bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a harmonized bronchopulmonary dysplasia definition: a study protocol for an international Delphi procedure
Authors: Katz Trixie A , Bancalari Eduardo , Gordijn Sanne J , Higgins Rosemary D , Isayama Tetsuya , Jensen Erik A , Offringa Martin , Pillow J Jane , Shah Prakesh S , Soll Roger F , Stoecklin Benjamin , Mugie Suzanne M , van Kaam Anton H , Onland Wes
Published: October 2023

Introduction

Bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth with lifelong consequences. Multiple BPD definitions are currently used in daily practice. Uniformity in defining BPD is important for clinical care, research and benchmarking. The aim of this Delphi procedure is to determine what clinicians and researchers consider the key features for defining BPD. With the results of this study, we hope to advance the process of reaching consensus on the diagnosis of BPD.

Methods and analysis

A Delphi procedure will be used to establish why, when and how clinicians propose BPD should be diagnosed. This semi-anonymous iterative technique ensures an objective approach towards gaining these insights. An international multidisciplinary panel of clinicians and researchers working with preterm infants and/or patients diagnosed with BPD will participate. Steering committee members will recruit potential participants in their own region or network following eligibility guidelines to complete a first round survey online. This round will collect demographic information and opinions on key features of BPD definitions. Subsequent rounds will provide participants with the results from the previous round, for final acceptance or rejection of key features. Statements will be rated using a 5-point Likert scale. After completing the Delphi procedure, an (online) consensus meeting will be organised to discuss the results.

Ethics and dissemination

For this study, ethical approval a waiver has been provided. However, all participants will be asked to provide consent for the use of personal data. After the Delphi procedure is completed, it will be published in a peer-reviewed journal and disseminated at international conferences.
Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation
Authors: Galloo Xavier , Fortuni Federico , Meucci Maria Chiara , Butcher Steele C , Dietz Marlieke F , Prihadi Edgard A , Cosyns Bernard , Delgado Victoria , Bax Jeroen J , Ajmone Marsan Nina
Published: October 2023

Objective

Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis.

Methods

Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion.

Results

A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size).

Conclusions

Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.
Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine
Authors: Faria Carla , Gava Fabien , Gravelle Pauline , Valero Juan Garcia , Dobaño-López Celia , Van Acker Nathalie , Quelen Cathy , Jalowicki Gael , Morin Renaud , Rossi Cédric , Lagarde Jean-Michel , Fournié Jean-Jacques , Ysebaert Loïc , Laurent Camille , Pérez-Galán Patricia , Bezombes Christine
Published: October 2023

Background

Follicular lymphoma (FL), the most common indolent non-Hodgkin’s Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses.

Methods

To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability.

Results

FL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+cells positive for PD-1 and TIM-3.

Conclusions

In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.
Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models
Authors: Sandker Gerwin Gerhard Wemke , Middelburg Jim , Wilbrink Evienne , Molkenboer-Kuenen Janneke , Aarntzen Erik , van Hall Thorbald , Heskamp Sandra
Published: October 2023

Background

CD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and CD3 for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the tumor uptake and the extracellular dose. To optimize their currently limited efficacy in solid tumors, increased understanding of their pharmacokinetics and in vivo internalization is needed.

Methods

Here, were studied the pharmacokinetics and in vivo internalization of CD3xTRP1, a fully murine Fc-inert bsAb, in endogenous TRP1-expressing immunocompetent male C57BL/6J mice bearing TRP1-positive and negative tumors over time. Matching bsAbs lacking TRP1-binding or CD3-binding capacity served as controls. BsAbs were radiolabeled with111In to investigate their pharmacokinetics, target binding, and biodistribution through SPECT/CT imaging and ex vivo biodistribution analyses. Co-injection of111In- and125I-labeled bsAb was performed to investigate the in vivo internalization by comparing tissue concentrations of cellular residing111In versus effluxing125I. Antitumor therapy effects were evaluated by monitoring tumor growth and immunohistochemistry.

Results

SPECT/CT and biodistribution analyses showed that CD3xTRP1 specifically targeted TRP1-positive tumors and CD3-rich lymphoid organ and uptake peaked 24 hours pi (KPC3-TRP1: 37.7%ID/g±5.3%ID/g, spleen: 29.0%ID/g±3.9%ID/g). Studies with control bsAbs demonstrated that uptake of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues was primarily receptor-mediated. Together with CD3xTRP1 in the circulation being mainly unattached, this indicates that CD3+T cells are generally not traffickers of CD3-bsAbs to the tumor. Additionally, target-mediated clearance by TRP1-expressing melanocytes was not observed. We further demonstrated rapid internalization of CD3xTRP1 in KPC3-TRP1 tumors (24 hours pi: 54.9%±2.3% internalized) and CD3-rich tissues (spleen, 24 hours pi: 79.7%±0.9% internalized). Therapeutic effects by CD3xTRP1 were observed for TRP1-positive tumors and consisted of high tumor influx of CD8+T cells and neutrophils, which corresponded with increased necrosis and growth delay.

