bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of potent and selective CK1α Molecular Glue Degraders
Authors: Geng Qixiang , Jiang Zixuan , Byun Woong Sub , Donovan Katherine A , Zhuang Zhe , Jiang Fen , Jones Hannah Marie , Razumkov Hlib , Tang Michelle T , Sarott Roman C , Fischer Eric S , Corsello Steven M , Hinshaw Stephen M , Gray Nathanael S
Published: October 2024

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind to cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation. By scaffold hopping and rational modification of the chemical scaffold, we identified an imidazo[1,2-a]pyrimidine compound that induces potent and selective CK1α degradation. A structure-activity relationship study of the lead compound, QXG-6442, identified the structural features that contribute to degradation potency and selectivity compared to other frequently observed neosubstrates. The glutarimide library screening and structure activity relationship medicinal chemistry approach we employed is generally useful for developing new molecular glue degraders towards new targets of interest.
The effects of an abundance of natural resources on the healthcare industry: The global evidence
Authors: Katircioglu Setareh
Published: October 2024

The current study investigates the effects of an abundance of natural resources on the healthcare industry worldwide. Various natural resources proxies such as rents for coal, mineral, natural gas, and oil are used and analyzed by using a quarterly datasets for the period 2000:Q1–2020:Q4. Results from regional and income group datasets show that various forms of natural resources abundance around the globe exert statistically significant, but a mix of positive and adverse effects on the healthcare sector. Results also reveal that changes in and shocks given to natural resources precede significant changes in the healthcare sector in general. This study advises that countries need to achieve careful resource management, open governance, and economic diversification top priority in order to lessen reliance on a single resource and mitigate any negative effects. Further implications are provided at the end of this study.
Tissue ontogeny and chemical composition influence bacterial biodiversity in the wood and shoot tip of Populus nigra
Authors: Bose T. , Mahomed T. G. , Mbatha K. C. , Joubert J. C. , Hammerbacher A.
Published: October 2024

Plant–microbe interactions significantly influence plant growth dynamics and adaptability. This study explores the impact of metabolites on microbial biodiversity in shoot tips and wood of Populus nigra under greenhouse conditions, using high‐throughput sequencing and metabolite profiling.

Branches from P. nigra were harvested, rooted, and transplanted into pots for growth. After 3 months, tissue samples from shoot tips and wood were collected, and metabolites extracted and analysed using GC‐MS and LC‐MS. Genomic DNA was extracted and subjected to high‐throughput sequencing for bacterial biodiversity profiling. Both datasets were analysed using bioinformatic and statistical pipelines.

Metabolite profiling indicated that shoot tips had a higher relative abundance of primary and secondary metabolites, including sugars, fatty acids, organic acids, phenolic acid derivatives and salicinoids, while wood was enriched in flavonoids. Bacterial biodiversity also differed significantly between these tissues, with Clostridiales, Bacteroidales and Bacillales dominating in shoot tips, associated with rapid growth and anaerobic fermentation, while wood tissues were characterized by diazotrophs from Rhizobiales, Sphingomonadales and Frankiales. PCoA clustering confirmed tissue‐specific microbial differences. Functional analysis revealed an enrichment of fundamental cellular processes in shoot tips, while wood exhibited pathways related to degradation and mortality.

Metabolite profiling revealed significant variations in primary and secondary metabolites, highlighting their influence on microbial biodiversity across plant tissues. The dominance of specific bacterial orders and distinct functional pathways in each tissue suggests a tailored microbial response to the unique environments of shoot tips and wood.
Conservatism in response to rising universalism? Linking individuals' conservation values, right‐wing attitudes, and nationalism to perceived prevalence of universalism among fellow citizens
Authors: Rupar Mirjana , Kołeczek Maryna , Jamróz‐Dolińska Katarzyna , Sekerdej Maciej
Published: October 2024

Increased openness and tolerance have marked the twenty‐first century, yet recent years witnessed a decline marked by nationalist movements and reduced support for diversity. We explore the potential link between these two societal changes by examining the association between the perception of universalism values in society and the endorsement of conservation values, right‐wing political attitudes, and nationalism in Poland. Across six correlational studies (total N = 2644), perception of the prevalence of universalism values in fellow citizens was positively linked to one's endorsement of conservation values, right‐wing political attitudes, and nationalism. These links were (a) stronger when participants believed that a considerable part of society still supported conservation values and (b) underlined by a greater perception of the threat posed by universalism values to the traditional way of living. The experimental results (N = 307) did not support causal link between these links but only the underlying role of perceiving a threat from universalism to society, particularly when participants perceived high universalism and conservation values in others. However, this effect was observed only when controlling for one's endorsement of conservation values and the perception of threat from conservation values.
The relationship among the innovation environment, transactive memory system of the R&D team, and knowledge collaboration
Authors: Cheng Qiang , Xu Linna , Liu Yiling , Liu Yue , Peng Chun , He Xingsong , Fu Yilin , Chang Yanru
Published: October 2024

