bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclophilin D induces necrotic core formation by promoting mitochondria-mediated macrophage apoptosis in advanced atherosclerotic lesions
Authors: Koga Jun-ichiro , Umezu Ryuta , Shirouzu Tomohiro , Kondo Yuki , Orkhonselenge Nasanbadrakh , Ueno Hiromichi , Katsuki Shunsuke , Matoba Tetsuya , Nishimura Yosuke , Kataoka Masaharu
Published: September 2023

Background

In advanced atherosclerotic lesions, apoptotic cell death of plaque macrophages results in necrotic core formation and plaque vulnerability. Cyclophilin D (CypD) is a mitochondria-specific cyclophilin involved in the process of cell death after organ ischemia-reperfusion. However, the role of CypD in atherosclerosis, especially in necrotic core formation, is unknown.

Methods

To clarify the specific role of CypD, apolipoprotein-E/CypD-double knockout (ApoE-/-CypD-/-) mice were generated. These mice were fed a high-fat diet containing 0.15% cholesterol for 24 weeks to accelerate atherosclerotic lesion development.

Results

The deletion of CypD decreased the necrotic core size, accompanied by a reduction of macrophage apoptosis compared to control ApoE-/-mice. In RAW264.7 cells treated with endoplasmic reticulum stress inducer thapsigargin, the release of cytochrome c to the cytosol was attenuated by siRNA-mediated knockdown of CypD. Ly-6Chighinflammatory monocytes in the peripheral blood leukocytes and mRNA expression ofIl1bin the aorta were decreased by the deletion of CypD. In contrast, siRNA-mediated knockdown of CypD did not significantly decreaseIl1bnorCcl2mRNA expression in RAW264.7 cells treated with LPS and IFN-γ, suggesting that inhibition of inflammationin vivois likely due to decreased cell death in the atherosclerotic lesions rather than a direct action of CypD deletion on the macrophage.

Conclusions

This is the first report showing that CypD induces macrophage death and promotes necrotic core formation in advanced atherosclerotic lesions. CypD could be a novel therapeutic target for treating atherosclerotic vascular diseases.
High-throughput, microscopy-based screening, and quantification of genetic elements
Authors: Zhang Rongrong , Huang Yajia , Li Mei , Wang Lei , Li Bing , Xia Aiguo , Li Ye , Yang Shuai , Jin Fan
Published: September 2023

Synthetic biology relies on the screening and quantification of genetic components to assemble sophisticated gene circuits with specific functions. Microscopy is powerful tool for characterizing complex cellular phenotypes with increasing spatial and temporal resolution to library screening of genetic elements. Microscopy-based assays are powerful tools for characterizing cellular phenotypes with spatial and temporal resolution, and can be applied to large-scale samples for library screening of genetic elements. However, strategies for high-throughput microscopy experiments remain limited. Here, we present a high-throughput, microscopy-based platform that can simultaneously complete the preparation of an 8×12-well agarose pads plate, allowing for the screening of 96 independent strains or experimental conditions in a single experiment. Using this platform, we screened a library of natural intrinsic promoters fromPseudomonas aeruginosaand identified a small subset of robust promoters that drives stable levels of gene expression under varying growth conditions. Additionally, the platform allowed for single-cell measurement of genetic elements over time, enabling the identification of complex and dynamic phenotypes to map genotype in high-throughput. We expected that the platform could be employed to accelerate the identification and characterization of genetic elements in various biological systems, as well as to understand the relationship between cellular phenotypes and internal states, including genotypes and gene expression programs.

Impact statement

The high-throughput microscopy-based platform, presented in this study, enables efficient screening of 96 independent strains or experimental conditions in a single experiment, facilitating the rapid identification of genetic elements with desirable features, thereby advancing synthetic biology. The robust promoters identified through this platform, which provide predictable and consistent control over gene expression under varying growth conditions, can be utilized as reliable tools to regulate gene expression in various biological applications, including synthetic biology, metabolic engineering, and gene therapy, where consistent system performance is required.
Structural Degeneration of the Nucleus basalis of Meynert in Mild Cognitive Impairment and Alzheimer’s Disease – Evidence from an MRI-based Meta-Analysis
Authors: Mieling Marthe , Meier Hannah , Bunzeck Nico
Published: September 2023

Recent models of Alzheimer’s Disease (AD) suggest that neuropathological changes of the medial temporal lobe, especially entorhinal cortex, are preceded by degenerations of the cholinergic Nucleus basalis of Meynert (NbM). Evidence from imaging studies in humans, however, is limited. Therefore, we performed an activation-likelihood estimation meta-analysis on whole brain voxel-based morphometry (VBM) MRI data from 54 experiments and 2581 subjects in total. It revealed, compared to healthy older controls, reduced gray matter in the bilateral NbM in AD, but only limited evidence for such an effect in patients with mild cognitive impairment (MCI), which typically precedes AD. Both patient groups showed less gray matter in the amygdala and hippocampus, with hints towards more pronounced amygdala effects in AD. We discuss our findings in the context of studies that highlight the importance of the cholinergic basal forebrain in learning and memory throughout the life span, and conclude that they are partly compatible with pathological staging models suggesting initial and pronounced structural degenerations within the NbM in the progression of AD.
Functional development of eye movements and visuomotor circuits in lampreys
Authors: Barandela Marta , Núñez-González Carmen , Suzuki Daichi G. , Jiménez-López Cecilia , Pombal Manuel A. , Pérez-Fernández Juan
Published: September 2023

