bluuebunny/crossref_metadata_2025 huggingface dataset:
Writing violence
Authors: Tansman Alan
Published: September 2023

The vibration of the world: in the fourteenth century, Buddhist monk and essayist Yoshida Kenkô evoked the realm of the invisible through the world of concrete things. His work was one aesthetic summit of this dominant strain of the tradition. How, then, did writers render the most concrete of experiences, that of violence? Through the centuries Japanese writers have also grappled with bringing literary form to the experience of violence, natural and man-made. Before the twentieth century, this steam of writing reached its apogee in the thirteenth-century Tale of Heike and An Account of My Hut, and in the eighteenth-century puppet plays of Chikamatsu Monzaemon. In these works, violence is rendered poetically and cast in a melancholy Buddhist light.
The spirit of wordplay
Authors: Tansman Alan
Published: September 2023

It has been in the popular genres that Japanese literature also displayed its greatest flights of unbridled imagination. In the first decades of the twentieth century, detective fiction sometimes incorporated thinly disguised social critique: promoting the promise of science and rationality and the certainty of progress or indicting the judicial system. Detective fiction in Japan was not weighed down by generic constraints and could be used as a loose envelope for amalgamating ideas about urbanization, sexuality both conventional and perverse, science, ethics, war, and colonialism. In the 1930s, detective fiction engaged the vexing reality of Japanese colonial rule in the South Seas, Korea, Manchuria, and Taiwan. Popular fiction brought together streams of thought and culture in brilliantly creative and unexpected ways.
Listeria monocytogenes infection in pregnant macaques alters the maternal gut microbiome
Authors: Hugon Anna Marie , Deblois Courtney L , Simmons Heather A , Mejia Andres , Schotzo Michele L , Czuprynski Charles J , Suen Garret , Golos Thaddeus G
Published: September 2023

Objectives

The bacterium Listeria monocytogenes (Lm) is associated with adverse pregnancy outcomes. Infection occurs through consumption of contaminated food that is disseminated to the maternal–fetal interface. The influence on the gastrointestinal microbiome during Lm infection remains unexplored in pregnancy. The objective of this study was to determine the impact of listeriosis on the gut microbiota of pregnant macaques.

Methods

A non-human primate model of listeriosis in pregnancy has been previously described. Both pregnant and non-pregnant cynomolgus macaques were inoculated with Lm and bacteremia and fecal shedding were monitored for 14 days. Non-pregnant animal tissues were collected at necropsy to determine bacterial burden, and fecal samples from both pregnant and non-pregnant animals were evaluated by 16S rRNA next-generation sequencing.

Results

Unlike pregnant macaques, non-pregnant macaques did not exhibit bacteremia, fecal shedding, or tissue colonization by Lm. Dispersion of Lm during pregnancy was associated with a significant decrease in alpha diversity of the host gut microbiome, compared to non-pregnant counterparts. The combined effects of pregnancy and listeriosis were associated with a significant loss in microbial richness, although there were increases in some genera and decreases in others.

Conclusions

Although pregnancy alone is not associated with gut microbiome disruption, we observed dysbiosis with listeriosis during pregnancy. The macaque model may provide an understanding of the roles that pregnancy and the gut microbiota play in the ability of Lm to establish intestinal infection and disseminate throughout the host, thereby contributing to adverse pregnancy outcomes and risk to the developing fetus.
A metasystem approach to designing environmental flows
Authors: Messager Mathis L , Olden Julian D , Tonkin Jonathan D , Stubbington Rachel , Rogosch Jane S , Busch Michelle H , Little Chelsea J , Walters Annika W , Atkinson Carla L , Shanafield Margaret , Yu Songyan , Boersma Kate S , Lytle David A , Walker Richard H , Burrows Ryan M , Datry Thibault
Published: September 2023

Accelerating the design and implementation of environmental flows (e-flows) is essential to curb the rapid, ongoing loss of freshwater biodiversity and the benefits it provides to people. However, the effectiveness of e-flow programs may be limited by a singular focus on ensuring adequate flow conditions at local sites, which overlooks the role of other ecological processes. Recent advances in metasystem ecology have shown that biodiversity patterns and ecosystem functions across river networks result from the interplay of local (environmental filtering and biotic interactions) and regional (dispersal) ecological processes. No guidelines currently exist to account for these processes in designing e-flows. We address this gap by providing a step-by-step operational framework that outlines how e-flows can be designed to conserve or restore metasystem dynamics. Our recommendations are relevant to diverse regulatory contexts and can improve e-flow outcomes even in basins with limited in situ data.
Nicotinamide for skin cancer chemoprevention in transplant recipients: a critically appraised topic
Authors: Riddle Ashley O , Jambusaria-Pahlajani Anokhi
Published: September 2023

This paper critically appraises a phase III trial examining the impact of oral nicotinamide on reducing keratinocyte carcinoma (KC) incidence in solid organ transplant recipients. Despite a well-conducted study finding no significant difference in KC rates between nicotinamide and placebo groups, we suggest that the conclusion could be premature due to the study’s underpowered sample size and lack of analysis on more invasive cancers.
Factors influencing patient experience during incision and drainage procedures in hidradenitis suppurativa: an analysis of patient-reported outcomes
Authors: Revankar Rishab R , Blum Franklin , Yeung Howa , Patel Heli A , Holahan Heather , Vedak Priyanka , Sayed Christopher J
Published: September 2023