Conclusions

We show that CD3xTRP1 efficiently targets TRP1-positive tumors and CD3-rich tissues primarily through receptor-mediated targeting. We further demonstrate rapid receptor-mediated internalization of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues. Even though this significantly decreases the therapeutical available dose, CD3xTRP1 still induced effective antitumor T-cell responses and inhibited tumor growth. Together, our data on the pharmacokinetics and mechanism of action of CD3xTRP1 pave the way for further optimization of CD3-bsAb therapies.
Facilitators and barriers to hypertension management in urban Nepal: findings from a qualitative study
Authors: Bhattarai Sanju , Bajracharya Swornim , Shrestha Archana , Skovlund Eva , Åsvold Bjørn Olav , Mjolstad Bente Prytz , Sen Abhijit
Published: October 2023

Introduction

In Nepal, one-fourth of the adult population has hypertension. Despite provision of comprehensive hypertension services through the primary healthcare system, huge gaps in treatment and control of hypertension exist. Our study explored the individual, interpersonal, health system and community-level barriers and facilitators affecting hypertension management in urban Nepal.

Methods

We used a qualitative methodology informed by Kaufman’s socioecological model, conducting focus group discussions with hypertension patients and their family members. In-depth interviews with hypertension patients, healthcare providers and municipal officials were also conducted.

Results

We found that inadequate knowledge about hypertension and harmful cultural beliefs hindered effective treatment of hypertension. Interrupted medical supply and distrust in primary healthcare providers affected the poor’s access to hypertension services. Poor communication between family members and gender norms affected adaptation of treatment measures. This study emphasised the role of family members in supporting patients in adhering to treatment measures and rebuilding community trust in primary healthcare providers for better access to hypertension services. The findings guided the development of a manual to be used by community health workers during home visits to support patients to control high blood pressure.

Conclusion

The study highlights the importance of integrating various aspects of care to overcome the multiple barriers to hypertension management in urban settings in low-resource countries. Participatory home visits have the potential to empower individuals and families to develop and implement feasible and acceptable actions for home management of hypertension through improved adherence to antihypertensive medication, and behaviour change.
Serum calprotectin and renal function decline in ANCA-associated vasculitides: a post hoc analysis of MAINRITSAN trial
Authors: Romand Xavier , Paclet Marie Hélène , Chuong Minh Vu , Gaudin Philippe , Pagnoux Christian , Guillevin Loïc , Terrier Benjamin , Baillet Athan
Published: October 2023

Objective

Serum calprotectin appears to be an interesting biomarker associated with renal vascular disease activity in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to assess whether serum calprotectin levels can predict decline in renal function in AAV patients receiving maintenance therapy.

Methods

Serum calprotectin levels were assessed at inclusion and month 6 in AAV patients, in complete remission after induction therapy, randomly assigned to rituximab or azathioprine. Renal function decline was defined as a 25% decrease in estimated glomerular filtration rate (eGFR) and a change in the eGFR category, or a decrease of 15 mL/min/1.73 m2. Relapse was defined as a Birmingham Vasculitis Activity Score >0 attributable to active vasculitis.

Results

Seventy-six AAV were included. Serum calprotectin increased from baseline to month 6 in patients with renal function decline (7940 (−226.0, 28 691) ng/ml vs −4800 (−18 777, 3708) ng/ml; p<0.001). An increase of calprotectin level was associated with a higher risk of subsequent renal function decline even after adjustment (OR 6.50 (95% CI 1.7 to 24.9) p=0.006). A significantly higher risk of relapse was observed in proteinase 3- AAV patients with an increase of serum calprotectin levels (OR 5.6 (95% CI 1.0 to 31.2), p=0.03).

Conclusion

An increase in serum calprotectin by month 6 compared with inclusion during remission-maintenance therapy in AAV was associated with a higher risk of renal function decline in the following 12 months.

Trial registration number

NCT00748644.
MSD applied to the construction of the British Library basement: a multi-stage excavation in London Clay
Authors: Crispin Jamie J. , Bateman Abigail H. , Voyagaki Elia , Campbell Alexandra , Mylonakis George , Bolton Malcolm D. , Vardanega Paul J.
Published: October 2023

This note presents the application of the mobilisable strength design (MSD) method to the monitoring results of the multi-propped excavation in the south area of the British Library Euston, constructed in a highly overconsolidated stiff clay deposit. The MSD method is an energy-based approach (a nonlinear finite-element method for a single-degree-of-freedom soil-wall system) introduced to develop a simplified design methodology that satisfies both ultimate and serviceability limit states. Wall displacement predictions based on the MSD method are compared with considerable field monitoring data. The sensitivity of the method to reasonable variations in input parameters is considered. A spreadsheet and python code demonstrating the MSD analysis from this paper are provided in the online supplement alongside details of the mathematical formulation.
Contrasting strengths of eDNA and electrofishing compared to historic records for assessing fish community diversity and composition
Authors: Brantschen Jeanine , Altermatt Florian
Published: October 2023

