bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer
Authors: Morgensztern Daniel , Ready Neal , Johnson Melissa L. , Dowlati Afshin , Choudhury Noura , Carbone David P. , Schaefer Eric , Arnold Susanne M. , Puri Sonam , Piotrowska Zofia , Hegde Aparna , Chiang Anne C. , Iams Wade , Tolcher Anthony , Nosaki Kaname , Kozuki Toshiyuki , Li Tianhong , Santana-Davila Rafael , Akamatsu Hiroaki , Murakami Haruyasu , Yokouchi Hiroshi , Wang Song , Zha Jiuhong , Li Rui , Robinson Randy R. , Hingorani Pooja , Jeng Edwin E. , Furqan Muhammad 
Published: September 2024

Abstract

Purpose:
Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.

Patients and Methods:
ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3–2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.

Results:
As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41–79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6–6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5–4.2).

Conclusions:
ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
Cancer in Multilineage Mosaic RASopathies due to Pathogenic Variants in HRAS or KRAS: A Systematic Review and Meta-analysis
Authors: Windrich Jonas , Ney Gina M. , Rosenberg Philip S. , Kim Jung , Zenker Martin , Stewart Douglas R. , Kratz Christian P. 
Published: September 2024

Abstract

Purpose:
To determine the cancer risk and spectrum in patients with multilineage mosaic RASopathies with pathogenic variants (PV) in HRAS or KRAS.

Experimental Design:
We conducted a systematic literature review to identify multilineage mosaic RASopathy cases with a PV in HRAS or KRAS to create a retrospective cohort. We calculated cumulative incidence, cancer-free survival, and hazard rates for cancer and standardized incidence rates (SIR).

Results:
This study identified 69 patients. Of these, 17% had cancer, including rhabdomyosarcoma (RMS) located in the urogenital region (n = 7), skin cancer (n = 3), Wilms tumor (n = 1), and bladder cancer (n = 1). Cumulative cancer incidence by age 20 was 20% (95% confidence interval, 4%–37%). The annual cancer hazard rate peaked at 14% within the first 2 years of life. The highest SIR was found for RMS (SIR = 800; 95% confidence interval, 300–1648).

Conclusions:
This is the first investigation of cancer risk in KRAS or HRAS PV–positive mosaic RASopathies to date. The high incidence and SIR values found highlight the need for rigorous RMS surveillance in young children and skin cancer surveillance in adults with this high-risk condition.
Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D. 
Published: September 2024

Abstract
High-grade serous ovarian cancer remains a poorly understood disease with a high mortality rate. Although most patients respond to cytotoxic therapies, a majority will experience recurrence. This may be due to a minority of drug-resistant cancer stem-like cells (CSC) that survive chemotherapy and are capable of repopulating heterogeneous tumors. It remains unclear how CSCs are supported in the tumor microenvironment (TME) particularly during chemotherapy exposure. Tumor-associated macrophages (TAM) make up half of the immune population of the ovarian TME and are known to support CSCs and contribute to cancer progression. TAMs are plastic cells that alter their phenotype in response to environmental stimuli and thus may influence CSC maintenance during chemotherapy. Given the plasticity of TAMs, we studied the effects of carboplatin on macrophage phenotypes using both THP1- and peripheral blood mononuclear cell (PBMC)–derived macrophages and whether this supports CSCs and ovarian cancer progression following treatment. We found that carboplatin exposure induces an M1-like proinflammatory phenotype that promotes SOX2 expression, spheroid formation, and CD117+ ovarian CSCs, and that macrophage-secreted CCL2/MCP-1 is at least partially responsible for this effect. Depletion of TAMs during carboplatin exposure results in fewer CSCs and prolonged survival in a xenograft model of ovarian cancer. This study supports a role for platinum-based chemotherapies in promoting a transient proinflammatory M1-like TAM that enriches for CSCs during treatment. Improving our understanding of TME responses to cytotoxic drugs and identifying novel mechanisms of CSC maintenance will enable the development of better therapeutic strategies for high-grade serous ovarian cancer.
Significance: We show that chemotherapy enhances proinflammatory macrophage phenotypes that correlate with ovarian cancer progression. Given that macrophages are the most prominent immune cell within these tumors, this work provides the foundation for future translational studies targeting specific macrophage populations during chemotherapy, a promising approach to prevent relapse in ovarian cancer.
The Psychedelic Renaissance: A Catholic Perspective
Authors: Carroll Thomas 
Published: September 2024

