bluuebunny/crossref_metadata_2025 huggingface dataset:
Audit outcomes of non‐financial misconduct
Authors: Chakrabarty Bidisha , Hyman Michael , Krishnan Gopal V.
Published: April 2024

We examine how non‐financial misconduct by corporations impacts audit outcomes. We use a novel database of penalties received by firms from federal, state and local agencies for legal violations not directly related to their financial reports and find that auditors raise fees following these violations. The magnitudes are economically significant: violating firms pay about $162,000 or 6% more in audit fees than comparable firms without violations. Additionally, auditors charge more when the penalty amounts are higher and infractions are more egregious. Companies fined for non‐financial misconduct are also more likely to receive going concern opinions. Our results are robust to propensity score matching, falsification tests and firm‐fixed effects and are not attributable to lax firm culture or “tone at the top”. These results highlight that firms' unethical conduct, even those that do not directly lead to financial reporting infractions, has consequences beyond just the penalties imposed by enforcement agencies.
Savings trajectories and cohort differences among older Chinese couples
Authors: Chen Lu , Zhang Wenjuan
Published: April 2024

Based on longitudinal data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study, we examined savings and savings changes among older couples in China using hierarchical linear models, explored any cohort differences, and analyzed the effects of the accessibility of the employee pension and the number of children on parents' savings. The results indicate that the savings of older couples continued to increase in old age, but the growth slowed down with age. For the cohort born before 1940, savings declined in later years. The cohorts born after 1940 had higher savings, but their savings grew less in later years. Older adults with access to the employee pension saved more and faster. Older adults with more than two children had lower savings, while those from younger cohorts were less impacted.
The association between flavonoids intake and hypertension in U.S. adults: A cross‐sectional study from The National Health and Nutrition Examination Survey
Authors: Hu Ben , Wang Yan , Feng Jun , Hou Linlin
Published: April 2024

Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross‐sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70–0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92–0.98). In addition, in restricted cubic spline regression, we found that flavan‐3‐ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of ‐1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension.
Editorial: Are government early years learning and development frameworks evidence‐based? A scientist's perspective
Authors: Ronald Angelica
Published: April 2024

Not all young children attend nurseries, childminders or other group settings before they start school, but many do. It is common for countries to set out a framework to guide practice for early years providers (such as nurseries) to follow. The conundrum regarding these frameworks for young children is that proving evidence of a causal link between early environments and later outcomes is very challenging scientifically. So how do governments choose what learning and development practices and goals to make mandatory for childcare providers? And is it realistic to expect early years providers to meet the legal requirements that these frameworks impose? We do not know which learning and development practices impact positively on later outcomes, and we certainly do not know if there is a one‐size‐fits‐all approach for an early years framework that is guaranteed to work.
Should sacrouterine plication be added to lateral suspension surgery? A prospective study
Authors: Şahin Fatih , Özdemir Savaş , Doğan Ozan
Published: April 2024

Aim

Laparoscopic lateral suspension is a novel approach for repairing anterior and apical pelvic organ prolapse (POP). According to integral theory, urinary symptoms and pelvic pain are believed to originate from suspensory ligaments. We aimed to investigate the objective and subjective outcomes of adding sacroterine plication to apical prolapse surgery.

Methods

Sixty patients with Grade 2 or higher symptomatic apical POP were included in the study. The study sample was categorized into two groups: Group 1 underwent lateral suspension and Group 2 underwent lateral suspension and sacroterine plication. Anatomical cure was defined separately for the apical and anterior compartments as POP‐Q scores for sites C and Ba of less than −1 cm for each compartment. A subjective cure was defined as the absence of bulge symptoms. Patient satisfaction, sexual function, prolapse‐related quality of life, voiding dysfunction, nocturia, and constipation were assessed.

Results

In Group 1, anatomical cure rates for apical and anterior prolapse were 100% and 70%, respectively (p <0.001). In Group 2, these rates were 100% for apical prolapse and 73.3% for anterior prolapse (p <0.001). The subjective cure was 96.6% in both groups. Furthermore, improvement in sexual and urinary symptoms was more significant in the group that underwent sacroterine plication (p <0.001).

Conclusions

The additional sacroterine plication (shortening) procedure with lateral suspension proved to be an effective and successful surgical approach for apical prolapse. Its routine addition to existing lateral suspension surgery can contribute significantly to the improvement of urinary and prolapse symptoms.
Pregnancy in the shadow of psychosis: Navigating first‐time motherhood with increased likelihood of postpartum psychosis and postnatal depression
Authors: Walsh Alison
Published: April 2024

Accessible Summary

What is known on the subject?

