bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in SLE: report from a cohort of 417 Caucasian patients
Authors: Trentin Francesca , Signorini Viola , Manca Maria Laura , Cascarano Giancarlo , Gualtieri Luca , Schilirò Davide , Valevich Anastasiya , Cardelli Chiara , Carli Linda , Elefante Elena , Ferro Francesco , Stagnaro Chiara , Zucchi Dina , Tani Chiara , Mosca Marta
Published: April 2023

Background

SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended.

Objectives

To describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE.

Methods

Retrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up.

Results

417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death.

Conclusions

In our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
The European strategy for accelerator-based photon science
Authors: Abela R. , Biscari C. , Daillant J. , Dosch H. , Rivkin L.
Published: April 2023

The League of European Accelerator-based Photon Sources (LEAPS), comprising 19 large-scale user facilities in 10 member and associated states, has put forward for the first time a European strategy for a transformative way of cooperation, thereby mobilizing the members’ substantial expertise in photon science and technology, in infrastructure management and service to users and stakeholders. This European Strategy for Accelerator-based Photon Sources—ESAPS 2022—is a coherent pan-European plan addressing the future challenges and needs of the new era in research and innovation, designed to put Europe in a global leadership position in important future key technologies. In ESAPS2022, ambitious facility upgrades and technology development plans as well as a new strategic challenge-driven use of these facilities are discussed.
Influence of pressure on structural stability and physical properties of NaCaZ (Z=N, P and As) half-Heusler semiconductor materials
Authors: Azouaoui A. , Harbi A. , Moutaabbid M. , Benzakour N. , Hourmatallah A. , Bouslykhane K. , Masrour R. , Chahboun A.
Published: April 2023

Based on density functional theory (DFT), the structural and physical properties of NaCaZ (Z[Formula: see text]N, P, As) half-Heusler (HH) semiconductor materials have been studied under pressure up to 20[Formula: see text]GPa. The ground state results show that the NaCaZ are chemically stable in [Formula: see text]-phase structure and exhibit semiconducting behavior with an indirect bandgap. The optical parameters like the real and imaginary components of complex dielectric function, the absorption coefficient and refractive index are investigated and discussed. The obtained results show that NaCaZ have low value of reflectivity and high absorption coefficient in low ultraviolet and visible regions and exhibit small changes under pressure. Pressure-based elastic constants and their derivative parameters show that NaCaZ are mechanically stable and have brittle nature. Above 10[Formula: see text]GPa, NaCaP and NaCaAs have ductile nature. The phonon dispersions calculations with pressure show that NaCaN and NaCaP are dynamically stable, in contrast, NaCaAs is dynamically unstable at ambient pressure. Above 10[Formula: see text]GPa, the studied compounds are dynamically stable. The mechanically, dynamically stable with low reflectivity and high absorption coefficient in the low ultraviolet and visible regions make these materials more promising as absorbers of solar cells, optoelectronic and 2D applications.
Numerical study of the nanoparticles effect on the desalination process
Authors: lahcen J. Ait , Ezaier Y. , Hader A. , Moushi S. , Touizi R. Et , Hariti Y. , Tarras I. , Krimech F. Z. , Wakif A.
Published: April 2023

The nanofiltration (NF) process becomes the most recently used technologies for the desalination of seawater and brackish water. The porous media transport properties are first related to the geometrical complexity of the product. However, the membrane transport models used in desalination process constitute approximatively the less understood process. The objective of this work is to address modeling and numerical study of the desalination process of the water and ions fluxes by using a porous membrane with nanoparticles. Our filtration system used is constituted by two different zones that the membrane sheets are sandwiched. The fluid undergoes a first simple filtration and a second NF process by the injected nanoparticles. The impacts of the permeability K and porosity S of the membrane under the effect of a pressure [Formula: see text] were discussed. Our findings are obtained in the framework of the dynamic Langevin approach based on the competitiveness between the stochastic process and dissipation. The results show that the performance of the rejection membrane is significant as the nanoparticle concentration decreases, and increases as a power law with the ratio of the viscosity of the salty fluid to the pure fluid.
A Novel Copy–Move Forgery Detection Algorithm via Gradient-Hash Matching and Simplified Cluster-Based Filtering
Authors: Yang Jixiang , Liang Zhiyao , Li Jianqing , Gan Yanfen , Zhong Junliu
Published: April 2023