The innovation environment is the basis for the operation of the innovation ecosystem. In an era where knowledge resources are increasingly recognized as core assets, the advent of transactive memory system (TMS) has significantly enhanced the knowledge collaboration among R&D (Research & Development) teams, thereby boosting their innovation performance. Based on the empirical analysis of 235 valid questionnaires, this paper explores the relationship among the innovation environment, R&D Team's TMS, and knowledge collaboration. The results show that: (1) the Innovation environment has a direct and significant positive effect on the team's TMS and knowledge collaboration; (2) Team's TMS has some direct and significant positive effects and mediating effects on Knowledge Collaboration, and the Coordination of team's TMS has no significant effect on the Knowledge Integration process of Knowledge Collaboration; (3) The innovation environment can indirectly affect the knowledge collaboration process through the Specialization and Credibility of the TMS. This study further enriches the relevant research in the field of knowledge management and provides theoretical support and countermeasures for enterprises to promote innovation and development by optimizing knowledge management.
Supplemental Material: Continental crustal growth in the post-collisional setting: Insights from the Late Triassic high-Mg andesites in the eastern Central Asian Orogenic Belt
Authors: Zhang Liying , al. et
Published: October 2024

Supplemental figures (Figs. S1 and S2) and data (Tables S1–S4). 
Supplemental Material: Multicyclic Phanerozoic orogeny recorded in the Qaidam continent, northern Tibet: Implications for the tectonic evolution of the Tethyan orogenic system
Authors: Wu Chen , al. et
Published: October 2024

Table S1: LA-ICP-MS results of zircon U-Pb geochronology for this study. Table S2: Zircon Lu-Hf results of the samples collected for this study. Table S3: Whole-rock major and trace elements of the samples collected for this study. Table S4: Whole-rock Sr-Nd isotopes of the samples collected for this study. Table S5: LA-ICP-MS results of zircon U-Pb geochronology and zircon Lu-Hf, whole-rock major- and trace-element, and whole-rock Sr-Nd isotope analyses from previous studies.
Effect of Etching Methods on Dielectric Losses in Transmons
Authors: Chudakova T. A. , Mazhorin G. S. , Trofimov I. V. , Rudenko N. Yu. , Mumlyakov A. M. , Kazmina A. S. , Egorova E. Yu. , Gladilovich P. A. , Chichkov M. V. , Maleeva N. A. , Tarkhov M. A. , Chichkov V. I.
Published: October 2024

Superconducting qubits are considered as a promising platform for implementing a fault tolerant quantum computing. However, surface defects of superconductors and the substrate leading to qubit state decoherence and fluctuations in qubit parameters constitute a significant problem. The amount and type of defects depend both on the chip materials and fabrication procedure. In this work, transmons produced by two different methods of aluminum etching: wet etching in a solution of weak acids and dry etching using a chlorine-based plasma are experimentally studied. The relaxation and coherence times for dry-etched qubits are more than twice as long as those for wet-etched ones. Additionally, the analysis of time fluctuations of qubit frequencies and relaxation times, which is an effective method to identify the dominant dielectric loss mechanisms, i-ndicates a significantly lower impact of two-level systems in the dry-etched qubits compared to the wet-etched ones.
Relationship between the albumin-corrected anion gap and short-term prognosis among patients with cardiogenic shock: a retrospective analysis of the MIMIC-IV and eICU databases
Authors: Wang Yuxing , Tao Yuhang , Yuan Ming , Yu Pengcheng , Zhang Kai , Ying Hangying , Jiang Ruhong
Published: October 2024

Objectives

We aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS).

Design

A multicentre retrospective cohort study.

Setting

Data were collected from the Medical Information Mart for Intensive Care (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD) datasets.

Participants

808 and 700 individuals from the MIMIC-IV and eICU-CRD, respectively, who were diagnosed with CS.

Primary and secondary outcomes

The primary endpoint was short-term all-cause mortality, including intensive care unit (ICU), in-hospital and 28-day mortality. The secondary endpoints were the 28-day free from the ICU duration and the length of ICU stay.

Results

CS patients were divided into two groups according to the admission ACAG value: the normal ACAG group (≤20 mmol/L) and the high ACAG group (> 20 mmol/L). CS patients with higher ACAG values exhibited increased short-term all-cause mortality rates, including ICU mortality (MIMIC-IV cohort: adjusted HR: 1.43, 95% CI=1.05–1.93, p=0.022; eICU-CRD cohort: adjusted HR: 1.38, 95% CI=1.02–1.86, p=0.036), in-hospital mortality (MIMIC-IV cohort: adjusted HR: 1.31, 95% CI=1.01–1.71, p=0.03; eICU-CRD cohort: adjusted HR: 1.47, 95% CI=1.12–1.94, p=0.006) and 28-day mortality (adjusted HR: 1.42, 95% CI: 1.11 to 1.83, p=0.007). A positive linear correlation was observed between the ACAG value and short-term mortality rates via restricted cubic splines. Compared with the AG, the ACAG presented a larger area under the curve for short-term mortality prediction. In addition, the duration of intensive care was longer, whereas the 28-day free from the ICU duration was shorter in patients with a higher ACAG value in both cohorts.

