bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of MXene and SWCNTs Effectiveness for Osteoblast Differentiation: A Preliminary Study with MG-63 Cells
Authors: Elkodous Mohamed Abd , Elkhenany Hoda , Mansell Jason Peter
Published: April 2024

The exceptional chemical and physical properties of nanomaterials have attracted growing interest in the field of bone tissue engineering. Single walled carbon nanotubes (SWCNTs) and MXenes are two types of unique nanomaterials that have shown promising potential for tissue engineering applications. In this study, we aimed to compare the differentiation capacity of MG-63 cells in the presence of carbon nanotubes (CNTs) and MXene nanomaterials. Methods: The cytotoxic effect of MXene and SWCNTs based nanocomposites was evaluated using the MTS assay. Also, the differentiation potential was evaluated using two models of stimulation. The first model was a co-stimulation of MG-63’s with EB1089 and an analogue of lysophosphatidic acid (LPA), (3S)-1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP). The second model utilized [Formula: see text]-glycerophosphate ([Formula: see text]GP) and ascorbic acid (ASC). Results: MXene and SWCNTs showed no cytotoxic effect after 48[Formula: see text]h of culture. MXene could enhance the maturation of MG-63 in both models of differentiation compared to controls and SWCNTs. Conclusion: The incorporation of MXene into MG-63 cell culture suggests that it has a promising potential as a biomaterial for bone regeneration as it demonstrated improved osteoblast maturation compared to SWCNTs.
Misused Words and Phrases
Authors: Yaffe Philip
Published: April 2024

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.

Using commonly recognized colorful words, phrases, and quotations can enhance the interest and impact of an expository (non-fiction) text. However, pay close attention when doing so, because those words, phrases, and quotations don't always mean what you might think they mean.
Development of the Binocular Circuit
Authors: Herrera Eloísa , Chédotal Alain , Mason Carol
Published: April 2024

Seeing in three dimensions is a major property of the visual system in mammals. The circuit underlying this property begins in the retina, from which retinal ganglion cells (RGCs) extend to the same or opposite side of the brain. RGC axons decussate to form the optic chiasm, then grow to targets in the thalamus and midbrain, where they synapse with neurons that project to the visual cortex. Here we review the cellular and molecular mechanisms of RGC axonal growth cone guidance across or away from the midline via receptors to cues in the midline environment. We present new views on the specification of ipsi- and contralateral RGC subpopulations and factors implementing their organization in the optic tract and termination in subregions of their targets. Lastly, we describe the functional and behavioral aspects of binocular vision, focusing on the mouse, and discuss recent discoveries in the evolution of the binocular circuit.
Theories of Democratic Backsliding
Authors: Grillo Edoardo , Luo Zhaotian , Nalepa Monika , Prato Carlo
Published: April 2024

We review recent contributions to the modeling of democratic backsliding. We organize these theories according to (a) the source of constraints on the executive (vertical or horizontal restrainers) and (b) the target of backsliding (electoral manipulation or executive aggrandizement), and then use these concepts to build a scaffold for a meta-model of democratic backsliding. This meta-model allows us to describe and compare the premises and insights of this scholarship. We further apply our two-dimensional classification to more than 30 empirical papers and show how these theories can guide research design. We conclude by highlighting open issues for future research.
Leveraging Experience Sampling/Ecological Momentary Assessment for Sociological Investigations of Everyday Life
Authors: Browning Christopher R. , Pinchak Nicolo P. , Calder Catherine A. , Boettner Bethany
Published: April 2024

Experience sampling (ES)—also referred to as ecological momentary assessment (EMA)—is a data collection method that involves asking study participants to report on their thoughts, feelings, behaviors, activities, and environments in (or near) real time. ES/EMA is typically administered using an intensive longitudinal design (repeated assessments within and across days). Although use of ES/EMA is widespread in psychology and health sciences, uptake of the method among sociologists has been limited. We argue that ES/EMA offers key advantages for the investigation of sociologically relevant phenomena, particularly in light of recent disciplinary emphasis on investigating the everyday mechanisms through which social structures and micro (individual and relational) processes are mutually constitutive. We describe extant and potential research applications illustrating the advantages of ES/EMA regarding enhanced validity, illuminating micro-temporal processes, and the potential for linkage with spatially and temporally referenced data sources. We also consider methodological challenges facing sociological research using ES/EMA.
The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID
Authors: Kane Abigail S. , Godfrey Madeleine , Noval Rivas Magali , Arditi Moshe , Fasano Alessio , Yonker Lael M.
Published: April 2024

The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.
The Emergence and Evolution of SARS-CoV-2
Authors: Holmes Edward C.
Published: April 2024

