bluuebunny/crossref_metadata_2025 huggingface dataset:
Porcine deltacoronavirus nucleocapsid protein antagonizes JAK-STAT signaling pathway by targeting STAT1 through KPNA2 degradation
Authors: Hu Yating , Hao Chenlin , Wang Donghan , Guo Meng , Chu Hongyan , Jin Xiaohui , Zu Shaopo , Ding Xueyan , Zhang Honglei , Hu Hui
Published: June 2024

Porcine deltacoronavirus (PDCoV) is an enteric pathogenic coronavirus that causes acute and severe watery diarrhea in piglets and has the ability of cross-species transmission, posing a great threat to swine production and public health. The interferon (IFN)-mediated signal transduction represents an important component of virus-host interactions and plays an essential role in regulating viral infection. Previous studies have suggested that multifunctional viral proteins encoded by coronaviruses antagonize the production of IFN via various means. However, the function of these viral proteins in regulating IFN-mediated signaling pathways is largely unknown. In this study, we demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I IFN-mediated JAK-STAT signaling pathway. We identified that PDCoV infection stimulated but delayed the production of IFN-stimulated genes (ISGs). In addition, PDCoV inhibited JAK-STAT signal transduction by targeting the nuclear translocation of STAT1 and ISGF3 formation. Further evidence showed that PDCoV N is the essential protein involved in the inhibition of type I IFN signaling by targeting STAT1 nuclear translocation via its C-terminal domain. Mechanistically, PDCoV N targets STAT1 by interacting with it and subsequently inhibiting its nuclear translocation. Furthermore, PDCoV N inhibits STAT1 nuclear translocation by specifically targeting KPNA2 degradation through the lysosomal pathway, thereby inhibiting the activation of downstream sensors in the JAK-STAT signaling pathway. Taken together, our results reveal a novel mechanism by which PDCoV N interferes with the host antiviral response.

IMPORTANCE

Porcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that receives increased attention and seriously threatens the pig industry and public health. Understanding the underlying mechanism of PDCoV evading the host defense during infection is essential for developing targeted drugs and effective vaccines against PDCoV. This study demonstrated that PDCoV and its encoded nucleocapsid (N) protein antagonize type I interferon signaling by targeting STAT1, which is a crucial signal sensor in the JAK-STAT signaling pathway. Further experiments suggested that PDCoV N-mediated inhibition of the STAT1 nuclear translocation involves the degradation of KPNA2, and the lysosome plays a role in KPNA2 degradation. This study provides new insights into the regulation of PDCoV N in the JAK-STAT signaling pathway and reveals a novel mechanism by which PDCoV evades the host antiviral response. The novel findings may guide us to discover new therapeutic targets and develop live attenuated vaccines for PDCoV infection.
Ice Age megafloods through the Cheney-Palouse Scabland Tract, eastern Washington, USA
Authors: Bjornstad Bruce N. , Kiver Eugene P. , Pritchard Chad J.
Published: June 2024

A two-day, ~300-mile field trip follows the path of ancient Ice Age megafloods through the eastern Channeled Scabland plexus and explores abundant evidence for the last outburst floods from the late Pleistocene within the Cheney-Palouse Scabland Tract, Washington, USA. Features unique to the scablands include spectacular, headward-retreating cataract canyons; giant ripples, bars, and scour holes along with dry waterfalls; battleship-sized, streamlined loess islands; and anastomosing channel networks. Some noteworthy flood features within the Cheney-Palouse tract include a massive 530-ton, ice-rafted, granitic boulder; the hidden Cove Coulees; and a close-up inside a giant flood bar covered with giant current ripples. Also, along the route are two regions with bedrock fracture zones preferentially and spectacularly eroded by megafloods.

Less common, but no less significant, is evidence for much older (>130,000 yr) exhumed, middle-to-early Pleistocene flood deposits. These are recognized by >1-m-thick, pedogenic, calcrete caps and paleosols overlying flood deposits. Some of these ancient flood deposits also have a reversed magnetic polarity of early Pleistocene age >780 ka (i.e., Matuyama Reversed Epoch). Older flood deposits like these sometimes lie deeply buried within eolian Palouse loess. Thus, it appears the growth and erosion of windblown loess hills in the Channeled Scabland also extend back to the early Pleistocene.
Prevalence of urinary incontinence in Brazilian para athletes
Authors: Barbosa Pê Nascimento , Rodrigues Marina Petter , Costa e Silva Anselmo de Athayde , Lemos Carla Iasmin Lima , Magno e Silva Marília Passos
Published: June 2024

Objective

To describe the prevalence of urinary incontinence (UI) in para athletes in Brazil.

Methods

This is a cross-sectional study with Brazilian para athletes with physical impairments from all para sports. The data from 86 participants of both sexes (60 males and 26 females) were collected through an online survey that gathered sociodemographic data and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, from March to July 2023.