Patients with hidradenitis suppurativa who undergo incision and drainage experience higher levels of dread and lower levels of benefit due to poor anaesthesia and wound packing practices, and lower levels of provider compassion. Higher levels of dread were associated with increased pain during incision (coefficient 0.3, 95% CI 0.19–0.42) and wound packing or drain vs. simple bandaging (coefficient 2.25, 95% CI 0.61–3.90). Higher perceived benefits over drawbacks were associated with higher physician compassion (coefficient 0.21, 95% CI 0.06–0.36) and decreased pain during incision (coefficient 0.14, 95% CI 0.03–0.27).
Keeping up with melanoma: celebrity influence on skin cancer awareness
Authors: Blyth Rachel , Ho Bernard
Published: September 2023

A prominent celebrity’s disclosure of a facial melanoma diagnosis in April 2023 garnered widespread media attention, emphasizing the importance of self-skin assessment and timely dermatologist consultations for changing pigmented lesions. The disclosure had unexpected positive effects on public health, including increased awareness, early detection and reduced stigma, potentially leading to improved outcomes for patients with melanoma and skin cancer.
Case report: septic embolism through patent foramen ovale in mitral valve endocarditis
Authors: Abumehdi Mohammad , Spada Maraisa Fachini , Semple Thomas , di Salvo Giovanni , Fraisse Alain
Published: September 2023

Background

Infective endocarditis with septic emboli is a well-recognized sequala. However, emboli almost invariably are found ‘downstream’ to the vegetation. In the absence of congenital heart disease, the embolization from the left heart to the pulmonary circulation has never been described.

Case summary

A 4-year-old boy presents with a background history of pharyngitis treated with antibiotics. Upon ambulatory review, he is noted to have a new murmur. Transthoracic echocardiogram demonstrated mitral valve vegetation with severe mitral regurgitation; in addition, there was a patent foramen ovale (PFO), and there were no congenital heart defects. The patient was treated for infective endocarditis on high clinical suspicion. He subsequently developed septic pulmonary emboli in the absence of right-sided vegetation. Subsequent mitral valve vegetectomy, resection of infected native anterior mitral valve leaflet, mitral valve repair, and valvuloplasty. The patient made an excellent recovery following the completion of antibiotic therapy.

Discussion

Although not possible to confirm with certainty, this case demonstrates the most plausible explanation for this child's presentation being septic pulmonary emboli originating from left-sided heart vegetation migrating through a PFO.
Elevated arsenic level in fasting serum via ingestion of fish meat increased the risk of hypertension in humans and mice
Authors: Kagawa Takumi , Ohgami Nobutaka , He Tingchao , Tazaki Akira , Ohnuma Shoko , Naito Hisao , Yajima Ichiro , Chen Dijie , Deng Yuqi , Tamura Takashi , Kondo Takaaki , Wakai Kenji , Kato Masashi
Published: September 2023

Aims

There has been a shortage of human studies to elucidate the association between serum arsenic levels and the prevalence of hypertension. This study multidirectionally investigated associations among arsenic exposure, dietary ingestion, and the risk of hypertension by combined human epidemiological and mouse experimental studies.

Methods and results

This study focused on the total arsenic level in fasting serum, a biomarker of arsenic exposure. Associations among ingestion frequencies of 54 diet items of Japanese food separated into six categories, total arsenic level in fasting serum, and the prevalence of hypertension were investigated in 2709 general people in Japan. Logistic regression analysis demonstrated a dose-dependent association between serum arsenic level and hypertension and a positive association between the ingestion of fish meat and hypertension. Further analysis showed that the latter association was fully mediated by increased fasting serum arsenic levels in humans. Similarly, oral exposure to the putative human-equivalent dose of arsenic species mixture with the same ratios in a common fish meat in Japan increased systolic blood pressure and arsenic levels in fasting serum in mice.

Conclusion

This interdisciplinary approach suggests that fish-meat ingestion is a potential risk factor for arsenic-mediated hypertension. Because the increased consumption of fish meat is a recent global trend, health risks of the increased ingestion of arsenic via fish meat should be further investigated.
Clinical and economic outcomes of a systematic same-day discharge programme after pulmonary vein isolation: comparison between cryoballoon vs. radiofrequency ablation
Authors: Jimenez-Candil Javier , Hernandez Hernandez Jesus , Cruz Galban Alba , Blanco Fabian , Moriñigo Jose Luis , Sanchez García Manuel , Oterino Armando , Sanchez Pedro L
Published: September 2023

Aims

Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme.

Methods and results

We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8).