The origin of SARS-CoV-2 has evoked heated debate and strong accusations, yet seemingly little resolution. I review the scientific evidence on the origin of SARS-CoV-2 and its subsequent spread through the human population. The available data clearly point to a natural zoonotic emergence within, or closely linked to, the Huanan Seafood Wholesale Market in Wuhan. There is no direct evidence linking the emergence of SARS-CoV-2 to laboratory work conducted at the Wuhan Institute of Virology. The subsequent global spread of SARS-CoV-2 was characterized by a gradual adaptation to humans, with dual increases in transmissibility and virulence until the emergence of the Omicron variant. Of note has been the frequent transmission of SARS-CoV-2 from humans to other animals, marking it as a strongly host generalist virus. Unless lessons from the origin of SARS-CoV-2 are learned, it is inevitable that more zoonotic events leading to more epidemics and pandemics will plague human populations.
A Robust Model Order Reduction Scheme for Lithium-Ion Batteries in Control-Oriented Vehicle Models
Authors: Masoudi Ramin , Taghavipour Amir , Azad Nasser L. , McPhee John
Published: April 2024

The role of batteries in electrification of vehicles is eminent; thus, a dynamic model that represents the physics-based phenomena of the battery system at a minimum computational cost is essential in the model-based design of electrified vehicle control systems. Furthermore, robustness of the reduced-order battery model when maintaining the dominant physics-based phenomena governing the dynamic behavior of the battery system is crucial. Characterization of the power signal applied to the lithium-ion battery in the energy management controller of a plug-in hybrid electric vehicle shows that there is a dominant frequency range in the input signal to the battery. This key feature can be considered as a basis to construct a reduced-order model in which the training input is different from the original power signal. The original idea in this paper is to generate the training input by applying a low-pass filter to the white-noise random signal to maintain the same dominant frequency range observed in the original power signal. Response of the reduced-order model, constructed using the proper orthogonal decomposition, compared to the high-fidelity battery model shows promising results; a maximum relative error of 1% was obtained for the battery state of charge while simulation time was reduced by 42.9%.
Biomass-Derived Integrated Hierarchical Porous Carbon Embedded with Ni@C Nanoparticles for High-Performance and Cost-Effective Microwave Absorbent Design
Authors: Bi Xinran , Dai Weipeng , Lu Xiaocheng , Zhang Zidong , Men Junhui
Published: April 2024

High-performance and cost-effective microwave absorbing materials are of vital importance in not only military but also civil fields. Here, an in situ generation-carbonization one-step method is proposed to synthesize excellent absorbents based on a common solid waste, willow catkins. The results demonstrate that the microwave absorption performance has been successfully improved owing to the magnetic particles, the core–shell nanoparticles, and the hierarchical porous structure, which results in strong conductivity loss, dielectric loss, magnetic loss, interface polarization, and multiple scattering. The maximum reflection loss (RLmax) reaches up to −50.66 dB and −49.09 dB, respectively, at 16.6 and 17.1 GHz with the thickness of 1.65 mm, resulting in double-peak absorption. What’s more, the effective absorption bandwidth (EAB, RL < −10 dB) can get up to 5.7 GHz (from 12.4 to 18 GHz) with the thickness of 1.84 mm. Great absorption performance can be obtained simply through impregnation and carbonization, which constructs a fruitful and cost-effective paradigm for resource utilization of solid waste such as willow catkins.
Impacts of Low Energy Argon Beam on Enhancing the Surface Wettability and Electrical Performance of CA/PANI Films
Authors: Altuijri Reem , Atta A. , Abdeltwab E. , Abdelhamied M. M.
Published: April 2024

This work study the impacts of argon irradiation on surface wettability of CA/PANI using home made ion source with fluences (4 × 1014, 8 × 1014, and 12 × 1014 ions cm−2). The EDX, SEM and FTIR methods verified the successful fabrication of the composites. Surface wettability, contact angle, and work of adhesion were measured for the untreated and irradiated composites. Raising the ion flux from 4 × 1014 ions.cm−2 to 12 × 1014 ions.cm−2, it decreases the contact angle of CA/PANI from 62.1° to 43.4° and increases the surface free energy from 46.7 to 63.9 mJ m−2. The results showed that the CA/PANI changed after exposed to radiation, proving that the irradiated surface properties were improved. In addition, their electrical conductivity was tested in frequency of 50 to106 Hz. When subjected to 12 × 1014 ions.cm−2, the conductivity rose from 1.1 × 10−8 S cm−1 for CA/PANI to 6.5 × 10−7 S cm−1. The results showed that the irradiated CA/PANI had better electrical and surface properties, which is crucial for many devices including batteries and supercapacitors.
Exploring Cinnamic Acids as Potent Antimetastatic Agents for Cancer Therapy: Molecular Docking and Dynamic Simulation against MMP2
Authors: Shojaei Setareh , Zandieh Mohammad-Reza , Jamshidi Shokoofeh , Taherkhani Amir , Azadian Zahra
Published: April 2024

