bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: June 2023

AbstractPurpose:
Histone deacetylase (HDAC) inhibition has been shown to induce pharmacologic “BRCAness” in cancer cells with proficient DNA repair activity. This provides a rationale for exploring combination treatments with HDAC and PARP inhibition in cancer types that are insensitive to single-agent PARP inhibitors (PARPi). Here, we report the concept and characterization of a novel bifunctional PARPi (kt-3283) with dual activity toward PARP1/2 and HDAC enzymes in Ewing sarcoma cells.
Experimental Design:
Inhibition of PARP1/2 and HDAC was measured using PARP1/2, HDAC activity, and PAR formation assays. Cytotoxicity was assessed by IncuCyte live cell imaging, CellTiter-Glo, and spheroid assays. Cell-cycle profiles were determined using propidium iodide staining and flow cytometry. DNA damage was examined by γH2AX expression and comet assay. Inhibition of metastatic potential by kt-3283 was evaluated via ex vivo pulmonary metastasis assay (PuMA).
Results:
Compared with FDA-approved PARP (olaparib) and HDAC (vorinostat) inhibitors, kt-3283 displayed enhanced cytotoxicity in Ewing sarcoma models. The kt-3283-induced cytotoxicity was associated with strong S and G2–M cell-cycle arrest in nanomolar concentration range and elevated DNA damage as assessed by γH2AX tracking and comet assays. In three-dimensional spheroid models of Ewing sarcoma, kt-3283 showed efficacy in lower concentrations than olaparib and vorinostat, and kt-3283 inhibited colonization of Ewing sarcoma cells in the ex vivo PuMA model.
Conclusions:
Our data demonstrate the preclinical justification for studying the benefit of dual PARP and HDAC inhibition in the treatment of Ewing sarcoma in a clinical trial and provides proof-of-concept for a bifunctional single-molecule therapeutic strategy.
Data from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Abstract
Purpose: Resistance to third-generation epidermal growth factor receptor (EGFR) inhibitors including osimertinib arises in part from the C797S mutation in EGFR. Currently, no targeted treatment option is available for these patients. We have developed a new EGFR tyrosine kinase inhibitor (TKI), BBT-176, targeting C797S mutation. Patients and Methods: Recombinant EGFR proteins and Ba/F3 cell lines, patient-derived cells and patient-derived xenografts expressing mutant EGFRs were used to test the inhibitory potency and the efficacy of BBT-176 both in vitro and in vivo. Patient cases are derived from an ongoing phase 1 clinical trial (NCT04820023). Results: The half maximal inhibitory concentration (IC50) of BBT-176 against EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, and EGFR L858R/C797S protein were measured at 4.36, 1.79 and 5.35 nM, respectively (vs. 304.39, 124.82, and 573.72 nM, for osimertinib). IC50 values of BBT‑176 against Ba/F3 cells expressing EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, EGFR L858R/C797S, and EGFR L858R/T790M/C797S were 42, 49, 183 and 202 nM, respectively (vs 869, 1134, 2799, and 2685 nM for osimertinib). N-Ethyl-N-nitrosourea (ENU) mutagenesis suggested that BBT-176 treatment does not introduce any secondary mutations in the EGFR gene but increases EGFR expression levels. Combined with the EGFR antibody cetuximab, BBT‑176 effectively suppressed the growth of BBT-176-resistant clones. BBT‑176 strongly inhibited the tumor growth, and in some conditions induced tumor regression in mouse models. In the clinical trial, two patients from harboring EGFR 19Del/T790M/C797S in blood showed tumor shrinkage and radiological improvements. Conclusions: BBT-176 is a fourth-generation EGFR inhibitor showing promising preclinical activity against NSCLC resistant to current EGFR TKIs.
Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
Authors: Ellingsen Espen B. , O'Day Steven , Mezheyeuski Artur , Gromadka Agnieszka , Clancy Trevor , Kristedja Timothy S. , Milhem Mohammed , Zakharia Yousef
Published: June 2023

Purpose:

Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone. In this trial, a telomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma.

