bluuebunny/crossref_metadata_2025_split huggingface dataset:
CETP inhibition Reduces Cardiovascular Events by Lowering of Cumulative LDL Exposure: Reconciling Evidence from Human Genetics and Clinical Trials
Authors: Landfors Fredrik , Kastelein John J.P. , Chorell Elin 
Published: December 2024

AbstractBackgroundGenetic studies consistently demonstrate that individuals born with reduced Cholesteryl Ester Transfer Protein (CETP) activity experience lower rates of atherosclerotic vascular disease throughout their lives. In contrast, short-term randomized controlled trials of CETP inhibitors have yielded mixed results, with only one of four trials reporting a reduction in clinical events. Several theories have been proposed to explain this discrepancy, but none fully account for the central mechanism of atherosclerosis: the cumulative lifetime exposure to circulating low-density lipoprotein (LDL) particles in the arterial walls.ObjectivesWe aimed to reconcile these conflicting findings by examining the relationship between cumulative LDL exposure and atherosclerosis risk across both genetic studies and clinical trials.MethodsWe analyzed 679 carriers ofCETPprotein-truncating variants (resulting in reduced or non-functional CETP protein) and 505,837 non-carriers in a population with 95,568 atherosclerosis events. Additionally, we assessed treatment effects relative to cumulative LDL reductions in 34 cardiovascular prevention trials involving 328,036 participants and 53,161 events.ResultsHeterozygousCETPprotein-truncating variant carrier status reduced atherosclerotic disease risk (odds ratio, 0.70; 95% confidence interval, 0.57– 0.85;P=5×10-4). In clinical trials, we observed a significant interaction between the magnitude and duration of LDL lowering on treatment effects (hazard ratio, 0.69 per 10– mmol/L×years; 95% confidence interval, 0.52–0.90;P=0.007), supporting that reducing cumulative LDL exposure is key to lowering cardiovascular risk. When comparing genetics with trial outcomes, accounting for differences in timing, duration, and follow-up, we observed consistent effects on atherosclerosis-related events per LDL years across genetic and pharmacological CETP inhibition, as well as with statins, ezetimibe, PCSK9 inhibitors, and familial hypercholesterolemia-associated variants (hazard ratio, 0.74 and 0.69 per 10–mmol/L×years, respectively). This suggests that CETP inhibition reduces cardiovascular risk primarily through LDL. Notably, several trials failed to achieve sufficient cumulative LDL reduction to impact clinical events, and this was not unique to CETP inhibitors.ConclusionOur findings indicate that future CETP inhibitor trials achieving substantial and sustained LDL reduction will demonstrate efficacy in preventing cardiovascular events. These results highlight the importance of long-term LDL lowering and support further investigation of CETP inhibition as a strategy for cardiovascular prevention.GRAPHICAL ABSTRACT
Similarity in Early Life Stress Exposure is Associated with Similarity in Neural Representations in Early Adulthood
Authors: Ilomäki Miro , Lindblom Jallu , Flykt Marjo , Vänskä Mervi , Punamäki Raija-Leena , Wikman Patrik 
Published: December 2024

ABSTRACTEarly life stress (ELS) has profound implications for developmental trajectories, yet the neural mechanisms underlying its long-term effects remain incompletely understood. In the present study, we examined whether interindividual similarity in ELS exposure aligns with similarity in neural representations and behavioral task performance in early adulthood. Leveraging a 20-year longitudinal dataset of Finnish families, we evaluated 87 young adults who underwent functional magnetic resonance imaging (fMRI) during an emotional go/no-go task. Intersubject representational similarity analysis (IS-RSA) was used to assess the associations between pairwise similarities in prospectively or retrospectively measured ELS, neural representations in 360 cortical regions, and task performance. We incorporated multidimensional scaling and Procrustes alignment to visualize interindividual differences in representational spaces. Prospective ELS, but not Retrospective ELS, was significantly associated with neural representational similarity across 40 cortical regions, including the anterior insula, frontal operculum, and anterior cingulate cortex. Higher Prospective ELS was also linked to reduced detection sensitivity, mediated by neural responses to angry facial expressions. These findings highlight the systematic and chronic effects of more moderate ELS on brain development and emphasize the value of prospective measurements and advanced similarity analyses in capturing the nuanced influences of ELS. By integrating spatial and shape analytical techniques, the present study provides new insights into the long-term neurobiological correlates of ELS and introduces novel methodological tools for neurodevelopmental research.
Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection
Authors: Chatterjee Debotri , Kurup Drishya , Smeyne Richard Jay 
Published: December 2024