Copy–move forgery is one of the most frequently used methods for producing fake digital images. Current algorithms for copy–move forgery detection (CMFD) cannot combine high accuracy and fast speed. Motivated by the observation, we propose a novel CMFD algorithm whose workflow is as follows. First, we use a keypoint-extraction method with the lowest contrast threshold to extract more keypoints from the input image. Second, a new technique, gradient-hash matching, finds pairs of similar keypoints quickly and effectively using a hash table, where the hash value is computed using gradients of keypoints. Subsequently, a new method called simplified cluster-based filtering exploits the density pattern of keypoints in the copy–move regions to remove false matching keypoint pairs. Finally, image matting is applied to indicate the forgery regions vividly. Extensive experiments show that not only the new algorithm is better than the state-of-the-art algorithms in terms of computation correctness, but also its computation time is drastically less. Commonly only about half time is needed. The relative time saving is even higher when images are larger. Different algorithms modules are compared through experiments to choose the best combination.
Genetic Algorithm-Based Optimal Resource Trust Line Prediction in Cloud Computing
Authors: Mercy S. , Jaiganesh M. , Nagaraja R. , Sudha G.
Published: April 2023

A cloud computing signifies a novel computing paradigm that endorses reactive delivery of resources and services. A distinctive cloud service of such data center deploys over many computing nodes requesting services from the data centers. The organization of resources and trustworthiness of client is a hot topic of research in cloud computing. One of the major threats in cloud computing is unauthorized access of hardware and their resources. To conquer the issue, this novel work proposes an Optimal Resource Trust line prediction using Genetic Algorithm (GAORTL). The main aim of the work is to find the allocated optimal resource utilization of clients through an evolutionary algorithm. Implementation is evaluated to prove the benefit of the algorithm. Subsequently, we perform a comprehensive investigation that the proposed GAORTL delivers a better prediction of trustworthiness in variety of client sizes for a big scale batch of occurrences.
A Design Flow Based on Docker and Kubernetes for ROS-based Robotic Software Applications
Authors: Lumpp Francesco , Panato Marco , Bombieri Nicola , Fummi Franco
Published: April 2023

Human-centered robotic applications are becoming pervasive in the context of robotics and smart manufacturing, and such a pervasiveness is even more expected with the shift to Industry 5.0. The always increasing level of autonomy of modern robotic platforms requires the integration of software applications from different domains to implement artificial intelligence, cognition, and human-robot/robot-robot interaction. Developing and (re)configuring such a multi-domain software to meet functional constraints is a challenging task. Even more challenging is customizing the software to satisfy non-functional requirements such as real-time, reliability, and energy efficiency. In this context, the concept of Edge-Cloud continuum is gaining consensus as a solution to address functional and non-functional constraints in a seamless way. Containerization and orchestration are becoming a standard practice, as they allow for better information flow among different network levels as well as increased modularity in the use of multi-domain software components. Nevertheless, the adoption of such a practice along the design flow, from simulation to the deployment of complex robotic applications by addressing the de facto development standards (e.g., ROS - Robotic Operating System) is still an open problem. We present a design methodology based on Docker and Kubernetes that enables containerization and orchestration of ROS-based robotic SW applications for heterogeneous and hierarchical HW architectures. The methodology aims at (i) integrating and verifying multi-domain components since early in the design flow, (ii) mapping software tasks to containers to minimize the performance and memory footprint overhead, (iii) clustering containers to efficiently distribute load across the edge-cloud architecture by minimizing resource utilization, and (iv) enabling multi-domain verification of functional and non-functional constraints before deployment. The article presents the results obtained with a real case of study, in which the design methodology has been applied to program the mission of a Robotnik RB-Kairos mobile robot in an industrial agile production chain. We have obtained reduced load on the robot’s HW with minimal performance and network overhead, thanks to the optimized distributed system.
Molecular Allergy Diagnostics in Children with Cow’s Milk Allergy: Prediction of Oral Food Challenge Response in Clinical Practice
Authors: Tosca Maria Angela , Schiavetti Irene , Olcese Roberta , Trincianti Chiara , Ciprandi Giorgio
Published: April 2023