New parents who have previously experienced psychosis outside and/or following childbirth have an increased likelihood of experiencing an episode during the postpartum period.

The decision to try to conceive can be agonising.

Receiving care from a specialist perinatal community mental health team can improve outcomes.

What does this paper add to existing knowledge?

This article offers a first‐person insight into the steps the author took to minimise the impact of an episode of postpartum psychosis and/or postnatal depression whilst navigating new motherhood.

What are the implications for practice?

This lived experience narrative aligns with the evidence base that demonstrates specialist perinatal community mental health services improve outcomes.

It highlights the importance of maternity care providers asking about mental health history to identify any previous episodes or family history and offering referral to a specialist perinatal mental health service if available.

Introduction

Postpartum psychosis is a life‐changing but treatable condition that usually occurs in the first few days to weeks after childbirth affecting 1–2 in 1000 pregnancies. Those who have experienced psychosis before, either as a single episode, related or unrelated to childbirth or as part of a long‐term mental health condition have a higher likelihood of experiencing an episode in the postnatal period.

Aim

In this lived experience narrative the author shares personal experience of planning and navigating pregnancy with a higher likelihood of experiencing postpartum psychosis and postnatal depression around this major life transition due to previous episodes.

Methods

The author utilises a first‐person approach to share and reflect on her lived experience.

Findings

The author shares her experience of receiving care and some of the steps she took to try to manage the impact of pregnancy and birth on her mental health during this major life transition. She describes how care from a specialist perinatal community mental health team and peer support contributed significantly to her family's well‐being.

Discussion

Specialist perinatal community mental health services can improve outcomes for those with a higher likelihood of experiencing postpartum psychosis and postnatal depression by facilitating planning and mitigating some of the risks that could lead to relapse in the perinatal period.
Congressional town halls
Authors: Clarke Andrew J. , Markovits Daniel
Published: April 2024

Members of the US Congress held over 25,000 town hall meetings over the last eight years, and yet we know very little about the role that these events play in American politics. In this article, we present new data on congressional town hall meetings held in the 114th to 117th Congresses (2015–2022) to explore why politicians hold such meetings. In short, we do not find consistent evidence that electoral vulnerability drives legislators to their districts. Nor do we find support for claims of a zero‐sum tradeoff between lawmaking and district representation. However, members of the president's opposition party clearly and consistently host more town hall meetings, suggesting that party messaging may be at the heart of this often‐overlooked congressional behavior.
Indirect Defenses of Speciesism Make No Sense
Authors: Jaquet François
Published: April 2024

Animal ethicists often distinguish between direct and indirect defenses of speciesism, where the former appeal to species membership and the latter invoke other features that are simply associated with it. The main extant charge against indirect defenses rests on the empirical claim that any feature other than membership in our species is either absent in some humans or present in some nonhumans. This paper challenges indirect defenses with a new argument, which presupposes no such empirical claim. Instead, the argument from discordance resorts to the following principle: a certain feature can only justify discriminating on the basis of that feature.
A novel method based on a starburst pattern to register UAV and terrestrial lidar point clouds in forest environments
Authors: Feng Baokun , Nie Sheng , Wang Cheng , Wang Jinliang , Xi Xiaohuan , Wang Haoyu , Lao Jieying , Yang Xuebo , Wang Dachao , Chen Yiming , Yang Bo
Published: April 2024

Accurate and efficient registration of unmanned aerial vehicle light detection and ranging (UAV‐lidar) and terrestrial lidar (T‐lidar) data is crucial for forest structure parameter extraction. This study proposes a novel method based on a starburst pattern for the automatic registration of UAV‐lidar and T‐lidar data in forest scenes. It employs density‐based spatial clustering of applications with noise (DBSCAN) for individual tree identification, constructs starburst patterns separately from both lidar sources, and utilises polar coordinate rotation and matching to achieve coarse registration. Fine registration is achieved using the iterative closest point (ICP) algorithm. Experimental results demonstrate that the starburst‐pattern‐based method achieves the desired registration accuracy (average coarse registration error of 0.157 m). Further optimisation with ICP yields slight improvements with an average fine registration error of 0.149 m. Remarkably, the proposed method is insensitive to the individual tree detection number when exceeding 10, and the tree position error has minimal impact on registration accuracy. Furthermore, our proposed method outperforms two existing methods in T‐lidar and UAV‐lidar registration over forest environments.
Priming avocado with sodium hydrosulfide prior to frost conditions induces the expression of genes involved in protection and stress responses
Authors: Tiwari Vivekanand , Bussi Yuval , Kamara Itzhak , Faigenboim Adi , Irihimovitch Vered , Charuvi Dana
Published: April 2024

