transdiagnostic Structural Brain Signature of Parkinsonian and Essential Tremor
Authors: Ineichen Christian , Callaghan Fraser , Baumann-Vogel Heide , Büchele Fabian , O’Gorman Tuura Ruth , Baumann Christian R. , Schreiner Simon J. 
Published: June 2023

AbstractBackgroundParkinson’s disease (PD) and Essential Tremor (ET) are heterogeneous, yet distinct disorders. At the same time, PD and ET show overlapping features such as phenotypes with predominant tremor. These heterogeneities and overlaps pose challenges for clinical management and research and may indicate transdiagnostic, shared mechanisms for tremor.ObjectivesTo test the hypothesis that MRI may reveal structural brain changes related to tremor phenotypes rather than diagnoses in PD and ET patients. For this, we compared regional brain volumes between three patient groups with overlapping phenotypes and distinct diagnoses: ET, PD with tremor-dominant phenotype (PD-T), and PD with non-tremor-dominant phenotype (PD-nT).MethodsWe studied 164 patients (18 ET, 38 PD-T, 108 PD-nT) who were evaluated for deep brain stimulation. All patients underwent structural MRI, and standardized assessment of motor symptoms. We compared regional brain volumes between groups.ResultsVolumes of the thalamus, pallidum, and pre-cerebellar and upper brainstem (midbrain, pons, superior cerebellar peduncle) differed across groups and were smallest in ET, intermediate in PD-T, and largest in PD-nT. Differences reached significance when comparing ET or PD-T with PD-nT but not ET with PD-T. Thalamic and brainstem volumes correlated with more severe and less levodopa-responsive tremor in PD. In contrast to the subcortical findings, cortical thickness in frontal and parietal regions was thinner in PD-nT compared to PD-T patients.ConclusionsWe identified tremor-related volume loss in cerebellothalamic and interconnected regions (pallidum), potentially suggesting shared mechanisms of tremor in PD and ET and pointing towards a transdiagnostic structural brain signature of tremor.
Single-cell multiplex chromatin and RNA interactions in aging human brain
Authors: Wen Xingzhao , Luo Zhifei , Zhao Wenxin , Calandrelli Riccardo , Nguyen Tri C. , Wan Xueyi , Richard John Lalith Charles , Zhong Sheng 
Published: June 2023

SUMMARY PARAGRAPHThe dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA (caRNA)1–3. Chromatin complex compositions change during cellular differentiation and aging, and are expected to be highly heterogeneous among terminally differentiated single cells4–7. Here we introduce theMulti-Nucleic Acid Interaction Mapping inSingleCell (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within individual nuclei. Applied to 14 human frontal cortex samples from elderly donors, MUSIC delineates diverse cortical cell types and states. We observed the nuclei exhibiting fewer short-range chromatin interactions are correlated with an “older” transcriptomic signature and with Alzheimer’s pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci (cis eQTLs) and a promoter tends to be the cell type where these cis eQTLs specifically affect their target gene’s expression. Additionally, the female cortical cells exhibit highly heterogeneous interactions between the XIST non-coding RNA and Chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploring chromatin architecture and transcription at cellular resolution in complex tissues.
The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation
Authors: Xu Hang , Yuan Zihao , Qin Kunpeng , Jiang Shuai , Sun Li 
Published: June 2023

AbstractCaspase (CASP) is a family of proteases involved in cleavage and activation of gasdermin, the executor of pyroptosis. In human, CASP3 and CASP7 recognize the same consensus motif DxxD, which is present in gasdermin E (GSDME). However, human GSDME is cleaved by CASP3 but not by CASP7. The underlying mechanism of this observation is unclear. In this study, we identified a pyroptotic pufferfish GSDME that was cleaved by both pufferfish CASP3/7 and human CASP3/7. Domain swapping between pufferfish and human CASP and GSDME showed that the GSDME C-terminus and the CASP7 p10 subunit determined the cleavability of GSDME by CASP7. p10 contains a key residue that governs CASP7 substrate discrimination. This key residue is highly conserved in vertebrate CASP3 and in most vertebrate (except mammalian) CASP7. In mammals, the key residue is conserved in non-primate (e.g., mouse) but not in primate. However, mouse CASP7 cleaved human GSDME but not mouse GSDME. These findings revealed the molecular mechanism of CASP7 substrate discrimination and the divergence of CASP3/7-mediated GSDME activation in vertebrate. These results also suggested that mutation-mediated functional alteration of CASP probably enabled the divergence and specialization of different CASP members in the regulation of complex cellular activities in mammals.
Vibrio choleraeArrests Intestinal Epithelial Proliferation through T6SS-dependent Activation of the Bone Morphogenetic Protein Pathway
Authors: Xu Xinyue , Foley Edan 
Published: June 2023

