bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis
Authors: Abara Winston E , Kirkcaldy Robert D , Bernstein Kyle T , Galloway Eboni , Learner Emily R
Published: August 2024

Background

There is no licensed vaccine against gonorrhea, but Neisseria meningitidis serogroup B outer membrane vesicle–based vaccines, such as MenB-4C, may offer cross-protection against gonorrhea. This systematic review and meta-analysis synthesized the published literature on MenB-4C vaccine effectiveness against gonorrhea.

Methods

We conducted a literature search of electronic databases (PubMed, Medline, Embase, Global Health, Scopus, Google Scholar, CINAHL, and Cochrane Library) to identify peer-reviewed articles published in English from 1 January 2013 to 11 September 2024 that reported MenB-4C vaccine effectiveness estimates against gonorrhea and gonorrhea/chlamydia coinfection and the duration of MenB-4C vaccine–induced protection. We estimated pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea using the DerSimonian-Laird random effects model.

Results

Eight articles met our eligibility criteria. Receipt of ≥1 dose of MenB-4C vaccine was 23% to 47% effective against gonorrhea. Two doses of MenB-4C vaccine were 33% to 40% effective against gonorrhea, and 1 dose of MenB-4C vaccine was 26% effective. MenB-4C vaccine effectiveness against gonorrhea/chlamydia coinfection was mixed, with 2 studies reporting effectiveness estimates of 32% and 44% and 2 other studies showing no protective effect. MenB-4C vaccine effectiveness against gonorrhea was comparable in people with HIV (44%) and people without HIV (23%–47%). Pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea was 32.4%. One study concluded that MenB-4C vaccine effectiveness against gonorrhea may wane approximately 36 months postvaccination.

Conclusions

MenB-4C vaccine is moderately effective against gonorrhea in various populations. Prospective clinical trials that assess the efficacy of MenB-4C against gonorrhea, gonorrhea/chlamydia coinfection, and duration of protection are warranted to strengthen this evidence.
Anaerobic hydrocarbon biodegradation by alkylotrophic methanogens in deep oil reservoirs
Authors: Zhang Cui-Jing , Zhou Zhuo , Cha Guihong , Li Ling , Fu Lin , Liu Lai-Yan , Yang Lu , Wegener Gunter , Cheng Lei , Li Meng
Published: August 2024

In subsurface biodegraded oil reservoirs, methanogenic biodegradation of crude oil is a common process. This process was previously assigned to the syntrophy of hydrocarbon-degrading bacteria and methanogenic archaea. Recent studies showed that archaea of the Candidatus Methanoliparum named as alkylotrophic methanogens couple hydrocarbon degradation and methane production in a single archaeon. To assess the geochemical role of Ca. Methanoliparum, we analyzed the chemical and microbial composition and metabolites of 209 samples from 15 subsurface oil reservoirs across China. Gas chromatography–mass spectrometry analysis revealed that 92% of the tested samples were substantially degraded. Molecular analysis showed that 85% of the tested samples contained Ca. Methanoliparum, and 52% of the tested samples harbored multiple alkyl-coenzyme M derivatives, the intercellular metabolites of alkylotrophic archaea. According to metagenomic and metatranscriptomic analyses, Ca. Methanoliparum dominates hydrocarbon degradation in biodegraded samples from the Changqing, Jiangsu, and Shengli (SL) oilfields, and it is persistently present as shown in a 15-year-long sampling effort at the Shengli oilfield. Together, these findings demonstrate that Ca. Methanoliparum is a widely distributed oil degrader in reservoirs of China, suggesting that alkylotrophic methanogenesis by archaea plays a key role in the alteration of oil reservoirs, thereby expanding our understanding of biogeochemical process in the deep biosphere.
“Making Democracy Safe for the World”: Kenneth Waltz on Realism, Democracy, and War
Authors: MacKay Joseph
Published: August 2024

This paper reevaluates the history of how some anti-war realists have assessed the relationship between democracy and armed conflict. To do so, I turn to a central realist figure: Kenneth Waltz. Drawing on newly available archival sources and his published work, I explore Waltz’s shifting relationship with American democracy, foreign policymaking, and war. I focus on his career-long anti-war commitments, tracing his foreign policy engagements over the half century of his academic career. Early on, Waltz argued in favor of American democracy as a source of adaptive, effective foreign policy. Gradually, however, his views shifted. After the Cold War and especially after 9/11, his anti-war beliefs and belief in democratic foreign policymaking came increasingly into tension. He moved from defending American democratic foreign policymaking to calling for structural constraints from without. We see this in Waltz’s late-life endorsement of the Iranian nuclear program, which was motivated not just by his well-known optimism about proliferation, but also by the hope that an Iranian nuclear arsenal would deter American intervention in the Middle East. Waltz’s experience has implications both for how we read his body of work and for how we understand realist attempts to shape foreign policy.
Regulation, Reform, Sustainability in Space
Authors: Powell Grant
Published: August 2024