Objective. Matrix metalloproteinase-2 (MMP2) overexpression has been considered as a hallmark of tumor aggressiveness. The significant roles of MMP2 in other human disorders, such as cardiovascular diseases and dental caries, have also been demonstrated. Herein, we used in silico approaches to evaluate the binding affinity of selected cinnamic acids to the MMP2 catalytic domain. The obtained findings were subsequently juxtaposed with those attributed to oleandrin, utilized as a reference pharmaceutical agent. Methods. This research employed the AutoDock software to assess the affinity of 19 herbal compounds derived from cinnamic acid to the catalytic cleft of MMP2. The ligands attaining the most negative scores, as determined by the Gibbs free binding energy assessments, were accorded the highest rankings. The interactions between the MMP2 and cinnamic acids ranked highest were elucidated using the Discovery Studio Visualizer tool. Molecular dynamics simulations were performed to investigate the structural stability of MMP2 backbone atoms when forming complexes with both the top-ranked inhibitor from this study and a standard drug. Results. Eight cinnamic acids were indicated with ΔGbinding values less than −10 kcal/mol. Cynarin emerged as the most potent inhibitor of the enzyme, with the ΔGbinding score and inhibition constant value of −15.19 kcal/mol and 7.29 pM, respectively. The MMP2 backbone atoms achieve stability around the 20 ns mark, displaying a root mean square deviation of approximately 3.2 Å when influenced by the top-ranked cinnamic acid, the standard drug, or in their free form. Conclusion. The inhibition of MMP2 by cinnamic acids, particularly cynarin, holds promise as a valuable therapeutic strategy for various human disorders, encompassing cancer, cardiovascular conditions, and dental caries.
Challenges in Diagnosing Dermoid Cyst in a Neurocognitive Patient
Authors: Safia Alaa , Shehadeh Rabie , Merchavy Shlomo
Published: April 2024

This case report presents a unique and challenging scenario involving the diagnosis and management of a sublingual dermoid cyst in a 12‐year‐old male with autism disorder. Dermoid cysts within the oral cavity are exceptionally rare entities, constituting less than 0.01% of all oral cavity cysts. In addition, their co‐occurrence with neurocognitive disorders further complicates the diagnostic process. The patient’s clinical presentation was marked by recurrent epistaxis and behavioral changes, which were compounded by his communication limitations due to autism disorder. A thorough physical examination revealed a sublingual mass causing tongue displacement. However, due to the patient’s inability to effectively communicate symptoms, parental input played a pivotal role in constructing the clinical narrative. Imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), provided essential insights into the cyst’s size, location, and structural characteristics. The successful integration of these modalities aided in achieving a definitive diagnosis. The subsequent intraoral surgical excision of the 6.5 cm cyst yielded a positive outcome, with an uneventful recovery and a six‐month follow‐up demonstrating no signs of recurrence. This report underscores the significance of multidisciplinary collaboration in navigating the complexities of diagnosing and managing rare oral lesions in patients with neurocognitive disorders. The confluence of two rare conditions necessitates a tailored approach that takes into account communication barriers and the patient’s overall well‐being. This case offers valuable insights to healthcare practitioners, highlighting the importance of leveraging advanced imaging technologies and adapting strategies to address the unique challenges posed by such cases. By presenting this exceptional clinical scenario, this report contributes to the medical community’s understanding of nuanced diagnostic processes and patient‐centered management techniques.
Perspectives on Work in the Continuing Care Sector during and after the COVID-19 Pandemic: A Mixed-Method Design
Authors: Guest Lindsay M. , McCabe Janet , O’Halloran Chase , Rana Maryam , Sun Winnie , Rudoler David
Published: April 2024

Background. Improving the recruitment and retention of healthcare workers in the continuing care sector is critical to ensuring adequate care for older adults, which was highlighted following the COVID-19 pandemic. Purpose. The purpose of this study was to understand the perceptions of prospective registered nurses about working in the continuing care sector and identify workplace attributes that attract prospective nurses to the sector. Methods. A sequential mixed methods study was conducted with nursing students at Ontario Tech University. Focus groups (n = 14) asked students to comment on views about working in the continuing care sector, and job attributes that may attract them to the sector. Focus group data were analyzed using thematic analysis. Subsequently, a cross-sectional survey asked students to respond to elicited choice job scenarios that varied job attributes. The job attributes were shaped by the focus group interview data. To assess respondent’s preferences, the survey data (n = 139) were analyzed to generate willingness-to-pay (WTP) values for each job attribute. Results. Focus group interviews suggested that fair compensation, optimal client-to-staff ratios, unionized work environments, comprehensive benefits packages, and flexible work arrangements were important job attributes. In survey results, 18.0% expressed interest in working in the continuing care sector compared to 75.5% in acute care. Regression analysis suggested that higher amounts of paid vacation (WTP: −5.983; 95% CI: −13.749 and −0.037) and higher risk of injury (WTP: 0.684; 95% CI: 0.124 and 1.208) were associated with work in the continuing care sector. Impact. Continuing care workplaces can attract nurses by offering flexible options such as part-time positions and paid vacation and by taking actions that can mitigate the risk of workplace injury, violence, and abuse. Nursing students should be shown the positive aspects of working with older adults and dispel negative perceptions about the continuing care sector. Further research is needed to understand the preferences for work and risk perceptions among currently employed nursing staff.
An Unconventional Solution for Persistent Lateral Hip Prosthetic Friction Syndrome (LHPFS) after Revision Total Hip Arthroplasty
Authors: Wittauer Matthias , Stoffel Karl
Published: April 2024