After being outlawed in 1970, psychedelics have reemerged in the consciousness of Western society in the form of the so-called psychedelic renaissance. This has led to widespread interest in psychedelic compounds being used for recreation, treatment of mental illness and addiction, and even the so-called “enhancement” of individuals and society. This renewed interest in psychedelics has resulted in seemingly endless publications in both the popular and the academic press, including authors from fields as diverse as philosophy, theology, pharmacology, neuroscience, and clinical medicine. A common thread in this developing literature is the claim that psychedelic compounds mediate their reported benefits by inducing the so-called psychedelic mystical experience (PME). The nature of PME is hotly debated, with some claiming that it is entirely psychological and others proposing that it involves contact with extramental reality. This raises a number of important questions for Catholics, especially whether PME should be considered properly “mystical,” how PME compares with traditionally understood Catholic mysticism, and whether, and if so under what conditions, psychedelics could be licitly used by the Catholic faithful. This paper is an attempt to begin the process of reconciling empiric scientific data regarding psychedelics generally, and PME specifically, with Catholic philosophical and theological considerations, with the goal of both providing recommendations regarding the licitness of the use of psychedelic compounds and inviting conversation about this important and challenging topic. Summary Over the past 20 years, there has been a renewed interest in of psychedelics. Many articles have been published extoling the benefits of psychedelics, including for the treatment of mental illness and addiction, recreation, and “enhancement” of individuals and society. A common claim is that the benefits of psychedelics are a result of the psychedelic mystical experience (PME). This paper considers both the use of psychedelics and PME from the perspective of Catholic theology, provides recommendations about their use for the Catholic faithful, and invites further conversation about this important and challenging topic. Short Summary This paper considers challenges posed by psychedelics, considers licitness of use, and calls for further discussion.
Minimal invasive extracorporeal circulation: A bibliometric network analysis of the global scientific output
Authors: D’Andria Ursoleo Jacopo , Losiggio Rosario , Licheri Margherita , Barucco Gaia , Lazzari Stefano , Faustini Carolina , Monaco Fabrizio ,   Collaborators
Published: September 2024

Introduction Minimal Invasive Extracorporeal Circulation (MiECC) has recently emerged as a more ‘physiologic’ alternative to conventional extracorporeal circulation. However, its adoption is still limited due to lack of robust scientific evidence and ongoing debate about its potential benefits. This bibliometric analysis aims to analyze the scientific articles on MiECC and identify current research domains and existing gaps to be addressed in future studies. Methods Pertinent articles were retrieved from the Web of Science (WOS) database. The search string included ‘minimal invasive extracorporeal circulation’ and its synonyms. The VOSviewer (version 1.6.17) software was used to conduct comprehensive analyses. Semantic and research networks, bibliographic coupling and journal analysis were performed. Results Of the 1777 articles identified in WOS, 292 were retrieved. The trend in publications increased from 1991 to date. Most articles focused on transfusion requirements, acute kidney injury, inflammatory markers and cytokines, inflammation and delirium, though the impact of intraoperative optimal fluid and hemodynamic management as far as the occurrence of postoperative complications were poorly addressed. The semantic network analysis found inter-connections between the terms “cardiopulmonary bypass”, “inflammatory response”, and “cardiac surgery”. Perfusion contributed the highest number of published documents. The most extensive research partnerships were between Germany, Greece, Italy, and England. Conclusions Notwithstanding the scientific community’s growing interest in MiECC, crucial topics (i.e., the best anesthetic management and intraoperative need for inotropes, vasopressors and fluids) still require more comprehensive exploration. This investigation may prove to be a useful tool for clinicians, scientists, and students concerning global publication output and for the use of MiECC in cardiac surgery.
Increased CCT5 expression is a potential unfavourable factor promoting the growth of nasopharyngeal carcinoma
Authors: Wu Shaoyu , Peng Lingrong 
Published: September 2024