Conclusion

The ACAG value was independently and strongly associated with the prognosis of patients with CS, indicating that the ACAG value is superior to the conventional AG value.
Cohort profile: Understanding the influence of early life environments and health and social service system contacts over time and across generations through the Western Australian Aboriginal Child Health Survey (WAACHS) Linked Data Study
Authors: Mitrou Francis , Milroy Helen , Coffin Juli , Hamilton Sharynne L , Brennan-Jones Christopher G , Schurer Stefanie , Davis Elizabeth A , Richmond Peter , Passmore Hayley M , Pearson Glenn , Brown Alex , O'Donnell Melissa , Bowen Asha C , Azzopardi Peter , Conigrave Katherine M , Downs Jenny , Cooper Matthew M , Ramsey Kathryn A , Ferrante Anna , Johnson Sarah E , Cave Leah , Vlaskovsky Philip , Hopkins Katrina D , D'Antoine Heather A , Wilkes Ted , Zubrick Stephen R
Published: October 2024

Purpose

Despite the volume of accumulating knowledge from prospective Aboriginal cohort studies, longitudinal data describing developmental trajectories in health and well-being is limited. The linkage of child and carer cohorts from a historical cross-sectional survey with longitudinal health-service and social-service administrative data has created a unique and powerful data resource that underpins the Western Australian Aboriginal Child Health Survey (WAACHS) linked data study. This study aims to provide evidence-based information to Aboriginal communities across Western Australia, governments and non-government agencies on the heterogeneous life trajectories of Aboriginal children and families.

Participants

This study comprises data from a historical cross-sectional household study of 5289 Aboriginal children from the WAACHS (2000–2002) alongside their primary (N=2113) and other (N=1040) carers, and other householders. WAACHS data were linked with Western Australia (WA) government administrative datasets up to 2020 including health, education, child protection, police and justice system contacts. The study also includes two non-Aboriginal cohorts from WA, linked with the same administrative data sources allowing comparisons of outcomes across cohorts in addition to between-group comparisons within the Aboriginal population.

Findings to date

Linked data coverage rates are presented for all WAACHS participants. Child health outcomes for the WAACHS children (Cohort 1) are described from birth into adulthood along with other outcomes including child protection and juvenile justice involvement.

Future plans

Analysis of data from both the child and carer cohorts will seek to understand the contribution of individual, family (intergenerational) and community-level influences on Aboriginal children’s developmental and health pathways, identify key developmental transitions or turning points where interventions may be most effective in improving outcomes, and compare service pathways for Aboriginal and non-Aboriginal children. All research is guided by Aboriginal governance processes and study outputs will be produced with Aboriginal leadership to guide culturally appropriate policy and practice for improving health, education and social outcomes.
Extensivist: improving the delivery of enhanced health in older people’s care homes
Authors: Ma Nan , Stanley Gerard , Miller Debi , Ajagunna David , Jones Nicola , Kinirons Mark , Dallmeyer Rebecca , Kalsi Tania
Published: October 2024

Background

Older people living in care homes are often frail and clinically complex. The Enhanced Health in Care Homes (EHCH) framework supports organisational and clinical strategies to deliver good care, promoting proactive person-centred care by whole system collaboration. We evaluate the impact of a new role, the Extensivist, in the delivery of EHCH for older people living in care homes.

Aims

To evaluate implementation processes and the clinical utility of the Extensivist in older people care homes in the London borough of Southwark.

Methods

The Extensivist (Band 8a Advanced Nurse Specialist skilled in frail older people) was embedded within the care home general practitioners (GP) service for a 2-year pilot (2019–2021). Implementation processes were evaluated. Impact of the Extensivist role was evaluated by the number of Comprehensive Geriatric Assessment (CGA) completed, interventions and other clinical activity performed as well as qualitative case studies and semistructured feedback from care home workers and professionals.

Results

The Extensivist feasibly delivered CGA and implemented intervention plans. The role iteratively developed to support wider aspects of care including advance care planning (ACP) and training. Challenges included building trust, the time-consuming nature of CGA, ACP and coordinated communication. Case studies and semistructured feedback indicated the role was considered valuable in the delivery of clinical care, supporting residents, families, care homes and GPs and as a resource for education for care home workers.

