bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells
Authors: Hoeger Birgit , Nadolni Wiebke , Hampe Sarah , Hoelting Kilian , Fraticelli Marco , Zaborsky Nadja , Madlmayr Anna , Sperrer Viktoria , Fraticelli Laura , Addington Lynda , Steinritz Dirk , Chubanov Vladimir , Geisberger Roland , Greil Richard , Breit Andreas , Boekhoff Ingrid , Gudermann Thomas , Zierler Susanna 
Published: September 2023

Abstract
Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High constitutive COX-2 expression enhances survival and proliferation of cancer cells, and adversely impacts antitumor immunity. The expression of COX-2 is modulated by various signaling pathways. Recently, we identified the melastatin-like transient-receptor-potential-7 (TRPM7) channel-kinase as modulator of immune homeostasis. TRPM7 protein is essential for leukocyte proliferation and differentiation, and upregulated in several cancers. It comprises of a cation channel and an atypical α-kinase, linked to inflammatory cell signals and associated with hallmarks of tumor progression. A role in leukemia has not been established, and signaling pathways are yet to be deciphered. We show that inhibiting TRPM7 channel-kinase in chronic myeloid leukemia (CML) cells results in reduced constitutive COX-2 expression. By utilizing a CML-derived cell line, HAP1, harboring CRISPR/Cas9-mediated TRPM7 knockout, or a point mutation inactivating TRPM7 kinase, we could link this to reduced activation of AKT serine/threonine kinase and mothers against decapentaplegic homolog 2 (SMAD2). We identified AKT as a direct in vitro substrate of TRPM7 kinase. Pharmacologic blockade of TRPM7 in wildtype HAP1 cells confirmed the effect on COX-2 via altered AKT signaling. Addition of an AKT activator on TRPM7 kinase-dead cells reconstituted the wildtype phenotype. Inhibition of TRPM7 resulted in reduced phosphorylation of AKT and diminished COX-2 expression in peripheral blood mononuclear cells derived from CML patients, and reduced proliferation in patient-derived CD34+ cells. These results highlight a role of TRPM7 kinase in AKT-driven COX-2 expression and suggest a beneficial potential of TRPM7 blockade in COX-2-related inflammation and malignancy.
Firearm violence exposure and health in 2 national samples of Black and American Indian/Alaska Native adults
Authors: Semenza Daniel C , Baker Nazsa , Ziminski Devon 
Published: September 2023

Abstract
Exposure to firearm violence is widespread and disproportionately experienced by communities of color, with implications for broad health disparities. Survey data were collected from 2 nationally representative samples of Black (n = 3015) and American Indian/Alaska Native (AI/AN) (n = 527) adults in the United States in April and May 2023. The exposure measures were 4 types of firearm violence exposure. The outcome measures were self-rated health, number of poor physical health days, and number of poor mental health days. Regression results demonstrate that being threatened with a firearm and hearing about or witnessing a shooting were associated with poorer self-rated, mental, and physical health across both samples. Cumulative exposure to firearm violence was particularly associated with increasing harms to health for all outcomes. In general, individual and cumulative firearm violence exposures are linked to poorer health among Black and AI/AN adults in the United States. Significant enhancements and long-term investment are needed for firearm violence prevention to yield improvements to population health, particularly among communities burdened with high levels of exposure to firearm violence.
Solid surfaces
Authors: Atkins Peter , de Paula Julio , Friedman Ronald 
Published: September 2023

Contents

Surface growth	912

The collision flux	913

Physisorption and chemisorption	913

Fractional coverage	914

Experimental techniques	914

Microscopy	915

Ionization techniques 916 Brief illustration 95.3: A UPS spectrum 916 Brief illustration 95.4:...
Heterogeneous catalysis
Authors: Atkins Peter , de Paula Julio , Friedman Ronald 
Published: September 2023