Saffron Price-Finnerty has completed a one year assignment as Deputy Head of Space Regulation at the DSIT. Here she talks to Grant Powell MBCS about her work.
Professional Standards in Aerospace and Defence IT
Authors: Justice Stuart , Oliver Jonathan
Published: August 2024

Stuart Justice, Engineering Director, and Jonathan Oliver, Engineering Capability and Skills Manager, both of BAE Systems Naval Ships, explain the importance of demonstrable professionalism within their industry.
Buckland and the IT Profession
Authors: Aldcroft-Colling Peter , LeClair Beckett , Evans Mark Cross Dafydd , Davey Simon , Goblot Marc , Goucher Wendy , Bellringer Matthew
Published: August 2024

Co-created at an online event organised and run by the BCS NeurodiverseiT Specialist Group, this article responds to the Buckland Review of Autism Employment. During the event we explored the five main themes identified by the Buckland Review, and then the implications of what we had discussed for BCS.
Navigating Data Loss Grief
Authors: Clark Tim
Published: August 2024

Tim Clark, Chair of the BCS Early Careers Executive, takes us through the structures behind data storage on discs, and explains different approaches to data recovery.
Futurology
Authors: Lucas Matt
Published: August 2024

Matt Lucas FBCS writes on the evolving role of AI in the future of defence, the risks of innovation outpacing legislation, and how working with policymakers can ensure AI is a benefit to defence organisations.
The Cutting Edge of Computing
Authors: Sardis Antonia Bascam Fragkiskos
Published: August 2024

People Consultant, Antonia Basca, and Cloud Transformation Architect, Fragkiskos Sardis, at KPMG offer an informative overview of edge computing and its benefits. They also explore what the technology might mean for sectors like the arts, construction and healthcare.
Future-Proofing Through Architecture and IT Strategy
Authors: Barker Natasha
Published: August 2024

Domain Architect Natasha Barker MBCS, at Matalan, considers why future-proofing in IT is not just a buzzword — it's a critical imperative for organisations looking to thrive in today's rapidly evolving business landscape.
Optimization of oral isavuconazole dose for population in special physiological or pathological state: a physiologically based pharmacokinetics model-informed precision dosing
Authors: Zhou Jianxing , Xu Baohua , Zheng You , Huang Huiping , Wei Zipeng , Chen Shengyang , Huang Wei , Liu Maobai , Zhang Yifan , Wu Xuemei
Published: August 2024

Objective

To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states.

Methods

Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration–time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization.

Results

The developed PBPK model was successfully validated in different populations. Most predicted concentration–time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested.

Conclusion

The predicted value aligns with observations, suggesting ISA’s potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.
Effects of maize development and phenology on the field infestation dynamics of the European corn borer (Lepidoptera: Crambidae)
Authors: Revillon Sacha , Dillmann Christine , Galic Nathalie , Bauland Cyril , Palaffre Carine , Malvar Rosa Ana , Butron Ana , Rebaudo François , Legrand Judith
Published: August 2024

Phenological match/mismatch between cultivated plants and their pest could impact pest infestation dynamics in the field. To explore how such match/mismatch of plant and pest phenologies may interact with plant defense dynamics, we studied the infestation dynamics of maize by one of its main pests in Europe, the European Corn Borer (Ostrinia nubilalis; Lepidoptera: Crambidae). A two-year field experiment was carried out on a collection of 23 maize inbred lines contrasted for their earliness. Each inbred line was sown at three different dates in order to expose different developmental stages of maize to natural European corn borer infestation. The effect of the sowing date depended on the inbred line, the pest generation, and the year. In 2021, the final pest incidence ranged from 36% to 91% depending on inbred lines and sowing date. In 2022, it ranged from 2% to 77%. This variability in final pest incidence can be related to variations in plant development during plant exposure to pest infestation. However, this relationship was not straightforward. Indeed, the shape and intensity of the relationship depended on the timing of the onset of the pest infestation. When infestation occurred while plants were in a vegetative stage, a nonlinear relationship between development and pest incidence was observed with the least and most developed plants being the most infested. When infestation occurred when all plants were in the mature phase, the most developed plants were the least infested. Our results highlight the effect of plant–pest phenological match/mismatch on pest infestation dynamics and underline the importance of taking plant–pest interactions into account to propose relevant control strategies.
G-CSF induces neutrophil extracellular traps formation and promotes ovarian cancer peritoneal dissemination
Authors: Bun Michiko , Kawano Mahiru , Yamamoto Gaku , Sakata Mina , Shimura Kotaro , Toda Aska , Nakamura Koji , Kinose Yasuto , Kodama Michiko , Hashimoto Kae , Kobayashi Eiji , Sawada Kenjiro , Kimura Tadashi
Published: August 2024

Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination; however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was cocultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the PAD4 inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF–producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia.
Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer
Authors: Massa Davide , Vernieri Claudio , Nicolè Lorenzo , Criscitiello Carmen , Boissière-Michot Florence , Guiu Séverine , Bobrie Angélique , Griguolo Gaia , Miglietta Federica , Vingiani Andrea , Lobefaro Riccardo , Taurelli Salimbeni Beatrice , Pinato Claudia , Schiavi Francesca , Brich Silvia , Pescia Carlo , Fusco Nicola , Pruneri Giancarlo , Fassan Matteo , Curigliano Giuseppe , Guarneri Valentina , Jacot William , Dieci Maria Vittoria
Published: August 2024

Background

The cutoff of <1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1%-9%) BC, comparing them to ER-negative (ER <1%) and ER-intermediate (ER 10%-50%) tumors.

Methods

Among 921 patients with early-stage I-III, ER ≤50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81). Tumor-infiltrating lymphocytes (TILs) were evaluated. CD8+, FOXP3+ cells, and PD-L1 status were assessed by IHC and quantified by digital pathology. We analyzed 776 BC-related genes in 116 samples. All tests were 2-sided at a <.05 significance level.

Results

ER-low and ER-negative tumors exhibited similar median TILs, statistically significantly higher than ER-intermediate tumors. CD8/FOXP3 ratio and PD-L1 positivity rates were comparable between ER-low and ER-negative groups. These groups showed similar enrichment in basal-like intrinsic subtypes and comparable expression of immune-related genes. ER-low and ER-intermediate tumors showed significant transcriptomic differences. High TILs (≥30%) were associated with improved relapse-free survival (RFS) in ER-low (5-year RFS 78.6% vs 66.2%, log-rank P = .033, hazard ratio [HR] 0.37 [95% CI = 0.15 to 0.96]) and ER-negative patients (5-year RFS 85.2% vs 69.8%, log-rank P < .001, HR 0.41 [95% CI = 0.27 to 0.60]).

Conclusions

ER-low and ER-negative tumors are similar biological and molecular entities, supporting their comparable clinical outcomes and treatment responses, including to immunotherapy. Our findings contribute to the growing evidence calling for a reevaluation of ER-positive BC classification and management, aligning ER-low and ER-negative tumors more closely.
God’s Unity and Unity with God: Polemical Interpretations of John 17:20–23 in the Fourth Century
Authors: Foley Holmes Austin
Published: August 2024

There are no previous studies of Christ’s prayer in John 17:20–23 as a key text which was debated from multiple theological perspectives in the fourth-century controversies. This article provides a close study of the polemical interpretation of John 17:20–23 in Eusebius of Caesarea, Athanasius of Alexandria, and Hilary of Poitiers. The article considers each interpreter’s exegetical techniques, the views of his opponent(s), and his own positive theological claims. In the conclusion, a taxonomy of these interpretations is provided according to the following criteria: (1) Father–Son unity; (2) καθὼς clauses; (3) God–creature unity. The primary question for each interpreter is: to what extent is the Son’s own unity with the Father paradigmatic for the saints’ unity with the Father? Both Eusebius and Hilary argued that the Son’s own unity with the Father is (with qualifications) actually bestowed upon the saints. They each understood the objective of Christ’s prayer as the realization of a God–creature unity in which the saints are united to the Father ‘just as’ the Son. Athanasius, by contrast, argued that Christ’s prayer exhorts the saints to become one among themselves by learning from the example of the Son’s unity with the Father. Insofar as the saints become one with God, Athanasius insists that such a God–creature unity is radically distinct from the Son’s unity of nature with the Father. Yet for Hilary, this natural unity with the Father is also granted to creatures: to the Son’s own humanity, and to all who are united with it.
How Exercise Works for Your Mental Health Goals
Authors: Otto Michael W. , Smits Jasper A. J.
Published: August 2024

This chapter showcases how exercises work for mental health goals. It argues that exercise is a useful treatment for low mood and depression, with increasing evidence for similar benefits for anxiety disorders and resilience for habit control. Exercise also has important effects on a crucial brain-maintenance molecule known as BDNF (brain-derived neurotrophic factor). The chapter cites how exercise affects cognition, brain function, neurotransmitters, and sleep patterns. Regardless of how exercise positively affects multiple things at once, it does not mean people should ignore other treatment options since certain types of psychotherapy and medication are effective for treating mood and anxiety disorders.
Thinking Strategies for Exercise
Authors: Otto Michael W. , Smits Jasper A. J.
Published: August 2024