We report on a 77‐year‐old male patient, who presented with excessive bone loss at the area of the greater trochanter after several hip revision surgeries resulting in a persistent friction syndrome caused directly by the rough surface and sharp edges of the prosthetic shoulder of a well‐fixed Wagner‐type revision stem. Surgery was performed by creating a cemented neotrochanter with an attached polyester patch around the proximal lateral shaft and performing a Z‐plasty of the iliotibial tract. Twelve months postoperatively, the patient reported a reduction in subjective pain of 50% and improvement of the Harris Hip Score from 45 to 75 points. Without a definition in the current literature, the authors propose the term “lateral hip prosthetic friction syndrome” (LHPFS) to describe this medical condition.
Studies toward Morphological Changes of Silver/Carbon Fiber Composites and Their Optimization for High‐Performance Electrochemical Electrodes
Authors: Yeo Taehan , Kim Kyungmin , Lee Jaeho , Seo Byungseok , Park Seonghyun , Choi Wonjoon
Published: April 2024

The integration of micro/nanostructured metal/metal oxides with carbon‐based materials has emerged as a promising approach for developing electrochemical electrodes. However, the fabrication of such hybrids entails complex and multistep procedures involving the grain boundaries and interfaces between the constituent materials, thus, degrading the overall performance. Herein, we report a facile electrothermal process (ETP) for the scalable fabrication of hybrid carbon fiber (CF) sheets integrated with tunable morphology of silver micro/nanoparticles. The application of an electric field across the layered film, consisting of AgNO3 and CF, enabled the rapid dissipation of thermochemical energy in an open‐air environment via ETP. The ETP facilitated ultrafast heat dissipation within a few milliseconds, leading to the rapid decomposition of AgNO3, which resulted in the formation of liquefied Ag on the CF surface affording a reduced Ag‐CF composite with adjustable structures through input power. The capability of ETP driven by controlling duration and number of electrical pulses was demonstrated by examining the corresponding physiochemical and electrochemical characteristics of the resulting composite. The Ag‐CF composite fabricated using three cycles of a screened ETP pulse (1500 W and 75 ms for power and duration) acted as a supercapacitor electrode demonstrating excellent area capacitance (13 F/cm2) and exceptional capacitance retention (98% after 10,000 cycles). Thus, the utilization of ETP can provide manufacturing strategies enabling scalable synthesis of functional hybrids in vacuum‐free ambient environments within milliseconds. These hybrids possess unique interfaces and particle boundaries, exhibiting considerable potential for diverse electrochemical applications.
Adolescents and Young Adults with Type 1 Diabetes Present Changes in Arterial Compliance and Resistance and Increased Arterial Stiffness
Authors: Carvalho-Ribeiro Igor A. , Cunha Letícia C. F. , Ribeiro Lorena R. , Lima Matheus N. , Ferreira-Silva Breno A. , S. Rajão Juliana , Bittencourt Juliana C. , F. A. Pinheiro Juliana , Rodrigues-Machado Maria da Glória
Published: April 2024

Introduction. Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1DM) and is responsible for a significant reduction in life expectancy. Objective. To compare the arterial stiffness indices, arterial compliance and vascular resistance assessed centrally and peripherally between healthy adolescents and young adults (CTRL group) and those with T1DM. Methods. This is an observational cross-sectional study involving 90 adolescents and young adults, with half of them being considered healthy (n = 45) and the other half with T1DM (n = 45), matched by age and sex. Cardiovascular parameters were evaluated using the oscillometric method of brachial artery pressure assessment for a noninvasive estimation of central arterial pressures. Results. Weight and body mass index were significantly higher in the T1DM group. AIx@75 was significantly higher in the T1DM group (24.96% ± 8.88%) compared to the CTRL (20.16% ± 9.95%). Peripheral and central arterial compliance were significantly lower in the T1DM group (0.79 ± 0.21; 1.16 ± 0.27 ml/m2/mmHg) compared to the CTRL (0.98 ± 0.32; 1.47 ± 0.61 ml/m2/mmHg). Peripheral and central vascular resistance were significantly higher in the T1DM group (1.32 ± 0.32; 0.91 ± 0.21 mmHg/ml/m2) compared to the CTRL (1.11 ± 0.30; 0.75 ± 0.22 mmHg/ml/m2). Conclusion. Our data confirm premature aging of the vascular system in adolescents and young adults with T1DM and extend our knowledge by showing important changes in central and peripheral hemodynamics indices.
Supplementary Figure from Association between Receipt of Guideline-Concordant Lung Cancer Treatment and Individual- and Area-Level Factors: A Spatio-Temporal Analysis
Authors: Wah Win , Stirling Rob G. , Ahern Susannah , Earnest Arul
Published: April 2024

Supplementary Figure from Association between Receipt of Guideline-Concordant Lung Cancer Treatment and Individual- and Area-Level Factors: A Spatio-Temporal Analysis
Supplementary Data from Association between Receipt of Guideline-Concordant Lung Cancer Treatment and Individual- and Area-Level Factors: A Spatio-Temporal Analysis
Authors: Wah Win , Stirling Rob G. , Ahern Susannah , Earnest Arul
Published: April 2024