ABSTRACTTo maintain an effective barrier, intestinal epithelial progenitor cells must divide at a rate that matches the loss of dead and dying cells. Otherwise, epithelial breaches expose the host to systemic infection by gut-resident microbes. Unlike most pathogens,Vibrio choleraeblocks tissue repair by arresting progenitor proliferation in theDrosophilainfection model. At present, we do not understand howVibriocircumvents such a critical antibacterial defense. In a series of genetic experiments, we found thatV. choleraeblocks epithelial repair by activating the growth inhibitor Bone Morphogenetic Protein (BMP) pathway in progenitors. Specifically, we discovered that interactions betweenVibrioand gut commensals initiate BMP signaling via host innate immune defenses. Notably, we found thatVibrioalso activates BMP and arrests proliferation in zebrafish intestines, indicating an evolutionarily conserved link between infection, BMP and failure in tissue repair. Combined, our study highlights how enteric pathogens engage host immune and growth regulatory pathways to disrupt intestinal epithelial repair.
Chemically induced partial unfolding of the multifunctional Apurinic/apyrimidinic endonuclease 1
Authors: Rai Ratan , Dawodu Olabode I. , Johnson Steven M. , Vilseck Jonah Z. , Kelley Mark R. , Ziarek Joshua J. , Georgiadis Millie M. 
Published: June 2023

AbstractTargeting of the multifunctional enzyme apurinic/apyrimidinic endonuclease I/redox factor 1 (APE1) has produced small molecule inhibitors of both its endonuclease and redox activities. While one of the small molecules, the redox inhibitor APX3330, completed a Phase I clinical trial for solid tumors and a Phase II clinical trial for Diabetic Retinopathy/Diabetic Macular Edema, the mechanism of action for this drug has yet to be fully understood. Here, we demonstrate through HSQC NMR studies that APX3330 induces chemical shift perturbations (CSPs) of both surface and internal residues in a concentration-dependent manner, with a cluster of surface residues defining a small pocket on the opposite face from the endonuclease active site of APE1. Furthermore, APX3330 induces partial unfolding of APE1 as evidenced by a time-dependent loss of chemical shifts for approximately 35% of the residues within APE1 in the HSQC NMR spectrum. Notably, regions that are partially unfolded include adjacent strands within one of two beta sheets that comprise the core of APE1. One of the strands comprises residues near the N-terminal region and a second strand is contributed by the C-terminal region of APE1, which serves as a mitochondrial targeting sequence. These terminal regions converge within the pocket defined by the CSPs. In the presence of a duplex DNA substrate mimic, removal of excess APX3330 resulted in refolding of APE1. Our results are consistent with a reversible mechanism of partial unfolding of APE1 induced by the small molecule inhibitor, APX3330, defining a novel mechanism of inhibition.
Impact of virtual reality immersion on customer experience: moderating effect of cross-sensory compensation and social interaction
Authors: Mou Yupeng , Fan Jiao , Ding Zhihua , Khan Inayat 
Published: June 2023

Purpose In order to encourage customers to try experience virtual tourism, researchers and practitioners pay more attention on how to improve customers' perception of authenticity.Design/methodology/approach Using the theory of cross-sensory compensation, through 4 experiments, this study examines the impact of social interaction and cross-sensory strategies on the relationship between virtual reality (VR) and improving customers' perception of authenticity and customer experience.Findings Through experimental research, this paper finds that (1) VR immersion has a significant positive impact on perception of authenticity, which in turn acts on customers' virtual tourism experience. (2) In addition, social interaction strengthens the relationship between VR immersion and customers' perception of authenticity. (3) The cross-sensory compensation has a positive effect on VR immersion to enhance customers' perception of authenticity.Originality/value The research conclusion provides a direction for further discussion on how to improve customers' perception of authenticity and provides theoretical guidance and reference for the virtual tourism industry.
Sustainability practices and challenges in the meat supply chain: a systematic literature review
Authors: Caccialanza Andrea , Cerrato Daniele , Galli Davide 
Published: June 2023