Background. Cow’s milk allergy (CMA) is the most common food allergy in early childhood. Children with CMA require a precise and punctual diagnosis. Oral food challenge (OFC) is the gold-standard procedure for diagnosing allergies, but it is laborious and requires a particular setting. The aim of the study was to identify the cutoff value of serum allergen-specific IgE values able to predict a positive response to OFC. Methods. Children with suspected CMA performed OFC with cow’s milk (CM) or derivatives. Total IgE and specific IgE to raw CM, α-lactalbumin, β-lactoglobulin, and casein were measured. Results. Seventy-two children performed OFC, and 30 (41.6%) had a positive response. The significant predictive factors were sensitization to raw CM extract (

p
=
0.03

), α-lactalbumin (

p
=
0.013

), β-lactoglobulin (

p
=
0.09

), and casein (

p
=
0.019

). The cutoff was, respectively: 5.13 kUA/L for raw CM, 1.47 for α-lactalbumin, 1.35 for β-lactoglobulin, and 4.87 for casein. Conclusions. This study allowed us to define a set of cutoff values for CM protein-specific IgE. However, these cutoffs should be interpreted not as a diagnostic tool for CMA but only predictive of response to OFC in a specific territory. Thus, the practical message may be that a value above the cutoff allows a good approximation to identify children to be started on OFC.
Surgical Management of Giant Prolactinomas: A Descriptive Study
Authors: Lundholm Michelle D. , Yogi-Morren Divya , Pantalone Kevin M. , Recinos Pablo F. , Kshettry Varun R. , Rao Pratibha P. R.
Published: April 2023

Introduction. Giant prolactinoma (GP) is a rare pituitary lactotropic cell tumor larger than 4 cm in its widest dimension, and is less likely than a smaller prolactinoma to achieve prolactin normalization on dopamine agonist (DA) monotherapy. There is a paucity of data on the circumstances and outcomes of second-line management of GP with surgery. Herein, our institution’s experience with the surgical management of GPs is described. Methods. A single-center retrospective analysis was conducted of patients who underwent surgery for giant prolactinoma from 2003 to 2018. A chart review was conducted for demographic data, clinical features, laboratory and radiographic findings, operative and pathology reports, perioperative management, and clinical outcomes in follow-up. Descriptive statistics were used. Results. Of 79 prolactinoma cases, 8 patients had GP with a median age of 38 years (range 20–53), 75% (6/8) were male, with a median largest tumor dimension of 6 cm (range 4.6–7.7), and a median prolactin level of 2,500 μg/L (range 100–>13,000). Six patients had transsphenoidal surgery for dopamine agonist (DA) resistance or intolerance. Two patients had a craniotomy for a missed diagnosis; one was due to the hook effect. No tumor resections were complete by either surgical approach; all had persistent hyperprolactinemia requiring postoperative DA therapy, and two patients had an additional craniotomy procedure for further tumor debulking. There was no recovery of pituitary axes and postoperative deficits were common. Remission as defined by prolactin normalization occurred in 63% (5/8) at a median time of 36 months (range 14–63 months) on DA therapy after surgery with a follow-up of 3–13 years. Conclusions. GPs infrequently require surgical resection, which is generally incomplete and requires adjuvant therapy. Given the rarity of surgery for GPs, multi-institutional or registry studies would yield clearer guidance on optimal management.
Ferroptosis Is a Potential Therapeutic Target for Pulmonary Infectious Diseases
Authors: Zhang Yurong , Qian Dianlun , Bai Xiangfeng , Sun Shibo
Published: April 2023

Ferroptosis is a new type of iron-dependent cell death caused by lipid peroxide (LPO) accumulation and involved in disease of pulmonary infection. The dysregulation of iron metabolism, the accumulation of LPO, and the inactivation and consumption of glutathione peroxidase 4 (GPX4) are the crucial cause of ferroptosis. Pulmonary infectious diseases caused by Pseudomonas aeruginosa (PA), Mycobacterium tuberculosis (MTB), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are associated with ferroptosis. Ferroptosis may be a potential therapeutic target for pulmonary infectious diseases. However, the mechanisms by which these infections are involved in ferroptosis and whether pulmonary infectious diseases caused by Staphylococcus aureus, Klebsiella pneumoniae, and Leishmania spp are related to ferroptosis are unclear. Accordingly, more researches are needed.
Novel Architecture for Transactive Energy Management Systems with Various Market Clearing Strategies
Authors: Arun S. L. , Bingi Kishore , Vijaya Priya R. , Jacob Raglend I. , Hanumantha Rao B.
Published: April 2023