Supplementary Data from Association between Receipt of Guideline-Concordant Lung Cancer Treatment and Individual- and Area-Level Factors: A Spatio-Temporal Analysis
Data from Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor–Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti–HER2-Based Therapy
Authors: Pascual Tomás , Fernandez-Martinez Aranzazu , Tanioka Maki , Dieci M. Vittoria , Pernas Sonia , Gavila Joaquin , Guarneri Valentina , Cortes Javier , Villagrasa Patricia , Chic Núria , Vidal Maria , Adamo Barbara , Muñoz Montserrat , Griguolo Gaia , Llombart Antonio , Conte Pierfranco , Oliveira Mafalda , Conte Benedetta , Paré Laia , Galvan Patricia , Carey Lisa A. , Perou Charles M. , Prat Aleix
Published: April 2024

AbstractPurpose:
We do not yet have validated biomarkers to predict response and outcome within hormone receptor–positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemo-endocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor–positive/HER2-negative (HR+/HER2−) breast cancer. Here, we evaluate the relationship of CES with response and survival in HR+/HER2+ breast cancer.
Experimental Design:
Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS).
Results:
A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR = 0.42; P = 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; P = 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 (P = 0.012).
Conclusions:
In HER2+/HR+ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics.
Supplementary Table S3 from First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors
Authors: Yarchoan Mark , Powderly John D. , Bastos Bruno R. , Karasic Thomas B. , Crysler Oxana V. , Munster Pamela N. , McKean Meredith A. , Emens Leisha A. , Saenger Yvonne M. , Ged Yasser , Stagg Robert , Smith Steven , Whiting Chan C. , Moon Anne , Prasit Peppi , Jenkins Yonchu , Standifer Nathan , Dubensky Thomas W. , Whiting Sam H. , Ulahannan Susanna V.
Published: April 2024

Summary of Differentially Expressed Genes in PR Patients (p-value < 0.05 by Mann-Whitney U-test vs. PR/SD patients) on Cycle 1 Day 8
Supplementary Table S2 from First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors
Authors: Yarchoan Mark , Powderly John D. , Bastos Bruno R. , Karasic Thomas B. , Crysler Oxana V. , Munster Pamela N. , McKean Meredith A. , Emens Leisha A. , Saenger Yvonne M. , Ged Yasser , Stagg Robert , Smith Steven , Whiting Chan C. , Moon Anne , Prasit Peppi , Jenkins Yonchu , Standifer Nathan , Dubensky Thomas W. , Whiting Sam H. , Ulahannan Susanna V.
Published: April 2024

Summary of pharmacokinetics of 600 mg TPST-1120 twice daily as a single agent and in combination with nivolumab after single dose or at steady state (cycle 1 day 8)
FIGURE 3 from First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors
Authors: Yarchoan Mark , Powderly John D. , Bastos Bruno R. , Karasic Thomas B. , Crysler Oxana V. , Munster Pamela N. , McKean Meredith A. , Emens Leisha A. , Saenger Yvonne M. , Ged Yasser , Stagg Robert , Smith Steven , Whiting Chan C. , Moon Anne , Prasit Peppi , Jenkins Yonchu , Standifer Nathan , Dubensky Thomas W. , Whiting Sam H. , Ulahannan Susanna V.
Published: April 2024

Genes differentially expressed on treatment day 8 versus treatment baseline, as a function of TPST-1120 exposure. A, Linear associations of day 8 log2 fold change in expression levels of indicated genes and TPST-1120 AUC0–24. All genes exhibited FDR P < 0.05 and effect size > 0.5. Data are shown for both TPST-1120 monotherapy (part 1) and TPST-1120 + nivolumab combination therapy (part 2). An AUC0–24 value of 66,180 ng⋅hour/mL was excluded as an outlier. B, Comparison of differential gene expression on day 8 as a function of AUC0–24 tertile. Median elevation magnitudes in highest tertile were statistically increased above baseline values (*, P < 0.05 by Wilcoxon pair-wise comparison).
FIGURE 1 from First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors
Authors: Yarchoan Mark , Powderly John D. , Bastos Bruno R. , Karasic Thomas B. , Crysler Oxana V. , Munster Pamela N. , McKean Meredith A. , Emens Leisha A. , Saenger Yvonne M. , Ged Yasser , Stagg Robert , Smith Steven , Whiting Chan C. , Moon Anne , Prasit Peppi , Jenkins Yonchu , Standifer Nathan , Dubensky Thomas W. , Whiting Sam H. , Ulahannan Susanna V.
Published: April 2024

Clinical efficacy of TPST-1120 monotherapy (A, B) and in combination with nivolumab (C, D). In swimmer plots shown in A and C, study treatment discontinuations for other than disease progression are shown as *Adverse event, ^Symptomatic deterioration, #Investigator decision, or §Consent withdrawn. For monotherapy, scans were every 6 weeks until week 12, followed by an increase to 9-week intervals between scans. For combination therapy, scans occurred every 8 weeks. The RCC responder in the 600 mg BID + nivolumab dose group had an unscheduled scan at day 24 during hospitalization for treatment-unrelated AEs. This patient discontinued treatment one day prior to the scan but was unable to restart and had disease progression during the posttreatment follow-up period. BID, twice daily; CCA, cholangiocarcinoma; CRC, colorectal carcinoma; HCC, hepatocellular carcinoma; mCRPC, metastatic castration-resistant prostate cancer; NSCLC, non–small cell lung cancer; Panc, pancreatic cancer; PD, progressive disease; PR, partial response; RCC, renal cell carcinoma; SD, stable disease.
Association between the Combination of Speed-Eating and Eating until Full and Overweight/Obesity in Part-Time High School Students
Authors: Kojima Akane , Kameyama Yoshiko , Kajiura Akane , Murayama Yuuki , Kato Masahiko
Published: April 2024