Results

The prevalence of UI was 45.3% (n=39), with the average impact on quality of life scored at 6.1±3.5 on a scale of 0–10. Most para athletes reported moderate (43.5%) or severe (38.4%) symptoms. The most common type was mixed UI (46.1%), with an average of 3±1.9 episodes of urinary loss per athlete in the last 4 weeks. Adjusted Poisson regression (controlling for sex, age and level of competition) revealed that para athletes with orthopaedic impairments had a 58% lower prevalence of UI (prevalence ratio=0.42; 95% CI 0.24, 0.83) compared with those with neurological impairments. Furthermore, ordinal regression indicated that para athletes with neurological impairments were 147% more likely to experience a progression from ‘severe’ to ‘very severe’ UI (OR=2.47; 95% CI 1.59, 3.93).

Conclusions

UI is highly prevalent among para athletes, particularly those with neurological impairments, underscoring the need for specialised genitourinary healthcare and the need for further treatment and monitoring of the condition. There is a critical need to raise awareness among coaches, healthcare providers and the athletes themselves about UI and its impact to foster the comprehensive well-being of these athletes.
Evaluation of an ambulatory care pathway for patients with nitrous oxide-induced myeloneuropathy
Authors: Zaloum Safiya A , Paris Alvar , Mair Devan , Gutteridge Charles , Ayling Ruth M , Onen Barbara L , Walton Joseph , Workman Anna , Villanueva Nelia , Noyce Alastair J
Published: June 2024

Introduction

Cases of nitrous oxide (N2O)-induced myeloneuropathy are increasing at UK hospitals. At our centre, a dedicated ambulatory care pathway, endorsed nationally, was established to treat and monitor patients with N2O-myeloneuropathy in 2021 and refined through three audit cycles. We analysed the outcomes of patients on this pathway to better understand factors associated with non-engagement. Alongside, a novel approach using WhatsApp for questionnaire delivery was trialled in an attempt to improve engagement with treatment.

Methods

Patients on the N2O ambulatory care pathway were identified from MDT meeting lists from 9 September 2022 to 25 April 2023. Clinical data were collected via electronic clinical records, including the most recent neurological examination and reason for discharge from the pathway. Patients identified from MDT lists from 27 January 2023 to 14 March 2023 were approached to participate in weekly 12-item surveys, delivered via WhatsApp. This was approved as a service development project with approval for WhatsApp use given by the chief clinical information officer.

Results

35/56 (62.5%) patients were discharged from ambulatory care due to non-attendance and 17/56 (30.4%) completed their treatment course. The median time from initial presentation to discharge was 49 days. 24/40 (60.0%) of patients with a final neurological examination documented had a residual deficit, with objective sensory deficits most common. 12 patients were approached to receive weekly questionnaires via WhatsApp. 5/8 who expressed interest returned a consent form. All participants were withdrawn due to non-response or participant choice. 1/5 returned more than two surveys.

Conclusion

Despite poor participation in surveys delivered via WhatsApp, novel approaches are needed to improve engagement with patients on the N2O ambulatory care pathway.
Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours
Authors: Fierz Fabienne C , Locher Silvan , Bachmann Lucas , Baenninger Philipp B , Bochmann Frank , Kaufmann Claude , Mitrovic Irena , Rossi Marco , Thiel Michael A , Howell Jeremy P
Published: June 2024

Background

Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate.

Methods

We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control.

Results

110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples.

Conclusion

The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.
How the ‘Health Leader-as-Coach’ benefits health leaders, their teams, peers, organisation and the system
Authors: Day Fiona Jane
Published: June 2024

One of the main ways in which health leaders at all levels can be developed on a daily basis has been neglected by clinical leadership research, and by the research community generally, relating to the leader consciously using evidence-based coaching skills to positively impact their direct reports, team members, peers, organisations and the wider system in the context of their vocational role, as ‘Leader-as-Coach’.

This paper summarises the research on the role of ‘Leader-as-Coach’, and translates the learning from this into the practice of clinical leadership development.

Line managers are increasingly expected to use a coaching approach and are in an ideal position to do so. While there are many similarities with professional external coaching, the behaviours of the ‘Leader-as-Coach’ are also not identical and multiple ethical issues can arise.

There is no consistent academic definition to describe the behaviours of coaching in the context of a leader’s vocational role, nor yet specific competencies for training or supervision purposes.

The outcomes are summarised from the known literature in this field. Individual and system challenges are then discussed and conclusions are drawn about what this research means in practice for clinical leaders and their systems.
Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document
Authors: Farrell Michael Steven , Agapian John Varujan , Appelbaum Rachel D , Filiberto Dina M , Gelbard Rondi , Hoth Jason , Jawa Randeep , Kirsch Jordan , Kutcher Matthew E , Nohra Eden , Pathak Abhijit , Paul Jasmeet , Robinson Bryce , Cuschieri Joseph , Stein Deborah M
Published: June 2024

The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).
Managing career transitions in the profession of acute care surgery
Authors: Fitzgerald Caitlin Anne , Dumas Ryan Peter , Cripps Michael W , Gurney Jennifer M , Davis Kimberly A , Knowlton Lisa Marie
Published: June 2024