Patients and Methods:

Thirty treatment-naïve patients with advanced melanoma were enrolled. Patients received intradermal injections of UV1 with adjuvant GM-CSF at two dose levels, and pembrolizumab according to the label. Blood samples were assessed for vaccine-induced T-cell responses, and tumor tissues were collected for translational analyses. The primary endpoint was safety, with secondary objectives including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Results:

The combination was considered safe and well-tolerated. Grade 3 adverse events were observed in 20% of patients, with no grade 4 or 5 adverse events reported. Vaccination-related adverse events were mostly mild injection site reactions. The median PFS was 18.9 months, and the 1- and 2-year OS rates were 86.7% and 73.3%, respectively. The ORR was 56.7%, with 33.3% achieving complete responses. Vaccine-induced immune responses were observed in evaluable patients, and inflammatory changes were detected in posttreatment biopsies.

Conclusions:

Encouraging safety and preliminary efficacy were observed. Randomized phase II trials are currently ongoing.
Supplementary Methods S1 from Examining the Barriers and Opportunities for Human Papillomavirus Vaccine Delivery in Cancer Care Settings: A Mixed-Methods Study
Authors: Garcia Melany A. , Schlecht Nicolas F. , Rokitka Denise A. , Attwood Kristopher M. , Rodriguez Elisa M.
Published: June 2023

Supplementary Methods S1 contains the survey questionnaire items discussed in section 2 of the main text.
Supplementary Table S9 from Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi
Published: June 2023

Supplementary Table S9
Supplementary Figures from Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi
Published: June 2023

Supplementary Figures 1-10
AXL Inhibition Improves the Antitumor Activity of Chimeric Antigen Receptor T Cells
Authors: Sakemura R. Leo , Hefazi Mehrdad , Cox Michelle J. , Siegler Elizabeth L. , Sinha Sutapa , Hansen Michael J. , Stewart Carli M. , Feigin Jennifer M. , Manriquez Roman Claudia , Schick Kendall J. , Can Ismail , Tapper Erin E. , Horvei Paulina , Adada Mohamad M. , Bezerra Evandro D. , Kankeu Fonkoua Lionel Aurelien , Ruff Michael W. , Forsman Cynthia L. , Nevala Wendy K. , Boysen Justin C. , Tschumper Renee C. , Grand Cory L. , Kuchimanchi Kameswara R. , Mouritsen Lars , Foulks Jason M. , Warner Steven L. , Call Timothy G. , Parikh Sameer A. , Ding Wei , Kay Neil E. , Kenderian Saad S.
Published: June 2023

The receptor tyrosine kinase AXL is a member of the TYRO3, AXL, and proto-oncogene tyrosine-protein kinase MER family and plays pleiotropic roles in cancer progression. AXL is expressed in immunosuppressive cells, which contributes to decreased efficacy of immunotherapy. Therefore, we hypothesized that AXL inhibition could serve as a strategy to overcome resistance to chimeric antigen receptor T (CAR T)–cell therapy. To test this, we determined the impact of AXL inhibition on CD19-targeted CAR T (CART19)–cell functions. Our results demonstrate that T cells and CAR T cells express high levels of AXL. Specifically, higher levels of AXL on activated Th2 CAR T cells and M2-polarized macrophages were observed. AXL inhibition with small molecules or via genetic disruption in T cells demonstrated selective inhibition of Th2 CAR T cells, reduction of Th2 cytokines, reversal of CAR T-cell inhibition, and promotion of CAR T-cell effector functions. AXL inhibition is a novel strategy to enhance CAR T-cell functions through two independent, but complementary, mechanisms: targeting Th2 cells and reversing myeloid-induced CAR T-cell inhibition through selective targeting of M2-polarized macrophages.
Host Interactions with Engineered T-cell Micropharmacies
Authors: Bourne Christopher M. , Wallisch Patrick , Dacek Megan M. , Gardner Thomas J. , Pierre Stephanie , Vogt Kristen , Corless Broderick C. , Bah Mamadou A. , Romero-Pichardo Jesus E. , Charles Angel , Kurtz Keifer G. , Tan Derek S. , Scheinberg David A.
Published: June 2023

Genetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Herein, we expanded the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with T-cell receptor (TCR)–engineered T cells. We demonstrate that SEAKER cells localized specifically to tumors, and activated bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells were efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.
Supplementary Tables 1-7 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Tables
Supplementary Figure 7 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Fig. 7 shows Single-Cell transcriptomics; Identifies epithelial to mesenchymal transition (EMT) marker TGFB1 in ARLow/mCRPC/NEPC (PC-3 spheroid CONT-No treatment vs, extended exposure-EE and conventional exposure-CONV). Result showed TGFB1 expression decreases after EE compared to CONV treatment, which indicated EE moderated stemness in ARLow/mCRPC/NEPC. Single-cell RNA sequencing used the droplet sequencing method (10X Genomics). Each dot represents a single cell. t-distributed stochastic neighbor embedding (tSNE) plots showing the comparison between the single-cell clusters as shown.
Supplementary Figure 6 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Fig. 6 shows Cytotoxicity Profiling of ARLow/mCRPC/NEPC (PC-3 and PC-3M) and Taxane Resistance ARLow/mCRPC (DUTXR): PC-3, PC-3M and DUTXR cell lines were treated with CONV-TOPO, METRO-TOPO, CONV-DTX and combination (CONV-DTX+METRO-TOPO) treatment, and cell cytotoxicity and caspase3/7 levels ware assed A) Cytotoxicity profiling by MTT showed combination (CONV-DTX+METRO-TOPO) reduces highest cell survival compared with other treatments for all PCa cell lines, CONV-TOPO>CONV-DTX>METRO-TOPO B) Caspase3/7 activity showed combination (CONV-DTX+METRO-TOPO) treatment reduced apoptosis the greatest compared to other treatments in all cell lines. C) Cytation5 images showed treatment effects on the cell lines PC-3M and DUTXR. Results showed significantly higher cell death in METRO compared to CONV treatment for both the cell lines and combination (CONV-DTX+METRO-TOPO) treatment reduced cell death greater for both PCa cell lines. ImageJ analysis showed significant differences in cell density for CONV-TOPO, CONV-DTX, METRO-TOPO, and combination (CONV-DTX+METRO-TOPO) treatment in PC-3, PC-3M, and DUTXR cell lines. (*p ≤ 0.05).
Supplementary Figure 2 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Fig. 2 shows Ingenuity pathway analysis (IPA) predictions for European American/ Caucasian American (EA/CA) ARHigh/mCSPC (LNCaP, VCAP, 22RV1), ARLow/mCRPC/NEPC (PC-3, PC-3M, DU145) and African American (AA) ARHigh/mCSPC (MDA-Pca-2b) PCa cell lines as well as normal prostate cell lines RWPE1 and RWPE2.
 
IPA predicted A) Diseases and biological pathways for development of ARLow/mCRPC/NEPC. Major pathways are cell movement, morbidity, mortality, migration, invasion, survival, viability and development of vasculature- vasculogenesis and angiogenesis. B) Causal network pathway for development of ARLow/mCRPC/NEPC, which include oxidative phosphorylation, p70S6K, unfolded response, TREM1 signaling, NF-kB signaling, ERK5 signaling, IL-8 signaling, BAG2 signaling, Integrin signaling and VEGF signaling. C) IPA predicted HIF1α and EMT as key pathways associated with PCa development in African Americans (AA).
Supplementary Table 2 from Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Supplementary Table 2: A classification of the immune cell subtypes.
Infarct Core Growth During Interhospital Transfer For Thrombectomy Is Faster At Night
Authors: Seners Pierre , Mlynash Michael , Sreekrishnan Anirudh , Ter Schiphorst Adrien , Arquizan Caroline , Costalat Vincent , Henon Hilde , Bretzner Martin , Heit Jeremy J. , Olivot Jean-Marc , Lansberg Maarten G. , Albers Gregory W. , Schmitt Perrine , Sablot Denis , Lalu Thibault , Bricout Nicolas , Albucher Jean-François , Cognard Christophe , Cordonnier Charlotte , Christensen Soren , Scheldeman Lauranne
Published: June 2023

BACKGROUND:

Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans.

METHODS:

We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00–22:59) and nighttime (23:00–06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status.

RESULTS:

Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2–9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4–3.5;
P
<0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate (
P
<0.05).

CONCLUSIONS:

Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow.
Merchants of Light and Lamps: John Evelyn’s Transition from Descriptive to Experimental Natural History
Authors: Matei Oana
Published: June 2023

This paper discusses the methodological relation between natural history and natural philosophy in the case of John Evelyn (1620–1706). I propose to examine Evelyn’s tree cultivation projects and to identify relevant aspects of his attempt to move from descriptive natural history to experimental natural history. My central argument is that Evelyn’s intention in this endeavour was to develop a series of experimental natural history projects that could provide general laws and axioms of nature as foundations for natural philosophy. I suggest that, considering Bacon’s methodological recommendations regarding the relation between natural history and natural philosophy, Evelyn evolved from one “Baconian” role to another. While in the 1650s Evelyn acted as a “merchant of light,” as he devoted his interest to writing natural history projects based on collecting data and commonplacing different sources, in the 1660s he moved to an advanced role, that of a “compiler” or a “lamp,” in which he composed projects of experimental natural history. In Evelyn’s view, the latter kind of natural history would serve as a methodological step in building a natural philosophy.
Thomas Aquinas on the Metaphysical Structure of Artifacts
Authors: Skrzypek Jeremy W.
Published: June 2023