The recent advancements in demand‐side management techniques add significant benefits to the distribution systems. One such technique is transactive energy management systems (TEMS) which motivate the energy end‐users to take part in local energy trading. The end‐users can effectively increase the monetary benefits by trading the surplus generation/demand within the local energy market (LEM). The LEM operator frames a viable market clearing strategy to fix the market clearing price to enhance the monetary benefits of all the market players. In this study, LEM architecture with different market clearing strategies is proposed for TEMS to ensure profitable power transactions between the neighboring end‐users. An optimal energy management algorithm is also proposed for time scheduling the operation of flexible loads and batteries, considering dynamics in end‐users’ behavior, variations in utility parameters, and the intermittent nature of renewable power generation. Further, an optimal load scheduling algorithm is developed at the end‐users’ premises to improve the profits in the LEM. Correspondingly, the trading strategies are extended to increase market reliability by penalizing participants for their abnormal activities in energy trading. The proposed framework is validated with different case studies considering ten residential participants in a locality.
Hybrid Model for Stock Market Volatility
Authors: Agyarko Kofi , Frempong Nana Kena , Wiah Eric Neebo
Published: April 2023

Empirical evidence suggests that the traditional GARCH-type models are unable to accurately estimate the volatility of financial markets. To improve on the accuracy of the traditional GARCH-type models, a hybrid model (BSGARCH (1, 1)) that combines the flexibility of B-splines with the GARCH (1, 1) model has been proposed in the study. The lagged residuals from the GARCH (1, 1) model are fitted with a B-spline estimator and added to the results produced from the GARCH (1, 1) model. The proposed BSGARCH (1, 1) model was applied to simulated data and two real financial time series data (NASDAQ 100 and S&P 500). The outcome was then compared to the outcomes of the GARCH (1, 1), EGARCH (1, 1), GJR-GARCH (1, 1), and APARCH (1, 1) with different error distributions (ED) using the mean absolute percentage error (MAPE), the root mean square error (RMSE), Theil’s inequality coefficient (TIC) and QLIKE. It was concluded that the proposed BSGARCH (1, 1) model outperforms the traditional GARCH-type models that were considered in the study based on the performance metrics, and thus, it can be used for estimating volatility of stock markets.
Vulnerability of Parkinson’s Patients to COVID-19 and Its Consequences and Effects on Them: A Systematic Review
Authors: Rezayi Sorayya , Rahmani Katigari Meysam , Shahmoradi Leila , Nilashi Mehrbakhsh
Published: April 2023

Introduction. Parkinson’s disease (PD) is the second most common neurological disorder. Patients with PD were affected by the COVID-19 pandemic in many different ways. This study’s principal purpose is to assess PD patients' vulnerability to COVID-19 and its consequences. Method. This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. A thorough search was conducted in the Medline (through PubMed) and Scopus databases from inception to January 30, 2022. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to evaluate the studies. Results. Most of the studies (38%) had been conducted in Italy. Of the total number of studies, 17 (58%) were cross-sectional, seven (22%) were cohort, four (12%) were quasiexperimental, two (6%) were case-control, and one (3%) was a qualitative study. The PD duration in patients ranged from 3.26 to 13.40 years (IQR1: 5.7 yrs., median: 3.688 yrs., and IQR3: 8.815 yrs.). Meanwhile, the sample size ranged from 12 to 30872 participants (IQR1: 46, median: 96, and IQR3: 211). Despite worsening PD symptoms in the targeted population (persons with COVID-19 and Parkinson’s disease), some studies found PD to be a risk factor for more severe COVID-19 disease. There are many adverse effects during the pandemic period in PD patients such as abnormalities of motor, nonmotor functioning, clinical outcomes, activities of daily living, and other outcomes. Conclusion. This study confirmed the negative effect of the COVID-19 pandemic on health-related quality of life and its determinants in patients with PD and their caregivers. Thus, due to the worsening symptoms of PD patients in the current pandemic, these people should be given more care and supervision to minimize their coronavirus exposure.
S
-FP-Projective Modules and Dimensions
Authors: Assaad Refat Abdelmawla Khaled , Zhang Xlaolei , Kim Hwankoo
Published: April 2023