Career shifts are a naturally occurring part of the trauma and acute care surgeon’s profession. These transitions may occur at various timepoints throughout a surgeon’s career and each has their own specific challenges. Finding a good fit for your first job is critical for ensuring success as an early career surgeon. Equally, understanding how to navigate promotions or a change in job location mid-career can be fraught with uncertainty. As one progresses in their career, knowing when to take on a leadership position is oftentimes difficult as it may mean a change in priorities. Finally, navigating your path towards a fulfilling retirement is a complex discussion that is different for each surgeon. The American Association for the Surgery of Trauma (AAST) convened an expert panel of acute care surgeons in a virtual grand rounds session in August 2023 to address the aforementioned career transitions and highlight strategies for successfully navigating each shift. This was a collaboration between the AAST Associate Member Council (consisting of surgical resident, fellow and junior faculty members), the AAST Military Liaison Committee and the AAST Healthcare Economics Committee. Led by two moderators, the panel consisted of early, mid-career and senior surgeons, and recommendations are summarized below and in figure 1.
Reaching back to enhance the future: the American Association for the Surgery of Trauma Diversity, Equity and Inclusion Pipeline Program
Authors: Strong Bethany Lauren , Silverton Latoya , Wical William , Berry Cherisse , Brasel Karen J , Henry Sharon M
Published: June 2024

Objectives

There are significant disparities in the surgical workforce in comparison with medical student demographics. Pipeline programs have shown to be effective in addressing gaps. The American Association for the Surgery of Trauma Diversity, Equity and Inclusion Committee designed a longitudinal pipeline program with high school student mentees and surgeon mentors providing an in-person hands-on workshop.

Methods

The mentee demographics and socioeconomic status at the time of application were determined using overall percentages and the Area Deprivation Index (ADI). Program application essays were qualitatively analyzed for common themes. The pre-workshop and post-workshop and 6-month follow-up surveys were analyzed for mentee experience and areas for improvement.

Results

Mentees selected were 30% male (N=3 of 10), 70% female (N=7 of 10), 50% black or African American (N=5 of 10) and 30% Hispanic or Latinx (N=3 of 10). The majority of mentees were in the most disadvantaged groups in their state by the ADI (N=8 of 9, 89%). Many of the application essays highlighted a personal loss as driving the interest in a health career with several of those losses based on ‘gun violence’. There was under-representation in medicine racial/ethnic or gender concordance for 80% (N=8 of 10) of the mentee–mentor pairings. In the pre-workshop survey, even those students with high-grade point averages and strong academic achievement in science courses indicated low confidence in their ability to succeed. Most students (N=7 of 10, 70%) reported a strong positive connection with their mentor in the post-workshop survey. There was a reduction in self-identified modifiable barriers to success for 83% (N=5 of 6) of the mentees. One-third of students who responded to the 6-month survey indicated that they had issues with maintaining contact with their mentors after the workshop.

Conclusion

The pipeline program was able to reach the target demographic and increase interest in surgery. Positive mentee/mentor relationships were formed. There are improvements to be made in longitudinal components of the program to ensure lasting results.

Level of evidence

III.
Conundrums in the surgical intensive care unit: fevers and antibiotic prophylaxis
Authors: Haddad Diane N , Martinez Quinones Patricia , Gummadi Sriharsha , Martin Niels D
Published: June 2024

This editorial is in response to the three latest clinical consensus guidelines authored by the Critical Care Committee of the American Association for the Surgery of Trauma. Herein, we discuss their main findings and recommendations and their impact on the practice of Surgical Critical Care.
Exploring the contribution of inter-individual factors to the development of physiological heat strain in older adults exposed to simulated indoor overheating
Authors: Meade Robert D. , Akerman Ashley P. , Notley Sean R. , Kirby Nathalie V. , Sigal Ronald J. , Kenny Glen P.
Published: June 2024

Older adults are at elevated risk of heat-related mortality due to age-associated declines in thermoregulatory and cardiovascular function. However, the inter-individual factors that exacerbate physiological heat strain during heat exposure remain unclear, making it challenging to identify more heat-vulnerable subgroups. We therefore explored factors contributing to inter-individual variability in physiological responses of older adults exposed to simulated hot weather. Thirty-seven older adults (61–80 years, 16 females) rested for 8 h in 31 and 36 °C (45% relative humidity). Core (rectal) temperature, heart rate (HR), HR variability, mean arterial pressure (MAP), and cardiac autonomic responses to standing were measured at baseline and end-exposure. Bootstrapped least absolute shrinkage and selection operator regression was used to evaluate whether variation in these responses was related to type 2 diabetes (T2D, n = 10), hypertension ( n = 18), age, sex, body morphology, habitual physical activity levels, and/or heat-acclimatization. T2D was identified as a predictor of end-exposure HR (with vs. without: 13 beats/min (bootstrap 95% confidence interval: 6, 23)), seated MAP (−7 mmHg (−18, 1)), and the systolic pressure response to standing (20 mmHg (4, 36)). HR was also influenced by sex (female vs. male: 8 beats/min (1, 16)). No other predictors were identified. The inter-individual factors explored did not meaningfully contribute to the variation in body temperature responses in older adults exposed to simulated indoor overheating. By contrast, cardiovascular responses were exacerbated in females and individuals with T2D. These findings improve understanding of how inter-individual differences contribute to heat-induced physiological strain in older persons.
Optimizing Viscous Damper Placement for Stochastic Performance of Buildings with Plan Asymmetry
Authors: Chan Peng-Tai , Ma Quincy Tsun Ming
Published: June 2024