Objective Chaperonin containing TCP1 subunit 5 ( CCT5) encodes the CCT5 protein subunit of chaperonin-containing TCP-1 (CCT/TRiC) complex, and is shown to be upregulated in tumour pathogenesis. The study aim was to investigate the differential expression of CCT5 between nasopharyngeal carcinoma (NPC) and noncancerous nasopharyngeal tissues, and the correlation between CCT5 expression and clinicopathological parameters/prognosis in patients with NPC. Methods Microarray assay data were evaluated for differential expression between NPC and noncancerous nasopharyngeal tissues. CCT5 expression in NPC and noncancerous nasopharyngeal tissues was determined at mRNA and protein levels by quantitative reverse transcription–polymerase chain reaction (qRT–PCR) and immunohistochemistry. Relationships between CCT5 expression in NPC, clinical parameters, and prognosis were statistically analysed. CCT5-mediated cell proliferation was assessed using EdU and cell counting kit-8. Western blot and co-immunoprecipitation were utilized to explore E3 ubiquitin-protein ligase parkin (PARK2)-induced degradation of CCT5. Results Microarray data showed CCT5 levels to be significantly increased in NPC versus noncancerous nasopharyngeal tissues, which was confirmed by qRT-PCR and immunohistochemical assays. Increased CCT5 protein levels positively correlated with tumour size, tumour recurrence, and clinical stage, and inversely correlated with patient’s overall survival. Multivariate Cox regression analysis showed that enhanced CCT5 protein expression is an independent prognostic factor for patients with NPC. Overexpression of CCT5 markedly induced NPC cell proliferation. Finally, PARK2, as a suppressive E3 ubiquitin-ligase enzyme, was shown to bind CCT5 and induce degradation in NPC. Conclusions Increased CCT5 may be an unfavourable factor promoting NPC growth. Binding of PARK2 to CCT5 was associated with CCT5 degradation, suggesting that PARK2 is an upstream negative modulator in NPC.
Factors Influencing Health Professionals’ Decisions Regarding the Indication of Infant Formula: A Qualitative Exploration in Uruguay
Authors: Girona Alejandra , Brunet Gerónimo , Ares Gastón , Rodríguez Raquel , León Carolina de , Lozano Mónica , Vidal Leticia 
Published: September 2024

Background: Health systems are fundamental to the promotion and protection of breastfeeding. Health professionals have a pivotal influence on families’ infant feeding decisions and may act as facilitators or barriers to adequate breastfeeding practices. Research Aim: To explore factors influencing health professionals’ decisions regarding the indication of infant formula in Montevideo, the capital of Uruguay, an emerging Latin American country. Method: This was a qualitative study based on semi-structured interviews with 30 health professionals (neonatologists, pediatricians, family doctors, and nurses) working in primary and secondary care in both private and public health institutions. The interviews were audio-recorded, transcribed, and analyzed using content analysis based on deductive-inductive coding. Results: The narratives of the participants identified maternity wards as the healthcare sites where the indication of infant formula occurs most frequently. Motives underlying the indication of infant formula by health professionals were diverse. The type of birth and the conditions of the child and the mother were the most relevant in secondary care, whereas maternal work was the main determining factor in primary care. A wide range of factors encouraging and discouraging the indication of infant formula were identified by health professionals in primary and secondary healthcare locations, which were related to all the levels of influence of the socioecological model. Conclusions: Strategies to reduce the use of infant formula in Uruguay should include improving the support and guidance provided to families in the maternity ward, strengthening the implementation and monitoring of the Baby-Friendly Hospital Initiative, and improving the current maternity leave regulations.
Technical Anonymity and Employees’ Willingness to Speak Up: Influences of Voice Solicitation, General Timeliness, and Psychological Safety
Authors: Liu Chun , Yuan Qin , Luo Jiang 
Published: September 2024

Purpose: In recent years, many enterprises have established anonymous online forums to encourage employees to speak up. However, questions remain regarding whether these anonymous communication channels work. This research explores how and when technical anonymity influences employees’ willingness to speak up. Design/methodology/approach: Via an experimental method (study 1), we investigated the effects of technical anonymity and the moderating effects of voice solicitation. Via an experimental method (study 2), we examined the effects of technical anonymity and the moderating effects of time delay. Findings: The results of two studies consistently indicate that employees are more willing to speak up in the anonymous condition than in the nonanonymous condition and that psychological safety mediates the relationship between technical anonymity and employees’ willingness to speak up. In addition, we identify the boundary conditions of the effects of technical anonymity. In the prohibitive voice solicitation condition and in the delay condition, the above effects exist. Originality/value: First, we contribute to the literature on organizational media affordance by examining the effects of the anonymity affordance. Second, we contribute to the literature on organizational anonymity communication by exploring the impacts of technical anonymity on employees’ willingness to speak up in the workplace. Third, we extend the literature on employee voice by theorizing and demonstrating the moderating roles of two novel variables.
Studies on fuels and engine attributes powered by bio-diesel and bio-oil derived from stone apple seed (Aegle marmelos) for bioenergy
Authors: Sriariyanun Malinee , U Elaiyarasan , R Sakthivel , P Baranitharan , Tawai Atthasit , T Arunkumar 
Published: September 2024