PurposeThis study comprehensively depicts the state of the art on sustainability research in the meat supply chain to advance the debate on challenges and issues associated with developing sustainable supply chain management practices.Design/methodology/approachThe authors conducted a systematic literature review of 333 articles published in peer-reviewed journals and organized the extant literature into five areas of supply chain management practices: strategic orientation, continuity, collaboration, risk management, and proactivity.FindingsSince 2016, the meat supply chain has received increasing scholarly attention. The literature shows the diffusion of highly heterogeneous sustainability practices related to multiple management areas and levels of analysis (institutional, industry, firm). The need for integrated, multilevel initiatives involving different stakeholders becomes increasingly crucial to the transition towards more sustainable meat supply chains.Practical implicationsThis study highlights the importance of regulatory and stakeholder pressures in the sustainability transition. Beyond setting regulatory requirements, policymakers may facilitate the establishment of collaborations within the meat supply chain and foster the development of support services that help firms to integrate sustainability in their business models. The review also alerts entrepreneurs and managers to the benefits from cooperating with their supply chain partners to navigate the industry transition and thus more effectively respond to the demands of stakeholders and to the increasing customers’ awareness of sustainability issues.Originality/valueThis study is the first to systematize the corpus of knowledge on the sustainability of the meat supply chain by adopting a comprehensive approach to analyze relevant management and agriculture literature.
Perceived/experienced sexism and perceptions of support and job attitudes
Authors: Deuling Jacqueline , Wittmer Jenell Lynn-Senter , Wilson Kimberly , Thomas Adrian 
Published: June 2023

Purpose
This study aims to provide a psychometrically sound measure intended to capture perceived/experienced sexism in the workplace, the perceived/experienced sexism scale (PESS). PESS is used to consider the effects of perceived experiences of benevolent and hostile sexism at work, as well their relationships with perceived organizational support and the job attitudes of job satisfaction and turnover intentions.

Design/methodology/approach
This study revised the Ambivalent Sexism Inventory (Glick and Fiske, 1996) to create and validate the PESS. Amazon Mechanical Turk was used to collect two samples (220 and 183) of perceptions of female employees.

Findings
Results suggest perceived organizational support and trust perceptions mediate the relationships between perceptions of sexism and organizational outcomes of job satisfaction and turnover intentions.

Originality/value
Existing measures of sexism are intended to identify and measure sexism by examining perpetrators’ actions or thoughts. However, researchers must make assumptions as to the effect such sexist acts or behaviors has on the target. Thus, this study provides a measure of sexism from the perspective of the target.
“What it do?” The effects of racial code-switching on industry turnover intention
Authors: Garlington Jaimi , Shum Cass , Wong-Padoongpatt Gloria , Book Laura 
Published: June 2023

Purpose
Racial code-switching is an impression management behavior for people to blend into social and professional situations by adhering to norms outside their own. Drawing on the identity threat perspective, this study aims to examine the harmful effects of racial code-switching on employee psychological depression and hospitality industry turnover intentions.

Design/methodology/approach
The current study used a two-wave time-lagged survey of 286 restaurant frontline employees. Participants were asked to rate their racial code-switching, identity threat and shame in the first survey. Participants reported their depression and industry turnover intention in the second survey one week later.

Findings
The results showed that employees that engaged in racial code-switching had higher intentions to leave the hospitality industry via the sequential mediating roles of identity threat, shame and depression.

Practical implications
The findings provide practical implications on how hospitality practitioners can foster employee authenticity and tenure by evaluating impression management strategies. This paper provides a discussion, suggestions and future research directions on how to take sustainable actions toward diversity, equity, inclusion, justice and belonging.

Originality/value
Although racial code-switching is a common behavioral strategy for whites and people of color, research on racial code-switching in the hospitality industry is limited. This study is among the first to examine racial code-switching’s health and career consequences.
Advancing Dialogue About Consent and Molecular HIV Surveillance in the United States: Four Proposals Following a Federal Advisory Panel's Call for Major Reforms
Authors: MOLLDREM STEPHEN , SMITH ANTHONY K J , McCLELLAND ALEXANDER 
Published: June 2023

Policy Points
Molecular HIV surveillance and cluster detection and response (MHS/CDR) programs have been a core public health activity in the United States since 2018 and are the “fourth pillar” of the Ending the HIV Epidemic initiative launched in 2019.
MHS/CDR has caused controversy, including calls for a moratorium from networks of people living with HIV. In October 2022, the Presidential Advisory Council on HIV/AIDS (PACHA) adopted a resolution calling for major reforms.
We analyze the policy landscape and present four proposals to federal stakeholders pertaining to PACHA's recommendations about incorporating opt‐outs and plain‐language notifications into MHS/CDR programs.
Comparison of 95% effective dose of remimazolam besylate and propofol for gastroscopy sedation on older patients: A single‐centre randomized controlled trial
Authors: Ye Enci , Wu Keyang , Ye Hui , Zhang Wenyuan , Chu Lihua , Zhang Kai , Xie Guohao , Jin Yue , Fang Xiangming 
Published: June 2023