Animals constantly redirect their gaze away or towards relevant targets and, besides these goal-oriented responses, stabilizing movements clamp the visual scene avoiding image blurring. The vestibulo-ocular (VOR) and the optokinetic reflexes are the main contributors to gaze stabilization, whereas the optic tectum integrates multisensory information and generates orienting/evasive gaze movements in all vertebrates. Lampreys show a unique stepwise development of the visual system whose understanding provides important insights into the evolution and development of vertebrate vision. Although the developmental emergence of the visual components, and the retinofugal pathways have been described, the functional development of the visual system and the development of the downstream pathways controlling gaze are still unknown. Here, we show that VOR followed by light-evoked eye movements are the first to appear already in larvae, despite their burrowed lifestyle. However, the circuits controlling goal-oriented responses emerge later, in larvae in nonparasitic lampreys but during late metamorphosis in parasitic lampreys. The appearance of stabilizing responses earlier than goal-oriented likely reflects their evolution, and its stepwise emergence offers a unique opportunity to isolate the functioning of their underlying circuits.
Bis(4-acetoxy-N-ethyl-N-n-propyltryptammonium) fumarate–fumaric acid (1/1)
Authors: Pham Duyen N. K. , Sackett Nathan B. , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: September 2023

The solid-state structure of the title salt/adduct (systemic name: bis{[2-(4-acetyloxy-1H-indol-3-yl)ethyl](ethyl)propylazanium} but-2-enedioate–(E)-butenedioic acid (1/1)), 2C17H25N2O2
+·C4H2O4
2−·C4H4O4, was determined by single-crystal X-ray diffraction. The asymmetric unit consists of a singly protonated tryptammonium cation, one half of a fumarate dianion and one half of a fumaric acid molecule. In the crystal, the ions and molecules are linked together in infinite chains propagating along [001] through a series of N—H...O and O—H...O hydrogen bonds.
Rosalind Brewer – the leadership journey
Authors: Kumar K B S , Perepu Indu
Published: September 2023

Social implications

Addresses the issue of Gender Equality – UN Sustainable Development Goal No.5. Discusses the topic of diversity, equity and inclusion. Presents the challenges faced by women of color in workplace and shows the capabilities needed to overcome these challenges.

Learning outcomes

Analyze the capabilities that women of color need to become successful leaders. Explore the importance of Diversity, Equity and Inclusion (DEI) in organizations and the role played by leaders in promoting DEI. Understand what inclusive leadership is. Examine the strategic leadership skills that leaders need to possess.

Case overview/synopsis

In March 2021, one of the largest drugstore chains in the USA, Walgreens Boots Alliance, a US$140bn company, announced that Rosalind Brewer (Brewer) (she) would be its new CEO. With the announcement, Brewer became the third black woman in history to lead a Fortune 500 company. After graduating in organic chemistry, Brewer joined Kimberly Clark and went on to lead the Nonwovens business. She then joined Walmart as Vice President. Brewer then moved to Starbucks as Head of Operations. Being an inclusive leader, Brewer brought in several changes to smoothen the operations and make the organizations employee-friendly. At the same time, as a black woman in a leadership position, she faced several challenges, which she overcame. As an advocate of DEI, Brewer strove to take diversity beyond just numbers. After becoming the CEO Boots Walgreens, Brewer was looking at taking medicines to masses and making healthcare affordable and available.

Complexity academic level

MBA/MS/Executive Education.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CCS 6: Human Resources.
Shopper’s Darbar: entrepreneurial initiative by the women, for the women (Case A)
Authors: Singh Namrata , Chakraborty Ishani , Khare Aparna
Published: September 2023

Learning outcomes

The learning outcomes of this study are as follows: this case deliberates the strategic design and business model that provides entrepreneurial opportunities to re-sellers and small business owners; this case discusses the complexities and opportunities related to using social media (Facebook) as a selling platform; this case provides a thorough understanding of the direct-to-consumer model; this case helps students understand the concept of social commerce in emerging markets; and this case discusses brand-building tactics, particularly for online businesses.

Case overview/synopsis

This case is about the entrepreneurial venture of three women on Facebook. A venture that started with the simple thought of creating a trusted selling and buying platform with convenience has turned into an opportunity for thousands of other women to become entrepreneurs and start their businesses with minimum investment and low risk. Shoppers Darbar is an online shopping portal on Facebook that started in 2016. This is a private group exclusively for women with more than 165,000 registered members, which saw a boom during the pandemic and merged as a parallel platform of e-commerce retail sites and physical stores and exhibitions. Although social commerce in India is still in its growing stage, it is facing indirect competition and an identity crisis. Hence, to build Shoppers Darbar as a brand and retain vendors, founders need to find methods within Shoppers Darbar’s limited means to sustain and create a community of sellers and buyers for getting more and more business for the vendors associated with them.

