bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute activation of SERCA with CDN1163 attenuates IgE‐mediated mast cell activation through selective impairment of ROS and p38 signaling
Authors: Hunter Katie D. , Crozier Robert W. E. , Braun Jessica L. , Fajardo Val A. , MacNeil Adam J. 
Published: January 2023

AbstractMast cells are granulocytic immune sentinels present in vascularized tissues that drive chronic inflammatory mechanisms characteristic of allergic pathologies. IgE‐mediated mast cell activation leads to a rapid mobilization of Ca2+ from intracellular stores, which is essential for the release of preformed mediators via degranulation and de novo synthesized proinflammatory cytokines and chemokines. Given its potent signaling capacity, the dynamics of Ca2+ localization are highly regulated by various pumps and channels controlling cytosolic Ca2+ concentrations. Among these is sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA), which functions to maintain low cytosolic Ca2+ concentrations by actively transporting cytosolic Ca2+ ions into the endoplasmic reticulum. In this study, we characterized the role of SERCA in allergen‐activated mast cells using IgE‐sensitized bone marrow‐derived mast cells (BMMCs) treated with the SERCA activating compound, CDN1163, and simultaneously stimulated with allergen through FcεRI under stem cell factor (SCF) potentiation. Acute treatment with CDN1163 was found to attenuate early phase mast cell degranulation along with reactive oxygen species (ROS) production. Additionally, treatment with CDN1163 significantly reduced secretion of IL‐6, IL‐13, and CCL3, suggesting a role for SERCA in the late phase mast cell response. The protective effects of SERCA activation via CDN1163 treatment on the early and late phase mast cell response may be driven by the selective suppression of p38 MAPK signaling. Together, these findings implicate SERCA as an important regulator of the mast cell response to allergen and suggest SERCA activity may offer therapeutic potential targeting allergic pathologies, warranting further investigation.
Circadian disruption in lung fibroblasts enhances NF‐κB activity to exacerbate neutrophil recruitment
Authors: Cox Shannon L. , O'Siorain James R. , He Yan , Lordan Ronan , Naik Amruta , Tang Soon Yew , Sengupta Shaon , FitzGerald Garret A. , Carroll Richard G. , Curtis Annie M. 
Published: January 2023

AbstractFibroblasts are stromal cells abundant throughout tissues, including the lungs. Fibroblasts are integral coordinators of immune cell recruitment through chemokine secretion. Circadian rhythms direct the recruitment of immune cells to the lung, which in turn impacts response to infection and survival. Although fibroblasts display robust circadian rhythms, the contribution of the fibroblast molecular clock to lung‐specific migration of immune cells and recruitment remains to be established. Mice challenged intranasally with lipopolysaccharide (LPS) at dusk showed increased expression of the pro‐inflammatory cytokine IL‐1β and chemokine CXCL5 in the lung, which was accompanied by increased neutrophil recruitment. Primary lung fibroblasts with knockdown of the core clock gene Bmal1 and immortalized Bmal1−/− lung fibroblasts also displayed increased Cxcl5 expression under IL‐1β stimulation. Conditioned media obtained from IL‐1β‐stimulated Bmal1−/− immortalized fibroblasts‐induced greater neutrophil migration compared with Bmal1+/+ lung fibroblast controls. Phosphorylation of the NF‐κB subunit, p65, was enhanced in IL‐1β‐stimulated Bmal1−/− lung fibroblasts, and pharmacological inhibition of NF‐κB attenuated the enhanced CXCL5 production and neutrophil recruitment observed in these cells. Collectively, these results demonstrate that Bmal1 represses NF‐κB activity in lung fibroblasts to control chemokine expression and immune cell recruitment during an inflammatory response.
A universal method to analyze cellular internalization mechanisms via endocytosis without non‐specific cross‐effects
Authors: Itagaki Mai , Nasu Yoshinori , Sugiyama Chiaki , Nakase Ikuhiko , Kamei Noriyasu 
Published: January 2023