Conclusions

The Extensivist is a valuable resource and a linchpin in the delivery of EHCH framework in care homes for older adults in Southwark. Further evaluations to assess reproducibility in other areas of the UK are warranted.
Video laryngoscopy may improve the intubation outcomes in critically ill patients: a systematic review and meta-analysis of randomised controlled trials
Authors: Zhang Kai , Zhong Chao , Lou Yuhang , Fan Yushi , Zhen Ningxin , Huang Tiancha , Chen Chengyang , Shan Hui , Du Linlin , Wang Yesong , Cui Wei , Cao Lanxin , Tian Baoping , Zhang Gensheng
Published: October 2024

Background

The role of video laryngoscopy in critically ill patients requiring emergency tracheal intubation remains controversial. This systematic review and meta-analysis aimed to evaluate whether video laryngoscopy could improve the clinical outcomes of emergency tracheal intubation.

Methods

We searched the PubMed, Embase, Scopus and Cochrane databases up to 5 September 2024. Randomised controlled trials comparing video laryngoscopy with direct laryngoscopy for emergency tracheal intubation were analysed. The primary outcome was the first-attempt success rate, while secondary outcomes included intubation time, glottic visualisation, in-hospital mortality and complications.

Results

Twenty-six studies (6 in prehospital settings and 20 in hospital settings) involving 5952 patients were analysed in this study. Fifteen studies had low risk of bias. Overall, there was no significant difference in first-attempt success rate between two groups (RR 1.05, 95% CI 0.97 to 1.13, p=0.24, I2=89%). However, video laryngoscopy was associated with a higher first-attempt success rate in hospital settings (emergency department: RR 1.13, 95% CI 1.03 to 1.23, p=0.007, I2=85%; intensive care unit: RR 1.16, 95% CI 1.05 to 1.29, p=0.003, I2=68%) and among inexperienced operators (RR 1.15, 95% CI 1.03 to 1.28, p=0.01, I2=72%). Conversely, the first-attempt success rate with video laryngoscopy was lower in prehospital settings (RR 0.75, 95% CI 0.57 to 0.99, p=0.04, I2=95%). There were no differences for other outcomes except for better glottic visualisation (RR 1.11, 95% CI 1.03 to 1.20, p=0.005, I2=91%) and a lower incidence of oesophageal intubation (RR 0.42, 95% CI 0.24 to 0.71, p=0.001, I2=0%) when using video laryngoscopy.

Conclusions

In hospital settings, video laryngoscopy improved first-attempt success rate of emergency intubation, provided superior glottic visualisation and reduced incidence of oesophageal intubation in critically ill patients. Our findings support the routine use of video laryngoscopy in the emergency department and intensive care units.

PROSPERO registration number

CRD 42023461887.
Comparison of subcutaneous and intravenous infliximab in patients with inflammatory bowel disease showed no differences in immunogenicity or treatment persistence at 1 year
Authors: Hancox Sarah , Morda Francesco , Black Christopher J , Selinger Christian Philipp
Published: October 2024

Background

Infliximab (IFX) effectiveness in inflammatory bowel disease (IBD) can be impaired by antidrug antibodies (ADA). Subcutaneous IFX has a different pharmacokinetic profile compared with intravenous administration, potentially affecting immunogenicity.

Methods

Retrospective audit of adult patients starting IFX between January 2019 and June 2022. All participants received induction with three intravenous doses, followed by either maintenance subcutaneous IFX every 2 weeks (from 2021) or maintenance intravenous IFX (historic control). We compared ADA levels, IFX trough levels and treatment persistence between groups after 12 months of treatment.

Results

101 patients receiving maintenance subcutaneous IFX were compared with 108 patients with maintenance intravenous IFX. At 12 months, prevalence of ADA positivity was similar in both groups (48.1% subcutaneous vs 50.6% intravenous; p=0.775). There were no differences in detectable IFX trough levels and treatment persistence between both groups. Patients receiving combination therapy with IFX and immunomodulators (34.8%) had less often ADA (65.2%; OR 0.28 (95% CI 0.13 to 0.58); p=0.001) irrespective of route of IFX administration. Treatment persistence was higher in those receiving combination therapy compared with monotherapy at 12 months (73.3% vs 51.9%; p=0.004).

Conclusions

There were no significant differences in ADA levels, IFX levels and treatment persistence between the subcutaneous and intravenous routes of IFX administration after 12 months. Concurrent use of immunomodulators was associated with reduced immunogenicity and better treatment persistence. Clinicians should advise patients on the benefits of immunomodulator combination therapy regardless of route of administration.
Workplace violence in trauma centers: an American Trauma Society Position Statement
Authors: Robinson Kathy , Finch Heather , Sieracki Heather , Oberle Andrew , Anderson Melissa , Wells Matthew , Tinkoff Glen H
Published: October 2024

In 1966, the National Academy of Sciences and National Research Council published ‘Accidental Death and Disability: the Neglected Disease of Modern Society’ which served as a national call to action to address the apparent public apathy towards the devastating and unnecessary toll that injury was taking on America. This white paper recommended the establishment of a National Trauma Association to drive public demand for injury prevention and mitigation. The American Association for the Surgery of Trauma heeding that call, founded the American Trauma Society (ATS) in 1968. Since its founding and with a mission of ‘Save Lives. Improve Care. Empowering Survivors’, the ATS has had a 56-year legacy of service to improve trauma care by providing professional and public education, advocacy for injury and violence prevention, and attending to the unique needs of trauma survivors and their families.