Let

R

be a ring and let

S

be a multiplicative subset of

R

. An

R

-module

M

is said to be a

u

-

S

-absolutely pure module if

Ext

R

1

N
,
M

is

u

-

S

-torsion for any finitely presented

R

-module

N

. This paper introduces and studies the notion of

S

-FP-projective modules, which extends the classical notion of FP-projective modules. An

R

-module

M

is called an

S

-FP-projective module if

Ext

R

1

M
,
N

=
0

for any

u

-

S

-absolutely pure

R

-module

N

. We also introduce the

S

-FP-projective dimension of a module and the global

S

-FP-projective dimension of a ring. Then, the relationship between the

S

-FP-projective dimension and other homological dimensions is discussed.
Production and Testing of Bamboo Composite for Door of a Three-Wheeled Vehicle
Authors: Denanto Mulugeta , Nallamothu Ramesh Babu , Firew Deresse , Ilmi Idiris
Published: April 2023

Natural fiber reinforced composite material has recently attracted interest due to its low density, low cost, acceptable specific characteristics, ease of separation, improved energy recovery, CO2 neutrality, biodegradability, and renewable nature. The goal of this paper is to design and construct a three-wheeled Bajaj door panel using composite materials reinforced with bamboo fiber. Design, manufacture of the component, and experimental techniques are used to meet the goals given. The bamboo plant is the raw material chosen for this thesis project. The matrix material (polyester resin) and hardener used in this investigation, as well as the woven bamboo fiber strip that has been used as reinforcement, were all obtained from local markets. Bamboo fiber that has been chemically treated with 5% NaOH and 95% purified water is used. Keeping in mind the needs of varied testing conditions and characterization standards, polyester resin and E-glass fibers were simply stirred together by hand for 15 minutes. The mixture was then put into the molds. In three distinct orientations (0°, 90°, and 0/90°), composite samples of bamboo fiber were created. In order for the part to respond to axial loads, shear loads, and side loads, it may need 0°, 45°, and 90° plies, respectively. The paper model’s 0° orientation was chosen in accordance with the findings of the samples’ analysis. Due to the direction of the applied load, it affects the strength design requirements. Based on the findings of the experimental data examination, it was determined that the respective values for tensile, compression, bending, and water absorption were 160 MPa (0°), 2709.2 MPa (90°), 110 N (0/90°), and 4%, respectively. The geometric model of the door panel on the three-wheel Bajaj vehicle’s door was designed. Based on these findings, it is suggested that the new exterior structural car door panel of the three-wheel Bajaj Compact 205 model be made of composite materials made of bamboo fiber reinforced with polyester and having strength of 160 MPa.
Supplementary Table S7 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: April 2023

Response to combination therapy
Data from Somatic exonic deletions in RUNX1 constitutes a novel recurrent genomic abnormality in acute myeloid leukemia
Authors: Eriksson Anna , Engvall Marie , Mathot Lucy , Österroos Albin , Rippin Martin , Cavelier Lucia , Ladenvall Claes , Baliakas Panagiotis
Published: April 2023

Abstract
Purpose: In acute myeloid leukemia (AML), somatic mutations (commonly missense, nonsense and frameshift indels) in RUNX1 are associated with a dismal clinical outcome. Inherited RUNX1 mutations cause familial platelet disorder. As approximately 5-10% of germline RUNX1 mutations are large exonic deletions, we hypothesized that such exonic RUNX1 aberrations may also be acquired during the development of AML. Experimental Design: Sixty well-characterized AML patients were analyzed with Multiplex Ligation-dependent Probe Amplification (MLPA, n=60), micro-array (n=11) and/or whole genome sequencing (WGS, n=8). Results: In total, 25 (42% of the cohort) RUNX1-aberrant patients (defined by the presence of classical mutations and/or exonic deletions) were identified. Sixteen patients (27%) carried only exonic deletions, 5 (8%) carried classical mutations and 4 (7%) carried both exonic deletions and mutations. No significant difference was observed between patients with classical RUNX1 mutations and RUNX1 exonic deletions in median overall survival (OS, 53.1 vs 38.8 months respectively, p=0.63). When applying the European Leukemia Net (ELN) classification including the RUNX1-aberrant group, 20% of the patients initially stratified as intermediate-risk (5% of the whole cohort) were re-assigned to the high-risk group, which improved the performance of ELN classification regarding OS between intermediate and high-risk group (18.9 vs 9.6 months, p=0.09). Conclusions: Somatic RUNX1 exonic deletions constitute a novel recurrent aberration in AML. Our findings have important clinical implications regarding AML classification, risk-stratification and treatment decision. Moreover, they argue in favor of further investigating such genomic aberrations not only in RUNX1 but also in other genes implicated in cancer biology and management.
Data from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: April 2023