Priming plants with chemical agents has been extensively investigated as a means for improving their tolerance to many biotic and abiotic stresses. Earlier, we showed that priming young avocado (Persea americana Mill cv. ‘Hass’) trees with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide, improves the response of photosynthesis to simulated frost (cold followed by high light) conditions. In the current study, we performed a transcriptome analysis to gain insight into the molecular response of avocado ‘Hass’ leaves to frost, with or without NaHS priming. The analysis revealed 2144 (down‐regulated) and 2064 (up‐regulated) differentially expressed genes (DEGs) common to both non‐primed and primed trees. Non‐primed trees had 697 (down) and 559 (up) unique DEGs, while primed trees exhibited 1395 (down) and 1385 (up) unique DEGs. We focus on changes in the expression patterns of genes encoding proteins involved in photosynthesis, carbon cycle, protective functions, biosynthesis of isoprenoids and abscisic acid (ABA), as well as ABA‐regulated genes. Notably, the differential expression results depict the enhanced response of primed trees to the frost and highlight gene expression changes unique to primed trees. Amongst these are up‐regulated genes encoding pathogenesis‐related proteins, heat shock proteins, enzymes for ABA metabolism, and ABA‐induced transcription factors. Extending the priming experiments to field conditions, which showed a benefit to the physiology of trees following chilling, suggests that it can be a possible means to improve trees' response to cold stress under natural winter conditions.
Impact of Task Constraint on Agent Team Size of Self-Organizing Systems Measured by Effective Entropy
Authors: Ji Hao , Jin Yan
Published: April 2024

Self-organizing systems can perform complex tasks in unpredictable situations with adaptability. Previous work has introduced a multiagent reinforcement learning-based model as a design approach to solving the rule generation problem with complex tasks. A deep multiagent reinforcement learning algorithm was devised to train self-organizing agents for knowledge acquisition of the task field and social rules. The results showed that there is an optimal number of agents that achieve good learning stability and system performance. However, finding such a number is nontrivial due to the dynamic task constraints and unavailability of agent knowledge before training. Although extensive training can eventually reveal the optimal number, it requires training simulations of all agent numbers under consideration, which can be computationally expensive and time consuming. Thus, there remains the issue of how to predict such an optimal team size for self-organizing systems with minimal training experiments. In this article, we proposed a measurement of the complexity of the self-organizing system called effective entropy, which considers the task constraints. A systematic approach, including several key concepts and steps, is proposed to calculate the effective entropy for given task environments, which is then illustrated and tested in a box-pushing case study. The results show that our proposed method and complexity measurement can accurately predict the optimal number of agents in self-organizing systems, and training simulations can be reduced by a factor of 10.
A Novel Plate Fin Heat Sink Design With Rectangular Slots and Interruptions: A Computational Approach
Authors: Ray Rahul , Senapati Santosh Kumar , Mohanty Aurovinda
Published: April 2024

In the present work, we have studied the performance of vertical plate finned heat sinks that protrude from a vertical base. The difference between the heat sink base temperature and the ambient, i.e., ΔT, has been varied in the range of 10 °C to 60 °C, and the flow undergoes a natural convection regime. To enhance the thermal performance, we have explored different configurations of the heat sink by providing rectangular slots, varying the neck thickness, changing the neck location from the fin base, and providing interruptions along the fin height. The pertinent quantities, i.e., heat dissipation rate, Nusselt number, effectiveness, mass of heat sink, and heat dissipation per unit mass, have been obtained by performing 3D computational simulations. The results obtained are compared to assess the thermal performance of heat sinks. We found that among various designs of heat sinks proposed, the heat sink with two slots, with the location of neck closer to the fin base (xm = 9 mm), and with interrupted fins dissipates maximum heat (12.86% more compared to the commonly used rectangular plate finned heat sink). In addition to the heat transfer improvement, 19.82% mass reduction has also been achieved. Based on the simulation data, we have proposed a correlation for the mean Nusselt number as a function of relevant non-dimensional parameters.
The Inducers of an Elite Male Table Tennis Player’s Emotional Experience Throughout His Career: A Single Case Study Based on the Critical-Incident Method
Authors: Petiot Oriane , Kermarrec Gilles , Visioli Jérôme , Martin Guillaume
Published: April 2024