AbstractBasal ganglia disease has been reported as a post-infection sequela of several viruses, with documentation of this phenomenon from the H1N1 Spanish flu to the recent COVID-19 (SARS-CoV-2) pandemic. SARS-CoV-2 infection leads to multisystem deficits, including those affecting the nervous system. Here, we investigated whether a SARS-CoV-2 infection alone increases the susceptibility to develop parkinsonian phenotypes in C57BL/6J mice expressing the human ACE2 receptor, or in addition to two well-known toxin exposures, MPTP and paraquat. Additionally, we examined mice carrying a G2019S mutation in the LRRK2 gene. We also examined if vaccination with either an mRNA- or protein-based vaccine can alter any observed neuropathology. We find that the infection with the WA-1/2020 (alpha) or omicron B1.1.529 strains in ACE2 and G2019S LRRK2 mice both synergize with a subtoxic exposure to the mitochondrial toxin MPTP to induce neurodegeneration and neuroinflammation in the substantia nigra. This synergy appears toxin-dependent since we do not observe this following exposure to the direct redox-inducing compound paraquat. This synergistic neurodegeneration and neuroinflammation is rescued in WT mice that were vaccinated using either mRNA- and protein- based vaccines directed against the Spike protein of the SARS-CoV-2 virus. However, in the G2019S LRRK2 mutant mice, we find that only the protein-based vaccine but not the mRNA- based vaccine resulted in a rescue of the SARS-CoV-2 mediated neuropathology. Taken together, our results highlight the role of both environmental exposures and familial background on the development of parkinsonian pathology secondary to viral infection and the benefit of vaccines in reducing these risks.
Insights into Intestinal Barrier Disruption During Long-Term GutChlamydiaColonization in Mice: A Single-Cell Transcriptomic Approach
Authors: Jiang Yicun , Xie Sheng , Shu Chuqiang , Wan Jiao , Huang Youyou , Wang Luying , Zhang Qi , Zhou Zengzi , Sun Xin , Zhang Tianyuan , Tian Qi 
Published: December 2024

ABSTRACTChlamydia trachomatis, an intracellular pathogen, stands as the most prevalent sexually transmitted bacterial infection among women globally. Traditionally recognized as a genital pathogen, recent research indicates that the gastrointestinal tract may also act as a reservoir for its long-term colonization. However, the mechanisms underlyingChlamydia’s ability to persist in the gut remain poorly understood. This gap in knowledge limits our ability to develop effective treatments for persistentChlamydiainfections. In this study we utilized single-cell RNA sequencing to analyze the gene expression profiles and cellular heterogeneity of mouse colonic tissues duringChlamydialong-term infection. This approach provided detailed insights into the transcriptional changes and cellular interactions involved in the persistence ofChlamydiain the gut. Our results revealed significant alterations in the gene expression profiles of various intestinal cell populations, with distinct molecular pathways contributing toChlamydiapersistence. Notably, we observed a reduction in the expression of markers associated with epithelial tight junctions, indicating a potential breakdown of the intestinal epithelial barrier. This impairment may facilitate the penetration ofChlamydiainto deeper tissues and contribute to the initiation of infection. We also found dysregulation of the transcriptional networks in goblet cells and an imbalance in communication between immune and epithelial cells. These disruptions were linked to the pathogen’s ability to establish persistent colonization and infection.IMPORTANCEFew studies have exploredChlamydiapersistence in the gastrointestinal tract. In this study, we use single-cell RNA sequencing to identify the molecular and cellular mechanisms driving the pathogen’s long-term colonization. Our findings provide crucial insights into howChlamydiaovercomes the host’s immune defenses and epithelial barriers to establish chronic infection in the gut. Notably, we identify disruption of epithelial tight junctions and an imbalance in immune-cell interactions, offering new avenues for therapeutic interventions aimed at restoring mucosal integrity and preventing persistent infection.
Retromer Opposes Opioid-Induced Downregulation of the Mu Opioid Receptor
Authors: Dagunts Aleksandra , Adoff Hayden , Novy Brandon , Maria Monica De , Lobingier Braden T 
Published: December 2024