Complexity academic level

Postgraduate level.

Supplementary materials

Teaching Notes Consent Letter Annexure 1.

Subject code

CCS 3: Entrepreneurship
Avatar design in Metaverse: the effect of avatar-user similarity in procedural and creative tasks
Authors: Zhu Runge , Yi Cheng
Published: September 2023

Purpose

Through the lens of self-perception theory, this paper investigates how avatar design (i.e. avatar user similarity) affects users' self-awareness and shapes their task engagement and performance in the Metaverse.

Design/methodology/approach

The authors conducted a 2 (avatar user similarity: high vs low) × 2 (task type: procedural vs creative) lab experiment and collected data from questionnaires, the recording of users' behavior during tasks and their actual task performance.

Findings

The results show that higher avatar user similarity leads to higher task engagement in general. Furthermore, while a similar avatar promotes users to regulate their behaviors and achieve better performance in a procedural task, high similarity also inhibits users' creativity by invoking habitual thinking, resulting in worse performance in generating original ideas in a creative task.

Originality/value

This study is expected to contribute to the information systems literature by revealing the value of avatar design and providing new perspectives on improving users' experiences in the Metaverse.
The role of microbiota in esophageal squamous cell carcinoma: A review of the literature
Authors: Chiang Hsueh‐Chien , Hughes Michael , Chang Wei‐Lun
Published: September 2023

Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well‐known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF‐κB and IL‐6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid‐derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug‐resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.
A feast: Indigenous production and interregional exchange reflected by the bronze vessels unearthed from Shuangyuan Village Cemetery in southwestern China
Authors: Wang Xiaoting , Yang Yingdong , Wang Tianyou , Luo Wugan
Published: September 2023

Surprising combinations of bronze vessels with multiple cultural elements have been unearthed in Shu tombs in southwestern China, indicating a significant connection with the middle and lower reaches of the Yangtze River. However, there is currently no comprehensive evidence for the provenance of these foreign style vessels, and little emphasis has been given to the diachronic changes in the interaction between Shu culture and its surroundings. This article investigates the bronze vessels unearthed from the Shuangyuan Village Cemetery in Chengdu during the Eastern Zhou Dynasty and aims to deeply reveal the production and exchange of bronze vessels unearthed from Shuangyuan Village Cemetery from the perspective of lead sources through typological analysis and scientific analysis. The study clarified the ages of the local style Shu culture vessels and foreign style vessels, and the latter exhibited a strong influence of the Chu and Yue cultures. Lead isotope analysis shows that the lead source characteristics of foreign style vessels are consistent with those of vessels from Chu‐Yue culture at the same time, and they may be imported from Chu directly. The specific interaction modes of Shu and Chu underwent a clear transformation during the middle Warring States period.
Optimizing preclinical models of ageing for translation to clinical trials
Authors: Mitchell Sarah J. , MacArthur Michael R. , Kane Alice E.
Published: September 2023

Preclinical models have been the backbone of translational research for more than a century. Rats and mice are critical models in the preliminary stages of drug testing, both for determining efficacy and ruling out potential human‐relevant toxicities. Historically, most preclinical pharmacological studies have used young, relatively healthy, inbred male models in highly controlled environments. In the field of geriatric pharmacology, there is a growing focus on the importance of using more appropriate preclinical models both in the testing of therapeutics commonly used in older populations, and in the evaluation of potential geroprotective drug candidates. Here we provide a commentary on optimizing preclinical models of ageing for translation to clinical trials. We will discuss approaches to modelling clinically relevant contexts such as age, sex, genetic diversity, exposures and environment, as well as measures of clinically relevant outcomes such as frailty and healthspan. We will identify the strengths and limitations of these approaches and areas for improvement. We will also briefly cover new preclinical models that move beyond rodents. We hope this commentary will be a springboard for larger discussions on optimizing preclinical ageing models for testing therapeutics.
Neurocognitive mechanisms of co‐occurring math difficulties in dyslexia: Differences in executive function and visuospatial processing
Authors: Marks Rebecca A. , Pollack Courtney , Meisler Steven L. , D'Mello Anila M. , Centanni Tracy M. , Romeo Rachel R. , Wade Karolina , Matejko Anna A. , Ansari Daniel , Gabrieli John D. E. , Christodoulou Joanna A.
Published: September 2023

Children with dyslexia frequently also struggle with math. However, studies of reading disability (RD) rarely assess math skill, and the neurocognitive mechanisms underlying co‐occurring reading and math disability (RD+MD) are not clear. The current study aimed to identify behavioral and neurocognitive factors associated with co‐occurring MD among 86 children with RD. Within this sample, 43% had co‐occurring RD+MD and 22% demonstrated a possible vulnerability in math, while 35% had no math difficulties (RD‐Only). We investigated whether RD‐Only and RD+MD students differed behaviorally in their phonological awareness, reading skills, or executive functions, as well as in the brain mechanisms underlying word reading and visuospatial working memory using functional magnetic resonance imaging (fMRI). The RD+MD group did not differ from RD‐Only on behavioral or brain measures of phonological awareness related to speech or print. However, the RD+MD group demonstrated significantly worse working memory and processing speed performance than the RD‐Only group. The RD+MD group also exhibited reduced brain activations for visuospatial working memory relative to RD‐Only. Exploratory brain‐behavior correlations along a broad spectrum of math ability revealed that stronger math skills were associated with greater activation in bilateral visual cortex. These converging neuro‐behavioral findings suggest that poor executive functions in general, including differences in visuospatial working memory, are specifically associated with co‐occurring MD in the context of RD.