Conclusion

In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.
Is health promotion in sports clubs associated with adolescent participants’ fruit and vegetable consumption?
Authors: Heikkilä Laura , Korpelainen Raija , Aira Tuula , Alanko Lauri , Heinonen Olli J , Kokko Sami , Parkkari Jari , Savonen Kai , Toivo Kerttu , Valtonen Maarit , Vasankari Tommi , Villberg Jari , Vanhala Marja
Published: September 2023

Background

Although sports clubs’ potential for health promotion is acknowledged, research on whether they promote healthy eating is limited. We aimed to evaluate Finnish youth sports clubs’ health promotion orientation, as well as associations between sports clubs’ health promotion orientation, coaches’ nutritional discussions and sports club participants’ (SPs’) fruit and/or vegetable consumption.

Methods

The cross-sectional study included 554 SPs aged 14–16 years, 275 club officials and 311 coaches. Participants replied to questionnaires about sports clubs’ health promotion and their own health behaviours, including dietary habits. Health promotion orientation was estimated using a Health Promoting Sports Club (HPSC) index (range 0–22) and nutritional discussions and fruit and/or vegetable consumption as frequencies. A mixed-effects multivariable logistic regression was used to analyse the associations.

Results

Most sports clubs (69%) had a high health promotion orientation, but the variation between the clubs was wide (HPSC index range 5–21). SPs’ daily fruit and/or vegetable consumption was associated with female gender [odds ratio (OR) 3.48, 95% confidence interval (CI) 2.23–5.42, P < 0.001], better self-rated health (OR 3.26, 95% CI 1.13–9.41, P = 0.03), higher average school grades (OR 1.67, 95% CI 1.04–2.67, P = 0.03), and SPs’ responses that their coach had often discussed nutrition (OR 2.11, 95% CI 1.41–3.14, P < 0.001).

Conclusion

Although sports clubs’ orientation towards health promotion was mostly high, it seems not to be enough to promote healthy eating among adolescent participants. Instead, coaches’ nutritional discussions were associated with adolescents’ fruit and/or vegetable consumption.
The role of microorganisms in the biotransformation of psychoactive substances and its forensic relevance: a critical interdisciplinary review
Authors: de Campos Eduardo G , de Almeida Otávio G G , De Martinis Elaine C P
Published: September 2023

Microorganisms are widespread on the planet being able to adapt, persist, and grow in diverse environments, either rich in nutrient sources or under harsh conditions. The comprehension of the interaction between microorganisms and drugs is relevant for forensic toxicology and forensic chemistry, elucidating potential pathways of microbial metabolism and their implications. Considering the described scenario, this paper aims to provide a comprehensive and critical review of the state of the art of interactions amongst microorganisms and common drugs of abuse. Additionally, other drugs of forensic interest are briefly discussed. This paper outlines the importance of this area of investigation, covering the intersections between forensic microbiology, forensic chemistry, and forensic toxicology applied to drugs of abuse, and it also highlights research potentialities.

Key points
Post–COVID-19 Condition After SARS-CoV-2 Infections During the Omicron Surge vs the Delta, Alpha, and Wild Type Periods in Stockholm, Sweden
Authors: Hedberg Pontus , Nauclér Pontus
Published: September 2023

Little is known about the post–COVID-19 condition (PCC) after infections with different SARS-CoV-2 variants. We investigated the risk of PCC diagnosis after primary omicron infections as compared with preceding variants in population-based cohorts in Stockholm, Sweden. When compared with omicron (n = 215 279, 0.2% receiving a PCC diagnosis), the adjusted hazard ratio (95% CI) was 3.26 (2.80–3.80) for delta (n = 52 182, 0.5% PCC diagnosis), 5.33 (4.73–5.99) for alpha (n = 97 978, 1.0% PCC diagnosis), and 6.31 (5.64–7.06) for the wild type (n = 107 920, 1.3% PCC diagnosis). These findings were consistent across all subgroup analyses except among those treated in the intensive care unit.
Digital–Nondigital Assemblages: Data, Paper Trails, and Migrants’ Scattered Subjectivities at the Border
Authors: Canzutti Lucrezia , Tazzioli Martina
Published: September 2023

This paper argues that the border regime works through entanglements of digital and nondigital data and of “low-tech” and “high-tech” technologies. It suggests that a critical analysis of the assemblages between digital and nondigital requires exploring their effects of subjectivation on those who are labeled as “migrants.” The paper starts with a critique of the presentism and techno-hype that pervade research on borders and technology, and points to the importance of analyzing historical continuities and ruptures in the technologization of the border regime. It then explores the assemblages of high-tech and low-tech technologies used for controlling mobility and investigates the imbrication of digital and nondigital records that migrants need to deal with and show not only at the border but throughout their journeys and, eventually, to obtain refugee status. The third section discusses migrants’ tactical uses of digital and nondigital records, their attempts to erase or reconstruct traces of their passages, and states’ oscillation between politics of identification and nonidentification. Finally, the fourth section questions the image of the “data double” and contends that, rather than a discrete digital subject, migrants’ digital traces generate scattered digital subjectivities that migrants themselves cannot fully access.
How Organizational Leaders Negotiate Religious Differences: Frameworks of Mandate and Interpersonal Care
Authors: Seigler Carolina P , Cadge Wendy
Published: September 2023