In times of rapid environmental changes, baseline biodiversity data are crucial for management. In freshwaters, fish inventories are commonly based on the capture and morphological identification of specimens. The sampling of environmental DNA (eDNA) provides an alternative to assess diversity across large catchments. Here, we used extensive historic data of fish communities collected across 89 river sites in all major catchments of Switzerland and compared their diversity and community composition to a single campaign of eDNA and electrofishing, respectively. Locally, we found that eDNA provided diversity estimates similar to the integrated historic richness, while the electrofishing campaign captured a significantly lower local richness. Fish species locally recorded by electrofishing were nested (Jaccard's dissimilarity index) within the respective eDNA community for most sites. Finally, eDNA sequence reads positively correlated with the overall electrofishing biomass. Despite the congruences, the eDNA data did not correlate well with the electrofishing water quality index. Overall, eDNA was more accurately assessing overall diversity than a simultaneous electrofishing campaign, but yet cannot be directly used to calculate fish-based water quality indices.
Direct cellular reprogramming techniques for cardiovascular regenerative therapeutics
Authors: He Xingyu , Dutta Suchandrima , Liang Jialiang , Paul Christian , Huang Wei , Xu Meifeng , Chang Vivian , Ao Ian , Wang Yigang
Published: October 2023

Cardiovascular diseases remain a leading cause of hospitalization affecting approximately 38 million people worldwide. While pharmacological and revascularization techniques can improve the patient’s survival and quality of life, they cannot help reversing myocardial infarction injury and heart failure. Direct reprogramming of somatic cells to cardiomyocyte and cardiac progenitor cells offers a new approach to cellular reprogramming and paves the way for translational regenerative medicine. Direct reprogramming can bypass the pluripotent stage with the potential advantage of non-immunogenic cell products, reduced carcinogenic risk, and no requirement for embryonic tissue. The process of directly reprogramming cardiac cells was first achieved through the overexpression of transcription factors such as GATA4, MEF2C, and TBX5. However, over the past decade, significant work has been focused on enhancing direct reprogramming using a mixture of transcription factors, microRNAs, and small molecules to achieve cardiac cell fate. This review discusses the evolution of direct reprogramming, recent progress in achieving efficient cardiac cell fate conversion, and describes the reprogramming mechanisms at a molecular level. We also explore various viral and non-viral delivery methods currently being used to aid in the delivery of reprogramming factors to improve efficiency. However, further studies will be needed to overcome molecular and epigenetic barriers to successfully achieve translational cardiac regenerative therapeutics.
Cosmological solutions of chameleon scalar field model
Authors: Zaregonbadi Raziyeh , Saba Nasim , Farhoudi Mehrdad
Published: October 2023

We investigate cosmological solutions of the chameleon model with a non-minimal coupling between the matter and the scalar field through a conformal factor with gravitational strength. By considering the spatially flat FLRW metric and the matter density as a non-relativistic perfect fluid, we focus on the matter-dominated phase and the late-time accelerated-phase of the universe. In this regard, we manipulate and scrutinize the related field equations for the density parameters of the matter and the scalar fields with respect to the e-folding. Since the scalar field fluctuations depend on the background and the field equations become highly non-linear, we probe and derive the governing equations in the context of various cases of the relation between the kinetic and potential energies of the chameleon scalar field, or indeed, for some specific cases of the scalar field equation of state parameter. Thereupon, we schematically plot those density parameters for two different values of the chameleon non-minimal coupling parameter, and discuss the results. In the both considered phases, we specify that, when the kinetic energy of the chameleon scalar field is much less than its potential energy (i.e., when the scalar field equation of state parameter is $$\simeq - 1 $$

≃
-
1

), the behavior of the chameleon model is similar to the $$\Lambda CDM$$

Λ
C
D
M

model. Such compatibility suggests that the chameleon model is phenomenologically viable and can be tested with the observational data.
Generalized teleparallel de Sitter geometries
Authors: Coley A. A. , Landry A. , van den Hoogen R. J. , McNutt D. D.
Published: October 2023

Theories of gravity based on teleparallel geometries are characterized by the torsion, which is a function of the coframe, derivatives of the coframe, and a zero curvature and metric compatible spin-connection. The appropriate notion of a symmetry in a teleparallel geometry is that of an affine symmetry. Due to the importance of the de Sitter geometry and Einstein spaces within General Relativity, we shall describe teleparallel de Sitter geometries and discuss their possible generalizations. In particular, we shall analyse a class of Einstein teleparallel geometries which have a 4-dimensional Lie algebra of affine symmetries, and display two one-parameter families of explicit exact solutions.
Total 2-Rainbow Domination in Graphs: Complexity and Algorithms
Authors: Kumar Manjay , Reddy P. Venkata Subba
Published: October 2023

For a simple, undirected graph [Formula: see text] without isolated vertices, a function [Formula: see text] which satisfies the following two conditions is called a total 2-rainbow dominating function (T2RDF) of [Formula: see text].