Despite a growing interest in emotions in sport psychology, little has been written about the contextual elements triggering athletes’ emotional experience. This single case study aimed to analyze the inducers of an elite table tennis player’s emotional experience throughout his career. He was ranked among the 15 best players in the world, and his career spanned more than 20 years. Inspired by the critical-incident method, we conducted a lengthy interview with the player, during which he related the most significant moments of his career. The categorization of the 96 critical incidents collected highlighted four inducers of positive emotions and five inducers of negative emotions, emerging over five periods (exponential progression, first difficulties, major difficulties, second career, and end of career). These findings contribute to the development of an innovative single-case-study design, allowing an understanding of the contextual origin of athletes’ emotions over the long term. Finally, highlights are discussed and recommendations for the practice of sport psychology are formulated.
Using machine learning and robotics to discover plastic substitutes
Authors: Yashinski Melisa
Published: April 2024

Discovery of all-natural thin films with tunable properties was partially automated using robotics and machine learning.
Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis
Authors: Subah Galadu , Zeller Sabrina , Damodara Nitesh , Fortunato Michael , Garrett Jenna , Syed Shoaib , Uddin Anaz , Pak Issac , Feldstein Eric , Mayer Stephan , Gandhi Chirag D , Al-Mufti Fawaz
Published: April 2024

Background

Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH.

Methods

Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019.

Results

Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01).

Conclusion

SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT’s impact on SAH patients.
SELECTION OF BEST 3D PRINTING PARAMETERS FOR FUSED DEPOSITION MODELING PART USING A NOVEL HYBRID MULTI-CRITERIA OPTIMIZATION TECHNIQUE
Authors: RANJAN RAJEEV , SAHA ABHIJIT
Published: April 2024

One of the most widely used 3D printing techniques is fused deposition modeling (FDM) which builds things layer by layer by dispensing molten materials through a heated nozzle. To showcase the flexibility of 3D printing, test samples were made using polylactic acid (PLA). Trial runs with Taguchi’s (L27) orthogonal array were performed. Layer thickness, printing speed, and carbon deposition (C-deposition) were the three input parameters that were improved. This was accomplished by combining principal component analysis (PCA) with multi-objective optimization based on ratio analysis (MOORA) in an integrated approach to multi-criteria optimization. The main goal of this study is to maximize the input parameters for the Industry 4.0 technological production process of embossing components. The MOORA-PCA technique finds the best combinations of process variables; for example, printing at a speed of 75[Formula: see text]mm/s, layer thickness of 0.1[Formula: see text]mm, and carbon content of 15[Formula: see text]mg yield the required results. The results of this study will help production managers and researchers choose the best FDM 3D printing methods for improving mechanical qualities and surface roughness. The economic feasibility of the 3D printing businesses may be strengthened by these research findings, which will benefit customers looking for ecologically friendly items.
DUAL MODE FRACTURE BASED ON LOADING RATE DURING SLIDING INDENTATION OF Si–C–N HARD COATINGS ON 304SS SUBSTRATES
Authors: BHATTACHARYYA A. S. , BHATTACHARYYA KUSHAL
Published: April 2024

Scratch tests were performed on thermal-resistant hard Si–C–N coatings deposited on steel (SS) 304, by radio frequency (RF) magnetron sputtering. The abrasion and wear properties were studied by analyzing the changing failure complexion inside the scratch showing a mixture of ductile and brittle properties. The change in loading rate caused noticeable changes in the failure mode. The plasticity was found to have a peripheral domination initially with an increase in load but was replaced by brittle failure on increasing the loading rate. The work of adhesion and wear rate were determined.
Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb
Authors: Lazaridis Ioannis I. , Bosch Angela J. T. , Keller Lena , Low Andy J. Y. , Tamarelle Jeanne , Moser Seraina O. , Winter Denise V. , Gómez Cristina , Peterson Caspar J. , Schneider Romano , Kraljević Marko , Odermatt Alex , Vonaesch Pascale , Peterli Ralph , Delko Tarik , Cavelti-Weder Claudia
Published: April 2024