The religious composition of the United States is rapidly shifting. As institutions and their stakeholders negotiate the needs of an increasingly diverse public, leaders of national chaplaincy organizations offer insight into how actors can effectively understand and engage matters of religious pluralism. This article identifies two distinct institutional frameworks (“mandate” and “interpersonal care”) that provide chaplaincy leaders with different schemas, tools, and strategies to use when understanding and motivating their engagement with religiously diverse publics. Using interviews with sixteen national chaplaincy leaders working in public and private settings, we delineate how institutional leaders interpret, articulate, and fulfill their roles as negotiators of religious differences within their respective frameworks. Our findings allow scholars and leaders to better understand how institutions and their actors can successfully interact with a diversifying, religiously pluralistic public.
Insoluble fibers affect digesta transit behavior in the upper gastrointestinal tract of growing pigs, regardless of particle size
Authors: Dorado-Montenegro Sebastian , Lammers-Jannink Kim , Gerrits Walter , de Vries Sonja
Published: September 2023

Physicochemical characteristics of dietary fibers may modulate digesta transit behavior. The present study was conducted to clarify the effect of level and particle size (PS) of insoluble fibers on digesta mean retention time (MRT) in the proximal gastrointestinal tract (mouth-ileocecal junction). Six ileal-cannulated pigs (26.8 ± 2.08 kg) were assigned to 3 dietary treatments in a 3 × 3 replicated Latin-square design. Finely ground (1 mm screen) or coarse (intact) oat husks (OH) and soybean hulls (SBH) were added (50:50, w/w) to a maize–whey protein–wheat-based diet at 50 (low) or 250 g/kg (high) inclusion levels to obtain a low-fine fiber (LF), high-fine fiber (HF), and high-coarse fiber (HC) diet. Markers to follow liquids (Co-EDTA), fine solids (Y3O2), or fibrous particles (Yb-mordanted OH and Cr-mordanted SBH) were given as a single pulse dose and marker concentrations were subsequently measured hourly in digesta for 13 h after administration. Mean retention time values were obtained from the concentration of markers in digesta observed over time by fitting a generalized Michaelis–Menten equation and calculating the time of peak. Fiber addition and fiber particle size neither affected the MRT of liquid nor solid digesta phases (P = 0.903). Segregation between solid and liquid digesta phases was observed for all diets (P < 0.0001), although the extent of segregation was greater for LF compared with HF and HC (P = 0.0220). The MRT of SBH particles, but not of OH-particles was longer for coarse vs fine PS (96 min, P < 0.05). In conclusion, digesta MRT was influenced by the dietary concentration but not by PS of insoluble fibers. The addition of insoluble fibers reduces digesta phase segregation from mouth to distal ileum in growing pigs.
Improving Time to Diagnostic Resolution in the Breast Imaging Service: A Tertiary Center’s Experience and Process of Improvement
Authors: Fawzy Nader A , AlMuslem Noor F , Altayeb Afaf , Ghosheh Mohammad J , Khoumais Nuha A
Published: September 2023

Objective

Breast imaging services often experience a significant degree of variability in patient flow, leading to delay in time to diagnostic resolution, commonly referred to as time to resolution (TTR). This study applies Lean Six Sigma Methodology (LSSM) to reduce TTR and enhance patient outcomes.

Methods

This study was IRB-approved. A baseline audit was done using cases of mammographic recalls (BI-RADS 0) to measure baseline TTR. Multidisciplinary meetings with all members of the breast imaging service, alongside a study of patient complaint data, were utilized to identify issues that were causing prolonged TTR. Following that, possible solutions were proposed and implemented. A post-implementation audit was conducted, and the resulting TTRs were compared. Significant differences in TTR between the pre- and post-solution implementation were assessed using the Mann-Whitney U test.

Results

During the baseline audit of 8 months, 589 cases of mammographic recalls (BI-RADS 0) were identified, and the resulting average TTR was 86.3 days. During the post-implementation period of 3 months, 370 mammographic recalls (BI-RADS 0) occurred, with a resulting average TTR of 36.0 days. After applying LSSM, TTR was reduced by 58.3% (P < 0.01). Some changes implemented included training the coordinators, establishing a rapid diagnostic clinic using previously underutilized equipment, and having radiologists assigned full-time to the breast imaging service.

Conclusion

Our team has successfully managed to identify various causes behind the prolonged TTR using LSSM. Team collaboration was essential to study and decide on a more achievable TTR.
Data-driven Learning Systems and the Commission of International Crimes
Authors: Greipl Anna Rosalie
Published: September 2023

Current discussions on the military use of artificial intelligence (AI), in particular concerning autonomous weapons systems, have largely focused on the challenges for the attribution of individual criminal responsibility for war crimes whenever such systems do not perform as initially intended by human operators. Yet, recent observations evidence the pressing need to shift the discussion on the responsibility gap further to include challenges raised by the intentional use of AI systems for the commission of war crimes and other international crimes. Additionally, the increasing development and use of AI systems, based on data-driven learning (DDL) methods, demands particular attention due to the difficulty these systems’ lack of predictability and explainability poses in terms of anticipation of their effects. Against this background, this article complements the present discussion on the responsibility gap by discussing some concerns that the intentional use of DDL systems for the commission of international crimes raises regarding the required mental element and thus, the ascription of individual criminal responsibility. Ultimately, this article proposes preliminary avenues to address these concerns.
A probabilistic temporal epistemic logic: Decidability
Authors: Ognjanović Zoran , Stepić Angelina Ilić , Perović Aleksandar
Published: September 2023