(i) For all [Formula: see text], if [Formula: see text] then [Formula: see text] and (ii) Every [Formula: see text] with [Formula: see text] is adjacent to a vertex [Formula: see text] with [Formula: see text].

The weight of a T2RDF [Formula: see text] of [Formula: see text] is the value [Formula: see text]. The total 2-rainbow domination number is the minimum weight of a T2RDF on [Formula: see text] and is denoted by [Formula: see text]. The minimum total 2-rainbow domination problem (MT2RDP) is to find a T2RDF of minimum weight in the input graph. In this article, we show that the problem of deciding if [Formula: see text] has a T2RDF of weight at most [Formula: see text] for star convex bipartite graphs, comb convex bipartite graphs, split graphs and planar graphs is NP-complete. On the positive side, we show that MT2RDP is linear time solvable for threshold graphs, chain graphs and bounded tree-width graphs. On the approximation point of view, we show that MT2RDP cannot be approximated within [Formula: see text] for any [Formula: see text] unless [Formula: see text] and also propose [Formula: see text]-approximation algorithm for it. Further, we show that MT2RDP is APX-complete for graphs with maximum degree 4. Next, it is shown that domination problem and the total 2-rainbow domination problems are not equivalent in computational complexity aspects. Finally, an integer linear programming formulation for MT2RDP is presented.
Institutional Logics Among Returnee Entrepreneurs: A Study of the Vietnamese Information Technology Industry
Authors: Nguyen Hieu Thanh , Bui Van Cam , Nguyen Hung Vu , Le Hoa Phan , Vo Hanh Hong Thi
Published: October 2023

Returnee entrepreneurs are unique actors spanning between different environments. When coming back to their home countries to start new ventures, they inevitably face challenges in reconciling different logics from their home and host countries. The interplay of these different logics creates institutional complexity. This paper examines the interplay of multiple logics induced from home and host countries and the entrepreneurs’ responses to this situation. Multiple in-depth interviews with returnee entrepreneurs in the information technology industry in Vietnam have revealed that the entrepreneurs configure market and innovation logics among three sets of practices, including product/market, internal capacity, and reactions to institutional constraints. Four strategic responses to institutional complexity, namely non-learner, adaptor, camouflager, and innovator were also identified. Furthermore, this study finds the entrepreneurs’ strategic responses and their active influence on local institutions upon their return. Relevant implications and recommendations are also discussed.
Mazon Creek fossils brought to you by coal, concretions and collectors
Authors: Burke Patricia J. Coorough , Mayer Paul S. , McCoy Victoria E.
Published: October 2023

The late Carboniferous (Middle Pennsylvanian, ∼307 Ma ago) Mazon Creek Lagerstätte found in northern Illinois, USA, is unique for its exceptional biotic diversity as well as the human endeavours, both professional and avocational, that brought vast numbers of fossils and new species to science. In 1997, the Mazon Creek Fossil Beds, exposed along the Mazon River near Benson Road, Morris, IL, became a National Historic Landmark.

The fossils are preserved in siderite (iron carbonate, FeCO
3
) concretions within the lower 3–8 m of the Francis Creek Shale Member of the Carbondale Formation, and often retain outlines of original soft tissues. The Mazon Creek biota includes over 465 animal and 350 plant species representing more than 100 orders, which is attributed to the preservation of organisms from multiple habitats and the large number of specimens collected. That phenomenon was made possible by coal extraction bringing concretions to the surface and highly motivated amateur collectors pursuing them. Some of the formerly mined areas continue to draw collectors and are preserved as part of the Mazonia-Braidwood State Fish and Wildlife Area. The fossils, fossil collectors and collection sites are a significant part of the cultural and scientific geoheritage.
A Scalable Wear Leveling Technique for Phase Change Memory
Authors: Xu Wang , Koren Israel
Published: October 2023

Phase Change Memory (PCM), one of the recently proposed non-volatile memory technologies, has been suffering from low write endurance. For example, a single-layer PCM cell could only be written approximately 10
8
. This limits the lifetime of a PCM-based memory to a few days rather than years when memory-intensive applications are running. Wear leveling techniques have been proposed to improve the write endurance of a PCM. Among those techniques, the region-based start-gap (RBSG) scheme is widely cited as achieving the highest lifetime. Based on our experiments, RBSG can achieve 97% of the ideal lifetime, but only for relatively small memory sizes (e.g., 8–32GB). As the memory size goes up, RBSG becomes less effective and its expected percentage of the ideal lifetime reduces to less than 57% for a 2TB PCM. In this article, we propose a table-based wear leveling scheme called
block grouping
to enhance the write endurance of a PCM with a negligible overhead. Our research results show that with a proper configuration and adoption of partial writes (writing back only 64B subblocks instead of a whole row to the PCM arrays) and internal row shift (shifting the subblocks in a row periodically so no subblock in a row will be written repeatedly), the proposed block grouping scheme could achieve 95% of the ideal lifetime on average for the Rodinia, NPB, and SPEC benchmarks with less than 1.74% performance overhead and up to 0.18% hardware overhead. Moreover, our scheme is scalable and achieves the same percentage of ideal lifetime for PCM of size from 8GB to 2TB. We also show that the proposed scheme can better tolerate memory write attacks than WoLFRaM (Wear Leveling and Fault Tolerance for Resistive Memories) and RBSG for a PCM of size 32GB or higher. Finally, we integrate an error-correcting pointer technique into our proposed block grouping scheme to make the PCM fault tolerant against hard errors.
Impact of Process Parameters and Dopant Concentration on Structural, Magnetic, and Dielectric Properties of Dysprosium-doped Nickel-Zinc Ferrites Synthesized by Microwave Hydrothermal Method
Authors: Ramesh T. , Usha P. , Neelima P. , Kumar N. Pavan
Published: October 2023