Introduction: This cross-sectional study aimed to examine the association between overweight/obesity and the combined behavior of speed-eating and eating until full among part-time high school students. Methods: In 2015, 2,507 male and female part-time high school students from Hyogo Prefecture, Japan, who completed a self-reported questionnaire on lifestyle, were included in the analysis. Overweight/obesity was defined as a body mass index of 25 kg/m2 or more. Responses regarding speed-eating and eating until full were obtained by self-reporting. Logistic regression analysis was used to estimate the odds ratio (OR) for overweight/obesity. Results: Among the participants, 340 (13.6%) were overweight/obese and 468 (18.7%) reported both speed-eating and eating until full. Compared to neither speed-eating nor eating until full group, after adjustment for sex, age, work pattern, physical activity level, sleep duration, frequency of picky eating, frequency of snack intake, fast food intake frequency, frequency of adding salty condiments, frequency of eating less food to save money, and survey schools, the OR (95% CI) for overweight/obesity in speed-eating and not eating until full, eating until full and not speed-eating, and speed-eating and eating until full was 2.11 (1.38–3.22), 1.54 (1.12–2.10), and 2.94 (2.08–4.16), respectively. Conclusions: The combination of speed-eating and eating until full was associated with overweight/obesity among part-time high school students independent of other lifestyle factors.
Malnutrition Screening with Nutritional Risk Screening 2002 prior to Assessment as Part of GLIM Criteria in Patients Undergoing Major Abdominal Surgery for Gastrointestinal Cancer
Authors: Wobith Maria , Lurz Markus , Weimann Arved
Published: April 2024

Introduction: For diagnosing malnutrition as an important modifiable risk factor in surgical cancer patients, GLIM criteria offer a standardised diagnostic pathway. Before assessing malnutrition, it is suggested to screen for malnutrition with an implemented screening tool, i.e., the NRS-2002. Validated data regarding the applied screening tool and its relevance for predicting outcome parameters in surgical patients is sparse. Methods: 260 patients undergoing major abdominal surgery for cancer were retrospectively analysed. Between January 2017 and December 2019, patients were prospectively screened for malnutrition with the Nutritional Risk Score 2002 (NRS). Irrespective of their screening result malnutrition was assessed with GLIM criteria using CT scan at lumbar level 3 for measuring skeletal muscle mass (GLIM MMCT). Patients with negative screening results (NRS ≤2) were analysed regarding their malnutrition assessment and outcome parameters. Results: Thirty four of 67 patients with NRS ≤2, posing no risk for malnutrition, were diagnosed malnourished according to GLIM MMCT (n = 34, 50.7%). 19 patients (55.9%) with NRS ≤2 and malnutrition according to GLIM had at least one complication, 12 patients (35.3%) had a severe complication (Clavien-Dindo grade ≥ 3a), in 26.5% re-laparotomy was necessary, readmission within 1 month in 20.6% of patients, and length of hospital stay was 18.76 ± 12.66, which was in total worse in outcome compared to the whole study group (n = 260). Patients with NRS ≤2 but diagnosed malnourished by GLIM were at significant higher risk to develop a severe complication (OR 2.256, 95% CI: 1.038–4.9095, p = 0.036) compared to patients with NRS ≤2 but not being diagnosed malnourished. The risk for overall complications was significantly increased in patients with malnutrition diagnosed by the GLIM criteria using MMCT (OR 2.028, 95% CI: 1.188–3.463, p = 0.009). Patients screened at risk with NRS ≥3 and diagnosed malnourished by GLIM were also at significant higher risk for developing complications (OR 1.728, 95% CI: 1.054–2.832, p = 0.029). Conclusion: GLIM MMCT is suitable for diagnosing malnutrition and estimating postoperative risk in gastrointestinal cancer patients. Nutritional assessment only in patients with NRS >2 may bear the risk to miss malnourished patients with high risk for poor clinical outcome. In every patient undergoing major cancer surgery, regular assessment of nutritional status regardless of screening result should be performed exploiting CT body composition analysis.
Exploring Remission Dynamics and Prognostic Factors in Lichen Planopilaris: A Retrospective Cohort Study
Authors: Lyakhovitsky A. , Zilbermintz T. , Segal Z. , Galili E. , Shemer A. , Jaworowski B. , Baum S. , Hermush V. , Kaplan B. , Barzilai A.
Published: April 2024