We study a propositional probabilistic temporal epistemic logic $\textbf {PTEL}$ with both future and past temporal operators, with non-rigid set of agents and the operators for agents’ knowledge and for common knowledge and with probabilities defined on the sets of runs and on the sets of possible worlds. A semantics is given by a class ${\scriptsize{\rm Mod}}$ of Kripke-like models with possible worlds. We prove decidability of $\textbf {PTEL}$ by showing that checking satisfiability of a formula in ${\scriptsize{\rm Mod}}$ is equivalent to checking its satisfiability in a finite set of finitely representable structures. The same procedure can be applied to the class of all synchronous ${\scriptsize{\rm Mod}}$-models. We give an upper complexity bound for the satisfiability problem for ${\scriptsize{\rm Mod}}$.
Looking ahead to the sky with the Square Kilometre Array: simulating flux densities and resolved radio morphologies of 0 < z < 2.5 star-forming galaxies
Authors: Coogan Rosemary T , Sargent Mark T , Cibinel Anna , Prandoni Isabella , Bonaldi Anna , Daddi Emanuele , Franco Maximilien
Published: September 2023

SKA-MID surveys will be the first in the radio domain to achieve clearly sub-arcsecond resolution at high sensitivity over large areas, opening new science applications for galaxy evolution. To investigate the potential of these surveys, we create simulated SKA-MID images of a ∼0.04 deg2 region of GOODS-North, constructed using multi-band HST imaging of 1723 real galaxies containing significant substructure at 0 < z < 2.5. We create images at the proposed depths of the band 2 wide, deep, and ultradeep reference surveys (RMS = 1.0, 0.2, and 0.05 μJy over 1000, 10–30, and 1 deg2, respectively), using the telescope response of SKA-MID at 0.6 arcsec resolution. We quantify the star formation rate – stellar mass space the surveys will probe, and asses to which stellar masses the surveys will be complete. We measure galaxy flux density, half-light radius (R50), concentration, Gini (distribution of flux), second-order moment of the brightest pixels (M20), and asymmetry before and after simulation with the SKA response, to perform input-output tests as a function of depth, separating the effects of convolution and noise. We find that the recovery of Gini and asymmetry is more dependent on survey depth than for R50, concentration and M20. We also assess the relative ranking of parameters before and after observation with SKA-MID. R50 best retains its ranking, while asymmetries are poorly recovered. We confirm that the wide tier will be suited to the study of highly star-forming galaxies across different environments, whilst the ultradeep tier will enable detailed morphological analysis to lower SFRs.
Imaging rotating and orbiting exoplanets with the solar gravitational lens
Authors: Toth Viktor T , Turyshev Slava G
Published: September 2023

We utilize the well-established properties of the solar gravitational lens (SGL) to consider more realistic observational scenarios. Actual exoplanets, which may be the target of an SGL observational campaign, are not stationary. Their appearance also changes in a variety of ways, including changes due to their diurnal rotation and varying illumination due to their orbital motion around their host star. The nature of the SGL is such that imaging with one telescope is accomplished with a cadence of one pixel at a time, with substantial per-pixel integration times. Therefore, capturing a single snapshot of the target planet with a realistically sized telescope is not possible. Instead, the planetary surface must be reconstructed by inverting the combined effect of the SGL’s point-spread function and temporal changes induced by the planetary dynamics. Using the Earth as a stand-in, we demonstrate practical feasibility of this approach, by simulating a dynamical system and then recovering topographic images of acceptable quality. The dynamics-induced temporal variability of the exoplanet represents an added challenge, but even in the presence of such dynamics, use of the SGL for exoplanet imaging remains feasible.
CO, H2O, and CH4 in the dusty atmosphere of a ≲5 Myr-old exoplanet
Authors: Gaidos Eric , Hirano Teruyuki
Published: September 2023

Very young massive planets are sufficiently luminous by their internal heat of formation to permit detailed studies, including spectroscopy of their atmospheres with large telescopes at sufficient resolution (λ/Δλ ≳ 1000) to identify major constituents to inform models of planet formation and early evolution. We obtained 1–2.4 μm (YJHK) spectra of the planetary-mass ‘b’ companion of 2MASS J04372171+2651014, a 1–3 Myr-old M dwarf member of the Taurus star-forming region, and one of the youngest such objects discovered to date. These indicate the presence of CO and possibly H2O and CH4 in the atmosphere, all suggesting a Teff of around 1200 K, characteristic of a L-T transition spectral type and consistent with previous estimates based on its luminosity and age. The absence or attenuation of spectral features at shorter wavelengths suggests the presence of micron-size dust, consistent with the object’s red colour. The spectrum of 2M0437b resembles those of the HR 8799 planets, especially the innermost ‘b’ planet, with the exception of a pronounced flux deficit in the H-band of uncertain origin.
Larger tumor volume is associated with visual acuity loss and axonal degeneration in children with optic pathway gliomas secondary to neurofibromatosis type 1
Authors: Avery Robert A , Mansoor Awais , Liu Grant T , Trimboli−Heidler Carmelina , Ying Gui−Shuang , Centrella Cameron R , Eltoukhy Nadeen , Packer Roger J , Fisher Michael J , Linguraru Marius George
Published: September 2023

Background

We investigated whether volumetric magnetic resonance imaging (MRI) measures of the anterior visual pathway (AVP) in optic pathway gliomas secondary to Neurofibromatosis type 1 (NF1−OPG) are associated with visual acuity (VA) loss and axonal loss, as measured using optical coherence tomography (OCT).