Weight loss following OAGB surgery in obese mice was not influenced by BPL length, but a longer BPL was associated with improved metabolic outcomes, including glucose and lipid homeostasis. These changes could be mediated by bile acids upon altered gut microbiota. Further validation of these findings is required through a randomized human study.
System Pharmacological Approach to Investigate and Validate Multitargeted and Therapeutic Effect of Furocoumarins of Apium graveolens L. for Treatment of Kidney Disease
Authors: Yasheshwar  , Gaurav  , Ekkbal Rustam , Gupta Prem , Gyawali Rajendra
Published: April 2024

Background. System pharmacological approaches play important roles in drug discovery and development and in biomolecular exploration to investigate the multitarget therapeutic effects of phytochemicals for the treatment of acute and chronic ailments. Objectives. The aim of the study was to apply a system pharmacological approach to investigate the multitarget therapeutic effects of furocoumarins of Apium graveolens L. for the treatment of kidney disease. Methods. Several furocoumarins of Apium graveolens were screened from online databases. Network biology and poly-pharmacology analyses were performed to investigate the multitarget therapeutic effect of furocoumarins. The potential metabolites that showed significant interactions with various genes were selected for in silico docking analysis with CASP-3 and SOD proteins. In silico ADME analysis was also performed to investigate the pharmacokinetic behavior of targeted furocoumarins. Results. Out of thirteen furocoumarins selected for analysis, six showed partial or significant interaction with SOD and CASP-3 proteins. These metabolites may alleviate kidney dysfunction by reducing oxidative and inflammatory stress, regulating apoptosis, slowing down the progression of diabetic nephropathy, and reducing hypertension and glomerular vascular rigidity. In silico docking analysis revealed bergapten as a potential therapeutic agent for kidney disease treatment. In silico docking analysis showed anglicine, imperatorin, and sphondin exhibited strong interaction with CASP-3 and SOD with binding energy −6.5, −7.2, −6.5 and −6.8, −6.2 −5.7 kcal/mol, respectively. These components exhibited greater conventional hydrogen bonding with CASP-3 and SOD than other furocoumarins. Furthermore, in silico ADME analysis of metabolites showed that all furocoumarins have a highly lipophilic nature, good skin permeability, and GI absorption, as well as good blood-brain permeability (BBB). Conclusion. Furocoumarins reduce kidney dysfunction and associated pathophysiological complications via the reduction of glomerular vascular rigidity, diabetic nephropathy, and oxidative and inflammatory stress. However, further biomolecular and clinical examinations are necessary to validate and enhance the credibility of present findings.
An Ensemble Feature Selection Approach-Based Machine Learning Classifiers for Prediction of COVID-19 Disease
Authors: Hossen Md. Jakir , Ramanathan Thirumalaimuthu Thirumalaiappan , Al Mamun Abdullah
Published: April 2024

The respiratory disease of coronavirus disease 2019 (COVID-19) has wreaked havoc on the economy of every nation by infecting and killing millions of people. This deadly disease has taken a toll on the life of the entire human race, and an exact cure for it is still not developed. Thus, the control and cure of this disease mainly depend on restricting its transmission rate through early detection. The detection of coronavirus infection facilitates the isolation and exclusive care of infected patients. This research paper proposes a novel data mining system that combines the ensemble feature selection method and machine learning classifier for the effective identification of COVID-19 infection. Different feature selection approaches including chi-square test, recursive feature elimination (RFE), genetic algorithm (GA), particle swarm optimization (PSO), and random forest are evaluated for their effectiveness in enhancing the classification accuracy of the machine learning classifiers. The classifiers that are considered in this research work are decision tree, naïve Bayes, K-nearest neighbor (KNN), multilayer perceptron (MLP), and support vector machine (SVM). Two COVID-19 datasets were used for testing from which the best features supporting the dataset were extracted by the proposed system. The performance of the machine learning classifiers based on the ensemble feature selection methods is analyzed.
Maintenance Pembrolizumab Therapy in Patients with Metastatic HER2-negative Breast Cancer with Prior Response to Chemotherapy
Authors: Iwase Toshiaki , Cohen Evan N. , Gao Hui , Alexander Angela , Kai Megumi , Chiv Vivian , Wang Xiaoping , Krishnamurthy Savitri , Liu Diane , Shen Yu , Kida Kumiko , Reuben Alexandre , Layman Rachel M. , Ramirez David L. , Tripathy Debasish , Moulder Stacy L. , Yam Clinton , Valero Vicente , Lim Bora , Reuben James M. , Ueno Naoto T.
Published: April 2024

Purpose:

Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study.