AbstractEndocytosis is an essential biological process for nutrient absorption and intercellular communication; it can also be used to accelerate the cellular internalization of drug delivery carriers. Clarifying the cellular uptake mechanisms of unidentified endogenous and exogenous molecules and designing new effective drug delivery systems require an accurate, specific endocytosis analysis methodology. Therefore, we developed a method to specifically evaluate cellular internalization via three main endocytic pathways: clathrin‐ and caveolae‐mediated endocytosis, and macropinocytosis. We first revealed that most known endocytosis inhibitors had no specific inhibitory effect or were cytotoxic. Second, we successfully established an alternative method using small interfering RNA to knock down dynamin‐2 and caveolin‐1, which are necessary for clathrin‐ and caveolae‐mediated endocytosis, in HeLa cells. Third, we established another method to specifically analyze macropinocytosis using rottlerin on A431 cells. Finally, we validated the proposed methods by testing the cellular internalization of a biological molecule (insulin) and carriers (nanoparticles and cell‐penetrating peptides). Through this study, we established versatile methods to precisely and specifically evaluate endocytosis of newly developed biopharmaceuticals or drug delivery systems.
The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma
Authors: Patrich Tomas , Wang Yaqun , Elshaikh Mohamed A. , Zhu Simeng , Damast Shari , Li Jessie Y. , Fields Emma C. , Beriwal Sushil , Keller Andrew , Kidd Elizabeth A. , Usoz Melissa , Jolly Shruti , Jaworski Elizabeth , Leung Eric W. , Taunk Neil K. , Chino Junzo , Russo Andrea L. , Lea Jayanthi S. , Lee Larissa J. , Albuquerque Kevin V. , Hathout Lara 
Published: January 2023

Objective:
To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma.

Materials and Methods:
A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27.

Results:
The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively (P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 (P value=0.045) for OS and 1.487 (P value=0.116) for RFS. After PSM, black patients were more likely to receive the “Sandwich” approach and concurrent chemoradiotherapy compared with non-black (P=0.013) patients.

Conclusions:
Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the “Sandwich” approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.
Longitudinal Exposure to Tacrolimus and New-Onset Diabetes Mellitus in Renal Transplant Patients
Authors: Destere Alexandre , Premaud Aurélie , Monchaud Caroline , Marquet Pierre , Woillard Jean-Baptiste 
Published: January 2023

Purpose:
Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence.

Methods:
A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models.

Results:
The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43–2.10, P < 0.001)].

Conclusion:
This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.
What Is the Role of COVID-19 Monoclonal Antibody Programs in Promoting Posttreatment Vaccination?
Authors: Cowman Kelsie , Golia Austin , Guo Yi , Simpson Roxanne , Braithwaite Claire , Sunu Evans , Ros Theary , Rodriguez Maria , Brown Nativida , Laboy Eric , Bard Linda , Alsina Leslie , Cintron Angelica , Andrews Erin , Bao Hongkai , Chang Mei H. , McSweeney Terrence , Nori Priya 
Published: January 2023

Background
In addition to highly efficacious mRNA vaccines, there are multiple therapeutic tools to prevent COVID-19, reduce the severity of illness, and prevent death among high-risk patients. Monoclonal antibodies (mAb) are vital to prevent and to manage acute illness, but subsequent vaccination is essential to mitigate risk of reinfection. The objective of our study was to assess vaccination status after mAb treatment.

Methods
We conducted a retrospective, observational cohort study of high-risk adults who were treated with bamlanivimab for mild-moderate COVID-19 between December 2020 and March 2021 at an ambulatory infusion center or 3 emergency departments in the Bronx, NY. Demographics, mAb treatment information, and vaccination status as of February 28, 2022, were collected from the electronic medical record. Patient outreach phone calls were made to obtain information missing in the electronic medical record.

Results
A total of 722 adults were included. Forty patients (6%) were vaccinated before mAb treatment. Of patients who were unvaccinated at time of treatment (n = 682), 569 (83%) were subsequently vaccinated, 35 (5%) remained unvaccinated, and 78 (11%) had an unknown vaccination status as of March 2022. The mean age of vaccinated patients was 59 years and unvaccinated patients was 54 years (P = 0.05). Median time to vaccination was 99 days (interquartile range, 90–142 days). As of March 2022, 307 patients (43%) had received at least 1 vaccine booster dose.