Contents

Mechanisms of heterogeneous catalysis	931

Unimolecular reactions	932

Surface-catalysed unimolecular decomposition	932

The Langmuir-Hinshelwood mechanism	932

Writing a rate law based on the Langmuir-Hinshelwood mechanism	932

The Eley–Rideal mechanism	933

The Eley–Rideal...
Successful treatment with belimumab for immune thrombocytopenia associated with systemic lupus erythematosus: A report of two cases
Authors: Nakayama Kyohei , Tamimoto Yasuhiro , Nakayama Tsuyoshi 
Published: September 2023

ABSTRACT
Immune thrombocytopenia (ITP) is a common complication of systemic lupus erythematosus (SLE). Glucocorticoids (GCs) and hydroxychloroquine are first-line therapy for SLE-associated ITP (SLE-ITP). SLE-ITP in most of patients is less severe and well controlled with GCs, but some of the patients are GC resistant and require additional immunosuppressants including calcineurin inhibitors, azathioprine, and rituximab. We present two cases of SLE-ITP patients treated with belimumab who were resistant to GCs and achieved remission. For severe SLE-ITP, belimumab has emerged as a novel induction therapeutic option.
An approach for determining the reliability of manual and digital scoring of sleep stages
Authors: Gerardy Bethany , Kuna Samuel T , Pack Allan , Kushida Clete A , Walsh James K , Staley Bethany , Pien Grace W , Younes Magdy 
Published: September 2023

Abstract

Study Objectives
Inter-scorer variability in sleep staging is largely due to equivocal epochs that contain features of more than one stage. We propose an approach that recognizes the existence of equivocal epochs and evaluates scorers accordingly.

Methods
Epoch-by-epoch staging was performed on 70 polysomnograms by six qualified technologists and by a digital system (Michele Sleep Scoring [MSS]). Probability that epochs assigned the same stage by only two of the six technologists (minority score) resulted from random occurrence of two errors was calculated and found to be &lt;5%, thereby indicating that the stage assigned is an acceptable variant for the epoch. Acceptable stages were identified in each epoch as stages assigned by at least two technologists. Percent agreement between each technologist and the other five technologists, acting as judges, was determined. Agreement was considered to exist if the stage assigned by the tested scorer was one of the acceptable stages for the epoch. Stage assigned by MSS was likewise considered in agreement if included in the acceptable stages made by the technologists.

Results
Agreement of technologists tested against five qualified judges increased from 80.8% (range 70.5%–86.4% among technologists) when using the majority rule, to 96.1 (89.8%–98.5%) by the proposed approach. Agreement between unedited MSS and same judges was 90.0% and increased to 92.1% after brief editing.

Conclusions
Accounting for equivocal epochs provides a more accurate estimate of a scorer’s (human or digital) competence in scoring sleep stages and reduces inter-scorer disagreements. The proposed approach can be implemented in sleep-scoring training and accreditation programs.
Management of Retinitis Pigmentosa Via Wharton’s Jelly-Derived Mesenchymal Stem Cells or Combination With Magnovision: 3-Year Prospective Results
Authors: Ozmert Emin , Arslan Umut 
Published: September 2023

Abstract
To investigate whether the natural progression rate of retinitis pigmentosa (RP) can be decreased with subtenon Wharton’s jelly-derived mesenchymal stem cell (WJ-MSC) application alone or combination with Magnovision.
The study included prospective analysis of 130 eyes of 80 retinitis pigmentosa patients with a 36-month follow-up duration. Patients constitute 4 groups with similar demographic characteristics. The subtenon WJ-MSC-only group consisted of 34 eyes of 32 RP patients as Group 1; the Magnovision-only group consisted of 32 eyes of 16 RP patients as Group 2; the combined management group consisted of 32 eyes of 16 RP patients who received combined WJ-MSC and Magnovision as Group 3; the natural course (control) group consisted of 32 eyes of 16 RP patients who did not receive any treatment were classified as Group 4. Fundus autofluorescence surface area (FAF-field), horizontal and vertical ellipsoid zone width (EZW), fundus perimetry deviation index (FPDI), full-field electroretinography magnitude (ERG-m), and best corrected visual acuity (BCVA) changes were compared within and between groups after 36 months follow up period.
FAF-field delta changes were detected 0.39 mm2 in Group 1, 1.50 mm2 in Group 2, 0.07 mm2 in Group 3 and 12.04 mm2 in Group 4 (Δp 4 &gt; 2 &gt; 1 &gt; 3). Horizontal EZW, Vertical EZW, BCVA, and FPDI delta changes were detected Δp 4 &gt; 1,2 &gt; 3. ERG-m delta changes were detected Δp 3 &gt; 1,2,4.
Retinitis pigmentosa characterized by progressive loss of photoreceptors eventually leading to total blindness. The combination of WJ-MSC and Magnovision can significantly slow the progression of the disease in comparison to natural progression rate for 3 years in appropriate cases.
Trial Registration: ClinicalTrials.gov, NCT05800301.
Examining associations between school-level determinants and the implementation of physical activity opportunities
Authors: Craig Derek W , Walker Timothy J , Sharma Shreela V , Cuccaro Paula , Heredia Natalia I , Pavlovic Andjelka , DeFina Laura F , Kohl Harold W , Fernandez Maria E 
Published: September 2023