This chapter covers several thinking strategies for exercise. It explains how thoughts can have a powerful effect on influencing mood and can either boost or sap motivation. Thus, being a good observer of tone and thoughts is vital to making the most out of exercise-related changes in cognition. Some of the thinking strategies during exercise include redirecting negative thoughts and expecting to feel exercise sensations without caring about them. Meanwhile, the thoughts immediately after exercising should revolve around rehearsing benefits and enjoying the success of exercising. The chapter clarifies that miserable exercise sessions are inevitable, but people can still bounce back from these episodes.
Breaking the mass-sheet degeneracy in strong lensing mass modelling with weak lensing observations
Authors: Khadka Narayan , Birrer Simon , Leauthaud Alexie , Nix Holden
Published: August 2024

The Hubble constant ($H_0$), a crucial parameter in cosmology, quantifies the expansion rate of the universe so its precise measurement is important to understand the fundamental dynamics of our evolving universe. One of the major limitations of measuring $H_0$ using time-delay cosmography is the presence of the mass-sheet degeneracy (MSD) in the lens mass modelling. We propose and quantitatively assess the use of galaxy–galaxy shear measurements to break the MSD in the strong lensing mass modelling. We use stacked galaxy–galaxy lensing profiles and corresponding covariance matrices from Huang et al. to constrain the MSD in lens mass modelling with a highly flexible mass profile. Our analyses show that if ideally all galaxy–galaxy lensing measurements from the Hyper Suprime-Cam survey can be used to constrain the MSD, we can achieve $\sim 10~{{\ \rm per\ cent}}$ precision on the MSD constraint. We forecast that galaxy–galaxy lensing measurements from Legacy Survey of Space and Time (LSST)-like surveys can in general constrain the MSD with $\sim 1\,\mathrm{ per\,cent}-3~{{\ \rm per\ cent}}$ precision. Furthermore, if we push weak lensing measurements to a lower angular scale of $\sim 0.04\,\rm Mpc$, a survey like LSST can provide $\sim 1~{{\ \rm per\ cent}}$ precision on the MSD constraint, enabling a measurement of $H_0$ at the 1 per cent level. We demonstrate that galaxy–galaxy weak lensing can robustly constrain the MSD independent of stellar kinematics of the deflector, with wide-field survey data alone.
Dust formation in common envelope binary interactions – II: 3D simulations with self-consistent dust formation
Authors: Bermúdez-Bustamante Luis C , De Marco Orsola , Siess Lionel , Price Daniel J , González-Bolívar Miguel , Lau Mike Y M , Mu Chunliang , Hirai Ryosuke , Danilovich Taïssa , Kasliwal Mansi M
Published: August 2024

We performed numerical simulations of the common envelope (CE) interaction between thermally pulsing asymptotic giant branch (AGB) stars of 1.7 and 3.7 M$_{\odot }$, respectively, and a 0.6 M$_{\odot }$ compact companion. We use tabulated equations of state to take into account recombination energy. For the first time, formation and growth of dust is calculated explicitly, using a carbon dust nucleation network with a C/O abundance ratio of 2.5 (by number). The first dust grains appear within $\sim$1–3 yr after the onset of the CE, forming an optically thick shell at $\sim$10–20 au, growing in thickness and radius to values of $\sim$400–500 au over $\sim$40 yr, with temperatures around 400 K. Most dust is formed in unbound material, having little effect on mass ejection or orbital evolution. By the end of the simulations, the total dust yield is $\sim 8.4\times 10^{-3}$ and $\sim 2.2\times 10^{-2}$ M$_{\odot }$ for the CE with a 1.7 and a 3.7 M$_{\odot }$ AGB star, respectively, corresponding to a nucleation efficiency close to 100 per cent, if no dust destruction mechanism is considered. Despite comparable dust yields to single AGB stars, in CE ejections the dust forms a thousand times faster, over tens of years as opposed to tens of thousands of years. This rapid dust formation may account for the shift in the infrared of the spectral energy distribution of some optical transients known as luminous red novae. Simulated dusty CEs support the idea that extreme carbon stars and ‘water fountains’ may be objects observed after a CE event.
tessilator: a one-stop shop for measuring TESS rotation periods
Authors: Binks A S , Günther H M
Published: August 2024