This study aims to investigate the impact of substituting Dy3+ ions on the structural, magnetic and dielectric properties of Nickel Zinc (Ni-Zn) ferrites, which have the chemical formula Ni0.5Zn0.5DyxFe2-xO4 (where x = 0, 0.01, 0.03, 0.05, 0.07, and 0.09). These ferrites were synthesized using a microwave hydrothermal technique with different process parameters. Structural characterization of the synthesized powders was carried out using X-ray diffraction (XRD) and Fourier transformation infrared spectroscopy (FTIR). The XRD analysis confirmed the presence of a pure spinel phase for Dy concentrations (x) up to 0.05. However, when x ≥ 0.07, an additional orthoferrite phase (DyFeO3) was observed along with the spinel phase. FTIR spectra revealed a shift in low-frequency wave numbers due to Dy3+ ion substitution. The size and morphology of the synthesized powder particles were examined using field emission scanning electron microscopy (FESEM). The powder compacts were sintered using microwave processing at 900 °C for 40 min. The increase in dc. resistivity is observed with an increase in Dy3+ concentration, mainly due to the change in the hopping mechanism with the substitution concentration. Dielectric properties such as dielectric constant and loss are measured in the frequency range of 100 Hz to 1.8 GHz. The high value of dielectric constant and loss observed in the low-frequency region compared to the high-frequency region. Maxwell’s Wagner model and ‘Koop’s theory explains the variation in dielectric properties with the frequency. The magnetic hysteresis loops were measured at different temperatures and observed to enhance the low-temperature magnetic properties compared to room temperature. The results suggest that the magnetic and dielectric properties of the investigated samples can be adjusted by varying the concentration of Dy3+ ions, providing the ability to tailor these properties according to specific application requirements.
Atomic Layer Deposition of Cobalt Film from Dicobalt-hexacarbonyl-tert-butylacetylene and Hydrogen
Authors: Yamaguchi Jun , Sato Noboru , Tsukune Atsuhiro , Momose Takeshi , Shimogaki Yukihiro
Published: October 2023

Thermal atomic layer deposition (ALD) of Co using the highly volatile liquid precursor, dicobalt-hexacarbonyl-tert-butylacetylene (CCTBA) and H2 was examined for application to liner or cap layers in Cu interconnects. The ALD process parameters, including deposition temperature and precursor supply time, were examined, and film properties such as composition and resistivity were investigated. At a deposition temperature of 100 °C, no incubation period was observed on Cu underlayers, and the Co film growth exhibited a self-limiting behavior with a saturated growth per cycle (GPC) of 0.051 nm cycle−1. Conformal deposition was achieved on trench structures with an aspect ratio of 8.4. However, deposition at temperatures above 125 °C resulted in the thermal decomposition of CCTBA and a transition to chemical vapor deposition (CVD) mode. The as-deposited Co film contained 29% C and exhibited a high resistivity of 104
μΩ∙cm. Post-annealing at 300 °C under a hydrogen atmosphere significantly reduced the C impurities to 3%, and decreased the resistivity to 53 μΩ∙cm at a film thickness of 20 nm. Annealing at higher temperatures increased the surface roughness, leading to film agglomeration. Therefore, a two-step process of thermal ALD using CCTBA at 100 °C followed by post-annealing at 300 °C is a suitable approach for fabricating high-quality Co films.
Computational Modeling, Simulation and Tight–Binding Analysis of Electronic Characteristics of Defective Germanene Nanoribbons for Future Applications of High Sensitivity Ge-Based Nanosensors
Authors: Rahmani Komeil , Mohammadi Saeed
Published: October 2023