It is now standard to interpret Aquinas as recognizing two main types of material objects: substances and artifacts, where substances are those material objects that result from some particular substantial form inhering in prime matter, and artifacts are those material objects that result from some particular accidental form inhering in one or more material substances. There are two problems with this standard interpretation. First, there are passages in which Aquinas states that accidental forms should be understood not as inhering in substances from the outside, but as entering into their composition so as to be included among their metaphysical parts. Second, there are passages in which Aquinas states that it is impossible for any accidental form to be shared by two or more substances. This article considers what implications these two observations might have for how we understand the metaphysical structure of artifacts in Aquinas’s ontology.
Invader’s success: behavioural and reproductive plasticity of interacting exotic dung beetles
Authors: Esquivel-Román Andrea , Dáttilo Wesley , Cruz-Rosales Magdalena , del Val Ek , González-Tokman Daniel
Published: June 2023

Dung beetles have been introduced to non-native sites to perform dung removal function in cattle pastures. Despite some species becoming invasive, their behavioural and reproductive strategies remain to be elucidated in detail. Here we evaluated the shift in behaviour and reproduction of two species of dung beetles, Euoniticellus intermedius and Digitonthophagus gazella, when they interact with the same or other species out of their native range. Under natural conditions, E. intermedius brood masses were lighter in traps (i.e., field enclosures) with more total brood masses. In the laboratory, D. gazella induced faster dung colonization by E. intermedius and conspecifics. The presence of conspecifics or heterospecifics reduced reproductive success in D. gazella, revealing intense competition for dung. In the offspring, E. intermedius females emerged larger in the presence of D. gazella, revealing differential maternal investment triggered by competitors. In conclusion, behavioural and reproductive plasticity are fundamental for dung beetles to become successful invaders.
Innate response to first feeding in Octopus berrima hatchlings despite embryonic food imprinting
Authors: Hua Qiaz Q.H. , Nande Manuel , Doubleday Zoe A. , Gillanders Bronwyn M.
Published: June 2023

Food imprinting has both ecological and evolutionary significance but the generality of these patterns for octopods remains unknown. We aim to determine the prey preference of Octopus berrima hatchlings and whether it may be modified through imprinting. Firstly, hatchlings were given isopods, amphipods and mussels to determine their prey preference ranking. In a separate experiment, embryos were exposed to the visual and chemical stimuli of either isopods, amphipods or mussels separately at least a week before hatching. A prey preference test on hatchlings using all three prey types was conducted. We found that O. berrima had a preference ranking of isopods > amphipods > mussels. However, they retained their isopod prey preference regardless of the prey type they were embryonically exposed to, indicating that it is likely pre-determined as a result of innate biological processes rather than from life experience, providing evidence that imprinting does not occur in O. berrima.
Sexual and Gender-Based Violence Committed by Non-State Armed Groups Against Women/Girls and lgbti+ Persons in Non-International Armed Conflicts: Peru’s Case
Authors: Pérez-León-Acevedo Juan-Pablo
Published: June 2023

The Peruvian Communist Party/Shining Path or Sendero Luminoso (pcp-sl) and the Tupac Amaru Revolutionary Movement (mrta) committed rape and other sexual violence atrocities against women/girls and executions of lgbti+ persons during Peru’s non-international armed conflict (niac) (1980–2000). This article analyses sexual and gender-based violence (sgbv) perpetrated by these non-State armed groups (nsag s) against women/girls and lgbti+ persons under international humanitarian law (ihl) binding nsag s, complemented with a rebel governance approach (including female membership in these groups). This case-study can illustrate whether nsag s fulfil ihl obligations, also identifying inconsistencies between their doctrines and actions. After examining gender-related issues concerning the pcp-sl/mrta and their sgbv crimes against women/girls and lgbti+ persons, this article applies an analytical framework consisting of a gender-focused rebel governance approach and, mainly, ihl to sgbv perpetrated by the pcp-sl/mrta. ihl analysis involves: ihl bindingness over nsag s; prohibition of sgbv binding nsag s; and the nsag s’ (emerging) obligation to redress.
Ugly Book Feelings: Materiality and Negative Affect in Late Medieval Women’s Writing
Authors: Downes Stephanie , Trigg Stephanie
Published: June 2023