Methods

Children with NF1−OPGs enrolled in a prospective study of VA and OCT measures of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness were eligible if they had undergone 3-Tesla MRI that included a T1-weighted volumetric sequence. The linear dimension and volume of the optic nerves, chiasm, and optic tracts were measured using our semi-automated algorithm. The combined volume of these components comprising the proximal AVP was used as a surrogate of total tumor burden. Regression models for VA and cpRNFL thickness were reported on a per-eye basis.

Results

Fifty−two study eyes (26 children, mean 7.1 years) met inclusion criteria, of which 40% (N = 21 eyes) had abnormal VA. In regression analysis, only total AVP volume demonstrated a significant relationship to axonal loss, such that for every 1 mL increase in AVP volume, cpRNFL declined by 5.4 microns (P = .01). Total AVP volume > 1.75 mL predicted both axonal loss and abnormal VA (positive predictive value of 83.3% and 70.8%, respectively; negative predictive value of 80.0% and 88.0%, respectively).

Conclusions

Volumetric measures of NF1-OPGs identified children with VA loss and axonal degeneration. Total tumor burden, as measured by AVP volume, had the strongest relationship with axonal injury. NF1-OPG volumetric measures may be helpful in making treatment decisions.
The sex-dependent impact of PER2 polymorphism on sleep and activity in a novel mouse model of cranial-irradiation-induced hypersomnolence
Authors: Adegbesan Kendra A , Tomassoni Ardori Francesco , Yanpallewar Sudhirkumar , Bradley Sean P , Chudasama Yogita , Vera Elizabeth , Briceno Nicole , King Amanda L , Tessarollo Lino , Gilbert Mark R , Guedes Vivian A , Smart DeeDee K , Armstrong Terri S , Shuboni-Mulligan Dorela D
Published: September 2023

Background

Hypersomnolence is a common and disruptive side effect of cranial radiotherapy and is associated with fatigue and disturbances in mood and cognition in primary brain tumor (PBT) patients. The biological underpinnings of this effect are not understood. Our laboratory has previously found that the presence of a single nucleotide polymorphism (rs934945, G-E mutation) in the PERIOD2 (PER2) clock gene was associated with a decreased likelihood of fatigue in PBT patients. Here, we aim to understand the effects of PER2 polymorphism on radiation susceptibility within a murine model of cranial-irradiation-induced hypersomnolence (C-RIH).

Methods

Male and female transgenic mice were generated using CRISPR-Cas9, replacing the endogenous mouse PER2:CRY1 binding domain with its human isoform with (hE1244 KI) or without the SNP rs934945 (hG1244 KI). Activity and sleep were monitored continuously 10 days before and after cranial irradiation (whole brain, 15Gy, single fraction). Behavioral assessments measuring anxiety, depression, and working memory were used to assess mood and cognitive changes 2 months postradiation.

Results

During their active phase, hE1244 knock-ins (KIs) had less radiation-induced suppression of activity relative to hG1244 KIs and female hE1244 KIs saw a reduction of hypersomnolence over 10 days. hE1244 KIs displayed less anxiety behavior and were more ambulatory within all behavioral tests.

Conclusions

The PER2 rs934945 polymorphism had long-lasting behavioral effects associated with radiation toxicity, particularly in sleep in females and the activity of all animals. Our findings shed light on biological mechanisms underlying C-RIH.
Left Ventricular Ejection Fraction in Patients With Ovarian Cancer Treated With Avelumab, Pegylated Liposomal Doxorubicin, or Both
Authors: Bonaca Marc P , Moslehi Javid J , Ledermann Jonathan A , Michelon Elisabete , Wei Caimiao , Moran Michael , Monk Bradley J , Pujade-Lauraine Eric
Published: September 2023

In the phase III JAVELIN Ovarian 200 trial, 566 patients with platinum-resistant/refractory ovarian cancer were randomized 1:1:1 to receive avelumab alone, avelumab plus pegylated liposomal doxorubicin (PLD), or PLD alone. Cardiac monitoring was included for all patients. We report left ventricular ejection fraction (LVEF) data from the trial. Grade ≥3 cardiac adverse events (AEs) occurred in 4 (2.1%), 1 (0.5%), and 0 patients in the avelumab, combination, and PLD arms, respectively. LVEF decreases of ≥10% to below institutional lower limit of normal at any time during treatment were observed in 1 (0.8%), 3 (1.9%), and 2 (1.5%) patients, respectively; 4 had subsequent assessments, and these showed transient decreases. No patient had a cardiovascular AE related to LVEF decrease. This analysis is, to our knowledge, the first analysis of LVEF in patients receiving immune checkpoint inhibitors.