Optimized viscous dampers mitigate the dynamic response of building with plan asymmetry. Previous research efforts limit the optimization method to time domain requiring time history analyses to optimize damper placement for plan eccentricity-induced torsional response combined with translational response. This can consume high computational effort and lead to the variability in the ground motion selection. To expedite the optimization process while taking ground motion variability into account, this study will offer a novel criterion based on stochastic performance. This technique will skip the traditional approach of employing time history analyses and will take frequency domain variability into account. Through given distance between the center of mass (CM) and the target frame, the study establishes the stochastic criterion for the response at the perimeter of the building where the maximum torsional-translational response occurs. This allows the optimization methods to generate high quality solution with less computational efforts compared to traditional approach (i.e. time domain-based optimization). It is noteworthy that the proposed criterion is applicable to extensive kinds of responses (e.g. peak floor acceleration, story shear and etc.) once the geometric relationship is given. The proposed criterion as the objective function is compared against their counterpart in time domain through a case study. The case study is based on a reinforced concrete (RC) moment-resisting-frame (MRF) building with two-way asymmetric plan and adopts Element Exchange Method (EEM) to optimize the damper placement. The effectiveness of optimized design based in frequency domain and time domain is evaluated for their total running time and maximum peak interstory drift against a suite of ground motions. The result showed that the proposed criterion can offer the improvement against the traditional approach in terms of solution quality (i.e. performance in time domain and frequency domain) and computational efforts (i.e. total running time for optimization).
ANAGL: A Noise-Resistant and Anti-Sparse Graph Learning for Micro-Video Recommendation
Authors: Ma Jingwei , Bian Kangkang , Xu Yang , Zhu Lei
Published: June 2024

In recent years, graph convolutional networks (GCNs) have seen widespread utilization within micro-video recommendation systems, facilitating the understanding of user preferences through interactions with micro-videos. Despite the commendable performance exhibited by GCN-based methodologies, several persistent issues demand further scrutiny. Primarily, most user-micro-video interactions involve implicit behaviors, such as clicks or abstentions, which may inadvertently capture irrelevant micro-video content, thereby introducing significant noise (false touches, low watch-ratio, low ratings) into users’ histories. Consequently, this noise undermines the efficacy of micro-video recommendations. Moreover, the abundance of micro-videos has resulted in fewer interactions between users and micro-video content. To tackle these challenges, we propose a noise-resistant and anti-sparse graph learning framework for micro-video recommendation. Initially, we construct a denoiser that leverages implicit multi-attribute information (e.g., watch-ratio, timestamp, ratings, and so on) to filter noisy data from user interaction histories. This process yields high-fidelity micro-video information, enabling a more precise modeling of users’ feature preferences. Subsequently, we employ a multi-view reconstruction approach and utilize cross-view self-supervised learning to gain insights into user and micro-video features. This strategic approach effectively mitigates the issue of data sparsity. Extensive experiments conducted on two publicly available micro-video recommendation datasets validate the effectiveness of our proposed method. For in-depth details and access to the code, please refer to our repository at “
https://github.com/kbk12/ANAGL.git
.”
Learning Quantum Processes and Hamiltonians via the Pauli Transfer Matrix
Authors: Caro Matthias C.
Published: June 2024

Learning about physical systems from quantum-enhanced experiments can outperform learning from experiments in which only classical memory and processing are available. Whereas quantum advantages have been established for state learning, quantum process learning is less understood. We establish an exponential quantum advantage for learning an unknown
n
-qubit quantum process

\(\mathcal {N}\)

. We show that a quantum memory allows to efficiently solve the following tasks: (a) learning the Pauli transfer matrix (PTM) of an arbitrary

\(\mathcal {N}\)

, (b) predicting expectation values of Pauli-sparse observables measured on the output of an arbitrary

\(\mathcal {N}\)

upon input of a Pauli-sparse state, and (c) predicting expectation values of arbitrary observables measured on the output of an unknown

\(\mathcal {N}\)

with sparse PTM upon input of an arbitrary state. With quantum memory, these tasks can be solved using linearly-in-
n
many copies of the Choi state of

\(\mathcal {N}\)

. In contrast, any learner without quantum memory requires exponentially-in-
n
many queries, even when using adaptively designed experiments. In proving this separation, we extend existing shadow tomography bounds from states to channels. Moreover, we combine PTM learning with polynomial interpolation to learn arbitrary Hamiltonians from short-time dynamics. Our results highlight the power of quantum-enhanced experiments for learning highly complex quantum dynamics.
Tabular and Deep Learning for the Whittle Index
Authors: Robledo Relaño Francisco , Borkar Vivek , Ayesta Urtzi , Avrachenkov Konstantin
Published: June 2024