Drawing on the work of Sianne Ngai in Ugly Feelings (2005), in this essay we focus on two examples from early fifteenth-century medieval literature that represent medieval books as ‘ugly’ either because they arouse negative feelings of aversion or disgust or because they are considered in some way aesthetically lacking or inadequate. Christine de Pizan’s Livre de la cité des dames and Margery Kempe’s Book of Margery Kempe present women’s involvement with troubling or difficult books. The ‘ugly book feelings’ which both narrators encounter challenge not only their authority as writers, but their very sense of self. Such feelings, however, are transitory when placed in narrative context: in the two examples we discuss, a single material text serves as the catalyst for a moment of emotional transformation which may be spiritual and/or intellectual. Attending to literary representations of ugly book feelings, we argue, complements existing scholarship on late medieval women’s relationship to material textual culture by placing such feelings at the centre of a broad emotional spectrum.
Hedgerow Poiesis
Authors: Bernau Anke
Published: June 2023

This essay considers the iconic English hedgerow in light of its history as material, made object and its ontological status as vital ecology. It argues that both of these aspects are associated with particular ‘aesthetics of care’, which are entwined with one another in inextricable, and often agonistic, ways. Central to this argument are the interrelated aspects of the hedge understood as commodity or property, its role in materialising property relations, and the hedge’s own living ‘properties’. Caring for the hedge; the hedge as expression of care for the property that is demarcated and secured through it (and the ecological and social relations that ensue); caring with hedges as the needs of multispecies living need to be addressed – all of these are at stake, and care in these different relations is rooted in histories of suffering (physical as well as emotional cares) and histories of care as a form of disposition marked by attentiveness and effort. Both ‘property’ and ‘properties’ are deeply embedded in systems and stories of ownership, place and land use; both are coming under increasing pressure in the midst of climate crisis, which demands new forms of multispecies, multitemporal care.
The Stuff of Snuff: The Affective and Sensory Connotations of Snuffboxes in Eighteenth-Century Culture
Authors: Beaven Lisa , Martin Matthew
Published: June 2023

This essay explores the relationship between emotions and material culture in relation to one specific artefact, the snuffbox. Small in scale, capable of activating multiple senses and hugely fashionable, the snuffbox became an enormously popular accessory that was extensively used by both sexes in eighteenth-century society. Its scale, and intimate relationship to the body, made it an ideal gift between lovers or courting couples, and it could be personalised to carry affective inscriptions, imagery or even portraits. Often made of ornate or expensive materials, or studded with jewels, its materiality became part of its seductive charm. Its emotional potency extended to its role in the performance of public identities through the display and manipulation of the box in polite society, while its secret compartments facilitated the retention of mementos or the private display of explicitly pornographic imagery.
Smart Theology and Social Competency: Navigating Youth Engagement in the Digital Age
Authors: Müller Sabrina , Bruderer-Traber Nicole
Published: June 2023

Based on an interdisciplinary study of practical theology, pedagogy, and business education, this article elaborates on aspects of social competence, digitality, engagement, and lived theology. The article further describes in which areas and how often young adults completing vocational training are involved in society and the church and how they use their smartphones. In addition, the young people’s assessment of the opportunities and risks of digital possibilities is discussed as aspects of etiquette regarding manners with the smartphone. Furthermore, it is worked out how young adults perceive themselves as socially competent and what implications this has for social learning. Finally, the authors describe the significance of these findings for hybrid-liquid church life and the extent to which practical action promotes the theological productivity of young adults and supports their development.
Two new species of the ‘Big Yellows’ (Diptera: Sarcophagidae: Sarcophaga)
Authors: GEISLER LUCAS , PAPE THOMAS
Published: June 2023