Abstract
School-based physical activity (PA) opportunities can help students engage in greater amounts of daily PA, meet PA guidelines, and lead to improved health and educational outcomes. However, we do not completely understand the organizational challenges to implementing these opportunities successfully. This exploratory study examined associations between school-level determinants and the implementation of school-based PA opportunities. We analyzed cross-sectional survey data from schools (n = 46) participating in the Healthy Zone School Program (HZSP) (Dallas, Texas, USA) during 2019–2020. Respondents completed an electronic survey that included measures of school-level determinants (e.g. culture, leadership, priority) and the implementation of school-based PA opportunities. We used linear regression models to examine associations between determinants and implementation outcomes (number of PA opportunities delivered, perceived overall success of each PA program/activity used). After adjusting for campus type (i.e. elementary, middle, high, K-12), student race/ethnicity, and percentage of economically disadvantaged students, no constructs were associated with the number of PA opportunities implemented. Linear regression models suggest access to knowledge and information (β = 0.39, P = .012, 95% CI = 0.24–1.44) and implementation climate (β = 0.34, P = .045, 95% CI = 0.02–1.59) were positively associated with the success of school-based PA opportunities. Our findings provide suggestive evidence that access to knowledge and information and a supportive school climate may improve the overall success of PA opportunities provided to students. Future research should examine additional school-level determinants to understand their importance to implementation and inform the development of strategies to improve schools’ capacity for implementing PA opportunities successfully.
Discovery medicine – the HVTN's iterative approach to developing an HIV-1 broadly neutralizing vaccine
Authors: Martin Troy M. , Robinson Sam T. , Huang Yunda 
Published: September 2023

Purpose of review
In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine.

Recent findings
With recent preclinical success including induction of early stage bnAbs in mouse knockin models and rhesus macaques, successful priming of VRC01-class bnAbs with eOD-GT8 in a recent study in humans, and proof-of-concept that intravenous infusion of VRC01 prevents sexual transmission of virus in humans, the stage is set for a broad and comprehensive bnAb vaccine program. Leveraging significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, the HVTN has reconfigured its HIV-1 vaccine strategy by developing the Discovery Medicine Program to test promising vaccine candidates targeting six key epitopes.

Summary
The HVTN Discovery Medicine program is testing multiple HIV-1-neutralizing vaccine candidates.
Prevalence and Correlates of Dry Eye in a German Population Sample
Authors: Münch Kathrin , Nöhre Mariel , Westenberger Adrian , Akkus Dilek , Morfeld Matthias , Brähler Elmar , Framme Carsten , de Zwaan Martina 
Published: September 2023

Purpose:
In this cross-sectional survey, we assessed the prevalence of dry eye disease (DED) in a representative German population sample. In addition, we examined the associations between DED, health-related quality of life (HRQoL), and level of fatigue. Finally, we further validated the German version of the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and present norm data of the German population.

Methods:
A random sample of German residents aged 16 years and older was recruited between October and December 2021. All participants completed the SPEED, Short Form 36, and Multidimensional Fatigue Inventory 20 questionnaires.