AbstractThe mu opioid receptor (MOR) is protected from opioid-induced trafficking to lysosomes and proteolytic downregulation by its ability to access the endosomal recycling pathway through its C-terminal recycling motif, LENL. MOR sorting towards the lysosome results in downregulation of opioid signaling while recycling of MOR to the plasma membrane preserves signaling function. However, the mechanisms by which LENL promotes MOR recycling are unknown, and this sequence does not match any known consensus recycling motif. Here we took a functional genomics approach with a comparative genome-wide screen design to identify genes which control opioid receptor expression and downregulation. We identified 146 hits including all three subunits of the endosomal Retromer complex. We show that the LENL motif in MOR is a novel Retromer recycling motif and that LENL is a necessary, sufficient, and conserved mechanism to give MOR access to the Retromer recycling pathway and protect MOR from agonist-induced downregulation to multiple clinically relevant opioids including fentanyl and methadone.
Sex-specific thermoregulatory effects of estrogen signaling inReprimolineage cells
Authors: Park Jae W. , Cortes Laura R. , Sandoval Norma P. , Baron Alejandra G. , Vree Adriana R. , Fideles Higor J. , Hansen Mia R. , Lopez Julissa I. , Dilday Elizabeth A. , Rashid Sakina , Kammel Laura G. , van Veen J. Edward , Correa Stephanie M. 
Published: December 2024

AbstractMenopause affects over a million individuals annually and is characterized by variable and declining ovarian hormones. Decreasing estrogen levels impact energy homeostasis and increases the risk of metabolic disorders. Energy expenditure is largely directed towards thermoregulation, which is modulated in part by estrogen receptor (ER) α expressing neurons in the hypothalamus. Whether specific sub-populations of ERα+ neurons control the effects of estrogens on thermogenesis remains poorly understood. This study investigates the function of ERαin neurons that expressRprm(Reprimo), a gene we previously linked to thermoregulation in females. Here, we use a novelReprimoCremouse to selectively knock out ERαinRprmlineage neurons (Reprimo-specific estrogen receptor α KO; RERKO) and report changes in core temperature in female mice, with no changes in body weight, body composition, or food intake. RERKO females have elevated brown adipose tissue (BAT) temperature and lower tail temperature relative to controls, suggesting increased heat production and impaired heat dissipation, respectively. Developmental expression ofRprmwas detected in the brain, but not in BAT or white adipose tissue suggesting temperature changes may be mediated by the nervous system. Thus, we next ablatedRprmexpressing neurons in the ventrolateral area of the ventromedial nucleus of the hypothalamus (VMHvl) and observed a reduction in core temperature and increased fat mass in ablated female mice relative to controls. Taken together, these results show that estrogen signaling inRprmexpressing cells and VMHvlRprmneurons are critical for thermoregulation, mainly through the modulation of brown adipose tissue thermogenesis in female, but not male mice.
Floquet Schrieffer-Wolff transform based on Sylvester equations
Authors: Wang Xiao , Méndez-Córdoba Fabio Pablo Miguel , Jaksch Dieter , Schlawin Frank 
Published: December 2024