The Whittle index policy is a heuristic that has shown remarkably good performance (with guaranteed asymptotic optimality) when applied to the class of problems known as Restless Multi-Armed Bandit Problems (RMABPs). In this article, we present QWI and QWINN, two reinforcement learning algorithms, respectively tabular and deep, to learn the Whittle index for the total discounted criterion. The key feature is the use of two time-scales, a faster one to update the state-action
Q
-values, and a relatively slower one to update the Whittle indices. In our main theoretical result, we show that QWI, which is a tabular implementation, converges to the real Whittle indices. We then present QWINN, an adaptation of QWI algorithm using neural networks to compute the
Q
-values on the faster time-scale, which is able to extrapolate information from one state to another and scales naturally to large state-space environments. For QWINN, we show that all local minima of the Bellman error are locally stable equilibria, which is the first result of its kind for DQN-based schemes. Numerical computations show that QWI and QWINN converge faster than the standard
Q
-learning algorithm, neural-network based approximate Q-learning, and other state-of-the-art algorithms.
Heteroatom Sulfur-Modified ZIF-8 Derived Zn, N Co-Doped Carbon Nanocages as Highly Efficient ORR Catalysts for Zn-Air Batteries
Authors: Li Guang , Tang Xiangmei , Sheng Kuang , Fang Can , Zeng Yiduo , Lu Zhaomin , Wang Yaping , Zhou Hu , Yi Qingfeng
Published: June 2024

Carbon-based electrocatalysts derived from zeolitic imidazolate framework-8 (ZIF-8) have garnered significant attention, owing to their structural advantages, high surface area, and tunable active sites. Herein, we report the synthesis of heteroatom sulfur (S) modified ZIF-8 derived carbon nanocages (ZnS@N/S-C) for oxygen electrocatalysis through self-assembly and two-step pyrolysis. The resultant ZnS@N/S-C exhibits catalytic activity towards oxygen reduction reaction (ORR) with high half-wave potential (0.86 V) and stability (91.4%), separately, which is comparable to or superior to Pt/C. Furthermore, the application of ZnS@N/S-C as a cathode for Zn-air batteries (ZABs) demonstrates performance metrics such as an open-circuit voltage of 1.407 V, a power density of 114.4 mW cm−2, and a specific capacity of 764.6 mAh gZn
−1, etc surpassing Pt/C. The performance of ZnS@N/S-C can be attributed to the fact that the introduction of S significantly increases the specific surface area, pore volume, and defect extent of the catalyst, while optimizing the electronic structure and generating ZnS active nanocrystals. This work employs a simple sulfurization strategy to enhance the ORR activity of ZIF-8-derived Zn-based catalysts with fully filled 3d orbitals, providing guidance for the development of such materials.
Supplementary Methods S1 from Projecting the Impact of Multi-Cancer Early Detection on Late-Stage Incidence Using Multi-State Disease Modeling
Authors: Lange Jane M. , Gogebakan Kemal Caglar , Gulati Roman , Etzioni Ruth
Published: June 2024

Supplementary Methods S1: used for Projecting the impact of multi-cancer early detection on late-stage incidence using multi-state disease modeling.
Supplementary Table 2 from Cervical Cancer Screening and Treatment Algorithms Using Human Papillomavirus Testing—Lessons Learnt from a South African Pilot Randomized Controlled Trial
Authors: Sebitloane Hannah M. , Forestier Mathilde , Ginindza Themba G. , Dhlomo Wendy , Moodley-Govender Eshia , Darragh Teresa M. , Baena Armando , Herrero Rolando , Almonte Maribel , Broutet Nathalie , De Vuyst Hugo
Published: June 2024

Supplementary Table 2: HPV positivity from self- and nurse-taken samples in VIA triage arm, by HIV status
Supplementary Table 1 from Reproductive Factors Related to Childbearing and a Novel Automated Mammographic Measure, V
Authors: Yaghjyan Lusine , Wang Zifan , Warner Erica T. , Rosner Bernard , Heine John , Tamimi Rulla M.
Published: June 2024

Supplementary Table 1 presents age-standardized characteristics of the study population at the time of mammogram, by menopausal and nulliparity statuses
Supplementary Figure S1 from Assessing the Value of Incorporating a Polygenic Risk Score with Nongenetic Factors for Predicting Breast Cancer Diagnosis in the UK Biobank
Authors: Collister Jennifer A. , Liu Xiaonan , Littlejohns Thomas J. , Cuzick Jack , Clifton Lei , Hunter David J.
Published: June 2024

Supplementary Figure S1: Analysis population exclusion flowchart. This illustrates the selection of eligible study participants from the UK Biobank.
Data from Characterizing Cancer Burden in the American Indian Population in North Carolina
Authors: Spees Lisa P. , Jackson Bradford E. , Raveendran Yadurshini , Morris Hayley N. , Emerson Marc A. , Baggett Christopher D. , Bell Ronny A. , Salas Ana I. , Meernik Clare , Akinyemiju Tomi F. , Wheeler Stephanie B.
Published: June 2024