We present a software package designed to produce photometric light curves and measure rotation periods from full-frame images taken by the Transiting Exoplanet Survey Satellite (TESS), which we name ‘tessilator’. tessilator is the only publicly available code that will run a full light curve and rotation period ($P_{\rm rot}$) analysis based on just a (list of) target identifier(s) or sky position(s) via a simple command-line prompt. This paper sets out to introduce the rationale for developing tessilator, and then describes the methods, considerations, and assumptions for: extracting photometry; dealing with potential contamination; accounting for natural and instrumental systematic effects; light-curve normalization and detrending; removing outliers and unreliable data; and finally, measuring the $P_{\rm rot}$ value and several periodogram attributes. Our methods have been tuned specifically to optimize TESS light curves and are independent from the pipelines developed by the TESS Science Processing Operations Center (SPOC), meaning tessilator can, in principle, analyse any target across the entire celestial sphere. We compare tessilator$P_{\rm rot}$ measurements with TESS-SPOC-derived light curves of 1560 (mainly solar-type and low-mass) stars across four benchmark open clusters (Pisces–Eridanus, the Pleiades, the Hyades, and Praesepe) and a sample of nearby field M-dwarfs. From a vetted subsample of 864 targets we find an excellent return of $P_{\rm rot}$ matches for the first three open clusters ($\gt 85$ per cent) and a moderate ($\sim 60$ per cent) match for the 700 Myr Praesepe and MEarth sample, which validates tessilator as a tool for measuring $P_{\rm rot}$. The tessilator code is available at https://github.com/alexbinks/tessilator.
Loss of the DNA repair protein, polynucleotide kinase/phosphatase, activates the type 1 interferon response independent of ionizing radiation
Authors: Kate Wisdom Deebeke , Fanta Mesfin , Weinfeld Michael
Published: August 2024

DNA damage has been implicated in the stimulation of the type 1 interferon (T1IFN) response. Here, we show that downregulation of the DNA repair protein, polynucleotide kinase/phosphatase (PNKP), in a variety of cell lines causes robust phosphorylation of STAT1, upregulation of interferon-stimulated genes and persistent accumulation of cytosolic DNA, all of which are indicators for the activation of the T1IFN response. Furthermore, this did not require damage induction by ionizing radiation. Instead, our data revealed that production of reactive oxygen species (ROS) synergises with PNKP loss to potentiate the T1IFN response, and that loss of PNKP significantly compromises mitochondrial DNA (mtDNA) integrity. Depletion of mtDNA or treatment of PNKP-depleted cells with ROS scavengers abrogated the T1IFN response, implicating mtDNA as a significant source of the cytosolic DNA required to potentiate the T1IFN response. The STING signalling pathway is responsible for the observed increase in the pro-inflammatory gene signature in PNKP-depleted cells. While the response was dependent on ZBP1, cGAS only contributed to the response in some cell lines. Our data have implications for cancer therapy, since PNKP inhibitors would have the potential to stimulate the immune response, and also to the neurological disorders associated with PNKP mutation.
A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients
Authors: Lim-Fat Mary Jane , Cotter Jennifer A , Touat Mehdi , Vogelzang Jayne , Sousa Cecilia , Pisano Will , Geduldig Jack , Bhave Varun , Driver Joseph , Kao Pei-Chi , McGovern Alana , Ma Clement , Margol Ashley S , Cole Kristina , Smith Amy , Goldman Stewart , Kaneva Kristiyana , Truong AiLien , Nazemi Kellie J , Wood Matthew D , Wright Karen D , London Wendy B , Warren Katherine E , Wen Patrick Y , Bi Wenya Linda , Alexandrescu Sanda , Reardon David A , Ligon Keith L , Yeo Kee Kiat
Published: August 2024

Background

The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes.

Methods

Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2–4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (<19 years), young adult (YA; 19–39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher’s exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS).

Results

We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS.

Conclusions

IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.
When genetics and pediatric cancer collide: Understanding and optimizing families’ experiences
Authors: Hetherington Kate , Wakefield Claire E , McGill Brittany C , Tucker Katherine M , Donoghoe Mark W , Daly Rebecca , Hunter Jacqueline D , Ballinger Mandy , Fuentes-Bolanos Noemi A , Ziegler David S
Published: August 2024

Background

Advances in our understanding of the genetic basis of childhood cancer, including primary central nervous system cancers, are improving the diagnosis, treatment, and clinical management of pediatric patients. To effectively translate scientific breakthroughs into enhanced clinical care, it is essential we understand and learn from the experiences of patients, families, and health professionals.

Methods

This report summarizes findings from 4 Australian psychosocial substudies exploring the perspectives of patients, parents, clinicians, and scientists participating in research related to childhood cancer genetics. Specifically, these studies focus on the psychosocial impact of germline testing in children, surveillance for children with a cancer predisposition syndrome and the perspectives of healthcare professionals who deliver this testing and surveillance.