AbstractPurpose:
Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non–small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion–mediated osimertinib resistance has not previously been published.
Patients and Methods:
Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected.
Results:
Fourteen patients with EGFR-mutant and RET fusion–positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%–75%, n = 12], 83% (95% CI, 55%–95%), and 7.9 months (range, 0.8–25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4–ALK/STRN–ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms.
Conclusions:
For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination.
Data from Co-Clinical Study of [fam-] Trastuzumab Deruxtecan (DS8201a) in Patient-Derived Xenograft Models of Uterine Carcinosarcoma and Its Association with Clinical Efficacy
Authors: Yagishita Shigehiro , Nishikawa Tadaaki , Yoshida Hiroshi , Shintani Daisuke , Sato Sho , Miwa Maiko , Suzuki Mikiko , Yasuda Masanori , Ogitani Yusuke , Jikoh Takahiro , Yonemori Kan , Hasegawa Kosei , Hamada Akinobu
Published: April 2023

AbstractBackground:
Uterine carcinosarcoma (UCS), a subtype of endometrial carcinoma, is a rare and aggressive cancer with a poor prognosis. High clinical efficacy of trastuzumab deruxtecan (T-DXd) in HER2-expressing UCS was recently reported in a phase II trial (STATICE trial). We performed a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of participants in the STATICE trial.
Experimental design:
Tumor specimens were resected during primary surgery or biopsied at recurrence from patients with UCS and transplanted into immunodeficient mice. Seven UCS-PDXs from six patients were established and HER2, estrogen receptor (ER), and p53 expression in PDX and the original tumor was assessed. Drug efficacy tests were performed using six of the seven PDXs. Of the six UCS-PDXs tested, two were derived from patients enrolled in the STATICE trial.
Results:
The histopathological characteristics of the six PDXs were well-conserved from the original tumors. HER2 expression was 1+ in all PDXs, and ER and p53 expression was almost similar to that in the original tumors. Remarkable tumor shrinkage after T-DXd administration was observed in four of the six PDXs (67%), comparable with the response rate (70%) of HER2 1+ patients in the STATICE trial. Two patients enrolled in the STATICE trial showed partial response as the best response, and the clinical effect was well-replicated with marked tumor shrinkage.
Conclusion:
We successfully performed a co-clinical study of T-DXd in HER2-expressing UCS, along with the STATICE trial. Our PDX models can predict clinical efficacy and serve as an effective preclinical evaluation platform.
RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M.
Published: April 2023

Purpose:

To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

Experimental Design:

RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

Results:

RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status.

Conclusions:

RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.
Supplemental Figure S10 from Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy
Authors: Linde Miles H. , Fan Amy C. , Köhnke Thomas , Trotman-Grant Aaron C. , Gurev Sarah F. , Phan Paul , Zhao Feifei , Haddock Naomi L. , Nuno Kevin A. , Gars Eric J. , Stafford Melissa , Marshall Payton L. , Dove Christopher G. , Linde Ian L. , Landberg Niklas , Miller Lindsay P. , Majzner Robbie G. , Zhang Tian Yi , Majeti Ravindra
Published: April 2023

Primary B-ALL-derived TR-APCs activate T cells in an MHC-restricted manner according to the inflammatory milieu
Supplementary Table S5 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Primers used in real-time quantitative PCR experiments.
Supplementary Table S3 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

CD142 immunohistochemical analysis in scar tissue cores. Results from duplicate cores per do are shown when available.
Supplementary Table S1 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Cell surface profiling data of mutant and non-mutant desmoid tumor-derived colonies. Name of the sample indicates the mutation status (mutant (MUT) or wildtype (WT)) of the pooled colonies and the genotype (T41A or S45F) of the original primary sample.
Supplementary Figure S7 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Morphological differences in mutant and non-mutant cells isolated by FACS sorting
Supplementary Figure S5 from CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin A.
Published: April 2023