We present a Floquet Schrieffer-Wolff transform (FSWT) to obtain effective Floquet Hamiltonians and micromotion operators of periodically driven many-body systems for any nonresonant driving frequency. The FSWT perturbatively eliminates the oscillatory components in the driven Hamiltonian by solving operator-valued Sylvester equations with systematic approximations. It goes beyond various high-frequency expansion methods commonly used in Floquet theory, as we demonstrate with the example of the driven Fermi-Hubbard model. In the limit of high driving frequencies, the FSWT Hamiltonian reduces to the widely used Floquet-Magnus result. We anticipate this method will be useful for designing Rydberg multiqubit gates, controlling correlated hopping in quantum simulations in optical lattices, and describing multiorbital and long-range interacting systems driven in-gap.

Published by the American Physical Society
2024
Unconventional quantum oscillations and evidence of nonparabolic electronic states in quasi-two-dimensional electron system at complex oxide interfaces
Authors: Rubi Km , Candido Denis R. , Dumen Manish , Zeng Shengwei , Ammerlaan Emily L.Q.N. , Bangma Femke , Chan Mun K. , Goiran Michel , Ariando Ariando , Chakraverty Suvankar , Escoffier Walter , Zeitler Uli , Harrison Neil 
Published: December 2024

The simultaneous occurrence of electric-field controlled superconductivity and spin-orbit interaction makes two-dimensional electron systems (2DES) constructed from perovskite transition metal oxides promising candidates for the next generation of spintronics and quantum computing. It is, however, essential to understand the electronic bands thoroughly and verify the predicted electronic states experimentally in these 2DES to advance technological applications. Here, we present insights into the electronic states of the 2DES at oxide interfaces through comprehensive investigations of Shubnikov–de Haas oscillations in three different systems: EuO/KTaO3, LaAlO3/SrTiO3, and amorphous-LaAlO3/KTaO3. To accurately resolve these oscillations, we conducted transport measurements in high magnetic fields up to 60 T and low temperatures down to 100 mK. For 2D confined electrons at these interfaces, we observed a progressive increase of oscillations frequency and cyclotron mass with the magnetic field. We interpret these universal and intriguing findings by considering the existence of nontrivial electronic bands, for which the E−k dispersion incorporates both linear and parabolic relations. In addition to providing experimental evidence for nonparabolic electronic states in KTaO3 and SrTiO3 2DES, the unconventional oscillations presented in this study establish a paradigm for quantum oscillations in 2DES based on perovskite transition metal oxides, where the oscillation frequencies in 1/B exhibit quadratic dependence on the magnetic field.

Published by the American Physical Society
2024
Berrylush: scaling for growth
Authors: Lamba Harchitwan Kaur , Sengupta Santoshi , Paul Alok Jyoti , Dhir Sanjay 
Published: December 2024

Learning outcomes
Working through the case and the questions that follow will allow students to evaluate: critically assess the effectiveness and feasibility of Berrylush’s business model through the lens of the Business Model Canvas; understand: explain the strategies used by the organisation to gain and sustain a competitive advantage; apply: use the principles of judo strategy to develop tactics for competing effectively against well-established brands; analyse: examine how environmental changes affect the organisation; and create: formulate a growth strategy for Berrylush.

Case overview/synopsis
Two young MBA graduates from a top Indian management institution dreamed of running a large-scale business, providing women all over India with high-quality western clothing. In 2017, Berrylush was born with an initial business model where they designed and manufactured all their products in-house. While at one point, their maximum production capacity was only 900 units a month, within a handful of years, the brand saw its highest selling week of 2022 with sales of over 50,000 orders on India’s largest apparel and fashion website. Co-founder Alok Paul is spearheading the company’s channel expansion, taking it from only direct-to-consumer online sales to offline sales, creating an omnichannel experience for shoppers.