AbstractBackground:
The American Indian (AI) population in North Carolina has limited access to the Indian Health Service. Consequently, cancer burden and disparities may differ from national estimates. We describe the AI cancer population and examine AI–White disparities in cancer incidence and mortality.
Methods:
We identified cancer cases diagnosed among adult AI and White populations between 2014 and 2018 from the North Carolina Central Cancer Registry. We estimated incidence and mortality rate ratios (IRR and MRR) by race. In addition, between the AI and White populations, we estimated the ratio of relative frequency differences [RRF, with 95% confidence limits (CL)] of clinical and sociodemographic characteristics. Finally, we evaluated the geographic distribution of incident diagnoses among AI populations.
Results:
Our analytic sample included 2,161 AI and 204,613 White individuals with cancer. Compared with the White population, the AI population was more likely to live in rural areas (48% vs. 25%; RRF, 1.89; 95% CL, 1.81–1.97) and to have Medicaid (18% vs. 7%; RRF, 2.49; 95% CL, 2.27–2.71). Among the AI population, the highest age-standardized incidence rates were female breast, followed by prostate and lung and bronchus. Liver cancer incidence was significantly higher among the AI population than White population (IRR, 1.27; 95% CL, 1.01–1.59). AI patients had higher mortality rates for prostate (MRR, 1.72; CL, 1.09–2.70), stomach (MRR, 1.82; 95% CL, 1.15–2.86), and liver (MRR, 1.70; 95% CL, 1.25–2.33) cancers compared with White patients.
Conclusions:
To reduce prostate, stomach, and liver cancer disparities among AI populations in North Carolina, multi-modal interventions targeting risk factors and increasing screening and treatment are needed.
Impact:
This study identifies cancer disparities that can inform targeted interventions to improve outcomes among AI populations in North Carolina.
Choosing the Appropriate HPV Testing and Treatment Algorithm: What Works for Different Contexts?
Authors: Mwenda Valerian , McGrath Christine J.
Published: June 2024

Cervical cancer can be eliminated, and the global community intends to achieve this goal in the next century. For this to successfully occur, concerted efforts to implement and scale-up available, evidence-based strategies including human papillomavirus vaccination, screening and treatment of precancerous lesions, and early detection and treatment for invasive cancers is paramount. While the World Health Organization has offered technical guidance and recommendations on implementation, several questions remain unanswered and require urgent high-quality research to inform policy and practice. We discuss the findings from the Cervical Cancer Screening and Treatment Algorithms pilot study in the context of the evidence synthesis conducted for the second edition of the World Health Organization guidelines for screening and treatment of cervical precancer lesions for cervical cancer prevention. Policymakers at the national level must consider the weight of evidence with country-level resources to make decisions on screening, triage, and treatment approaches.

See related article by Sebitloane et al., p. 779
Supplementary Figure S3 from A First-in-Human Phase 1 Study of a Tumor-Directed RNA-Interference Drug against HIF2α in Patients with Advanced Clear Cell Renal Cell Carcinoma
Authors: Brugarolas James , Obara Gregory , Beckermann Kathryn E. , Rini Brian , Lam Elaine T. , Hamilton James , Schluep Thomas , Yi Min , Wong So , Mao Zhongping Lily , Gamelin Erick , Tannir Nizar M.
Published: June 2024

Figure S3: ARO-HIF2 Plasma Concentration-Time Profiles by Treatment and Dosing Week
Supplemental Video 2 from GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma
Authors: Ciccone Roselia , Quintarelli Concetta , Camera Antonio , Pezzella Michele , Caruso Simona , Manni Simona , Ottaviani Alessio , Guercio Marika , Del Bufalo Francesca , Quadraccia Maria Cecilia , Orlando Domenico , Di Cecca Stefano , Sinibaldi Matilde , Aurigemma Mariasole , Iaffaldano Laura , Sarcinelli Andrea , D'Amore Maria Luisa , Ceccarelli Manuela , Nazio Francesca , Marabitti Veronica , Giorda Ezio , Pezzullo Marco , De Stefanis Cristiano , Carai Andrea , Rossi Sabrina , Alaggio Rita , Del Baldo Giada , Becilli Marco , Mastronuzzi Angela , De Angelis Biagio , Locatelli Franco
Published: June 2024

Supplemental Video 2. IncuCyte® live-cell System video of Cytotoxic activity of NT or CAR.GD2 T-cells vs DAOY-GFP-FF-Luc cell line. The video shows 84 hours of tumor growth (DAOY cell line) with only tumor (A) and with tumor cells co-cultured with NT T-cells (B) or CAR.GD2 T-cells (C).
Supplementary Table S1 from A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer
Authors: Zanoni Daniella K. , Demétrio De Souza França Paula , Valero Cristina , Peterson Gary , Ardigo Marco , Ghossein Ronald , Dusza Stephen W. , Matsuura Danielli , Scholfield Daniel W. , Adilbay Dauren , Montero Pablo H. , Migliacci Jocelyn , Pillarsetty Naga Vara Kishore , Kose Kivanc , Ganly Ian , Rajadhyaksha Milind , Patel Snehal G.
Published: June 2024