Research Highlights

Children with reading disabilities (RD) frequently have a co‐occurring math disability (MD), but the mechanisms behind this high comorbidity are not well understood.

We examined differences in phonological awareness, reading skills, and executive function between children with RD only versus co‐occurring RD+MD using behavioral and fMRI measures.

Children with RD only versus RD+MD did not differ in their phonological processing, either behaviorally or in the brain.

RD+MD was associated with additional behavioral difficulties in working memory, and reduced visual cortex activation during a visuospatial working memory task.
Right ventricular systolic function and mechanical dyssynchrony in ischemic or non‐ischemic dilated cardiomyopathy: A speckle‐tracking study
Authors: Ali Asmaa Ahmed , Habib Shaimaa Ahmed , AbdElaziz Ola Hassan , Mohammad Safaa Abouelfadl
Published: September 2023

Aim

This study assessed RV dyssynchrony (irrespective to QRS duration) and RV systolic function in non‐ischemic dilated cardiomyopathy (NIDCM) versus ischemic dilated cardiomyopathy (IDCM) patients by using different echo‐Doppler modalities.

Methods

Eighty‐five cases (48 patients with DCM [whether ischemic or non‐ischemic] and 37 age‐matched healthy controls) were studied. Conventional echo‐Doppler study, tissue Doppler (TDI), and speckle tracking (STE) were carried out to measure LV and RV systolic function. Time‐to‐peak negative longitudinal strain at the four RV sites were assessed by TDI derived strain and 2D speckle tracking.

Results

Patients with DCM (whether ischemic or non‐ischemic) had significantly lower fractional area change, RV tricuspid annular systolic velocity (p < .001 for both), tricuspid annular plane systolic excursion (p = .01), RV‐GLS whether TDI or 2D derived (p < .001). Twenty‐nine patients (60%) showed right intraventricular delay (RV4SD > 60 ms). The RV‐dyssynchrony index was negatively correlated to %FAC (r = −.362, p = .01), RV Sm (r = −.312, p = .04), and 2D‐RV GLS (r = −.305, p = .05). Insignificant higher RV‐dysynchrony index was detected in NIDCM compared to IDCM group; however, the basal septal segment was significantly delayed in dilated group. More impaired RV systolic function was detected in ischemic group. 2D STE and TDI showed a significant correlation in the assessment of the right‐intraventricular delay (p = .001).

Conclusion

Right‐intraventricular dyssynchrony are detectable in patients with dilated cardiomyopathy (whether ischemic or non‐ischemic) with a higher statistically insignificant value in non‐ischemic group by using tissue Doppler imaging and 2D speckle tracking. More impairment of the RV systolic function was noticed in the ischemic group. Impaired RV systolic function was associated with right intraventricular delay.
Overcoming a stubborn patent foramen ovale
Authors: Gallagher John , Dawdy John , Afonso Luis
Published: September 2023

Transesophageal echocardiography (TEE) with agitated saline contrast (“bubble study”) is the gold standard for detection of patent foramen ovale (PFO). Standard provocative maneuvers help facilitate right‐to‐left shunting necessary for diagnosing PFO but may be difficult to implement during TEE. Hypovolemia related to preprocedural fasting may challenge detection of PFO in TEE, and additional optimization measures such as fluid replenishment with passive leg raise (PLR) can enhance PFO detection. We present a 57‐year‐old male with history of cryptogenic stroke and stubborn PFO which during TEE bubble study responded only to ample fluid replenishment with PLR following a period of prolonged preprocedural fasting.
Adaptations to water gradient in three Rorippa plant species correspond with plant resistance against insect herbivory under drought and waterlogged conditions
Authors: Kamps Bram B. J. , Poelman Erik H.
Published: September 2023

Plants live in environments where they are constantly, and often simultaneously, exposed to different types of biotic and abiotic stress, such as insect herbivory and water availability. How plants are adapted to abiotic conditions may determine how a surplus or shortage of water affects plant resistance to insect herbivory. Moreover, this effect may vary depending on the feeding mode of the herbivore.

We explored how three closely related Rorippa plant species that vary in adaptations to different water levels, resist herbivory by four different insects (aphids: Myzus persicae, Lipaphis erysimi, and caterpillars: Pieris brassicae, Plutella xylostella) under waterlogging or drought conditions. We hypothesized that plants that are differently adapted to water availability will be disparately affected by water availability in their resistance to insect herbivory.