ClinicalTrials.gov Identifier

NCT02580058.
Predicting Response to Antibody Drug Conjugates: A Focus on Antigens’ Targetability
Authors: Ascione Liliana , Crimini Edoardo , Trapani Dario , Marra Antonio , Criscitiello Carmen , Curigliano Giuseppe
Published: September 2023

Antibody-drug conjugates (ADCs) represent a cornerstone in the treatment of many cancers nowadays. ADCs fulfill their function by binding a target on tumor cell membrane to deliver a cytotoxic payload; in addition, those moieties capable of crossing cancer cell membranes can achieve near-by cells that do not express the target antigen, exerting the so-called “bystander” cytotoxic effect. The presence of a specific target antigen expressed on cancer cells has been for long considered crucial for ADCs and commonly required for the inclusion of patients in clinical trials with ADCs. To date, only ado-trastuzumab-emtansine, fam-trastuzumab deruxtecan-nxki, and mirvetuximab soravtansine-gynx are approved according to the expression of a target antigen in solid tumors, while the clinical use of other ADCs (eg, sacituzumab govitecan) is not conditioned by the presence of a specific biomarker. Given the ever-growing number of approved ADCs and those under investigation, it is essential to find new biomarkers to guide their use, especially in those settings for which different ADCs are approved to establish the best therapeutic sequence based on robust biomarkers. Hence, this work addresses the role of target antigens in predicting response to ADCs, focusing on examples of antigens’ targetability according to their expression on cancer cells’ surface or to the presence of specific target aberrations (eg, mutation or over-expression). New methods for the assessment and quantification of targets’ expression, like molecular imaging and in vitro assays, might be key tools to improve biomarker analysis and eventually deliver better outcomes by refined patient selection.
Can Precision Oncology Benefit Patients With Cancers of Unknown Primary?
Authors: Rassy Elie , Andre Fabrice
Published: September 2023

This editorial calls for a strategic shift in our approach to cancers of unknown primary (CUP), one that generates a comprehensive multidimensional portrait of cancer in patients with CUP, to model the biology at the individual level and identify the right therapeutic target accordingly. The framework of this approach is based on the integration of basic biology, biotechnologies, data sciences, clinical research, and social sciences.
Cliff or bridge: breaking up with the paediatric healthcare system
Authors: Baumbusch Jennifer
Published: September 2023

Transition from paediatric to adult healthcare is a normal part of the care trajectory, yet the process often leaves much to be desired. In this commentary, I share my family’s journey of this care transition, particularly the handover aspect, by providing examples of different ways that relationships were ended by paediatric healthcare professionals. The ending of these relationships often felt like ‘breaking up’. I also share an example of a supported handover, which bridged the transition from paediatric to adult care. To improve transitions, we need genuine acknowledgement of the paediatric medical trauma stress (PMTS) experienced by families such as mine following years of interactions in the healthcare system. Along with following transition checklists, patients and families need authentic and meaningful closure to longitudinal relationships and trauma-informed care practices as we move forward into the adult care system.
Childhood Schizotypy and Adolescent Mental Disorder
Authors: O’Hare Kirstie , Watkeys Oliver , Dean Kimberlie , Laurens Kristin R , Tzoumakis Stacy , Harris Felicity , Carr Vaughan J , Green Melissa J
Published: September 2023

Background and Hypothesis

Schizotypy provides a framework for understanding the developmental nature of psychotic disorders and a means of identifying “at-risk” individuals early in the lifespan. However, there is a lack of prospective longitudinal research examining the relationship between schizotypy in childhood and later psychotic and other mental disorders. We hypothesized that distinct profiles of schizotypy in childhood would be differentially associated with psychotic and other mental disorders emerging later in adolescence.

Study Design

In a large population cohort of Australian young people (n = 26 837), we prospectively examined the relationship between person-centered profiles of schizotypy identified in middle childhood (age ~11 years) and adolescent diagnoses (age ~13–18 years) across 7 types of mental disorders using multinomial logistic regression.

Results

Membership in any of 3 childhood schizotypy profiles (true schizotypy, affective schizotypy, or introverted schizotypy) was associated with an increased likelihood of being diagnosed with any type of mental disorder in adolescence; effects were strongest for the true schizotypy group (aOR = 3.07, 95% CI = 2.64, 3.57), followed by the introverted (aOR = 1.94, 95% CI = 1.75, 2.15) and affective (aOR = 1.29, 95% CI = 1.13, 1.47) schizotypy groups. Six of the 7 types of mental disorders measured (including psychotic disorders) were associated with at least 1 schizotypy group.

Conclusions

Schizotypy in middle childhood is an important correlate of mental disorders in adolescence; however, it does not appear to be specifically associated with psychotic disorders in this age group.
Pleasure despite pain: Associations between experiences of vulvar pleasure, vulvar pain, and sexual function in patients with chronic vulvar pain conditions
Authors: Mautz Theodora T , Mulroy Maeve E , Krapf Jill M , Goldstein Andrew T , Pukall Caroline F
Published: September 2023

Background

Chronic pain can occur in the vulva, one of the primary pleasure centers of the body; however, the associations between pleasurable vulvar experiences and chronic vulvar pain have not yet been explored.