Introduction: Lichen planopilaris (LPP) is a common type of primary cicatricial alopecia. Previous studies focused on the epidemiology, clinical characteristics, and treatment of LPP. A lack of knowledge regarding LPP outcomes and prognostic factors remained. Methods: To delineate the rate and timing of remission in LPP, as well as the prognostic factors for achieving remission, a retrospective cohort study was conducted. The study included 126 patients, from a single tertiary center, diagnosed with LPP between January 2010 and December 2022, who were followed up for a minimum of 6 months. Results: There were 89 (70.6%) women and 37 (29.4%) men included in this study. The mean age of the patients was 47.92 ± 14.2 years. The mean time from disease onset to diagnosis was 33.85 (±30) months, indicating significant diagnostic delays. The mean duration of follow-up was 34.13 ± 22.7 months. Among the cohort, 43 patients achieved complete remission (CR) during the follow-up period, whereas 83 patients did not. Of the 83 patients who did not achieve CR, 35 partially improved and 48 did not improve or worsened. The median time for achieving CR was 46 ± 18.8 months. Milder disease at presentation and comorbid lichen planus were associated with higher CR rates. Conclusion: This study demonstrates significant diagnostic delays that should be addressed as LPP causes irreversible alopecia, suggests disease severity and comorbid lichen planus as potential prognostic factors. Further, it emphasizes the limited efficacy of current treatments and the need for prolonged treatment in patients with LPP to achieve remission.
Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024
Authors: Park-Simon Tjoung-Won , Müller Volkmar , Albert Ute-Susann , Banys-Paluchowski Maggie , Bauerfeind Ingo , Blohmer Jens-Uwe , Budach Wilfried , Dall Peter , Ditsch Nina , Fallenberg Eva M. , Fasching Peter A. , Fehm Tanja , Friedrich Michael , Gerber Bernd , Gluz Oleg , Harbeck Nadia , Hartkopf Andreas Daniel , Heil Jörg , Huober Jens , Jackisch Christian , Kolberg-Liedtke Cornelia , Kreipe Hans-Heinrich , Krug David , Kühn Thorsten , Kümmel Sherko , Loibl Sibylle , Lüftner Diana , Lux Michael Patrick , Maass Nicolai , Mundhenke Christoph , Reimer Toralf , Rhiem Kerstin , Rody Achim , Schmidt Marcus , Schneeweiss Andreas , Schütz Florian , Sinn Hans-Peter , Solbach Christine , Solomayer Erich-Franz , Stickeler Elmar , Thomssen Christoph , Untch Michael , Witzel Isabell , Wuerstlein Rachel , Wöckel Achim , Janni Wolfgang , Thill Marc
Published: April 2024

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.
Transcription Factor EB Overexpression through Glial Fibrillary Acidic Protein Promoter Disrupts Neuronal Lamination by Dysregulating Neurogenesis during Embryonic Development
Authors: Wang Lei , Cao Jiaxin , Chen Haichao , Ma Yuezhang , Zhang Yishu , Su Xiaomei , Jing Yuhong , Wang Yonggang
Published: April 2024

Introduction: Transcription factor EB (TFEB), a key regulator of autophagy and lysosomal biogenesis, has diverse roles in various physiological processes. Enhancing lysosomal function by TFEB activation has recently been implicated in restoring neural stem cell (NSC) function. Overexpression of TFEB can inhibit the cell cycle of newborn cortical NSCs. It has also been found that TFEB regulates the pluripotency transcriptional network in mouse embryonic stem cells independent of autophagy and lysosomal biogenesis. This study aims to explore the effects of TFEB activation on neurogenesis in vivo through transgenic mice. Methods: We developed a glial fibrillary acidic protein (GFAP)-driven TFEB overexpression mouse model (TFEB GoE) by crossing the floxed TFEB overexpression mice and hGFAP-Cre mice. We performed immunohistochemical and fluorescence staining on brain tissue from newborn mice to assess neurogenesis changes, employing markers such as GFAP, Nestin, Ki67, doublecortin (DCX), Tbr1, and NeuN to trace different stages of neural development and cell proliferation. Results: TFEB GoE mice exhibited premature mortality, dying 10–20 days after birth. Immunohistochemical analysis revealed significant abnormalities, including disrupted hippocampal structure and cortical layering. Compared to control mice, TFEB GoE mice showed a marked increase in radial glial cells (RGCs) in the hippocampus and cortex, with Ki67 staining indicating these cells were predominantly in a quiescent state. This suggests that TFEB overexpression suppresses RGC proliferation. Additionally, abnormal distributions of migrating neurons and mature neurons were observed, highlighted by DCX, Tbr1, and NeuN staining, indicating a disruption in normal neurogenesis. Conclusion: This study, using transgenic animals in vivo, revealed that GFAP-driven TFEB overexpression leads to abnormal neural layering in the hippocampus and cortex by dysregulating neurogenesis. Our study is the first to discover the detrimental impact of TFEB overexpression on neurogenesis during embryonic development, which has important reference significance for future TFEB overexpression interventions in NSCs for treatment.
Bowman-Layer-Onlay-Transplantation (BLOT) als minimal invasive Methode zur Therapie des fortgeschrittenen Keratokonus
Authors: Ghaly Mohamed
Published: April 2024