AimsAdvanced age is an important risk factor for adverse events during procedural sedation. Remimazolam is safe and effective in gastroscopic sedation. However, the ideal dose and application for older patients are not well known. We aim to investigate its 95% effective dose (ED95) for older patients undergoing gastroscopy and to assess its safety and efficacy, with propofol as the comparison.MethodsThe trial consists of 2 parts, patients aged >65 years and scheduled for outpatient painless gastroscopy were enrolled. In the first part, Dixon's up‐and‐down methodology was used to determine the ED95 of remimazolam besylate and propofol for gastroscopic insertion, in combination with 0.2 μg/kg remifentanil. In the second part, patients in each group received 0.2 μg/kg remifentanil and ED95 dose of the study drugs for sedation induction, supplemental doses were added to maintain sedation depth when necessary. The primary outcome was the incidence of adverse events. The secondary outcome was the recovery time.ResultsThe ED95 of remimazolam besylate and propofol induction were 0.2039 (95% confidence interval 0.1753–0.3896) mg/kg and 1.9733 (95% confidence interval 1.7346–3.7021) mg/kg respectively. Adverse events were reported in 26 (40.6%) patients in the remimazolam group and 54 (83.1%) in the propofol group (P < .0001), whereas the remimazolam group presented a higher incidence of hiccups (P = .0169). Besides, the median time to awakening was approximately 1 min shorter with remimazolam than with propofol (P < .05).ConclusionFor older patients undergoing gastroscopy, the ED95 dose of remimazolam is a safer alternative than propofol when inducing the same sedation depth.
Peripheral T‐cell lymphoma with a T follicular‐helper phenotype: A different entity? Results of the Spanish Real‐T study
Authors: Martín García‐Sancho Alejandro , Rodríguez‐Pinilla Socorro M. , Domingo‐Domenech Eva , Climent Fina , Sánchez‐Garcia Joaquín , López Jiménez Javier , García‐Cosío Piqueras Mónica , Castellvi Josep , González Ana Julia , González de Villambrosia Sonia , Gómez Codina José , Navarro Belén , Rodríguez Guillermo , Borrero Juan José , Fraga Máximo , Naves Andrea , Baeza Lourdes , Córdoba Raúl 
Published: June 2023

SummaryNodal peripheral T‐cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL‐TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL‐NOS) and angioimmunoblastic T‐cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL‐NOS, 55 as AITL and 23 as PTCL‐TFH. Median follow‐up was 56.07 months (95% CI 38.7–73.4). Progression‐free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL‐TFH than in those with PTCL‐NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL‐NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL‐NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL‐TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.
Ellagic acid inhibits the formation of hypertrophic scars by suppressing TGF‐β/Smad signaling pathway activity
Authors: Zhao Zun‐jiang , Wu De‐jin , Lv Da‐lun , Zhang Bao‐de , Chen Lei , Sun Yin‐qiao 
Published: June 2023

AbstractHypertrophic scar (HS) is a benign fibroproliferative skin disease, which lacks the ideal treatment and drugs. Ellagic acid (EA) is a natural polyphenol that prevents fibroblasts from proliferating and migrating. This study aimed to determine the role of EA in HS formation and its possible mechanism by in vitro experiments. HS fibroblasts (HSFs) and normal fibroblasts (NFs) were separated from HS tissue and normal skin tissue, respectively. HSFs were treated with 10 and 50 μM EA to assess their effect on HS formation. In particular, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and scratch assay were used to detect the viability and migration ability of HSFs. Quantitative reverse transcriptase real‐time polymerase chain reaction was used to measure the mRNA expression level of basic fibroblast growth factor (bFGF), extracellular matrix (ECM)‐related gene collagen‐I (COL‐I), and fibronectin 1 (FN1) in HSFs. Finally, Western blot was utilized to measure the expression level of TGF‐β/Smad signaling pathway–related proteins in HSFs. The viability of HSFs was significantly increased compared with NFs. 10 and 50 μM EA treatment markedly inhibition the cell viability and migration of HSFs. EA treatment upregulated the bFGF expression level and downregulated the COL‐I and FN1 expression level in HSFs. In addition, p‐Smad2, p‐Smad3, and transforming growth factor (TGF)‐β1 expression levels as well as p‐Smad2/Smad2 and p‐Smad3/Smad3 ratios remarkably decreased in HSFs after EA treatment. EA inhibited the formation of HSs by suppressing the viability and migration of HSFs and ECM deposition as well as by preventing the activation of TGF‐β/Smad signaling.