Patients and Methods:

Patients with a complete response, partial response, or stable disease (SD) after at least three cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 years of pembrolizumab exposure. The endpoints included the 4-month disease control rate (DCR), progression-free survival (PFS), overall survival, and response biomarkers in the blood.

Results:

Of 43 treated patients, 11 had metastatic IBC and 32 non-IBC TNBC. The 4-month DCR was 58.1% [95% confidence interval (CI), 43.4–72.9]. For all patients, the median PFS was 4.8 months (95% CI, 3.0–7.1 months). The toxicity profile was similar to the previous pembrolizumab monotherapy study. Patients with high T-cell clonality at baseline had a longer PFS with pembrolizumab treatment than did those with low T-cell clonality (10.4 vs. 3.6 months, P = 0.04). Patients who achieved SD also demonstrated a significant increase in T-cell clonality during therapy compared with those who did not achieve SD (20% vs. 5.9% mean increase, respectively; P = 0.04).

Conclusions:

Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.
Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors
Authors: Steeghs Neeltje , Gomez-Roca Carlos , Rohrberg Kristoffer S. , Mau-Sørensen Morten , Robbrecht Debbie , Tabernero Josep , Ahmed Samreen , Rodríguez-Ruiz Maria E. , Ardeshir Caroline , Schmid Daniela , Sleiman Nassim , Watson Carl , Piper-Lepoutre Hanna , Dejardin David , Evers Stefan , Boetsch Christophe , Charo Jehad , Teichgräber Volker , Melero Ignacio
Published: April 2024

Purpose:

Simlukafusp alfa [fibroblast activation protein α–targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an IL2 variant moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast activation protein α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors.

Patients and Methods:

Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intraparticipant uptitration regimens (15/20, 20/25, 20/20/35, and 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities, maximum tolerated dose, recommended expansion dose, and pharmacokinetics.

Results:

Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (uptitration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). The uptitration regimen 15/20 mg was determined as the maximum tolerated dose and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses [NK cells, 13-fold; CD4+ T cells (including regulatory T cells), 2-fold; CD8+ T cells, 3.5-fold] but without any percentage change in regulatory T cells. Clinical activity was observed from 5 mg [objective response rate, 5.1% (n = 3); disease control rate, 27.1% (n = 16)]. Responses were durable [n = 3, 2.8 (censored), 6.3, and 43.4 months].

Conclusions:

FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.
Low-Dose Ionizing γ-Radiation Elicits the Extrusion of Neutrophil Extracellular Traps
Authors: Teijeira Alvaro , Garasa Saray , Ochoa Maria C. , Sanchez-Gregorio Sandra , Gomis Gabriel , Luri-Rey Carlos , Martinez-Monge Rafael , Pinci Beatrice , Valencia Karmele , Palencia Belen , Barbés Benigno , Bolaños Elixabet , Azpilikueta Arantza , García-Cardosa Marina , Burguete Javier , Eguren-Santamaría Iñaki , Garate-Soraluze Eneko , Berraondo Pedro , Perez-Gracia Jose L. , de Andrea Carlos E. , Rodriguez-Ruiz Maria E. , Melero Ignacio
Published: April 2024

Purpose:

Patients with cancer frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NET), we have investigated the mechanisms, consequences, and occurrence of such phenomena in patients undergoing radiotherapy.

Experimental Design:

NETosis was analyzed in cultures of neutrophils isolated from healthy donors, patients with cancer, and cancer-bearing mice under confocal microscopy. Cocultures of radiation-induced NETs, immune effector lymphocytes, and tumor cells were used to study the effects of irradiation-induced NETs on immune cytotoxicity. Radiation-induced NETs were intravenously injected to mice for assessing their effects on metastasis. Circulating NETs in irradiated patients with cancer were measured using ELISA methods for detecting MPO–DNA complexes and citrullinated histone 3.

Results:

Irradiation of neutrophils with very low γ-radiation doses (0.5–1 Gy) elicits NET formation in a manner dependent on oxidative stress, NADPH oxidase activity, and autocrine IL8. Radiation-induced NETs interfere with NK cell and T-cell cytotoxicity. As a consequence, preinjection of irradiation-induced NETs increases the number of successful metastases in mouse tumor models. Increases in circulating NETs were readily detected in two prospective series of patients following the first fraction of their radiotherapy courses.