Measuring gene expression of F3 and PDPN after Wnt3a treatment of skin fibroblasts
Effects of Exercise on Physical Function and Quality of Life in Prostate Cancer Patients Receiving Androgen Deprivation Therapy: High-Intensity Interval Training versus Moderate-Intensity Continuous Training
Authors: Yoo Sangjun , Lee Kyung Hee , Jamrasi Parivash , Cho Min Chul , Song Wook , Jeong Hyeon
Published: April 2023

Introduction: We assessed the effects of exercise on the physical function and health quality of life (hQoL) in prostate cancer patients underwent androgen deprivation therapy (ADT). Additionally, the effects of high-intensity interval training (HIIT) on the physical function and hQoL in these patients were compared with those of moderate-intensity continuous training (MICT). Methods: Seventeen prostate cancer patients who underwent ADT were prospectively allocated to either HIIT (n = 9) or MICT (n = 8). In these patients, physical function and hQoL were measured before and after 12 weeks of exercise and 3–6 months after the exercise program, respectively. Results: Although the whole-body total mass significantly increased after the exercise program, it was equivalent regardless of the exercise methods. After the exercise program, muscle strength and endurance improved and tended to be maintained until 3–6 months later. Improvement in muscle endurance was more prominent after HIIT, and that in muscle strength was more prominent after MICT. Performance in the senior fitness test improved after the exercise program, and HIIT was more effective for lower and upper muscle endurance and flexibility, although MICT was more effective for the others. The hQoL significantly improved 3–6 months after the exercise program. Conclusion: The 12-week exercise program has a positive effect on the physical function and hQoL in prostate cancer patients who underwent ADT. In these patients, compared with MICT, HIIT may be a better option for improving muscle endurance, which is thought to be significant for preventing falls and fractures in elderly patients.
Calculated Globulin Is Clinically Useful as a Screening Test for Antibody Deficiency in Turkish Adult Patients
Authors: Yegit Osman Ozan , Karadağ Pelin , Eyice Deniz , Oztop Nida , Beyaz Şengül , Tüzer Özdemir Can , Can Ali , Demir Semra , Erdoğdu Derya , İşsever Halim , Genç Sema , Ömer Beyhan , Jolles Stephen , Gelincik Akkor Aslı
Published: April 2023

Introduction: Heterogeneous clinical features of antibody deficiency (AD) may cause diagnostic delays. Calculated globulin (CG) (total protein minus albumin) has been proposed as a screening test to prevent morbidity due to diagnostic delays in AD. Our aim was to validate CG as a screening test for AD in Turkish adult patients by comparing its role with gamma globulin analysis in protein electrophoresis. Methods: Fifty serum samples were randomly collected for each level of CG from 15 to 25 g/L and tested for serum IgG, IgA, IgM levels and protein electrophoresis. Cut-off values predicting low IgG levels were calculated for electrophoretically determined gamma globulin and CG. Additionally, the data of 47 patients followed up in our clinic with a diagnosis of primary antibody deficiency (PAD) were retrospectively analyzed. Results: A total of 550 adult patients were included in the study. The CG value predicting patients with IgG <6 g/L as a screening test was determined as <20 g/L with 83.8% sensitivity and 74.9% specificity. The gamma globulin value which predicted patients with the same IgG value of 89.0% sensitivity and 89.4% specificity was determined as <7 g/L. In the retrospective analysis, 37 of 47 patients (78.7%) with PAD had a CG value of <20 g/L at the time of the diagnosis and all 13 patients (100%) whose gamma globulin values were measured at the time of the diagnosis had a gamma globulin value of <7 g/L. Conclusion: The determined CG cut-off value of <20 g/L can be used as a screening test in Turkish adult patients.
Influence of Speech Recognition Ability on Acceptable Noise Level for Mandarin (Chinese) Speakers with Normal Hearing
Authors: Hu Xu Jun , Lau Chi Chuen
Published: April 2023