Purpose: To analyze the clinical outcomes after Bowman layer (BL) onlay grafting for the treatment of progressive, advanced keratoconus. Design: Prospective, interventional case series. Methods: Twenty-one eyes underwent BL onlay grafting. After removing the epithelium, a single or double BL graft was «stretched» onto the corneal surface, allowed to dry-in, and a soft bandage lens was placed until the graft was re-epithelialized. Best spectacle- and/or best contact lens-corrected visual acuity (BSCVA/BCLVA), corneal tomography, and postoperative complication rates were analyzed for the total group and 2 subgroups (group 1: preoperative maximum keratometry [Kmax] <69 diopters [D; n = 7); group 2: preoperative Kmax ≥69 D [n = 14]). Follow-up ranged from 6 to 36 months (mean 21 ± 11 months). Results: All 21 surgeries were uneventful. Overall, Kmax changed from 76 ± 12 D preoperatively to 72 ± 9 D at 6 to 36 months postoperatively (P = .015). Kmax decreased by 6 D in group 2 (P = .002) but did not change in group 1. Average BSCVA remained stable for group 1 and improved from preoperatively 0.8 ± 0.4 to 0.4 ± 0.2 logarithm of the minimum angle of resolution postoperatively in group 2 (P = .032); BCLVA remained stable (P > .05). Within the first postoperative weeks, 2 eyes required BL graft repositioning after inadvertent bandage lens removal and 4 eyes underwent BL retransplantation for incomplete re-epithelialization. One eye underwent BL regrafting 12 months postoperatively after traumatic corneal erosion. All eyes showed a completely re-epithelialized graft at the last available follow-up. Conclusion: BL onlay grafting is a completely extraocular, minimally invasive surgical technique, providing up to 6 D of corneal flattening in eyes with advanced progressive keratoconus, allowing for continued (scleral) contact lens wear and therefore preserving the BCLVA.
Health Promotion Models for Improving Footcare in Older Adults: A Scoping Review
Authors: Wong Yuen-Ting , Morrison Stewart C.
Published: April 2024

Introduction: Footcare is an important component of wellbeing in older adults and the promotion of appropriate footcare interventions is imperative for health professionals working with this population. In this scoping review, we describe the health promotion models informing footcare interventions for older adults. The objectives were to (i) understand the context(s) where health promotion models have informed footcare interventions; (ii) identify the health promotion models informing interventions; and (iii) document the effectiveness of theoretically informed health promotion interventions for improving footcare in older adults. Methods: Footcare interventions developed using health promotion models worldwide and published in English before July 2023 were searched using MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar. Results: A total of 2,078 articles were identified, of which 31 were retrieved and assessed for eligibility. Eight articles met the eligibility criteria, with most interventions delivered in Asia (n = 5) and using self-efficacy theory as their theoretical framework (n = 6). Most of the studies included people with diabetes (n = 6) and outcomes were measured using foot health outcomes, knowledge of foot health, and footcare behaviors and self-efficacy. Conclusion: This scoping review has identified a range of footcare interventions, with evidence of promising outcomes on improving footcare in older adults. Approaches toward methods and dosage of intervention varied across the studies and more broadly, we identified that few studies report the health promotion model informing the design of intervention(s). Further research is required to ascertain which health promotion model, modality of promotion, and implementation approach are the most effective for improving footcare in older adults.
Congenital Hypothyroidism with Thyroid in situ: A Case Report with NKX2-1 and DUOX2 Hypomorphic Variants
Authors: Uehara Erika , Hori Naoaki , Tanase-Nakao Kanako , Akiba Kazuhisa , Sueoka Hidefumi , Matsubara Keiko , Narumi Satoshi
Published: April 2024

Introduction: NK2 homeobox 1 (NKX2-1) encodes a transcription factor, NKX2-1, that is expressed in the thyroid gland, lung, and brain. Dual oxidase 2 (DUOX2) encodes an enzyme which generates hydrogen peroxide and is involved in the thyroid hormone synthesis. Cases of congenital hypothyroidism (CH) with dyshormonogenesis showing two or more genetic variants are increasingly reported. We describe the first case of transient dyshormonogenesis who had experimentally verified a loss-of-function NKX2-1 variant and DUOX2 variants. Case Presentation: The proband was a 15-year-old female patient with CH who was diagnosed in the frame of newborn screening for CH. She had a mildly elevated serum TSH level (14.56 mU/L), a low free thyroxine level (0.87 ng/dL), and a high thyroglobulin (Tg) level (>800 ng/mL). Ultrasonography revealed goiter. She was followed clinically without levothyroxine treatment and showed normal growth and development. She had slightly high Tg levels throughout the clinical course. Next-generation sequencing-based genetic analysis revealed that the patient was heterozygous for an NKX2-1 variant (p.Ile228Ser), a nonsense DUOX2 variant (p.[Lys530*;His678Arg]), and a functional DUOX2 polymorphism (p.His678Arg). NKX2-1 p.Ile228Ser showed about 50% reduced residual activity on the Tg promoter. Conclusion: A partial loss-of-function NKX2-1 variant with a monoallelic nonsense DUOX2 variant and a DUOX2 functional polymorphism can cause transient CH with high serum Tg levels.