In this research, the electronic characteristics of germanene sheet and nanoribbons using the computational modeling, simulation and tight binding approximation are investigated. Our analysis is focused on the pristine sheet of germanene as well as defective monolayer. The obtained results show that applying the Stone–Wales defect into the germanene monolayer changes the energy band structure. The E-k curves around the Dirac point are no longer linear, in which a band gap is opened, and the Fermi velocity is reduced. Furthermore, the main parameters such as density of states, carrier concentration in degenerate and non-degenerate limits, carrier effective mass, conductance and AC conductivity of germanene are analytically modeled with the inclusion of the spin–orbit coupling effect, temperature and ribbon width. Obtained results demonstrate that the inclusion of the spin–orbit coupling makes a small splitting of the energy levels and creating a small band gap. Finally, the Tight binding and computational values are compared with our simulation results and available data, and a rational agreement is reported in terms of trend and value. The findings of this study provide theoretical reference for the design of germanene-based nanosensors and optoelectronic devices.
A biologically validated mathematical model for decoding epithelial apical, basolateral, and paracellular electrical properties
Authors: Lewallen Colby F. , Chien Athena , Maminishkis Arvydas , Hirday Rishabh , Reichert Dominik , Sharma Ruchi , Wan Qin , Bharti Kapil , Forest Craig R.
Published: October 2023

This interdisciplinary paper integrates mathematics, biology, and physiology to measure epithelial tissue’s apical, basolateral, and paracellular transport pathways. A key advancement is the inclusion of intracellular voltage recordings using a sharp pipette, enabling precise quantification of relative impedance changes between apical and basolateral membranes. This enhanced electrochemical impedance spectroscopy technique offers insights into epithelial transport dynamics, advancing disease understanding, drug interactions, and cell therapies. Its broad applicability contributes significantly to epithelial physiology research.
The study of intercalated cells using ex vivo techniques: primary cell culture, cell lines, kidney slices, and organoids
Authors: Kang Min Ju , Ioannou Silvia , Lougheide Quinn , Dittmar Michael , Hsu Young , Pastor-Soler Nuria M.
Published: October 2023

The study of kidney intercalated cells has been limited by current cell culture and kidney tissue isolation techniques. This review is to be used as a reference to select ex vivo techniques to study intercalated cells. We focused on the use of cell lines and kidney slices as potential useful models to study membrane transport proteins. We also review how novel collecting duct organoids may help better elucidate the role of these intriguing cells.
Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins
Authors: Wilson Jessica N. , Mendez Dora A. , Dhoro Francis , Shevchenko Nikolay , Mascal Mark , Lund Kyle , Fitzgerald Robert , DiPatrizio Nicholas V. , Ortiz Rudy M.
Published: October 2023

Cannabis product use has grown in the last two decades despite the lack of research on Cannabidiol (CBD)-mediated effects on metabolism. Here, we provide seminal data on CBD effects during age-associated metabolic dysfunction. We gave 41-wk-old OLETF rats 200 mg H4CBD/kg by mouth for 4 wk and noted a high dose of H4CBD may improve glucose response, independent of static changes in insulin signaling, and these effects are likely a benefit of loss of visceral adiposity.
In vivo cytosolic H2O2 changes and Ca2+ homeostasis in mouse skeletal muscle
Authors: Kano Ryotaro , Tabuchi Ayaka , Tanaka Yoshinori , Shirakawa Hideki , Hoshino Daisuke , Poole David C. , Kano Yutaka
Published: October 2023

We developed an in vivo mouse myocyte H2O2 imaging model during exogenous H2O2 loading, ischemic hypoxia induced by cardiac arrest, and muscle contractions. In this study, the interrelationship between cytosolic H2O2 levels and Ca2+ homeostasis during muscle contraction and hypoxic conditions was revealed. These results contribute to the elucidation of the mechanisms of muscle fatigue and exercise adaptation.
Development and Validation of Gene-Based SSR Markers in the Genus Mesembryanthemum
Authors: Akash Muhanad , Shiyab Safwan , Saleh Mohammed , Hasan Shireen M. , AbuHussein Mahmoud , Al-Awaida Wajdy
Published: October 2023

Bioinformatics tools have been employed for the direct development of gene-based simple sequence repeat (SSR) markers. Through the analysis of 28,056 Mesembryanthemum expressed sequence tag (EST) sequences, a total of 5,851 ESTs containing SSRs were identified, amounting to approximately 17.07 Mb. Among these, 938 EST sequences harbored more than one SSR marker, and 788 EST-SSR sequences were found in compound form. The most prevalent types of SSR motifs were mononucleotide repeats (MNRs), accounting for 44%, followed by di-nucleotide repeats (DNRs) at 37%, and trinucleotide repeats (TNRs) at 16%. Notably, TNR or longer SSR motifs primarily consisted of shorter repeat lengths, with only 51 motifs containing 10 or more repeats. The BLASTX analysis successfully assigned functions to 4,623 (79%) of the EST sequences. Among the developed primer sets, 21 primers amplified a total of 65 alleles, with primer PMA79 EST-SSR exhibiting the maximum of six alleles. The polymorphic information content (PIC) values ranged from 0 to 0.76, with a mean of 0.47. The marker index (MI) and discriminating power (D) values reached 0.66 (primer PMA63) and 0.95 (primer PMA20), respectively. Utilizing the unweighted pair group method with arithmetic mean (UPGMA), a dendrogram was constructed, successfully segregating the 24 Mesembryanthemum genotypes into three distinct clusters, with a similarity coefficient ranging from 0.96 to 0.38. In this study, we have developed a total of 83 EST-SSR primer pairs specific to the Mesembryanthemum genus. These newly developed EST-SSRs will serve as valuable tools for researchers, particularly molecular breeders, enabling gene-based identification and trait selection through marker-assisted breeding approaches.
Evaluating In Vitro Performance of a Novel Stainless Steel Rotary System (Gentlefile) Based on Debris Extrusion and Instrumentation Time
Authors: Nouroloyouni Ahmad , Safavi Hir Fatemeh , Farhang Robab , Noorolouny Sara , Salem Milani Amin , Alyali Rashin
Published: October 2023