Results

Data presented highlight some of the opportunities and challenges associated with the changing context of genetic predisposition testing for children, adolescents and yound adults with cancer and illustrate how embedding psychosocial data collection in clinical research can answer important questions in the field and inform the design of patient-centric models of care, resources, and workforce training.

Conclusions

By embracing these perspectives, we can ensure that advances in genetic research translate into enhanced family experiences, and, ultimately, improved outcomes for children and young people with cancer, and their families.
Weight loss interventions for patients with prostate cancer: a scoping review
Authors: Yeary Karen Hye-cheon Kim , Yu Han , Varady Krista , Tang Li
Published: August 2024

Background

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review Guidelines were used to conduct a scoping review of weight loss interventions for patients with prostate cancer, with the goal to ascertain the impact of these interventions on body weight, body composition, metabolic biomarkers, and prostate cancer–related outcomes.

Methods

Six bibliographical databases were searched. Eligible studies included articles reporting weight loss behavioral interventions with at least dietary change as an intervention component, body weight as an outcome, and interventions not solely focused on weight loss maintenance. Patients with prostate cancer of any stage were included. At least 2 independent reviewers used a data-charting form to extract study characteristics and results.

Results

A total of 12 studies were included. The sample consisted predominately of White patients with prostate cancer (multiple stages) in the United States. Most interventions included both dietary and physical activity components and were delivered 1-on-1 in-person and/or by telephone. Most of the studies reported that participants experienced significant weight loss and beneficial body composition changes, with a higher proportion of studies with a longer intervention period and dose (time) reporting greater magnitude of changes in outcomes. There were mixed results regarding the interventions’ impact on metabolic biomarkers and prostate cancer–related outcomes.

Discussion

Understanding the impact of weight loss interventions on patients with prostate cancer is important. Studies including metabolic biomarkers, prostate cancer outcomes, and more diverse populations are needed.
Endoscopic balloon dilation of esophageal stricture in dystrophic epidermolysis bullosa patient: challenges faced and safety of procedure
Authors: Mishra Ruchi , Tetarbe Shivangi , Bedekar Vinit Vinod , Shah Ira
Published: August 2024

Background: Epidermolysis Bullosa (EB) stands as the prototype category of disorders featuring subepidermal fragility, characterized by skin blistering induced by minimal trauma. The gastrointestinal tract is a common site of extracutaneous injury. Esophageal stricture (ES) is one of the severe complications, with nearly 70% of patients experiencing ES within the initial 25 years of life. Case Report: We present a 11-year-old female child of dystrophic EB (DEB) who presented with dysphagia. Barium swallow showed a short segment proximal ES. We faced many challenges before endoscopy owing to difficult intravenous access, restricted mouth opening, multiple dental caries and low haemoglobin. Dental extraction under general anaesthesia and fibreoptic intubation with a smaller sized endotracheal tube guided over epidural catheter was done at another tertiary care institute. Child had severe bleeding due to airway manipulation. Management: At our centre endoscopy guided serial balloon dilation (BD) of ES was performed without intubation under total intravenous anaesthesia (TIVA) without any complications. The stricture was serially dilated under direct visualization till 12 mm in three sessions at three-weekly intervals using CRE (controlled radial expansion) fixed and wire-guided balloon dilators. During the first session 20 mg of triamcinolone acetate injection was also topically applied without mucosal invasion. No such further topical or submucosal applications were attempted due to risk of perforation. Conclusion: Endoscopy guided BD of ES is safe and effective in EB patients when done by experienced team.
Giant cell arteritis and therapeutic response: a dual facet of immunotherapy in metastatic clear cell renal carcinoma
Authors: Adjadé Ganiou , Haag Kelly , Meunier Jérôme , El Fadli Mohammed , Essadi Ismail , Belbaraka Rhizlane
Published: August 2024

Immune checkpoint inhibitors have emerged as a promising cancer treatment, allowing significant and long-term therapeutic responses. Nivolumab, an anti-programmed cell death protein-1, is one of the molecules of this therapeutic class with known and manageable side effects. Giant cell arteritis is a rare immune-related adverse event most often manifested by headaches poorly released by common antalgics and can result in visual loss. We report its occurrence in an 80-year-old patient on maintenance nivolumab for metastatic clear cell renal carcinoma. Prompt diagnosis and initiation of glucocorticoid therapy led to symptom improvement and visual recovery.
Treatment patterns for patients with BRCA1/2-positive metastatic castration-resistant prostate cancer
Authors: Bilen Mehmet A , Khilfeh Ibrahim , Rossi Carmine , Morrison Laura , Diaz Lilian , Hilts Annalise , Lefebvre Patrick , Pilon Dominic , George Daniel J
Published: August 2024

Background

Patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC) have an aggressive disease course. This study aimed to describe real-world treatment patterns among patients with BRCA-positive mCRPC.