The informal name ‘Big Yellows’ is proposed for a possibly non-monophyletic assemblage of large-bodied, yellow-coloured species of flesh flies found in the Melanesian archipelagoes of Bismarck, Solomon and Vanuatu. The group comprises several species of Sarcophaga Meigen subgenus Sarcorohdendorfia Baranov plus the only species of Sarcophaga subgenus Chrysosarcophaga Townsend. Two new species are described from Melanesia: Sarcophaga (Sarcorohdendorfia) confusio sp. nov. (Bismarck Archipelago: New Britain, Yalom) and S. (S.) narabondxii sp. nov. (Solomon Islands: Nggele Islands). A key to the species of this group is provided, and their distribution is summarised. The subgenus Sarcorohdendorfia is diagnosed, and the presence of a single row of downward-facing setae along the ventral margin of the mesopleural anatergite is suggested as an important diagnostic feature. Sarcorohdendorfia Baranov, 1938 is proposed as a senior synonym of Omarisca Kurahashi, Tan & Leh, 2021, syn. nov., and Chrysosarcophaga whitneyi Curran, 1936 is proposed as a senior synonym of Sarcorohdendorfia imitatrix Baranov, 1938, syn. nov. Sarcophaga aureolata Pape & Kurahashi, 2000, S. pattoni Senior-White, 1924 and S. saprianovae Pape & Bänziger, 2000 are transferred from the subgenus Lioproctia Enderlein, 1928 to the subgenus Sarcorohdendorfia Baranov, 1938.
One sample—three new species: an example of species richness of the genus Symplecis Förster, 1869 (Hymenoptera, Ichneumonidae: Orthocentrinae) in Burundi
Authors: VARGA OLEKSANDR
Published: June 2023

Three new orthocentrine species of the genus Symplecis Förster, 1869 are described and illustrated: S. aperta sp. n., S. glabroscutum sp. n. and S. kibiraensis sp. n. These species were all found in one sample collected by Malaise trap in Kibira National Park (Burundi) demonstrating potentially high species richness of the genus in the Afrotropics compared with other regions.
5. Reflections on the Israeli-Palestinian Conflict
Authors: Shlaim Avi
Published: June 2023

In this chapter I argue that the state of Israel is legitimate, but only within its original boundaries and that the Palestinians are the main victims of the conflict, victims of Israeli colonialism. The history of the region over the last sixty years can be convincingly explained in terms of the strategy of the ‘iron wall’, first expounded by Jabotinsky, which advocates negotiation only from a position of unassailable strength. The basic deal of ‘land for peace’ expressed in UN Resolution 242 was sound, but never effectively implemented and Rabin, the only Israeli prime minister prepared to negotiate, was murdered. The recent, brutal onslaughts on Gaza give little grounds for optimism.
16. Palestine is a Four-letter Word: Psychoanalytic Innocence and Its Malcontents
Authors: Sheehi Lara
Published: June 2023

If psychoanalysis is to transform itself from a disciplinary practice of quiet (and often explicit) violence, we are asked to confront the dynamics and paradigms that objectify rather than liberate. What follows in this chapter is an account of how contemporary psychoanalysis resists, subverts, and defangs such a possible revolutionary mutation and threats of transformation. But also, more importantly and simultaneously, this chapter highlights the real-time transformation of the field by Palestinian clinicians who wilfully enact and materialize the promise of mutation, and indeed liberation, across Palestine. To map out the counter-revolutionary forces that attempt to upset the life-affirming mutation happening in Palestine, I will use work that my partner and co-author, Stephen Sheehi and myself outline in our book, Psychoanalysis Under Occupation: Practicing Resistance in Palestine (Routledge, 2022). Importantly, our work and book utilizes a decolonial feminist solidarity building approach to map out, discuss and platform the work of our Palestinian colleagues, not as they are interpolated by and through settler colonial logic. Rather, we approach Palestinian clinicians through the understanding of them, following Sara Ahmed, as ‘willful subjects’.
A High De Ritis Ratio Predicts Poor Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Güvendi Şengör Büşra , Yılmaz Cemalettin , Zehir Regayip
Published: June 2023

Successful reperfusion of myocardial tissue is the goal of primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the association between the De Ritis ratio (AST/ALT) and myocardial reperfusion in patients with STEMI who underwent pPCI. We retrospectively investigated 1236 consecutive patients who were hospitalized for STEMI and underwent pPCI. ST-segment resolution (STR) was defined as the return of the deviated ST-segment to baseline; poor myocardial reperfusion was defined as <70% STR. Patients were divided into 2 groups according to the median De Ritis ratio (.921); 618 patients (50%) were assigned to the De Ritis low group while 618 patients (50%) were assigned to the De Ritis high group. Stent size, neutrophil-to lymphocyte ratio (NLR), and the De Ritis ratio found to be associated with poor myocardial reperfusion (Odds ratio (OR) 1.45, 95% CI 1.07–1.98, P = .01, OR 1.22, 95% CI 1.01–1.48, P = .03 and OR 10.9, 95% CI 7.9–15, P < .001, respectively). A high De Ritis ratio was associated with poor myocardial reperfusion in STEMI patients who underwent pPCI. As an easily obtainable test in clinical practice, the De Ritis ratio may help identify patients at major risk for impaired myocardial perfusion.
Facial Pain Triggered by Inferior Turbinate Partial Resection in a Patient with a Previous History of Inferior Meatal Antrostomy: A Case Report
Authors: Park Marn Joon , Jang Yong Ju
Published: June 2023