Introduction: Noise can induce hearing loss and reduce speech understanding. The Acceptable Noise Level (ANL) test has been widely used in audiology. However, strategies used by listeners to determine ANLs are unclear. The current study evaluated the role of speech recognition in selecting ANL and how well ANL could predict speech understanding in a noisy situation. Methods: Forty-five Mandarin speakers with normal hearing were tested in both ears. ANL is defined as Most Comfortable Level (MCL) minus Background Noise Level (BNL). To obtain ANL monaurally with an earphone, the study measured participants’ MCL to hear a Mandarin story in quiet and the maximum BNL to tolerate while following the story. Then, based on the participant’s ANL, speech recognition in noise was examined using a set of phonemic-balanced Mandarin words. The signal-to-noise ratio (SNR) was adjusted to ANL, ANL – 10 dB (“degraded noise condition”), and ANL + 10 dB (“improved noise condition”). Results: The mean ANLs were 2.4 dB and 2.6 dB for the left and right ears, respectively. The mean speech recognition with SNR adjusted to ANL was relatively high for both ears (81–83% correct). Even for those ear samples with very low ANL (<0 dB), speech performance obtained at SNR = ANL was still high. The mean speech recognition obtained at SNR = ANL was 5 percentage points lower than the mean speech recognition at the improved noise condition and 14 percentage points higher than the mean speech recognition at the degraded noise condition. Speech recognition obtained at SNR = ANL and ANL − 10 dB correlated significantly with ANL. Conclusion: Speech recognition in noise appears to play an important role for listeners with normal hearing in deciding their ANLs. Additionally, ANL can predict speech performance (r-squared = 53–61%) in the degraded noise condition.
Association between Endotype of Prematurity and Mortality: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Hundscheid Tamara M , Villamor-Martinez Eduardo , Villamor Eduardo
Published: April 2023

Introduction: Preterm birth represents the leading cause of neonatal mortality. Pathophysiological pathways, or endotypes, leading to prematurity can be clustered into infection/inflammation and dysfunctional placentation. We aimed to perform a systematic review and meta-analysis exploring the association between these endotypes and risk of mortality during first hospital admission Methods: PROSPERO ID: CRD42020184843. PubMed and Embase were searched for observational studies examining infants with gestational age (GA) ≤34 weeks. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for GA (SGA)/intrauterine growth restriction (IUGR). A random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals. Heterogeneity was studied using random-effects meta-regression analysis. Results: Of 4,322 potentially relevant studies, 150 (612,580 infants) were included. Meta-analysis showed positive mortality odds for chorioamnionitis (OR: 1.43, 95% confidence interval: 1.25–1.62) and SGA/IUGR (OR: 1.68, 95% confidence interval: 1.38–2.04) but negative mortality odds for HDP (OR 0.74, 95% confidence interval: 0.64–0.86). Chorioamnionitis was associated with a lower GA, while HDP and SGA/IUGR were associated with a higher GA. Meta-regression showed a significant correlation between these differences in GA and mortality odds. Conclusion: Our data suggest that the infectious/inflammatory endotype of prematurity has a greater overall impact on mortality risk as it is the most frequent endotype in the lower GAs. However, when the endotype of placental dysfunction is severe enough to induce growth restriction, it is strongly associated with higher mortality rates even though newborns are more mature.
Acute Hepatitis E Infection during Chemotherapy for Lung Cancer: A Case Report
Authors: Okumura Hiroki , Miyamoto Atsushi , Suzuki Fumitaka , Takaya Hisashi
Published: April 2023

Acute hepatitis E, one of the causes of acute liver injury, has been increasingly diagnosed in developed countries in recent years. Misdiagnosis of acute hepatitis E virus (HEV) infection as drug-induced liver injury (DILI) may lead to discontinuation of effective chemotherapy. Thus, viral hepatitis, including hepatitis E, must be ruled out in the diagnosis of DILI. A 78-year-old woman with lung adenocarcinoma and multiple bone metastases received maintenance therapy with pemetrexed + pembrolizumab for a year. Increased aspartate aminotransferase and alanine aminotransferase levels, indicating acute liver injury, were observed. Initially, DILI was suspected, and she was given medications to lower the levels of hepatic enzymes. She was later admitted to the hospital with the chief complaint of general malaise and anorexia. Serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated (381 and 854 U/L, respectively). Acute HEV infection was diagnosed based on the detection of serum HEV immunoglobulin A antibodies. The patient received liver support therapy, and the serum hepatic enzymes recovered to normal levels. Chemotherapy was resumed without any subsequent relapse of hepatic enzyme elevation. When DILI is suspected during chemotherapy, exclusion of viral hepatitis is mandatory, which can be achieved by measuring markers of hepatitis viruses, including HEV, and examining the patient’s detailed medical history.