On the semi‐aquatic plant species Rorippa amphibia, both aphid species reached a larger colony size under drought conditions. This indicates that R. amphibia was compromised in resistance to aphid feeding when under drought conditions, to which it is less well adapted. Water conditions did not affect aphid performance on the flood‐plain species Rorippa palustris. On the terrestrial plant species Rorippa sylvestris, aphids performed worse on waterlogged than drought‐treated plants. Neither caterpillar species was significantly affected by the water availability of their food plant.

Our findings suggest that water availability can have distinct effects on plant–insect interactions. We propose that plant adaptations to water conditions can be a major predictor towards explaining the variation of effects that water availability can have on plant–insect interactions.
Towards an electroencephalographic measure of awareness based on the reactivity of oscillatory macrostates to hearing a subject's own name
Authors: Șerban Cosmin‐Andrei , Barborică Andrei , Roceanu Adina‐Maria , Mîndruță Ioana‐Raluca , Ciurea Jan , Stancu Mihai , Pâslaru Alexandru C. , Zăgrean Ana‐Maria , Zăgrean Leon , Moldovan Mihai
Published: September 2023

We proposed that the brain's electrical activity is composed of a sequence of alternating states with repeating topographic spectral distributions on scalp electroencephalogram (EEG), referred to as oscillatory macrostates. The macrostate showing the largest decrease in the probability of occurrence, measured as a percentage (reactivity), during sensory stimulation was labelled as the default EEG macrostate (DEM). This study aimed to assess the influence of awareness on DEM reactivity (DER). We included 11 middle cerebral artery ischaemic stroke patients with impaired awareness having a median Glasgow Coma Scale (GCS) of 6/15 and a group of 11 matched healthy controls. EEG recordings were carried out during auditory 1 min stimulation epochs repeating either the subject's own name (SON) or the SON in reverse (rSON). The DEM was identified across three SON epochs alternating with three rSON epochs. Compared with the patients, the DEM of controls contained more posterior theta activity reflecting source dipoles that could be mapped in the posterior cingulate cortex. The DER was measured from the 1 min quiet baseline preceding each stimulation epoch. The difference in mean DER between the SON and rSON epochs was measured by the salient EEG reactivity (SER) theoretically ranging from −100% to 100%. The SER was 12.4 ± 2.7% (Mean ± standard error of the mean) in controls and only 1.3 ± 1.9% in the patient group (P < 0.01). The patient SER decreased with the Glasgow Coma Scale. Our data suggest that awareness increases DER to SON as measured by SER.
Ultrathin lithium disilicate and translucent zirconia crowns for posterior teeth: Survival and failure modes
Authors: Benalcazar Jalkh Ernesto B. , Ramalho Ilana S. , Bergamo Edmara T. P. , Alves Larissa M. M. , Tanaka Ricardo , Witek Lukasz , Coelho Paulo G. , Hirata Ronaldo , Bonfante Estevam A.
Published: September 2023

Purpose

To evaluate the reliability and failure modes of ultrathin (0.5 mm) lithium disilicate, translucent and ultra‐translucent zirconia crowns for posterior teeth restorations.

Materials and Methods

Fifty‐four mandibular first molar crowns of three ceramic materials: (1) Lithium disilicate (e.max CAD, Ivoclar Vivadent), (2) 3Y‐TZP (Zirconn Translucent, Vipi), and (3) 5Y‐PSZ (Cercon XT, Dentsply Sirona), with 0.5 mm of thickness were milled and cemented onto composite resin abutments. Eighteen samples of each group were tested under mouth‐motion step‐stress accelerated life testing in a humid environment using mild, moderate, and aggressive profiles. Data was subjected to Weibull statistics. Use level curves were plotted and reliability was calculated for a given mission of 100,000 cycles at 100, 200, and 300 N. Fractographic analyses of representative samples were performed in scanning electron microscope.

Results

Beta (β) values suggest that failures were dictated by material's strength for lithium disilicate and by fatigue damage accumulation for both zirconias. No significant differences were detected in Weibull modulus and characteristic strength among groups. At a given mission of 100,000 cycles at 100 N, lithium disilicate presented higher reliability (98% CB: 95–99) regarding 3Y‐TZP and 5Y‐PSZ groups (84% CB: 65%–93% and 79% CB: 37&–94%, respectively). At 200 N, lithium disilicate reliability (82% CB: 66%–91%) was higher than 5Y‐PSZ (20% CB: 4%–44%) and not significantly different from 3Y‐TZP (54% CB: 32%–72%). Furthermore, at 300 N no significant differences in reliability were detected among groups, with a notable reduction in the reliability of all materials. Fractographic analyses showed that crack initiated at the interface between the composite core and the ceramic crowns due to tensile stress generated at the intaglio surface.

Conclusions

Ultrathin lithium disilicate crowns demonstrated higher reliability relative to zirconia crowns at functional loads. Lithium disilicate and zirconia crown's reliability decreased significantly for missions at higher loads and similar failure modes were observed regardless of crown material. The indication of 0.5 mm thickness crowns in high‐load bearing regions must be carefully evaluated.