Objectives

Inferior meatal antrostomy (IMA) is regarded as a safe method, with minimal complications, for managing various lesions in the maxillary sinus. However, in patients with persisting IMA window, resection of the inferior turbinate may result in direct airflow into the antrum, irritating the antral mucosa.

Methods:

Case report and review of literature.

Results/Case:

The present report describes a 29-year-old man who previously underwent unilateral IMA for the excision of a dentigerous cyst. The patient did not report any facial pain following the excision of the cyst. One year later, this patient underwent partial resection of the inferior turbinate for the resolution of nasal stuffiness by another surgeon. Soon after surgery, the patient developed severe facial and ocular pain on the side of the IMA, with the pain being especially aggravated upon inhalation. Endoscopy and computed tomography (CT) revealed a persisting IMA window. The patient’s severe discomfort was thought to result from direct airflow into the maxillary sinus, as the resected turbinate may have altered normal nasal airflow. A unilateral inferior meatal augmentation procedure (IMAP) with an autologous ear cartilage implant was performed, resulting in complete relief of pain and discomfort.

Conclusions:

Although IMA alone is a relatively safe surgical procedure, care should be taken when performing inferior turbinoplasty in patients with persistent IMA opening.
Postoperative Pain Following Coblation of Sinonasal Hereditary Hemorrhagic Telangiectasias
Authors: Kraimer Kristen , Scott Brian , Farrell Nyssa , Geltzeiler Mathew , Smith Timothy , Detwiller Kara
Published: June 2023

Background:

Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant disease and epistaxis is the most common symptom. This can be treated conservatively but severe cases may require operative interventions. Endoscopic endonasal coblation of HHT lesions has been used successfully but postoperative pain management has not been well described.

Objectives:

This study aimed to assess levels of postoperative pain and opioid use among patients with HHT who underwent coblation of sinonasal lesions.

Methods:

This is a longitudinal, prospective cohort study of adult patients undergoing endoscopic endonasal coblation for treatment of HHT lesions with or without bevacizumab injection between November 2019 and March 2020 at a single academic university hospital. Patients were given preoperative questionnaires and contacted via telephone 48 hours after surgery. If they reported using opioids for pain control, they were called every 2 days until they no longer used these medications.

Results:

Fourteen cases, including 13 unique patients, were included in this study. Opioids were ordered on discharge in 4 cases and the average morphine milligram equivalent prescribed on discharge was 41. The median pain score on postoperative day (POD) 2 was 4 of 10. Twelve patients reported using acetaminophen and 4 were using opioid pain medications. Of those using opioid pain medications, only 1 patient was using opioid pain medication by POD 4 and denied any use after POD 10.

Conclusion:

This study is the first to analyze postoperative pain management and opioid prescribing patterns in HHT patients undergoing endonasal coblation of telangiectasias. Postoperative pain was mild to moderate and most patients stopped using opioid medications by POD 4, although the majority of patients solely used acetaminophen. Future studies with increased sample size will be useful to further identify predictors of need for analgesics postoperatively and other non-opioid adjuncts for pain control.
Pastoring in a Pandemic: Sources and Types of Social Support Used by United Methodist Clergy in the Early Period of the COVID-19 Pandemic
Authors: Johnston Erin F. , Headley Jennifer , Eagle David E.
Published: June 2023

COVID-19 and its associated restrictions around in-person gatherings fundamentally unsettled routine ways of doing ministry. In this article, we draw on 50 in-depth interviews conducted with United Methodist clergy in the early period of the COVID-19 pandemic (June 2020–January 2021) to examine the sources and t ypes of social support pastors relied on during this time. We found that most clergy reported drawing from a diverse eco-system of social supports and turned to different sources of support—for example, other clergy, local church members, and denominational leaders—for different types of support—for example, informational, instrumental, and/or emotional. This study extends existing research on clergy well-being by examining whether the social support used by clergy during the COVID-19 map onto those identified in previous research and by specifying the types of support that were most salient. In the discussion, we consider the broader implications of our findings for clergy well-being beyond the pandemic period.
What if Action Defined Leadership?
Authors: Dery David
Published: June 2023