Complexity academic level
The case can be used for an undergraduate or MBA program teaching a strategic management course after the fundamentals of strategic management have been taught but before strategy execution and implementation have been discussed.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.
The magic of preloved sarees, thrifting your way to elegance
Authors: Misra Susmita , Srivastava Ritu , Sinha Steffi 
Published: December 2024

Learning outcomes
The primary learning objective is to challenge students to evaluate the decision facing The Magic of Sarees (MOS) Preloved. The students will need to assess the risks involved versus maintaining the status quo. Students should apply strategic management concepts in their analysis. The second learning objective focuses on developing the students’ understanding of effective merchandising and pricing strategies for MOS Preloved. This case study discusses how MOS Preloved manages its inventory, the constant refreshing of collections and seasonal relevance and also discusses challenges and opportunities associated with managing a preloved inventory, considering factors like authenticity and quality control. This case study also considers pricing strategies (BCG matrix could be referenced for differential pricing) that could be used to strengthen the brand’s identity of “affordable, accessible, and authentic sustainable fashion”.

Case overview/synopsis
This case study is based on the brand “MOS Preloved”, an e-commerce market place in India for the buying and selling of preloved sarees. Founded by Susmita Misra in July 2021, the objective of the business is to create an online marketplace, buy and sell, for preowned sarees that facilitates circular economy. The accompanying saree stories add to the allure and ensure the magic of these sarees continues for the entire lifetime of each saree. Being an unstitched garment, the saree has no size limitation and with a little care could last for at least 100 wears. This case study discusses the founder’s dilemma of deciding to premiumize the merchandise which would include both adding higher priced preowned sarees as well as charging 50% of market price for current merchandise (currently being priced at 25%–40% of the current market price). The decision requires considerable investment in terms of information technology, infrastructure, human resources and marketing spends. Given how nascent, unorganized and unbranded the preloved saree market is, the founder is unsure of the time that it could take to get the return on investment. The risk: the longer she hesitates, the more vulnerable her monopoly becomes. The case study also discusses the evolution of saree into contemporary wear, the hurdles and possibilities in the preloved fashion sector and brand MOS Preloved’s attempts at creating a distinctive positioning.

Complexity academic level
This case study is suitable for postgraduate programme for MBA.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS11: Strategy.
Innovation potential scale (IPS): construction and validity evidence of a measure for the work context
Authors: Souza Gustavo Henrique Silva de , Cesar Lima Nilton , Queiroz Fernanda Cristina Barbosa Pereira , Gonçalves Rafael Farias , Queiroz Jamerson Viegas 
Published: December 2024

PurposeThis article aims to develop a measure that assesses and maps the behaviors and traits of an individual with potential for innovation in the work context. To do so, it gathers evidence of factor validity and internal consistency.Design/methodology/approachIn the work context, innovation is often linked with the idea of intrapreneurship. Some experts have pointed out that intrapreneurial activities are essential for promoting innovation. However, it is not just about the activities – the key is to create an environment that supports innovation, fostering a culture where new ideas can thrive. To achieve the objectives of this research, we conducted two studies. The first study involved the construction of the innovation potential scale (IPS). In a theoretical, empirical way, the second study involved the administration of the IPS and a sociodemographic questionnaire to a sample of 621 Brazilians from 25 different occupations.FindingsThe results introduce a nine-item measure for the innovative behavior assessment, along with its validity and psychometric properties. Furthermore, the results suggest that innovation potential is a unidimensional construct. Moreover, the study highlights the role of intrapreneurship as an explanatory axiom. This concept helps to understand the entrepreneurial behavior of various professionals and managers within their work context.Practical implicationsThis study contribute with as instrument that serves as a new powerful tool for understanding of the mechanisms that lead to innovation in the work context and stimulate the innovative potential of professionals and organizations.Originality/valueThis study helps fill gaps in the literature on self-report assessment of innovative behavior. The traits linked with the construct have a contingent nature and are only potential.