Materials and methods

De-identified electronic health record data from the Flatiron Health-Foundation Medicine Inc. Metastatic Prostate Cancer Clinico-Genomic Database (January 01, 2011 to June 30, 2022) were used to select patients with BRCA-positive mCRPC initiating first-line (1L) therapy with an oncologist-defined advanced line of therapy (LOT) or androgen deprivation therapy (ADT) monotherapy. Treatment sequences and reasons for censoring were described in 1L, and among patients who initiated a second-line (2L) therapy.

Results

A total of 98 treated patients with BRCA-positive mCRPC were identified. The top 3 treatment regimens in 1L, overall, were ADT monotherapy (19%), enzalutamide (14%), and olaparib (13%). The main reason for censoring patients with ADT monotherapy was death (52.6%). Among 79 patients treated with an advanced LOT in 1L, 43.0% (n = 34) did not initiate a 2L therapy, of which, 29.4% died. In patients who initiated a 2L (n = 45), the most common 1L to 2L treatment sequence was olaparib to docetaxel (11.1%). The most prescribed 2L therapies were docetaxel (22.2%), olaparib (20.0%), abiraterone acetate (13.3%), and enzalutamide (11.1%). From 1L initiation, the median time-to-next-treatment was 6.2 months.

Conclusion

Among patients with BRCA-positive mCRPC, ADT monotherapy, enzalutamide, and olaparib were most commonly used. Prognosis of BRCA-positive patients was poor, with most patients failing initial therapy resulting in a switch to a new therapy or death. These findings highlight the need for earlier and more effective treatments for patients with BRCA-positive mCRPC.
The New Year’s Eve Meeting
Authors: Yang Dali L.
Published: August 2024

Beginning with the China Centers for Disease Control and Prevention leadership learning of the Wuhan outbreak via social media posts on December 30, 2019, a complex interplay of factors, particularly hierarchical interactions within China’s party-government structure, shaped China’s response to the COVID-19 outbreak. This chapter focuses on the New Year’s Eve emergency meeting in Wuhan involving national, provincial, and municipal health officials and experts. Based on a substantial amount of clinical, epidemiological, and genomic investigations, officials and experts decided on the closure of the Huanan Seafood Market and on an action program to be followed. However, the assumptions about the Huanan Seafood Market being the source of the virus and the virus not yet being transmissible from human to human proved erroneous, creating a false sense of security and a missed opportunity to mobilize the public in containing the outbreak in Wuhan.
The China CDC, the Huanan Seafood Market, and Epidemiological Tunnel Vision
Authors: Yang Dali L.
Published: August 2024

During the initial Wuhan outbreak, the delay in recognizing the human-to-human transmission of the virus raises questions about the role of the China Centers for Disease Control and Prevention (China CDC) and the National Health Commission in intellectual and strategic leadership. Even though many cases of novel coronavirus infections very early on were not linked to the Huanan Seafood Market, the China CDC leadership did not review these crucial data until 3 weeks after the outbreak, leading to a gap in understanding and response. This chapter posits that this failure was likely due to an inadequacy in epidemiological imagination and intellectual leadership within a political-administrative environment of fragmented authoritarianism and information suppression. A rigid cognitive framework based on prior experiences with SARS was applied, leading to the downplaying of cases suggesting human-to-human transmission.
Insights on pathophysiology of hydrocephalus rats induced by kaolin injection
Authors: Zhang Kuo , Zhou Wanqi , Yu Huijie , Pang Meijun , Gao Huixin , Anwar Faheem , Yu Kai , Zhou Ziwei , Guo Fang , Liu Xiuyun , Ming Dong
Published: August 2024

Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague–Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 μL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin–eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin‐60 μL and kaolin‐90 μL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher‐grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 μL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus.
A Preliminary Data Visualization Approach to Vestibulocochlear Diseases Based on Multiple Scalar Dimensions
Authors: Cherchi Marcello
Published: August 2024

For vestibulocochlear diseases, traditional clinical history-taking, and the terminology of widely taught nosologic taxonomy, have misleading implications that can lead to errors in diagnosis and therefore in treatment. In the interest of facilitating differential diagnosis while simultaneously recognizing that many of these diseases may not be as discrete as textbooks suggest, we propose a data visualization approach focusing on several continuous scalar dimensions in the domains of anatomy, physiology, and chronology. We illustrate the application of this approach to several categories of clinical presentation.
Predictors of Delayed Clinical Benefit Following Surgical Treatment for Low Grade Spondylolisthesis
Authors: Djurasovic Mladen , Carreon Leah Y. , Bisson Erica F. , Chan Andrew K. , Bydon Mohamad , Mummaneni Praveen V. , Foley Kevin T. , Shaffrey Christopher I. , Potts Eric A. , Shaffrey Mark E. , Coric Domagoj , Knightly John J. , Park Paul , Wang Michael Y. , Fu Kai-Ming , Slotkin Jonathan R. , Asher Anthony L. , Virk Michael S. , Chou Dean , Haid Regis W. , Glassman Steven D.
Published: August 2024

Study Design.