Clinical Significance

Ultraconservative lithium disilicate and zirconia crowns of 0.5 mm thickness may be indicated in anterior restorations and pre‐molars. Their clinical indication in high‐load requirement regions must be carefully evaluated.
Addressing the unique challenges in studies of long‐term medication use and dementia risk
Authors: Lee Alexandra K. , Lee Sei J. , Dublin Sascha
Published: September 2023

This editorial comments on the article by Wu et al. in this issue.
Novel RXFP3 negative allosteric modulator RLX‐33 reduces alcohol self‐administration in rats
Authors: Van Voorhies Kalynn J. , Liu Wen , Lovelock Dennis F. , Lin Sophia , Liu Jiaqi , Guan Dongliang , Gay Elaine A. , Jin Chunyang , Besheer Joyce
Published: September 2023

There is much interest in identifying novel pharmacotherapeutic targets that improve clinical outcomes for the treatment of alcohol use disorder (AUD). One promising target for therapeutic intervention is the relaxin family peptide 3 (RXFP3) receptor, a cognate receptor for neuropeptide relaxin‐3, which has previously been implicated in regulating alcohol drinking behavior. Recently, we developed the first small‐molecule RXFP3‐selective negative allosteric modulator (NAM) RLX‐33. Therefore, the goal of the present work was to characterize the impact of this novel NAM on affective‐related behaviors and alcohol self‐administration in rats. First, the effects of RLX‐33 were tested on alcohol and sucrose self‐administration in Wistar and alcohol‐preferring P rats to determine the dose–response profile and specificity for alcohol. Then, we assessed the effects of systemic RLX‐33 injection in Wistar rats in a battery of behavioral assays (open‐field test, elevated zero maze, acoustic startle response test, and prepulse inhibition) and tested for alcohol clearance. We found that the lowest effective dose (5 mg/kg) reduced alcohol self‐administration in both male and female Wistar rats, while in alcohol‐preferring P rats, this effect was restricted to males, and there were no effects on sucrose self‐administration or general locomotor activity. The characterization of affective and metabolic effects in Wistar rats generally found few locomotor, affective, or alcohol clearance changes, particularly at the 5 mg/kg dose. Overall, these findings are promising and suggest that RXFP3 NAM has potential as a pharmacological target for treating AUD.

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Evaluation of efficacy of Silybum marianum flower extract on the mitigating hair loss in vitro and in vivo
Authors: You Jiyoung , Woo Jieun , Roh Kyung‐Baeg , Jeon Kyungeun , Jang Youngsu , Choi Song‐ah , Ryu Daehoon , Cho Eunae , Park Deokhoon , Lee Jeongkoo , Jang Min , Jung Eunsun
Published: September 2023

Background

Natural components that can exert a wide range of anti‐hair loss activity with fewer side effects are in high demand. The objective of this study was to investigate the anti‐hair loss potential of Silybum marianum flower extract (SMFE) in vitro and in vivo.

Methods

The effect of SMFE on dermal papilla cells was evaluated by measuring cell proliferation and VEGF production in hair follicle dermal papilla cells (HFDPCs). In addition, to confirm the effect of SMFE on dermal papilla senescence, SA‐β‐gal staining and senescence associated secretory phenotype (SASP) production such as IL‐6 was observed in both replicative and hydrogen peroxide (H2O2)‐induced senescence models. In a clinical study, hair growth was determined by reconstitution analysis after shaving the hair of the clinical subject's scalp and hair area.

Results

SMFE increased the proliferation and VEGF production of HFDPCs. It also suppressed cellular senescence of HFDPCs and IL‐6 production in replicative senescence and oxidative stress‐induced senescence models. The hair density and total hair count at 16 and 24 weeks after using hair shampoo containing SMFE were significantly increased compared with those of the placebo group.

Conclusion

SMFE has the potential to be used as a natural ingredient for alleviating hair loss.
Reconsidering sleep perception in insomnia: from misperception to mismeasurement
Authors: Stephan Aurélie M. , Siclari Francesca
Published: September 2023

So‐called ‘sleep misperception’ refers to a phenomenon in which individuals have the impression of sleeping little or not at all despite normal objective measures of sleep. It is unknown whether this subjective–objective mismatch truly reflects an abnormal perception of sleep, or whether it results from the inability of standard sleep recording techniques to capture ‘wake‐like’ brain activity patterns that could account for feeling awake during sleep. Here, we systematically reviewed studies reporting sleep macro‐ and microstructural, metabolic, and mental correlates of sleep (mis)perception. Our findings suggest that most individuals tend to accurately estimate their sleep duration measured with polysomnography (PSG). In good sleepers, feeling awake during sleep is the rule at sleep onset, remains frequent in the first non‐rapid eye movement sleep cycle and almost never occurs in rapid eye movement (REM) sleep. In contrast, there are patients with insomnia who consistently underestimate their sleep duration, regardless of how long they sleep. Unlike good sleepers, they continue to feel awake after the first sleep cycle and importantly, during REM sleep. Their mental activity during sleep is also more thought‐like. Initial studies based on standard PSG parameters largely failed to show consistent differences in sleep macrostructure between these patients and controls. However, recent studies assessing sleep with more refined techniques have revealed that these patients show metabolic and microstructural electroencephalography changes that likely reflect a shift towards greater cortical activation during sleep and correlate with feeling awake. We discuss the significance of these correlates and conclude with open questions and possible ways to address them.
Deductive automated pollen classification in environmental samples via exploratory deep learning and imaging flow cytometry
Authors: Barnes Claire M. , Power Ann L. , Barber Daniel G. , Tennant Richard K. , Jones Richard T. , Lee G. Rob , Hatton Jackie , Elliott Angela , Zaragoza‐Castells Joana , Haley Stephen M. , Summers Huw D. , Doan Minh , Carpenter Anne E. , Rees Paul , Love John
Published: September 2023