As a focus of the ATS’s advocacy efforts, the ATS’s Legislative and Policy Committee (LPC) formulates the organization’s legislative goals and strategy by reviewing proposed legislation and regulations that may favorably or adversely affect trauma professionals, and disseminating key information as position statements to the membership and public for edification and/or action. In accordance with this effort, the ATS has partnered with theTrauma Surgery and Acute Care Opento publish these important collaborative endeavors.

For this inaugural publication of an ATS position statement, the topic we chose is workplace violence (WPV) in trauma centers. A work group of the ATS’s LPC reviewed current literature gathered from a variety of organizational and agency sources addressing safety and protection of healthcare providers from WPV including federal and state legislative and regulatory initiatives. Based on the work groups review, we provide eight recommendations regarding the prevention, mitigation, or handling of WPV. We also review and discuss best practices and risk mitigation strategies, providing a listing of them in an accompanying appendix.
Bull kelp (Nereocystis luetkeana) growth rates as climate stress indicators for Canada’s Pacific coast
Authors: Pontier Ondine , Rhoades Olivia , Twist Brenton , Okamoto Dan , Hessing-Lewis Margot
Published: October 2024

Primary producers’ growth rates are ideal bioindicators of changing climate due to their sensitivity to environmental conditions. On the Central Coast of British Columbia, we assessed growth rates of Nereocystis luetkeana, a canopy-forming annual kelp, by assessing baseline variability in growth rates and their response to environmental conditions of over 600 individuals and across three sites (2016–2019). Optimal growth rates for blades and stipes (∼13–14 cm/day) occurred within a narrow range of local environmental conditions. Growth decreased at temperatures > 10 °C, below 1 µm/L nitrate concentration, and surface light availability reduced blade growth at low and high levels (daily light integral or DLI <20 and >40 mol/m2/day). Spatiotemporal variability in these environmental drivers co-occurred with differences in growth rates, suggesting that local conditions strongly influenced growth. In particular, temperature and nutrients were un-coupled seasonally in this region, with more variable responses in growth over the primary growing season (May to September). Overall, the sensitivity of the growth rates of this annual kelp to changing climatic conditions suggests that it is a useful bioindicator for management and marine planning efforts (e.g., restoration and aquaculture) across its species range and provides a feasible metric for monitoring.
A Multi-scale Framework for Advancing Battery Safety Through Early Calorimetric Analysis of Materials and Components
Authors: Bates Alex , Torres-Castro Loraine , Albertus Paul , Mukherjee Partha P. , Jeevarajan Judith , Johnson Nathan , Bhargava Bhuvsmita , Wang Zixuan , Ogundipe Taiwo , Vishnugopi Bairav S. , Karmakar Avijit , Tang Wan Si
Published: October 2024

Batteries are the cornerstone of the global shift toward electrification, powering applications from passenger transportation, like electric vehicles (EVs), to load shifting of renewable energy generation at the grid level. The demand for batteries is accelerating, and is projected to nearly quadruple by 2030. In response to increasing battery demands, in particular demand for longer range EVs, higher energy density and specific energy alternatives to conventional Li-ion battery technologies are being researched. However, higher energy density directly correlates with an increased potential for higher peak temperatures on failure. In addition, safety evaluation of conventional and new battery technologies generally occurs late in development, often at the commercialization stage when mandated by stakeholders or industry standards. This approach can be costly and challenging as it may require a change to manufacturing processes, a re-design of the battery, and even a change in chemistry to meet safety requirements. This is critical; scale-up efforts alone can take tens to hundreds of millions of dollars and >5 years to achieve. Safety risks discovered after commercialization can significantly exacerbate those figures. Furthermore, safety is still a major risk with already commercialized Li-ion batteries. These risks hinder adoption, slow commercialization, and when they become issues, the outcome may result in recalls, fires, injuries, and even fatalities. Providing additional levers to proactively mitigate safety risk at the materials and components scale (e.g., composite cathode) will lead to considerable time and money savings in the long run.
Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor–Targeted Therapy Drives Resistance in Breast Cancer
Authors: Gemma Carolina , Lai Chun-Fui , Singh Anup K. , Belfiore Antonino , Portman Neil , Milioli Heloisa Z. , Periyasamy Manikandan , Raafat Sara , Nicholls Alyssa J. , Davies Claire M. , Patel Naina R. , Simmons Georgia M. , Fan Hailing , Nguyen Van T.M. , Magnani Luca , Rakha Emad , Martin Lesley-Ann , Lim Elgene , Coombes R. Charles , Pruneri Giancarlo , Buluwela Laki , Ali Simak
Published: October 2024