Supplementary Table S1 shows a descriptive statistics of all the nominally scaled variables of patients included in phase II. The histopathological data presented in this table are derived from the final surgically resected specimen and not from the 3mm punch biopsies obtained for the study. Due to the timing of the data collection for this study, the AJCC 7th edition was used for TNM staging.
Supplementary Figure S8 from A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer
Authors: Zanoni Daniella K. , Demétrio De Souza França Paula , Valero Cristina , Peterson Gary , Ardigo Marco , Ghossein Ronald , Dusza Stephen W. , Matsuura Danielli , Scholfield Daniel W. , Adilbay Dauren , Montero Pablo H. , Migliacci Jocelyn , Pillarsetty Naga Vara Kishore , Kose Kivanc , Ganly Ian , Rajadhyaksha Milind , Patel Snehal G.
Published: June 2024

Supplementary Figure S8 shows in vivo RCM images of a tumor area in a 71-year-old male, never smoker and occasional alcohol exposure, harboring an ulcerated 1.5 cm moderately differentiated oral squamous cell carcinoma of the right lateral tongue.
Supplementary Figure 1 from Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses
Authors: D'Alise Anna Morena , Leoni Guido , Cotugno Gabriella , Siani Loredana , Vitale Rosa , Ruzza Valentino , Garzia Irene , Antonucci Laura , Micarelli Elisa , Venafra Veronica , Gogov Sven , Capone Alessia , Runswick Sarah , Martin‐Liberal Juan , Calvo Emiliano , Moreno Victor , Symeonides Stefan N. , Scarselli Elisa , Bechter Oliver
Published: June 2024

Supplementary Figure 1. IFN-γ ELISpot response post-IVS
Supplementary Figure S2 from Preclinical Efficacy of a PSMA-Targeted Actinium-225 Conjugate (225Ac-Macropa-Pelgifatamab): A Targeted Alpha Therapy for Prostate Cancer
Authors: Schatz Christoph A. , Zitzmann-Kolbe Sabine , Moen Ingrid , Klotz Monika , Nair Shankari , Stargard Stefan , Bjerke Roger M. , Wickstrøm Biseth Katrine , Feng Yuan Zeng , Indrevoll Bård , Cruciani Veronique , Karlsson Jenny , Haendler Bernard , Nielsen Carsten H. , Alfsen Maria Z. , Hammer Stefanie , Hennekes Hartwig , Cuthbertson Alan , Hagemann Urs B. , Larsen Åsmund
Published: June 2024

Figure S2. PSMA expression in CDX and PDX prostate cancer xenograft models as determined via IHC.
Supplementary Figure S2 from Safety and Preliminary Efficacy of Pembrolizumab Following Transarterial Chemoembolization for Hepatocellular Carcinoma: The PETAL Phase Ib Study
Authors: Pinato David J. , D'Alessio Antonio , Fulgenzi Claudia Angela Maria , Schlaak Alexandra Emilia , Celsa Ciro , Killmer Saskia , Blanco Jesus Miguens , Ward Caroline , Stikas Charalampos-Vlasios , Openshaw Mark R. , Acuti Nicole , Nteliopoulos Georgios , Balcells Cristina , Keun Hector C. , Goldin Robert D. , Ross Paul J. , Cortellini Alessio , Thomas Robert , Young Anna-Mary , Danckert Nathan , Tait Paul , Marchesi Julian R. , Bengsch Bertram , Sharma Rohini
Published: June 2024

Supplementary Figure S2.
Custom-developed bioinformatic variant calling pipeline to identify somatic SNVs and indels
Data from Cell-free DNA Concentration as a Biomarker of Response and Recurrence in HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy
Authors: Magbanua Mark Jesus M. , Ahmed Ziad , Sayaman Rosalyn W. , Brown Swigart Lamorna , Hirst Gillian L. , Yau Christina , Wolf Denise M. , Li Wen , Delson Amy L. , Perlmutter Jane , Pohlmann Paula , Symmans W. Fraser , Yee Douglas , Hylton Nola M. , Esserman Laura J. , DeMichele Angela M. , Rugo Hope S. , van 't Veer Laura J.
Published: June 2024

AbstractPurpose:
We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.
Experimental Design:
145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.
Results:
In TNBC, we observed a modest negative correlation between cfDNA concentration 3 weeks after treatment initiation and RCB, but none of the other timepoints showed significant correlation. In contrast, ctDNA was significantly positively correlated with RCB at all timepoints (all R > 0.3 and P < 0.05). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio, 2.12; P = 0.037). In TNBC, the difference in survival between high versus low cfDNA shedders at all timepoints was not statistically significant. In contrast, as previously reported, ctDNA at all timepoints was significantly correlated with DRFS in both subtypes.
Conclusions:
In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.
Incorporating Supramaximal Resection into Survival Stratification of IDH-wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis
Authors: Park Yae Won , Choi Kyu Sung , Foltyn-Dumitru Martha , Brugnara Gianluca , Banan Rouzbeh , Kim Sooyon , Han Kyunghwa , Park Ji Eun , Kessler Tobias , Bendszus Martin , Krieg Sandro , Wick Wolfgang , Sahm Felix , Choi Seung Hong , Kim Ho Sung , Chang Jong Hee , Kim Se Hoon , Wongsawaeng Doonyaporn , Pollock Jeffrey Michael , Lee Seung-Koo , Barajas Ramon Francisco , Vollmuth Philipp , Ahn Sung Soo
Published: June 2024

Purpose:

To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections.