Pollen and tracheophyte spores are ubiquitous environmental indicators at local and global scales. Palynology is typically performed manually by microscopic analysis; a specialised and time‐consuming task limited in taxonomical precision and sampling frequency, therefore restricting data quality used to inform climate change and pollen forecasting models. We build on the growing work using AI (artificial intelligence) for automated pollen classification to design a flexible network that can deal with the uncertainty of broad‐scale environmental applications.

We combined imaging flow cytometry with Guided Deep Learning to identify and accurately categorise pollen in environmental samples; here, pollen grains captured withinc.5500 Cal yr BP old lake sediments.

Our network discriminates not only pollen included in training libraries to the species level but, depending on the sample, can classify previously unseen pollen to the likely phylogenetic order, family and even genus.

Our approach offers valuable insights into the development of a widely transferable, rapid and accurate exploratory tool for pollen classification in ‘real‐world’ environmental samples with improved accuracy over pure deep learning techniques. This work has the potential to revolutionise many aspects of palynology, allowing a more detailed spatial and temporal understanding of pollen in the environment with improved taxonomical resolution.
Thalassemia and malignancies: Updates from the literature
Authors: Hodroj Mohammad Hassan , Taher Ali
Published: September 2023

Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been accompanied by the emergence of several new morbidities and chronic diseases, including cancer. Over the years, multiple cases of solid and hematologic malignancies in thalassemia patients have been reported in the literature, with no clear mechanism for the development of cancer in these patients despite a number of potential mechanisms. However, the results of many studies have been contradictory regarding the risk of development of malignancies in thalassemia. The present review aims to discuss the available data on cancer and thalassemia in the literature, with the latest updates regarding possible malignancy development mechanisms, risks, and the most commonly reported types.
Understanding prison violence in Aotearoa New Zealand using machine learning
Authors: Brabyn Lars , Day Andrew , Grace Randolph , Tamatea Armon
Published: September 2023

Prison violence is a major safety issue for people in prison and staff. In Aotearoa New Zealand, all prison incidents are recorded on the Department of Corrections (Ara Poutama Aotearoa) COBRA database. An analysis of prison violence at the unit level is applied using machine learning to provide a prediction model of prison violence as well as identify important factors associated with violence. The analysis identifies gang affiliation and security class as important predictors of violence in prison. The study also demonstrates the importance of the social environment and spatial scale when conducting an analysis of prison data.
Time‐resolved fluorescence anisotropy with Atto 488‐labeled phytochrome Agp1 from Agrobacterium fabrum
Authors: Elkurdi Afaf , Guigas Gernot , Hourani‐Alsharafat Latifa , Scheerer Patrick , Nienhaus Gerd Ulrich , Krauß Norbert , Lamparter Tilman
Published: September 2023

Phytochromes are photoreceptor proteins with a bilin chromophore that undergo photoconversion between two spectrally different forms, Pr and Pfr. Three domains, termed PAS, GAF, and PHY domains, constitute the N‐terminal photosensory chromophore module (PCM); the C‐terminus is often a histidine kinase module. In the Agrobacterium fabrum phytochrome Agp1, the autophosphorylation activity of the histidine kinase is high in the Pr and low in the Pfr form. Crystal structure analyses of PCMs suggest flexibility around position 308 in the Pr but not in the Pfr form. Here, we performed time‐resolved fluorescence anisotropy measurements with different Agp1 mutants, each with a single cysteine residue at various positions. The fluorophore label Atto‐488 was attached to each mutant, and time‐resolved fluorescence anisotropy was measured in the Pr and Pfr forms. Fluorescence anisotropy curves were fitted with biexponential functions. Differences in the amplitude A2 of the second component between the PCM and the full‐length variant indicate a mechanical coupling between position 362 and the histidine kinase. Pr‐to‐Pfr photoconversion induced no significant changes in the time constant t2 at any position. An intermediate t2 value at position 295, which is located in a compact environment, suggests flexibility around the nearby position 308 in Pr and in Pfr.
Haplotype‐resolved genome assembly of Populus tremula × P. alba reveals aspen‐specific megabase satellite DNA
Authors: Zhou Ran , Jenkins Jerry W , Zeng Yibing , Shu Shengqiang , Jang Hosung , Harding Scott A. , Williams Melissa , Plott Christopher , Barry Kerrie W. , Koriabine Maxim , Amirebrahimi Mojgan , Talag Jayson , Rajasekar Shanmugam , Grimwood Jane , Schmitz Robert J. , Dawe R. Kelly , Schmutz Jeremy , Tsai Chung‐Jui
Published: September 2023