Resistance to endocrine therapies (ET) is common in estrogen receptor (ER)–positive breast cancer, and most relapsed patients die with ET-resistant disease. Although genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance. By analyzing histone H3 lysine 27 acetylation profiles and transcriptional reprogramming in models of ET resistance, we discovered that selective ER degraders, such as fulvestrant, promote expression of vestigial-like 1 (VGLL1), a coactivator for TEF-1 and AbaA domain (TEAD) transcription factors. VGLL1, acting via TEADs, promoted the expression of genes that drive the growth of fulvestrant-resistant breast cancer cells. Pharmacological disruption of VGLL1–TEAD4 interaction inhibited VGLL1/TEAD-induced transcriptional programs to prevent the growth of resistant cells. EGFR was among the VGLL1/TEAD-regulated genes, and VGLL1-directed EGFR upregulation sensitized fulvestrant-resistant breast cancer cells to EGFR inhibitors. Taken together, these findings identify VGLL1 as a transcriptional driver in ET resistance and advance therapeutic possibilities for relapsed ER+ breast cancer patients.

Significance: Transcriptional reprogramming mediated by the upregulation of the TEAD coactivator VGLL1 confers resistance to estrogen receptor degraders in breast cancer but provides alternative therapeutic options for this clinically important patient group.
Supplemental Table 1 from Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children’s Oncology Group Registries
Authors: Ou Judy Y. , Kaddas Heydon K. , Alonzo Todd A. , Spector Logan G. , Fallahazad Negar , Owens Emily , Collin Lindsay J. , Green Adam L. , Kirchhoff Anne C.
Published: October 2024

Supplemental Table 1. Fit statistics for ordinal, proportional, and partial proportional odds models
Supplemental Figure 1 from Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children’s Oncology Group Registries
Authors: Ou Judy Y. , Kaddas Heydon K. , Alonzo Todd A. , Spector Logan G. , Fallahazad Negar , Owens Emily , Collin Lindsay J. , Green Adam L. , Kirchhoff Anne C.
Published: October 2024

Supplemental Figure 1 shows cohort creation from the Children's Oncology Group data.
Table S2 from Systematic Review and Meta-Analysis of Lifestyle and Reproductive Factors Associated with Risk of Breast Cancer in Asian Women
Authors: Ang Boon Hong , Teo Soo-Hwang , Ho Weang-Kee
Published: October 2024

Supplementary Table S2 presents a summary of study characteristics (including study quality and birth cohort) for the 128 studies included in this review, categorised by region, country, and study design, with relevant citations.
Data from Sociodemographic Disparities in HER2+ Breast Cancer Trastuzumab Receipt: An English Population-Based Study
Authors: Norris Ruth P. , Dew Rosie , Greystoke Alastair , Cresti Nicola , Cain Henry , Todd Adam , Sharp Linda
Published: October 2024

AbstractBackground:
Sociodemographic disparities in traditional breast cancer treatment receipt in nonpublicly funded healthcare systems are well documented. This study investigated trastuzumab receipt by sociodemographic factors within a female, HER2+ breast cancer population in England’s publicly funded National Health Service.
Methods:
The English national population-based cancer registry and linked Systemic Anti-Cancer Therapy database identified 36,985 women with HER2+ invasive breast cancer diagnosed between January 1, 2012 and December 31, 2017. Multivariable logistic regression determined the likelihood of trastuzumab receipt in early and metastatic disease by the deprivation category of area of residence and other sociodemographic characteristics.
Results:
Early-stage trastuzumab receipt followed a socioeconomic gradient. Women residing in the most deprived areas were 10% less likely to receive trastuzumab [multivariable OR 0.90; 95% confidence interval (CI), 0.83–0.98] compared with women residing in the least deprived areas. In both early and metastatic disease, trastuzumab receipt was less likely in older women with more comorbidities, estrogen receptor–positive disease, and who were not discussed at a multidisciplinary team meeting.
Conclusions:
Despite the provision of free care at the point of delivery in England, sociodemographic disparities in early-stage HER2+ trastuzumab receipt occur. Further research determining how inequities contribute to disparities in outcomes is warranted to ensure optimized trastuzumab use for all.
Impact:
Fair access to novel cancer treatments regardless of place of residence, sociodemographic characteristics, and/or cancer stage requires prioritization in future cancer improvement policies.

See related In the Spotlight, p. 1259
The Disconnect between Clinical Guidelines and Reality: The Case of Trastuzumab
Authors: Aranda-Gutierrez Alejandro , Soto-Perez-de-Celis Enrique
Published: October 2024

HER2-positive breast cancer accounts for 10% to 20% of all breast cancer diagnoses. The mAb trastuzumab is crucial in treating this disease, significantly improving survival outcomes. Despite its inclusion in the World Health Organization’s Model List of Essential Medicines, access to trastuzumab remains limited worldwide. In this issue of the journal, Norris and colleagues report that only 45% of eligible patients with HER2-positive breast cancer in the United Kingdom received trastuzumab between 2012 and 2017. This finding in a high-income country with universal health care is worrisome and points toward even greater barriers to access in developing nations. Some solutions to improve accessibility, which we discuss, include shorter durations of trastuzumab treatment and encouraging the registration and availability of biosimilars. The data presented by Norris and colleagues point toward a disconnect between the academic oncology landscape, focused on expensive drugs with marginal benefits, and everyday practice in which even essential interventions may not be available. Ensuring the accessibility to proven, essential medicines should be as relevant as innovation to improve patient outcomes and create a more sustainable healthcare system.