Retrospective review of prospectively collected data.

Objective.

To investigate what factors predict delayed improvement after surgical treatment of low grade spondylolisthesis.

Summary of Background Data.

Lumbar surgery leads to clinical improvement in the majority of patients with low grade spondylolisthesis. Most patients improve rapidly after surgery, but some patients demonstrate a delayed clinical course.

Methods.

The Quality and Outcomes Database (QOD) was queried for grade 1 spondylolisthesis patients who underwent surgery who had patient reported outcome measures (PROMs) collected at baseline, 3-, 6- and 12-months, including back and leg pain numeric rating scale (NRS), Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). Patients were stratified as “Early responders” reaching MCID at 3 months and maintaining improvement through 12 months and “Delayed responders” not reaching MCID at 3 months but ultimately reaching MCID at 12 months. These two groups were compared with respect to factors which predicted delayed improvement.

Results.

Of 608 patients enrolled, 436 (72%) met inclusion criteria for this study. Overall, 317 patients (72.7%) reached MCID for ODI at 12 months following surgery. Of these patients, 249 (78.5%) exhibited a rapid clinical improvement trajectory and had achieved ODI MCID threshold by the 3-month postop follow-up. 68 patients (21.4%) showed a delayed trajectory, and had not achieved ODI MCID threshold at 3 months, but did ultimately reach MCID at 12-month follow-up. Factors associated with delayed improvement included impaired preoperative ambulatory status, better baseline back and leg pain scores, and worse 3-month leg pain scores (P<0.01).

Conclusions.

The majority of patients undergoing surgery for low grade spondylolisthesis reach ODI MCID threshold rapidly, within the first three months after surgery. Factors associated with a delayed clinical course include impaired preoperative ambulation status, relatively better preoperative back and leg pain, and persistent leg pain at 3 months.
Interprofessional Staffing Pattern Clusters in U.S. ICUs
Authors: Gershengorn Hayley B. , Costa Deena Kelly , Garland Allan , Lizano Danny , Wunsch Hannah
Published: August 2024

OBJECTIVES:

To identify interprofessional staffing pattern clusters used in U.S. ICUs.

DESIGN:

Latent class analysis.

SETTING AND PARTICIPANTS:

Adult U.S. ICUs.

PATIENTS:

None.

INTERVENTIONS:

None.

ANALYSIS:

We used data from a staffing survey that queried respondents (n = 596 ICUs) on provider (intensivist and nonintensivist), nursing, respiratory therapist, and clinical pharmacist availability and roles. We used latent class analysis to identify clusters describing interprofessional staffing patterns and then compared ICU and hospital characteristics across clusters.

MEASUREMENTS AND MAIN RESULTS:

We identified three clusters as optimal. Most ICUs (54.2%) were in cluster 1 (“higher overall staffing”) characterized by a higher likelihood of good provider coverage (both intensivist [onsite 24 hr/d] and nonintensivist [orders placed by ICU team exclusively, presence of advanced practice providers, and physicians-in-training]), nursing leadership (presence of charge nurse, nurse educators, and managers), and bedside nursing support (nurses with registered nursing degrees, fewer patients per nurse, and nursing aide availability). One-third (33.7%) were in cluster 2 (“lower intensivist coverage & nursing leadership, higher bedside nursing support”) and 12.1% were in cluster 3 (“higher provider coverage & nursing leadership, lower bedside nursing support”). Clinical pharmacists were more common in cluster 1 (99.4%), but present in greater than 85% of all ICUs; respiratory therapists were nearly universal. Cluster 1 ICUs were larger (median 20 beds vs. 15 and 17 in clusters 2 and 3, respectively; p < 0.001), and in larger (> 250 beds: 80.6% vs. 66.1% and 48.5%; p < 0.001), not-for-profit (75.9% vs. 69.4% and 60.3%; p < 0.001) hospitals. Telemedicine use 24 hr/d was more common in cluster 3 units (71.8% vs. 11.7% and 14.1%; p < 0.001).

CONCLUSIONS:

More than half of U.S. ICUs had higher staffing overall. Others tended to have either higher provider presence and nursing leadership or higher bedside nursing support, but not both.