Populus species play a foundational role in diverse ecosystems and are important renewable feedstocks for bioenergy and bioproducts. Hybrid aspen Populus tremula × P. alba INRA 717‐1B4 is a widely used transformation model in tree functional genomics and biotechnology research. As an outcrossing interspecific hybrid, its genome is riddled with sequence polymorphisms which present a challenge for sequence‐sensitive analyses. Here we report a telomere‐to‐telomere genome for this hybrid aspen with two chromosome‐scale, haplotype‐resolved assemblies. We performed a comprehensive analysis of the repetitive landscape and identified both tandem repeat array‐based and array‐less centromeres. Unexpectedly, the most abundant satellite repeats in both haplotypes lie outside of the centromeres, consist of a 147 bp monomer PtaM147, frequently span >1 megabases, and form heterochromatic knobs. PtaM147 repeats are detected exclusively in aspens (section Populus) but PtaM147‐like sequences occur in LTR‐retrotransposons of closely related species, suggesting their origin from the retrotransposons. The genomic resource generated for this transformation model genotype has greatly improved the design and analysis of genome editing experiments that are highly sensitive to sequence polymorphisms. The work should motivate future hypothesis‐driven research to probe into the function of the abundant and aspen‐specific PtaM147 satellite DNA.
Passionate About Esports: Esports Players’ Motivation to Participate in and Watch Esports Events
Authors: Rhee Yong Chae , Kim Kyungun
Published: September 2023

Alderfer’s ERG (i.e., existence, relatedness, and growth) theory of motivation (1969) was adopted in this study to analyze individuals’ motivations for engaging in esports. This study investigated the relatively new field of esports viewership and participation by concentrating on the motivating factors behind esports consumption to establish whether esports viewership and participation are distinct markets that stand alone or are comparable to or complement each other for consumption. The study was conducted using qualitative methods consisting of semistructured focus-group interviews. The transcript was coded using open, axial, and selective coding to develop themes fitting within the ERG theory. The current study found similarities and unique findings in esports participation and consumption motivation factors under the ERG groups. Practical applications are proposed for employing the results of the study to further marketing and development efforts in this field.
Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors
Authors: Lv Xiangdong , Lu Xuan , Cao Jin , Luo Qin , Ding Yao , Peng Fanglue , Pataer Apar , Lu Dong , Han Dong , Malmberg Eric , Chan Doug W. , Wang Xiaoran , Savage Sara R. , Mao Sufeng , Yu Jingjing , Peng Fei , Yan Liang , Meng Huan , Maneix Laure , Han Yumin , Chen Yiwen , Yao Wantong , Chang Eric C. , Catic Andre , Lin Xia , Miles George , Huang Pengxiang , Sun Zheng , Burt Bryan , Wang Huamin , Wang Jin , Yao Qizhi Cathy , Zhang Bing , Roth Jack A. , O’Malley Bert W. , Ellis Matthew J. , Rimawi Mothaffar F. , Ying Haoqiang , Chen Xi
Published: September 2023

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response, causing severe proteostasis disturbances. However, IRE1α was selectively reactivated in an ER stress–independent manner in acquired KRASi-resistant tumors, restoring proteostasis. Oncogenic KRAS promoted IRE1α protein stability through extracellular signal–regulated kinase (ERK)–dependent phosphorylation of IRE1α, leading to IRE1α disassociation from 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) E3-ligase. In KRASi-resistant tumors, both reactivated ERK and hyperactivated AKT restored IRE1α phosphorylation and stability. Suppression of IRE1α overcame resistance to KRASi. This study reveals a druggable mechanism that leads to proteostasis reprogramming and facilitates KRASi resistance.
Carbon-doped metal oxide interfacial nanofilms for ultrafast and precise separation of molecules
Authors: Sengupta Bratin , Dong Qiaobei , Khadka Rajan , Behera Dinesh Kumar , Yang Ruizhe , Liu Jun , Jiang Ji , Keblinski Pawel , Belfort Georges , Yu Miao
Published: September 2023

Membranes with molecular-sized, high-density nanopores, which are stable under industrially relevant conditions, are needed to decrease energy consumption for separations. Interfacial polymerization has demonstrated its potential for large-scale production of organic membranes, such as polyamide desalination membranes. We report an analogous ultrafast interfacial process to generate inorganic, nanoporous carbon-doped metal oxide (CDTO) nanofilms for precise molecular separation. For a given pore size, these nanofilms have 2 to 10 times higher pore density (assuming the same tortuosity) than reported and commercial organic solvent nanofiltration membranes, yielding ultra-high solvent permeance, even if they are thicker. Owing to exceptional mechanical, chemical, and thermal stabilities, CDTO nanofilms with designable, rigid nanopores exhibited long-term stable and efficient organic separation under harsh conditions.
Geological hydrogen wins first major funding
Authors: Hand Eric
Published: September 2023

$20 million grant program by ARPA-E aims to jump-start work on climate-friendly fuel
Researchers applaud HHS push to ease cannabis restrictions
Authors: Jacobs Phie
Published: September 2023

Proposed rescheduling would make it easier for scientists to acquire and study the drug