Results:
Of the 2495 participants who completed the survey, 450 (21.6%; 95% confidence intervals 20.0–23.1) reported a SPEED total score of ≥4, indicating a positive screening for DED. DED was significantly more common in women and older age. Participants who screened positive for DED reported significantly higher levels of fatigue and lower values in all domains of HRQoL. A receiver operating characteristic curve of the SPEED was generated using an ophthalmologist's diagnosis. The area under the curve was estimated to be 0.886 (95% confidence intervals 0.858–0.913). A cutoff score ≥4 seemed to be appropriate as an indicator of DED. Cronbach's α was excellent (0.95).

Conclusions:
DED is common in the German population. We confirmed associations with sex, age, HRQoL, and fatigue level, indicating a high burden of DED. The German version of the SPEED is a valid instrument for the assessment of DED symptoms.
Using a Cone-Shaped Glass Funnel Adapter Reduces Endothelial Cell Loss Caused by Preloading Descemet Membrane Endothelial Keratoplasty Tissue
Authors: Kigin Matthew , Schmidt Gregory , Revis Benjamin , Vigmostad Sarah , Sales Christopher S. 
Published: September 2023

Purpose:
The aims of this study were (1) to compare “front” and “rear” methods for loading Descemet membrane endothelial keratoplasty (DMEK) tissue into both micro-Jones and standard-Jones tubes and (2) to evaluate the efficacy of a cone-shaped glass funnel adapter designed to make loading DMEK tissue safer for corneal endothelial cells.

Methods:
The corneal endothelium was stained with 0.06% trypan blue to confirm equivalence between mate corneas. The tissues were then processed using the Iowa Lions Eye Bank standard DMEK protocol. In comparison 1, one mate was loaded into the rear of a micro-Jones or standard-Jones tube and the other was loaded into the front of the same tube. In comparison 2, one mate was loaded into the front of the micro-Jones tube and the other was loaded through the cone-shaped funnel adapter into the rear. All tissues were ejected through the front of the modified Jones tubes and assessed for endothelial cell loss (ECL) with calcein AM staining, FIJI, and Trainable Weka Segmentation; scroll widths were measured digitally.

Results:
There were no statistically significant differences in ECL between front and rear loading [micro (N = 6 pairs): front 15.74% vs. rear 17.95%; standard (N = 6 pairs): front 19.58% vs. rear 19.17%; all P > 0.05]. DMEK scrolls loaded with the funnel adapter exhibited lower ECL compared with scrolls loaded through the front [micro (N = 8 pairs): front 13.53% vs. loading funnel 2.40%; P < 0.001]. Loading with the adapter was not faster (front 6.66 seconds vs. loading funnel 5.52 seconds; P = 0.24).

Conclusions:
Using a cone-shaped DMEK loading funnel may reduce ECL sustained during preloading.
Virtual biomarkers: predicting immune status using label-free holotomography of individual human monocytes and machine learning analysis
Authors: Lee Mahn Jae , Kim Geon , Lee Moo Sung , Shin Jeong Won , Lee Joong Ho , Ryu Dong Hun , Kim Young Seo , Chung YoonJae , Kim Kyu Seok , Park YongKeun 
Published: September 2023

AbstractSepsis is an abnormally dysregulated immune response against infection in which the human immune system ranges from a hyper-inflammatory phase to an immune-suppressive phase. Current assessment methods are limiting owing to time-consuming and laborious sample preparation protocols. We propose a rapid label-free imaging-based technique to assess the immune status of individual human monocytes. High-resolution intracellular compositions of individual monocytes are quantitatively measured in terms of the three-dimensional distribution of refractive index values using holotomography, which are then analyzed using machine-learning algorithms to train for the classification into three distinct immune states: normal, hyper-inflammation, and immune suppression. The immune status prediction accuracy of the machine-learning holotomography classifier was 83.7% and 99.9% for one and six cell measurements, respectively. Our results suggested that this technique can provide a rapid deterministic method for the real-time evaluation of the immune status of an individual.
Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection
Authors: Tomalka Jeffrey A. , Owings Anna , Galeas-Pena Michelle , Ziegler Carly G.K. , Robinson Tanya O. , Wichman Thomas G. , Laird Hannah , Williams Haley B. , Dhaliwal Neha S. , Everman Steven , Zafar Yousaf , Shalek Alex K. , Horwitz Bruce H. , Ordovas-Montanes Jose , Glover Sarah C. , Gibert Yann 
Published: September 2023