Conclusions
Most patients who were unvaccinated at time of treatment were subsequently vaccinated. Ambulatory COVID-19 encounters are valuable opportunities to provide vaccine education and counseling.
Superhydrophobic Rotation-Chip for Computer-Vision Identification of Drug-Resistant Bacteria
Authors: He Jiacheng , Peng Ruonan , Yuqing Henry , Karim Rafi , Chen Juhong , Lu Guoyu , Du Ke 
Published: January 2023

ABSTRACTThe transport, distribution, and mixing of microfluidics often require additional instruments, such as pumps and valves, which are not feasible when operated in point-of-care (POC) settings. Here, we present a simple microfluidic pathogen detection system known as Rotation-Chip that transfers the reagents between wells by manually rotating two concentric layers without using external instruments. The Rotation-Chip is fabricated by a simple computer numerical control (CNC) machining process and is capable of carrying out 60 multiplexed reactions with a simple 30-degree or 60-degree rotation. Leveraging superhydrophobic coating, a high fluid transport efficiency of 92.78% is achieved without observable leaking. Integrated with an intracellular fluorescent assay, an on-chip detection limit of 1.8×106CFU/mL is achieved for ampicillin-resistantEscherichia coli (E. coli), which is similar to our off-chip results. We also develop a computer vision method to automatically distinguish positive and negative samples on the chip, showing 100% accuracy. Our Rotation-Chip is simple, low-cost, high-throughput, and can display test results with a single chip image, ideal for various multiplexing POC applications in resource-limited settings.
Loss of PTPMT1 limits mitochondrial utilization of carbohydrates and leads to muscle atrophy and heart failure in tissue-specific knockout mice
Authors: Zheng Hong , Li Qianjin , Li Shanhu , Li Zhiguo , Brotto Marco , Weiss Daiana , Prosdocimo Domenick , Xu Chunhui , Reddy Ashruth , Puchowicz Michelle , Zhao Xinyang , Weitzmann M. Neale , Jain Mukesh K. , Qu Cheng-Kui 
Published: January 2023

ABSTRACTWhile mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here we report that the deletion ofPTPMT1,a mitochondria-based phosphatase, critically alters mitochondrial fuel selection – the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced.PTPMT1knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly,PTPMT1deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that PTPMT1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.
Functional Topography of the Neocortex Predicts Covariation in Complex Cognitive and Basic Motor Abilities
Authors: Whitman Ethan T. , Knodt Annchen R. , Elliott Maxwell L. , Abraham Wickliffe C. , Cheyne Kirsten , Hogan Sean , Ireland David , Keenan Ross , Lueng Joan H. , Melzer Tracy R. , Poulton Richie , Purdy Suzanne C. , Ramrakha Sandhya , Thorne Peter R. , Caspi Avshalom , Moffitt Terrie E. , Hariri Ahmad R. 
Published: January 2023

ABSTRACTAlthough higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g., hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.
Localized modulation of DNA supercoiling, triggered by theShigellaanti-silencer VirB, is sufficient to relieve H-NS-mediated silencing
Authors: Picker Michael A. , Karney Monika M. A. , Gerson Taylor M. , Karabachev Alexander D. , Duhart Juan C. , McKenna Joy A. , Wing Helen J. 
Published: January 2023

ABSTRACTIn Bacteria, nucleoid structuring proteins govern nucleoid dynamics and regulate transcription. InShigella spp., at ≤ 30 °C, the histone-like nucleoid structuring protein (H-NS) transcriptionally silences many genes on the large virulence plasmid. Upon a switch to 37 °C, VirB, a DNA binding protein and key transcriptional regulator ofShigellavirulence, is produced. VirB functions to counter H-NS-mediated silencing in a process called transcriptional anti-silencing. Here, we show that VirB mediates a loss of negative DNA supercoils from our plasmid-borne, VirB-regulatedPicsP-lacZreporter,in vivo. The changes are not caused by a VirB-dependent increase in transcription, nor do they require the presence of H-NS. Instead, the VirB-dependent change in DNA supercoiling requires the interaction of VirB with its DNA binding site, a critical first step in VirB-dependent gene regulation. Using two complementary approaches, we show that VirB:DNA interactionsin vitrointroduce positive supercoils in plasmid DNA. Subsequently, by exploiting transcription-coupled DNA supercoiling, we reveal that a localized loss of negative supercoils is sufficient to alleviate H-NS-mediated transcriptional silencing, independently of VirB. Together, our findings provide novel insight into VirB, a central regulator ofShigellavirulence and more broadly, a molecular mechanism that offsets H-NS-dependent silencing of transcription in bacteria.
Towards closing the housing gap in the UK: exploration of the influencing factors and the way forward
Authors: Daniel Emmanuel Itodo , Oshodi Olalekan , Dabara Daniel , Dimka Nenpin 
Published: January 2023