What if action defined leadership? By pushing the idea of “leadership-as-action” to its logical conclusion, I hope to show that it has the potential of introducing much needed discipline to a field of research that has been built on weak conceptual foundations and as a consequence is hampered by fragmentation and diversity. With action as an organizing idea, a pivot, around which leadership revolves, leadership theory and practice can be advanced toward a more unified and coherent body of knowledge. Following a brief discussion of some of the noted difficulties and weaknesses, the paper explores the notion of “act of leadership,” the peculiar conceptual field (labeled “the fourth domain”) within which such acts take place and the distinctive attitudes, behaviors, and evaluation standards that follow.
A Study Into the Relationship Between Adaptive Skills and Visual Impairment in Individuals With and Without Intellectual Disabilities
Authors: van der Aa Henriëtte , Jonker Femke , de Looff Peter , Didden Robert
Published: June 2023

Introduction: In this study, we explored if low vision or blindness affects adaptive functioning in individuals with and without intellectual disabilities, using the adaptive ability performance test (ADAPT). Method: Two hundred and nine ADAPTs were collected from individuals with low vision and blindness who were in care or lived independently. ADAPT scores were compared with 2642 ADAPT scores from sighted individuals. Separate comparisons were made for intellectually disabled and nonintellectually disabled groups. Results: ADAPT scores of low vision and blind individuals in both intellectually disabled and nonintellectually disabled groups were significantly lower than those of sighted individuals. ADAPT scores did not differ significantly between low vision and blind individuals. Reference values were established for individuals with visual impairments with and without intellectual disabilities. Discussion: Despite some limitations of this study, we conclude that adaptive skills are lower in individuals with visual impairments than in sighted individuals. Cross-cultural studies are required. Information for Practitioners: The results of this study provide insight into adaptive skills in individuals with visual impairments. Reference data on the ADAPT can be used for the classification of (the severity of) intellectual disabilities and assessment of the need for support or training of adaptive skills, which makes the ADAPT a useful instrument for professionals who work with individuals with visual impairments with and without intellectual disabilities.
Factors Associated With Agreement Between Parent and Childhood Cancer Survivor Reports on Child’s Health Related Quality of Life
Authors: Ochoa-Dominguez Carol Y. , Hamilton Ann S. , Zhuang Xueyan , Mack Wendy J. , Milam Joel E.
Published: June 2023

Pediatric Health Related Quality of Life (HRQoL) among childhood cancer survivors (CCS) measures the impact of illness and treatment from the patient’s perspective. However, parents often serve as proxies when the child cannot provide information directly. Studies of agreement between parents’ proxy assessment and child’s self-report have shown discrepancies. Understanding the reasons for discrepancies is under studied. Thus, this study examined the agreement of 160 parent-CCS dyads on the child’s domains of HRQoL by mean difference, intra-class correlation coefficients, and Bland-Altman plots. Differences in agreement were assessed by patients’ age, ethnicity, and whether or not they lived with their parents. Overall, the Physical Function Score showed good agreement between parents and CCS (ICC = 0.62), while the Social Function Score had fair agreement (ICC = 0.39). CCS were more likely to rate their Social Function Score higher than their parent. The lowest agreement for the Social Function Score was found for 18–20 years old’s (ICC = .254) versus younger or older CCS, and among non-Hispanic whites (ICC = 0.301) versus Hispanics. Differences in agreement varied by patient age and ethnicity, suggesting that other factors, including emotional, familial, and cultural factors, may influence parental awareness of CCS HRQoL.
The Safety Assessment of Cosmetic Perfumes by Using In Chemico and In Vitro Methods in Combination with GC-MS/MS Analysis
Authors: Dvořáková Markéta , Svobodová Lada , Rucki Marian , Ševčík Václav , Hošíková Barbora , Chrz Jan , Bendová Hana , Kejlová Kristina , Očadlíková Danuše , Malý Marek , Kolářová Hana , Mannerström Marika , Kanďárová Helena , Jírová Dagmar
Published: June 2023

Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential ( in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential ( in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption ( in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their ‘Opinion on Tea tree oil’ document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.