Aim

The aim of this study was to investigate associations between vulvar pleasure and pain experiences in patients with chronic vulvar pain.

Methods

This was a prospective cross-sectional study of 547 patients (aged ≥17 years) presenting over 10 months to 2 urban outpatient gynecology clinics specializing in vulvar pain. Prior to the initial evaluation, patients completed online validated questionnaires of pain-related anxiety, pain catastrophizing, and sexual functioning, as well as a researcher-developed questionnaire evaluating vulvar pleasure. Patients were divided into groups based on their pleasure and pain experiences. Between-group analyses consisting of t-tests, analyses of variance, and multivariate analyses of variance were conducted.

Outcomes

Outcomes consisted of total and subscale scores on the Pain Anxiety Symptoms Scale-20, Pain Catastrophizing Scale, Female Sexual Function Index, and a researcher-developed vulvar pleasure questionnaire.

Results

More than 70% of patients with chronic vulvar pain had experienced vulvar pleasure since the onset of their vulvar pain, with the clitoris as the most common source of pleasure. Average vulvar pleasure intensity was rated 7 (0, no pleasure; 10, extremely pleasurable). Masturbation ranked higher in pleasurable activities than vulvar stimulation by a partner or penetrative intercourse and was the most likely activity to lead to orgasm. When compared with patients who had not experienced vulvar pleasure since the onset of their vulvar pain, patients experiencing both pain and pleasure scored lower on the Pain Anxiety Symptoms Scale-20 total (P = .026) and fear subscale (P = .016), lower on the Pain Catastrophizing Scale total (P = .002) and all subscales (P = .008-.018), and higher on the Female Sexual Function Index total and all subscales (all P ≤ .001).

Clinical Implications

Incorporating strategies for cultivating vulvar pleasure in patients with chronic vulvar pain may be useful in comprehensive management approaches.

Strengths and Limitations

Strengths of this study include the novel examination of vulvar pleasure in a population with chronic vulvar pain and a large sample size. Limitations include the lack of a nonclinical comparator group and reliance on patient self-report.

Conclusion

Results suggest that greater vulvar pleasure is associated with lower pain-related anxiety, lower pain catastrophizing, and higher sexual functioning in patients with chronic vulvar pain conditions.
Abstract 2 Results of an Open Label Expanded Access Study of Omidubicel-onlv for Allogeneic Transplantation (allo-HCT) in Patients with Hematologic Malignancies
Authors: Horwitz Mitchell , Schiller Gary , Tsai Stephanie , Rezvani Andrew , Maziarz Richard , Goshen Uri , Levy Stuart , Schwarzbach Aurelie , Mazor Roei , Stiff Patrick
Published: September 2023

Introduction

Omidubicel, a nicotinamide expanded allogeneic hematopoietic progenitor cell therapy derived from umbilical cord blood (UCB) was recently FDA approved for use as a sole donor source in allo-HCT based on phase III study results showing improved hematopoietic recovery and decreased infection rate compared to standard UCB.

Objectives

Open label, single arm expanded access program (EAP) evaluating clinical outcomes for patients with hematologic malignancies following omidubicel allo-HCT.

Methods

Eligible patients (>12 years) received myeloablative conditioning with supportive care per institutional guidelines. Patients were followed for engraftment, infections, graft versus host disease (GVHD), and two year post-transplantation outcomes.

Results

Between July 2020 and April 2023, 36 patients were enrolled at 5 US centers, and 29 (18 male, 11 female) were transplanted; median age was 38 years (range: 20-73); 55.2% white, 17.2% Black, 20.7% Asian, 10.3% other. Diagnoses included AML (37.9%), ALL (27.6%), MDS (20.7%) and other (13.8%). Median transplanted CD34+ cell dose was 5.6x106 cells/kg and HLA match was 4/6 in 51.7%, 5/6 in 44.8%, and 6/6 in 3.5%.

Median follow-up was 6.25 months (range 0.33-27.7). At 100 and 365 days post-transplant, PFS rates were 95.5% and 82.9%, and OS rates were 96.3% and 84.4%, respectively. No infusion reactions were reported. Median neutrophil (>500/µl x3 days) and platelets (>20,000/µl x7 days) engraftment times were 12 and 33 days, respectively. Primary graft failure occurred in 2 (6.9%) patients, both alive >100 days after second transplant. Incidence of first grade 2 or 3 bacterial, viral, or invasive fungal infections through 100 days post-transplantation were 13.8%, 24.1% and 0%, respectively.

Acute GVHD was reported in 13 (44.8%) patients (grade II: 34.5%, grade III: 10.3%) and mild chronic GVHD in 1 (3.5%). There were 4 deaths (13.8%): 2 due to relapse @275 and 381 days, 1 due to infection (day 135) and 1 due to pulmonary failure on day 10. Post-transplant lymphoproliferative disease was reported in one.

Discussio

In this real-world EAP setting, allo-HCT with omidubicel was well tolerated, and observed engraftment and infections consistent with published Phase 3 data. These data further support the role of omidubicel particularly for patients from diverse racial backgrounds.