See related article by Norris et al., p. 1298
Adiposity throughout Adulthood and Risk of Young-Onset Breast Cancer Tumor Subtypes in the Young Women’s Health History Study
Authors: Marcus Post Lydia , Pathak Dorothy R. , Hamilton Ann S. , Hirko Kelly A. , Houang Richard T. , Guseman Emily H. , Sanfelippo Dan , Bohme Carnegie Nicole , Olson L. Karl , Rui Hallgeir , Schwartz Ann G. , Velie Ellen M.
Published: October 2024

Background:

The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

Methods:

In this population-based case (n = 1812)–control (n = 1,381) study of invasive YOBC (ages <50 years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes [i.e., luminal A, luminal B, HER2+, and triple negative (TN)] were calculated, overall and by parity, using multivariable weighted logistic regression.

Results:

Obese young adult BMI was inversely associated with luminal A YOBC (OR = 0.35, 95% CI, 0.16–0.79); other subtype associations were nonsignificant. Similarly, adult overweight and obese BMIs were inversely associated with luminal A (OR = 0.66, 95% CI, 0.48–0.91 and OR = 0.59, 95% CI, 0.46–0.87, respectively), but not other subtypes. Conversely, larger waist circumference was associated with higher odds of luminal B and TN YOBC (OR = 1.48, 95% CI, 1.01–2.15 and OR = 2.48, 95% CI, 1.52–3.88, respectively), but not other subtypes (with similar results for weight-to-height ratio); highest odds were among parous women.

Conclusions:

Findings show greater general adult adiposity is associated with reduced odds of luminal A YOBC, whereas greater central adiposity is associated with increased odds of luminal B and TN YOBC, particularly among parous women.

Impact:

Additional studies of central adiposity and YOBC subtype risk, especially incorporating pregnancy history, are warranted.
Supplementary Table S9 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

Immunohistochemistry (IHC) quantification of CD3+ and CD8+ T cells from tumor blocks
Supplementary Table S7 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

RNA-sequencing pseudo counts generated via Salmon algorithm
Supplementary Table S4 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

Peptide sequences included in each subject's personalized NeoVax peptide vaccine
Supplementary Table S1 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

Representativeness of study participants
Supplementary Figure S9 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

Bar graph displaying number of validated variants for each subject
Supplementary Figure S7 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

CDR3beta sequences ranked by abundance
Supplementary Figure S6 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: October 2024

Immunohistologic images
Supplementary Figure S4 from Lactate Induces Tumor Progression via LAR Motif-Dependent Yin-Yang 1 Degradation
Authors: Du Shujuan , Chen Xiaoting , Han Xiao , Wang Yuyan , Yu Dan , Li Ying , Zhu Caixia , Tong Yin , Gao Shujun , Wang Junwen , Wei Fang , Cai Qiliang
Published: October 2024

Supplementary Figure S4
Supplementary Table 6 from NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Authors: Noronha Katelyn J. , Lucas Karlie N. , Paradkar Sateja , Edmonds Joseph , Friedman Sam , Murray Matthew A. , Liu Samantha , Sajed Dipti P. , Sachs Chana , Spurrier Josh , Raponi Mitch , Liang Jiayu , Zeng Hao , Sundaram Ranjini K. , Shuch Brian , Vasquez Juan C. , Bindra Ranjit S.
Published: October 2024

Detailed information for RCC PDX samples.
Supplementary Table 2 from NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Authors: Noronha Katelyn J. , Lucas Karlie N. , Paradkar Sateja , Edmonds Joseph , Friedman Sam , Murray Matthew A. , Liu Samantha , Sajed Dipti P. , Sachs Chana , Spurrier Josh , Raponi Mitch , Liang Jiayu , Zeng Hao , Sundaram Ranjini K. , Shuch Brian , Vasquez Juan C. , Bindra Ranjit S.
Published: October 2024

Results from GO Pathway Analysis in FH-deficient cell lines.
Supplementary Figure 7 from NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Authors: Noronha Katelyn J. , Lucas Karlie N. , Paradkar Sateja , Edmonds Joseph , Friedman Sam , Murray Matthew A. , Liu Samantha , Sajed Dipti P. , Sachs Chana , Spurrier Josh , Raponi Mitch , Liang Jiayu , Zeng Hao , Sundaram Ranjini K. , Shuch Brian , Vasquez Juan C. , Bindra Ranjit S.
Published: October 2024