AbstractBackgroundMany questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found thataloxgenes, involved in eicosanoid synthesis, were up-regulated in high WHO score patients, especially in goblet cells. Herein, we aimed to further understand the roles played by eicosanoids during severe SARS-CoV-2 infection.Methods and findingsWe performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways.ConclusionsOur study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.
Fusarium graminearumSte2 and Ste3 Receptors Undergo Peroxidase Induced Heterodimerization
Authors: Sharma Tanya , Jomphe Robert Y. , Zhang Dongling , Magalhaes Ana C. , Loewen Michele C. 
Published: September 2023

AbstractF. graminearum FgSte2 andFgSte3 are G-protein coupled receptors (GPCRs) recently shown to play roles in mediating fungal hyphal chemotropism and plant pathogenesis in response to activity arising from host-released peroxidases. Here, we follow up on the previous observation that chemotropism is dependent on bothFgSte2 andFgSte3 being present at the same time; testing the possibility that this effect might be due to formation of anFgSte2-FgSte3 heterodimer. Initially the recombinant cell-surface expression of theF. graminearumGPCRs was validated inS. cerevisiaeby confocal immunofluorescence microscopy. Bioluminescence resonance energy transfer analyses were subsequently conducted, where the addition of horse radish peroxidase (HRP) was found to increase the transfer of energy from the inducibly-expressedFgSte3-Nano luciferase (FgSte3-NLuc) donor, to the constitutively-expressedFgSte2-yellow fluorescent protein (FgSte2-YFP) acceptor, compared to controls. A partial response was also detected when an HRP-derived ligand-containing extract was enriched fromF. graminearumspores and applied to theS. cerevisiaeBRET system directly. The selectivity of the interaction was demonstrated by comparison to treatment with pheromones as well as an unrelated bovine GPCR, rhodopsin, fused to YFP as acceptor, that yielded no response when co-expressed withFgSte3-NLuc. Finally, the peroxidase-stimulated heterodimerization was validated by affinity pulldown. Taken together these findings demonstrate the formation of HRP and HRP-derived ligand stimulated heterodimers betweenFgSte2 andFgSte3. Outcomes are discussed from the context of the roles of ligands and reactive oxygen species in GPCR dimerization.
Estimating US farmers' speed of climate change adaptation: the case of subsurface tile drainage
Authors: Comstock Haden , DeLay Nathan 
Published: September 2023

PurposeClimate change is expected to cause larger and more frequent precipitation events in key agricultural regions of the United States, damaging crops and soils. Subsurface tile drainage is an important technology for mitigating the risks of a wetter climate in crop production. In this study, the authors examine how quickly farmers adapt to increased precipitation by investing in drainage technology.Design/methodology/approachUsing farm-level data from the 2018 Agricultural Resource Management Survey (ARMS) of soybean producers, the authors construct a drainage adoption timeline based on when the operator began farming their land and when tile drainage was installed, if at all. The authors examine both the initial investment decision and the speed with which drainage is installed by adopters. A Heckman-style Poisson regression is used to model the count nature of adoption speed (measured in years taken to install tile drainage) and to correct for potential sample-selection bias.FindingsThe authors find that local precipitation is not a significant determinant of the drainage investment decision but may be highly influential in the timing of adoption among drainage users. Farms exposed to crop-damaging levels of precipitation install tile drainage faster than those with low to moderate levels of rainfall. Estimates of farm adaptation speeds are heterogeneous across farm and operator characteristics, most notably land tenure status.Originality/valueUnderstanding how US farmers adapt to extreme weather through technology adoption is key to predicting the long-term impacts of climate change on America's food system. This study extends the existing climate adaptation literature by focusing on the speed of adoption of an important and increasingly common climate-mitigating technology – subsurface tile drainage.