Experimental Design:

This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared with a previous Radiation Therapy Oncology Group (RTOG) RPA model.

Results:

In the developmental cohort, the RPA model included age, MGMTp methylation status, Karnofsky performance status, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis [class I: median overall survival (OS) 57.3 months], whereas low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared with the previous RTOG RPA model.

Conclusions:

The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

See related commentary by Karschnia et al., p. 4811
Early Evaluation of Risk Stratification and Clinical Outcomes for Patients with Advanced Breast Cancer through Combined Monitoring of Baseline Circulating Tumor Cells and DNA
Authors: Zhang Qiang , Cai Zheng , Gerratana Lorenzo , Davis Andrew A. , D’Amico Paolo , Chawla Akhil , Jacob Saya , Zhang Youbin , Jiao Jianhua , Qin Weijun , Reduzzi Carolina , Flaum Lisa , Shah Ami , Gradishar William J.
Published: June 2024

Purpose:

Early evaluation of tumor heterogeneity related to metastasis and outcomes is a major challenge in the management of advanced breast cancer (BCa) in the clinic. In this study, we introduced the value of baseline circulating tumor cells (CTC) and ctDNA for early differentiation of clinical stages, tumor heterogeneity, and prognosis in clinic.

Experimental Design:

A total of 292 patients with BCa were enrolled in this study, including 254 Stage IV and 38 Stage III patients, and examined the baseline levels of CTCs, CTC-clusters, and plasma ctDNA before initiating therapies. Outcomes including progression-free survival (PFS) and overall survival were evaluated using proportional hazards regression analysis.

Results:

The baseline CTCs, including HER2+ CTCs, in Stage IV patients were approximately 9.5 times higher than those detected in Stage III patients. Baseline CTC counts with a cutoff of 5 were significantly associated with the prognosis. Within each stage, patients with <5 CTCs had significantly longer PFS. Stage III patients with no CTCs exhibited the longest survival compared with patients with ≥1 CTC. CTC-clusters were only found in Stage IV patients, among whom 15 Stage IV patients with ≥5 CTC-clusters had the worst PFS compared with the 239 Stage IV patients with <5 CTC-clusters. Similar outcomes were observed in 28 out of 254 Stage IV patients who had at least one CTC-cluster detected, as these patients had shorter PFS compared with CTC-cluster negative group. The major differences in ctDNA mutations between patients with Stage III and Stage IV BCa were in PIK3CA and ESR1, which were associated with specific organ metastasis and worse outcomes.

Conclusions:

Assessing the baseline levels of CTCs, CTC-clusters, and mutational ctDNA profile could reliably aid in differentiation of clinical stage and early prediction of metastasis and outcomes in advanced BCa.
Supplementary Figure 13 from Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
Authors: Stutheit-Zhao Eric Y. , Sanz-Garcia Enrique , Liu Zhihui (Amy) , Wong Derek , Marsh Kayla , Abdul Razak Albiruni R. , Spreafico Anna , Bedard Philippe L. , Hansen Aaron R. , Lheureux Stephanie , Torti Dax , Lam Bernard , Yang Shih Yu Cindy , Burgener Justin , Luo Ping , Zeng Yong , Cheng Nicholas , Awadalla Philip , Bratman Scott V. , Ohashi Pamela S. , Pugh Trevor J. , Siu Lillian L.
Published: June 2024

Increase in both ctDNA metrics identifies a subgroup with particularly poor outcome. Post-hoc analysis of ΔCSM and ΔCMC together demonstrates that a decrease in either metric was sufficient to result in significantly improved PFS and OS, whereas increase in both metrics identified a group with particularly poor outcomes. PFS analysis at cycle 3 excludes one patient who progressed before the collection of cycle 3 sample.
Supplementary Figure 1 from Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors
Authors: Stutheit-Zhao Eric Y. , Sanz-Garcia Enrique , Liu Zhihui (Amy) , Wong Derek , Marsh Kayla , Abdul Razak Albiruni R. , Spreafico Anna , Bedard Philippe L. , Hansen Aaron R. , Lheureux Stephanie , Torti Dax , Lam Bernard , Yang Shih Yu Cindy , Burgener Justin , Luo Ping , Zeng Yong , Cheng Nicholas , Awadalla Philip , Bratman Scott V. , Ohashi Pamela S. , Pugh Trevor J. , Siu Lillian L.
Published: June 2024

Overview of the timepoints included in cfMeDIP-seq analysis for each patient. (A) Every sample included by patient and timepoint. (B) Numbers of samples analyzed per cohort and timepoint.