NAPRT is silenced in IDH1R132H U87 glioma model by promoter hypermethylation.
Table 1 from Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumors
Authors: Alcala Sonia , Serralta San Martin Gonzalo , Muñoz-Fernández de Legaria Marta , Moreno-Rubio Juan , Salinas Silvia , López-Gil Juan Carlos , Rojo López José Alberto , Martínez Alegre Javier , Cortes Bandy David Abraham , Zambrana Francisco , Jiménez-Gordo Ana-María , Casado Enrique , López-Gómez Miriam , Sainz Bruno
Published: October 2024

Clinicopathologic characteristics of patients according to AF levels
Figure 4 from Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumors
Authors: Alcala Sonia , Serralta San Martin Gonzalo , Muñoz-Fernández de Legaria Marta , Moreno-Rubio Juan , Salinas Silvia , López-Gil Juan Carlos , Rojo López José Alberto , Martínez Alegre Javier , Cortes Bandy David Abraham , Zambrana Francisco , Jiménez-Gordo Ana-María , Casado Enrique , López-Gómez Miriam , Sainz Bruno
Published: October 2024

Expression of the CSC markers AF, EpCAM, and EpCAM/AF in patients with colorectal cancer with or without relapse. A–C, Box plots according to AF, EpCAM, and EpCAM/AF expression levels in patients with or without relapse. D–F, Box plots according to AF, EpCAM, and EpCAM/AF expression levels including LN involvement. No statistically significant differences were found between groups.
Figure 1 from Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumors
Authors: Alcala Sonia , Serralta San Martin Gonzalo , Muñoz-Fernández de Legaria Marta , Moreno-Rubio Juan , Salinas Silvia , López-Gil Juan Carlos , Rojo López José Alberto , Martínez Alegre Javier , Cortes Bandy David Abraham , Zambrana Francisco , Jiménez-Gordo Ana-María , Casado Enrique , López-Gómez Miriam , Sainz Bruno
Published: October 2024

Expression of AF in different tumor entities. A, Workflow followed for the detection of AF cells. Tumors were digested and single-cell suspensions incubated overnight with riboflavin (Rb) prior to flow cytometric analysis of AF using a 4-laser Attune NxT Acoustic cytometer. B, Distribution of the percentage of AF-positive cells in the indicated tumors (colorectal cancer, n = 60; kidney, n = 16; breast, n = 10; stomach, n = 9; rectum, n = 7; liver, n = 4; larynx, n = 3). C, Representative flow cytometric plots depicting the percentage of AF cells in colorectal cancer and kidney tumors. D, Representative flow cytometric plots depicting the percentage of AF cells in a kidney tumor incubated with and without 100 μmol/L Rb. E, Left, Representative images of tumor formation achieved with 103 and 102 AF-positive (+) or AF-negative (−) FACS-sorted cells, injected subcutaneously (in duplicate) in athymic nude mice. Photographs correspond to 12 weeks after injection. Right, Table summarizing the number of tumors formed/number of injections per dilution for a colorectal cancer or stomach tumor, digested and sorted for AF cells. F, To confirm that the AF detected was a result of riboflavin accumulation in ABCG2-coated vesicles, parallel samples were incubated overnight (in parallel with Rb) with 150 µM FTC, an ABCG2 inhibitor. AF diminished in FTC-treated cells, confirming that AF is ABCG2 mediated.
Role of Dry Dynamics in the Maritime Continent Barrier Effect in the Madden–Julian Oscillation
Authors: Roundy Paul E.
Published: October 2024

Eastward-moving moist deep convection and atmospheric circulation signals associated with the tropical Madden–Julian oscillation (MJO) sometimes break down as they cross the Maritime Continent region, but other times, the signal propagates across the region maintaining amplitude or regaining it over the west Pacific basin. This paper assesses the hypothesis that upper-tropospheric zonal diffluence of the background wind over the Maritime Continent causes much of this Maritime Continent barrier effect and its variation over time, through two mechanisms: 1) by slowing down the MJO as stronger-than-average background upper-tropospheric zonal wind over the Indian Ocean advects the MJO circulation signal westward, slowing its eastward advance, and 2) through the zonal advection of the background wind by subseasonal zonal wind across a region of zonal diffluence of the background wind, which advects the background wind of the opposite sign to the MJO wind. Advection of the opposite-signed background wind counteracts the MJO wind and reduces its associated upper-tropospheric mass divergence, weakening the mechanisms of the upper-tropospheric Kelvin wave component of the MJO circulation. Composites of MJO-associated zonal wind and outgoing longwave radiation signals diminish as they cross the Maritime Continent region when the region’s background zonal winds are diffluent, and composites of data reconstructing the relevant advection terms reveal the direct action of the advection mechanisms.

Significance Statement

The Madden–Julian oscillation (MJO) is the leading subseasonal variation of the tropical atmosphere. This project addresses how diffluence of the upper-tropospheric background zonal wind can break down MJO events through advection of and by the background wind.