Conclusions:

NETosis is induced by low-dose ionizing irradiation in a neutrophil-intrinsic fashion, and radiation-induced NETs are able to interfere with immune-mediated cytotoxicity. Radiation-induced NETs foster metastasis in mouse models and can be detected in the circulation of patients undergoing conventional radiotherapy treatments.

See related commentary by Mowery and Luke, p. 3965
Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer
Authors: Peressini Melina , Garcia-Campelo Rosario , Massuti Bartomeu , Martí Cristina , Cobo Manuel , Gutiérrez Vanesa , Dómine Manuel , Fuentes José , Majem Margarita , de Castro Javier , Córdoba Juan F. , Diz María P. , Isla Dolores , Esteban Emilio , Carcereny Enric , Vila Laia , Moreno-Vega Alberto , Ros Silverio , Moreno Amaia , García Francisco J. , Huidobro Gerardo , Aguado Carlos , Cebey-López Victor , Valdivia Javier , Palmero Ramón , Lianes Pilar , López-Brea Marta , Vidal Oscar J. , Provencio Mariano , Arriola Edurne , Baena Javier , Herrera Mercedes , Bote Helena , Molero Magdalena , Adradas Vera , Ponce-Aix Santiago , Nuñez-Buiza Angel , Ucero Álvaro , Hernandez Susana , Lopez-Rios Fernando , Conde Esther , Paz-Ares Luis , Zugazagoitia Jon
Published: April 2024

Purpose:

Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC.

Experimental Design:

We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y).

Results:

Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy.

Conclusions:

This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.
Potential of Thermal Ablation Combined with Immunotherapy in Peripheral Lung Tumors: A Review and Prospect
Authors: Yang Rui , Gu Chuanjia , Xie Fangfang , Hong Siyuan , Herth Felix J.F. , Sun Jiayuan
Published: April 2024

Background: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. Summary: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. Key Messages: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.
Serum levels of the steroid hormone dehydroepiandrosterone (DHEA) are associated with psychological trauma and lymphocyte telomere integrity in women suffering from depression
Authors: de Punder Karin , Salinas-Manrique Juan , Dietrich Detlef E. , Karabatsiakis Alexander
Published: April 2024

Introduction: Emerging studies highlight the telomere system as an aging mechanism underlying the association between exposure to psychological trauma and the development of a wide range of physical and mental disorders, including major depressive disorder (MDD). Here, we investigated associations of circulating levels of the steroid hormone dehydroepiandrosterone (DHEA) with immune cell telomere length (TL) in the context of lifetime trauma exposure and MDD.
Methods: Lifetime traumatic events (trauma load) were assessed using the Essener Trauma Inventory (ETI) in n=22 postmenopausal female inpatients with MDD and n=22 non-depressed controls. All women completed the Beck’s Depression Inventory-II to assess the severity of current depressive symptoms. DHEA concentration in serum was measured by immunoassay and TL was quantified in kilobase units using quantitative fluorescent in situ hybridization (qFISH) in total peripheral blood mononuclear cells (PBMC) and in selected T cell subpopulations isolated by FACS separation.
Results: Higher trauma load was significantly associated with lower DHEA concentration, which in turn was linked to more depression-related fatigue. Furthermore, DHEA concentration was positively and significantly associated with TL in memory CD4+ T cells as well as in naïve and memory CD8+ T cells, but not in naïve CD4+ T cells and total PBMC. Mediational analysis suggested that DHEA concentration is a mediator in the relationship between trauma load and memory CD8+ T cell TL.
Conclusion: The current findings suggest a potential role of DHEA as a biological resilience factor that may exert beneficial effects on telomere integrity, especially in conditions related to distress.
The rehabilitation for visual cognitive impairment due to hippocampal infarction: a case report
Authors: Mano Tomoo , Kirimura Sakura , Uchihara Yuto , Takashima Hideki , Masuda Takashi
Published: April 2024

Introduction: Disturbances in the visual pathway cause visual cognitive impairment. There is a lack of information regarding the effect of rehabilitation on individuals affected by this condition. Therefore, it is crucial to understand the effectiveness of rehabilitation interventions in this condi-tion. Case Presentation: We present the case of an 87-year-old woman with hippocampal infarction. While the patient’s ability to perform daily activities and engage in conversations was normal, she faced challenges at the execution stage, such as naming, constructing sentences, and copying. We diagnosed cerebral embolism because of atrial fibrillation and initiated direct oral anticoagulant therapy. Subsequently, we initiated a rehabilitation treatment comprising visual agnosia training (attribute learning training), verbalization learning training (writing training), and semantic memory training (copying training) to address visual agnosia. Conclusion: Associative visual perception challenges arising from hippocampal infarcts are rare and can be improved with early intervention through a rehabilitation program for visual agnosia.
Characterizing the Validity of Using VASES to Derive DIGEST-FEES Grades
Authors: Curtis James A. , Tabor Gray Lauren , Arrese Loni , Borders James C. , Starmer Heather
Published: April 2024