The new Gentlefile (GF) system, made of stainless steel and developed by MedicNRG in Kibbutz Afikim, Israel, claims to have advantages over traditional nickel‐titanium files. However, research has shown that nickel‐titanium files are mechanically superior due to their increased flexibility, cutting efficiency, and ability to maintain canal anatomy with less risk of procedural errors. This study compared the amount of debris extrusion and the time required for root canal instrumentation using GF versus the nickel‐titanium ProTaper Universal (PTU) system and a manual step‐back (MSB) stainless steel technique. This in vitro experimental study utilized 66 extracted human single‐canal mandibular premolars with mature apices and root curvature of less than 10 degrees. The teeth were randomly divided into three groups (n = 22) and standardized for working length before being placed in preweighed vials. Group 1 was instrumented with PTU, Group 2 with GF, and Group 3 with the MSB technique. Extruded debris was collected in the vials, dried in an incubator, and weighed using the same scale. The change in weight indicates the debris amount. Instrumentation time was recorded using a stopwatch. The normal distribution of data was assessed using the Kolmogorov‐Smirnov test. The groups were then compared regarding the amount of extruded debris and instrumentation time using the Kruskal‐Wallis test and one‐way ANOVA, followed by the Games‐Howell test, respectively (alpha = 0.05). No significant difference in apical debris extrusion was found among the three groups (P > 0.05). However, a significant difference in instrumentation time was detected between the groups (P < 0.05). MSB instrumentation took significantly longer than both the PTU (P = 0.001) and GF (P = 0.001) systems. The GF system did not demonstrate reduced apical debris extrusion or faster instrumentation time compared to PTU. MSB had the longest instrumentation time compared to the other techniques.
Meta-Analysis of Assessment of Total Oxidative Stress and Total Antioxidant Capacity in Patients with Periodontitis
Authors: Mohideen Khadijah , Chandrasekaran Krithika , Veeraraghavan Harsha , Faizee Shahul Hameed , Dhungel Safal , Ghosh Snehashish
Published: October 2023

Background. Periodontitis is intricately linked to oxidative stress-antioxidant (redox) imbalance. The antioxidant system scavenges the oxygen free radicals in biological fluids in patients with periodontitis. However, little is still known about the free radicals mediated oxidative stress and reductive ability of the antioxidant system. Thus, the present meta-analysis aims to quantitatively review the literature that assessed the oxidative stress marker total oxidative stress (TOS) and total antioxidant capacity (TAC) in various biological fluids of patients with periodontitis. Methodology. Electronic databases were searched for studies that assessed TOS and TAC levels in various biological samples of patients with periodontitis. Results. From the 1,812 articles identified, 1,754 were excluded based on title and abstract screening due to irrelevance to the topic of interest. A full-text assessment of the remaining 58 articles led to the selection of 42 articles that satisfied the inclusion criteria. Of these, only 24 studies had consistent data for quantitative analysis. The periodontitis group displayed significantly elevated TOS levels (p<0.05) in serum, gingival crevicular fluid (GCF), and saliva samples in the studies evaluated. In contrast, the periodontitis group exhibited significantly attenuated TAC levels (p<0.01) compared to healthy controls in plasma, serum, and GCF samples of the studies evaluated, which was insignificant in salivary samples (p=0.433). At the same time, the periodontitis group displayed insignificantly elevated TAC levels after periodontal therapy (p=0.130). Conclusions. The present meta-analysis showed significantly higher TOS and lower TAC in periodontitis, reflecting the elevated oxidative stress level than the control group. Clinical Relevance. Scientific rationale for the study: The imbalance between oxidants and antioxidants (oxidative stress (OS)) plays a critical role in the onset and progression of periodontitis; the assessment of the relationship between OS-related biomarkers in regional samples and systemic samples of patients with periodontitis helps us to evaluate the periodontal disease progression. The OS biomarker levels can be used to assess periodontal disease and therapeutic efficacy.
Novel Approach to Accelerate Lung Cancer Research: Lung-MAP and the Potential of Public-Private Partnerships
Authors: Herbst Roy S. , Blanke Charles D. , Sigal Ellen V.
Published: October 2023