Biofuel is an alternative fuel for diesel engines which is necessary to reduce exhaust emissions and helps to balance the depletion of fossil fuels. This study details the synthesis of bio-diesel and bio-oil from stone apple seeds ( Aegle marmelos) through transesterification, direct oxygenate additive, and pyrolysis processes. The diesel engine is powered by the resulting stone apple methyl ester bio-diesel/diesel and bio-oil/diesel mixtures. In a test engine rig, the effectiveness and emission uniqueness of test fuel mixes were examined at various engine loads (EL = 3 kg–12 kg) and compression ratios (CR = 16–17.5) while maintaining a steady speed of 1500 r/min. Furthermore, engine performance and emissions for bio-diesel and bio-oil are measured and compared. The oxides of nitrogen (NOx) emission by bio-diesel and bio-oil opus were higher than neat diesel (FD). Also, carbon monoxide (CO) and hydrocarbon (HC) emissions were measured to be lower. The improvements of BTE by 4.87% and decrement of CO by 18.8%, HC by 13.26% were observed with the trans-esterified bio-diesel/diesel opus compared to diesel at a higher CR and rated load conditions. The engine analysis responses revealed that the FBD blend showed enhanced performance and lower emissions except NOx compared to diesel fuel. Hence, trans-esterified bio-diesel is a greater diesel alternative than FBDE and FBO.
Cognitive impairment in a Colombian cohort of patients with systemic lupus erythematosus: A cross-sectional study
Authors: Medina Yimy F , Rivera Manuela R , Duarte Liliana K , Rodriguez-Plata Carlos M , De León Emmanuel R , Rodríguez Martínez Sonia C 
Published: September 2024

Context Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. Objective To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. Methods and Patients This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. Results Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. Conclusion In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.
The experience and implications of pain in systemic lupus erythematosus: A qualitative interview study focusing on the patient’s perspective
Authors: Waldheim Eva , Welin Elisabet , Bergman Stefan , Pettersson Susanne 
Published: September 2024

Background Pain is one of the most frequently reported symptoms and often one of the first subjective symptoms in patients with systemic lupus erythematosus (SLE). A previous study indicated that most patients with SLE reported low levels of SLE-related pain. However, a subgroup of patients reported high levels of pain ≥40 mm (0-100 mm) and had a substantial symptom burden in terms of fatigue, anxiety, depression, and reduced health-related quality of life. Thus, there is a need to elucidate the implications of high levels of pain in everyday life. Aim This study explored the patient’s experiences and implications of SLE-related pain in daily life and the support requested from healthcare providers. Method A total of 20 patients, previously reported high levels of SLE-related pain intensity measuring ≥40 mm (0–100 mm) in a research context at one or two occasions participated in individual semi-structured interviews, which were transcribed and analysed with content analysis. Results The interviews revealed four main categories and 13 generic categories. SLE-associated pain was described by its multifaceted nature, exhibiting longstanding, unpredictable, migrating, and various physical sensations. The pain entailed multidimensional consequences, restricting everyday life by interfering with roles and relationships and causing various emotions, including existential thoughts. The informants used comprehensive strategies to deal with the pain, including their inner resources, support from family and significant others, and pharmaceuticals and relieving treatments. They expressed the need for security and acknowledgement, which involved individualized support and accessibility of healthcare. Conclusion This study provides comprehensive insights into the nature and multifaceted impact of SLE-related pain in different dimensions of the informants’ daily lives. Except for medications the informants used several strategies, including their inner resources and support from family and others, to manage the pain. Support requested from healthcare providers by the informants included understanding, compassion, individualized care and accessibility.