Introduction: Visual Analysis of Swallowing Efficiency and Safety (VASES) and Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES) are two complimentary methods for assessing swallowing during FEES. Whereas VASES is intended to facilitate trial-level ratings of pharyngeal residue, penetration, and aspiration, DIGEST-FEES is intended to facilitate protocol-level impairment grades of swallowing safety and efficiency. The aim of this study was to assess the validity of using VASES to derive DIGEST-FEES impairment grades. Methods: DIGEST-FEES grades were blindly analyzed from 50 FEES – first using the original DIGEST-FEES grading method (n = 50) and then again using a VASES-derived DIGEST-FEES grading method (n = 50). Weighted Kappa (κw) and absolute agreement (%) were used to assess the relationship between the original DIGEST-FEES grades and VASES-derived DIGEST-FEES grades. Spearman’s correlations assessed the relationship between VASES-derived DIGEST-FEES grades with measures of construct validity. Results: Substantial agreement (κw = 0.76–0.83) was observed between the original and VASES-derived grading methods, with 60–62% of all DIGEST-FEES grades matching exactly, and 92–100% of DIGEST-FEES grades within one grade of each other. Furthermore, the strength of the relationships between VASES-derived DIGEST-FEES grades and measures of construct validity (r = 0.34–0.78) were similar to the strength of the relationships between original DIGEST-FEES grades and the same measures of construct validity (r = 0.34–0.83). Conclusion: Findings from this study demonstrate substantial agreement between original and VASES-derived DIGEST-FEES grades. Using VASES to derive DIGEST-FEES also appears to maintain the same level of construct validity established with the original DIGEST-FEES. Therefore, clinicians and researchers may consider using VASES to increase the transparency and standardization of DIGEST-FEES ratings. Future research should seek to replicate these findings and explore the simultaneous use of VASES and DIGEST-FEES in a greater sampling of raters and across other patient populations.
A sociabilidade imaginada: processos de simbolização e ressignificação da identidade rural goiana
Authors: Christino Daniel , Limena Maria Margarida Cavalcanti , Nogueira Maria Francisca Magalhães
Published: April 2024

Pesquisa sobre o imaginário rural de Goiás cujo objetivo é estudar e compreender as motivações que levam o indivíduo a buscar o campo como espaço de lazer e sociabilidade, num estado no qual, culturalmente, predominam as características rurais. Inicialmente, levantou-se aspectos históricos com fins de reconstituir o que de fato existiu no imaginário rural da sociedade goiana através de autores reconhecidos. A seguir, realizou-se entrevistas aleatórias com turistas rurais, que na sua maioria tratava-se de turistas de origem rural, em decorrência da predominância do status rural existente no estado. A análise dos dados evidencia a predominância do status rural no estado, porém percebe-se mudanças na re-elaboração simbólica do rural tradicional. Conclui-se que o imaginário rural goiano está repleto de símbolos originados da tradição rural de Goiás, embora esteja em construção novos ressignificados, reflexos de um passado agregado à memória coletiva.
A experiência do trabalho de campo no universo da comunicação
Authors: Travancas Isabel Siqueira
Published: April 2024

El objetivo de esta comunicación es discutir de la experiencia del trabajo de campo a partir de dos investigaciones distintas: la primeira realizada con periodistas y la otra con jóvenes universitarios. La idea es problematizar las particularidades de la investigación antropológica y del método cualitativo, el cual incluye la observación participante, la realización de entrevistas abiertas en profundidad y la producción de un diario de campo. También se analizará la dificultad de trabajar de forma simultánea con los métodos cuantativos que aportan nuevas perspectivas  y que muchas veces son vistos como herramientas menores. En cada uno de estos trabajos surgieron dificultades diferentes. Las dos experiencias de trabajo dentro del campo de la comunicación permiten ahondar en la discusión sobre la utilización de distintos métodos de investigación y evaluar las contribuciones de la metodología antropológica.