The National Cancer Institute recently found that death rates for non–small cell lung cancer (NSCLC) have been reduced by over 6% overall in recent years. This reduction in mortality has been accompanied by an average increase in overall survival and largely credited to the therapeutic advancements for the effective treatment of NSCLC. Numerous molecular alterations have been identified in NSCLC that have enabled the development of new drugs capable of targeting these changes and efficiently kill cancerous cells. New treatments to modulate patients' immune systems have been shown to be effective in stimulating natural immune cells to have an improved anti-cancer effect. While these types of approaches to treat cancer are providing new options for patients, leadership from the Food and Drug Administration (FDA) recognized that the expansion of targeted therapy in NSCLC presented significant promise, but evaluation of the safety and efficacy of these new drugs would be slowed if new models for conducting clinical studies were not identified. Specifically, the FDA recommended that a comprehensive approach be implemented to identify the patients that are the best candidates for these, and other new treatments based upon the molecular characteristics of their tumors, and more efficiently conduct the clinical studies necessary to evaluate the safety and efficacy of new drugs. To address this growing challenge, leading lung cancer experts and stakeholders across academia, government, industry, and patient advocacy came together to design a clinical research approach that could serve as a sustainable infrastructure for new lung cancer treatments called the Lung Cancer Master Protocol.
Adoptive T Cell Therapy in Solid Tumors: State-of-the Art, Current Challenges, and Upcoming Improvements
Authors: Dougé Aurore , El Ghazzi Nathan , Lemal Richard , Rouzaire Paul
Published: October 2023

In solid tumors, three main complementary approaches of adoptive T-cell therapies were successively developed: tumor-infiltrating lymphocytes, chimeric antigen receptor engineered T cells, and high-affinity T-cell receptor engineered T cells. In this review, we summarized rational and main results of these three adoptive T-cell therapies in solid tumors field and gave an overview of encouraging data and their limits. Then, we listed the major remaining challenges (including tumor antigen loss, on-target/off-tumor effect, tumor access difficulties and general/local immunosubversion) and their lines of research. Finally, we gave insight into the ongoing trials in solid tumor.
Supplementary Table S3 from Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid
Authors: Frank Anderson R. , Li Vicky , Shelton Spencer D. , Kim Jiwoong , Stott Gordon M. , Neckers Leonard M. , Xie Yang , Williams Noelle S. , Mishra Prashant , McFadden David G.
Published: October 2023

Supplementary Table S3 shows the results of our genome-wide and targeted CRISPR-Cas9 screens.
T cell–Dependent Bispecific Therapy Enhances Innate Immune Activation and Antibody-Mediated Killing
Authors: Besla Rickvinder , Penuel Elicia , Del Rosario Geoff , Cosino Ely , Myrta Szymon , Dillon Mike , Lazar Greg A. , Nickles Dorothee , Spiess Christoph , Yu Shang-Fan , Polson Andrew G.
Published: October 2023

T cell–retargeting therapies have transformed the therapeutic landscape for hematologic diseases. T cell–dependent bispecific antibodies (TDB) function as conditional agonists that induce a polyclonal T-cell response, resulting in target cell destruction and cytokine release. The relationship between this response and its effects on surrounding innate immune populations has not been fully explored. Here we show that treatment with mosunetuzumab in patients results in natural killer (NK) cell activation in the peripheral blood. We modeled this phenomenon in vitro and found that TDB-mediated killing activated NK cells, increasing NK function and antibody-dependent cellular cytotoxicity (ADCC), and enhanced the capability of macrophages to perform antibody-dependent cellular phagocytosis (ADCP). This enhancement was triggered by cytokines released through TDB treatment, with IL2 and IFNγ being major drivers for increased ADCC and ADCP, respectively. Surprisingly, cytolytic ability could be further augmented through neutralization of IL10 for NK cells and TNFα for macrophages. Finally, we showed that TDB treatment enhanced the efficacy of Fc-driven killing to an orthogonal solid tumor target in vivo. These results provide rationale for novel antibody therapy combinations that take advantage of both adaptive and innate immune responses.
The Yin Yang of Complement and Cancer
Authors: Meri Seppo , Magrini Elena , Mantovani Alberto , Garlanda Cecilia
Published: October 2023

Cancer-related inflammation is a crucial component of the tumor microenvironment (TME). Complement activation occurs in cancer and supports the development of an inflammatory microenvironment. Complement has traditionally been considered a mechanism of immune resistance against cancer, and its activation is known to contribute to the cytolytic effects of antibody-based immunotherapeutic treatments. However, several studies have recently revealed that complement activation may exert protumoral functions by sustaining cancer-related inflammation and immunosuppression through different molecular mechanisms, targeting both the TME and cancer cells. These new discoveries have revealed that complement manipulation can be considered a new strategy for cancer therapies. Here we summarize our current understanding of the mechanisms by which the different elements of the complement system exert antitumor or protumor functions, both in preclinical studies and in human tumorigenesis. Complement components can serve as disease biomarkers for cancer stratification and prognosis and be exploited for tumor treatment.