Purpose
Housing provides constructed space for human activities. Literature indicates that housing impacts wealth, education attainment and health outcomes, among others. Because of its contributions to society, it is essential to develop and implement strategies that address the housing shortage experienced in most cities across the globe. This study aims to unpack the factors affecting housing production in the UK and chart the way forward.

Design/methodology/approach
In addressing this study's aim, an interprivitst approach was adopted and semi-structured interviews were conducted with 18 experienced professionals. Data were collected across the four nations of the UK (England, Wales, Scotland and Northern Ireland).

Findings
The results indicated that the opportunistic behaviour of stakeholders is one of the main factors affecting housing production in the study area. Also, modern construction methods, collaborative practices, government intervention and affordable housing schemes were identified as key strategies for addressing housing production factors.

Practical implications
This study identified strategies for mitigating housing production issues that provide a focal point to all stakeholders keen on filling the housing shortage gap and improving productivity to channel their resources and effort accordingly.

Originality/value
To the best of the authors’ knowledge, this study is one of the first to empirically analyse the influencing factors on the housing gap in the UK from the perspective of the supply side to provide information that could lead towards closing the said gap.
Leakages in affordable housing delivery: threat to achieving Sustainable Development Goal 11
Authors: Ebekozien Andrew , Aigbavboa Clinton Ohis , Samsurijan Mohamad Shaharudin , Adjekophori Bernard , Nwaole Angeline Ngozika Chibuike 
Published: January 2023

PurposeThe increasing growth of urbanisation, especially in developing countries, coupled with affordable housing leakages, may thwart achieving Sustainable Development Goal (SDG) 11 (sustainable cities and communities). Studies regarding affordable housing leakages and their aftermath to Goal 11 in one study are scarce in Malaysia. The study investigated Malaysia's low-cost housing (LCH) leakages and their aftermath to Goal 11 and proffered measures to achieving Goal 11 and its targets. The purpose of this paper is to address these issues.Design/methodology/approachThe researchers covered four of Malaysia's major cities via a qualitative approach. The study used 40 participants via semi-structured virtual interviews, and saturation was achieved. The study adopted a thematic approach for the collected data and honed them with secondary sources.FindingsFindings group Malaysia's LCH leakages into government/agencies/departments in housing, housing developers/building contractors and client/building owners' root causes in Malaysia's context. It shows a threat from Malaysia's LCH leakages to achieving Goal 11 and proffered measures to enhance achieving Goal 11. Achieving Goal 11 will strengthen and improve Malaysia's many SDGs accomplishments because of their link.Originality/valueApart from proffering measures to mitigate long-standing issues (leakages) in Malaysia's LCH delivery from achieving Goal 11, findings will stipulate the accomplishment of other SDGs related to housing delivery.
The role of equity crowdfunding campaigns in shaping firm innovativeness: evidence from Italy
Authors: Valenza Giuseppe , Balzano Marco , Tani Mario , Caputo Andrea 
Published: January 2023

PurposeThis paper aims to contribute to the scientific debate concerning the impact of equity crowdfunding on the performance of crowdfunded firms after campaigning. To this aim, the purpose of this paper is to investigate the relationship between the characteristics of the campaign and the subsequent firm innovativeness.Design/methodology/approachThis study adopts a quantitative research approach to evaluate if the entrepreneurial choices affecting the characteristics of the equity crowdfunding campaigns have an impact on the post-campaign firm innovativeness.FindingsThe results of the models show that the campaign characteristics have a direct impact on the firm innovativeness, both in terms of offering and communication and the campaign performance.Originality/valueThis paper presents one of the first studies to investigate the relationship between the choice of campaign characteristics and the post-campaign firm innovativeness. As such, the study contributes to both the literature concerning start-up innovation and the literature about the impact of equity crowdfunding.