bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications
Authors: Zeng Yutian , Wang Chun , Yang Cuiting , Shan Xudong , Meng Xiang-Qian , Zhang Ming
Published: June 2024

Ovarian aging, a natural process in women and various other female mammals as they age, is characterized by a decline in ovarian function and fertility due to a reduction in oocyte reserve and quality. This phenomenon is believed to result from a combination of genetic, hormonal, and environmental factors. While these factors collectively contribute to the shaping of ovarian aging, the substantial impact and intricate interplay of chronic inflammation in this process have been somewhat overlooked in discussions. Chronic inflammation, a prolonged and sustained inflammatory response persisting over an extended period, can exert detrimental effects on tissues and organs. This review delves into the novel hallmark of aging—chronic inflammation—to further emphasize the primary characteristics of ovarian aging. It endeavors to explore not only the clinical symptoms but also the underlying mechanisms associated with this complex process. By shining a spotlight on chronic inflammation, the aim is to broaden our understanding of the multifaceted aspects of ovarian aging and its potential clinical implications.
Apprenticeship in Diplomacy, or How I Became Another Replaceable Intern at the OECD
Authors: Windfeld Frederik Carl
Published: June 2024

What can we learn about diplomacy by studying its practice through the body of an apprentice? Drawing on the works of Loïc Wacquant, this article argues that to understand the making of background dispositions, tacit rules, and situated know-how in international politics’ diverse fields of practice, researchers ought to consider apprenticeship as a concept and a methodological device. This argument is based on ethnographic observations from the author’s internship at the Delegation of Denmark to the OECD. As a concept, apprenticeship cultivates a sensitivity to the embodied dynamics at play in acquiring habitus. An apprenticeship is structured as a participatory and corporeal process of socialization through which an aspirant acquires or fails to acquire a prospective identity within a given field of practice. Methodologically, studying practices of initiation through the body of an apprentice enables scholars to access tacit knowledge transmissions while recognizing that such knowledge operates beneath discursive representation and logical reasoning. In advancing this argument, the article foregrounds the figure of the apprentice and the experience of apprenticeship as conduits for gaining insights into social learning in diplomacy, other fields of practice, and the broader domain of socialization in International Relations.
Patient-centered clinical decision support challenges and opportunities identified from workflow execution models
Authors: Sittig Dean F , Boxwala Aziz , Wright Adam , Zott Courtney , Gauthreaux Nicole A , Swiger James , Lomotan Edwin A , Dullabh Prashila
Published: June 2024

Objective

To use workflow execution models to highlight new considerations for patient-centered clinical decision support policies (PC CDS), processes, procedures, technology, and expertise required to support new workflows.

Methods

To generate and refine models, we used (1) targeted literature reviews; (2) key informant interviews with 6 external PC CDS experts; (3) model refinement based on authors’ experience; and (4) validation of the models by a 26-member steering committee.

Results and Discussion

We identified 7 major issues that provide significant challenges and opportunities for healthcare systems, researchers, administrators, and health IT and app developers. Overcoming these challenges presents opportunities for new or modified policies, processes, procedures, technology, and expertise to: (1) Ensure patient-generated health data (PGHD), including patient-reported outcomes (PROs), are documented, reviewed, and managed by appropriately trained clinicians, between visits and after regular working hours. (2) Educate patients to use connected medical devices and handle technical issues. (3) Facilitate collection and incorporation of PGHD, PROs, patient preferences, and social determinants of health into existing electronic health records. (4) Troubleshoot erroneous data received from devices. (5) Develop dashboards to display longitudinal patient-reported data. (6) Provide reimbursement to support new models of care. (7) Support patient engagement with remote devices.

Conclusion

Several new policies, processes, technologies, and expertise are required to ensure safe and effective implementation and use of PC CDS. As we gain more experience implementing and working with PC CDS, we should be able to begin realizing the long-term positive impact on patient health that the patient-centered movement in healthcare promises.
The multifaceted roles of mitochondria in osteoblasts: from energy production to mitochondrial-derived vesicle secretion
Authors: Suh Joonho , Lee Yun-Sil
Published: June 2024

Mitochondria in osteoblasts have been demonstrated to play multiple crucial functions in bone formation from intracellular adenosine triphosphate production to extracellular secretion of mitochondrial components. The present review explores the current knowledge about mitochondrial biology in osteoblasts, including mitochondrial biogenesis, bioenergetics, oxidative stress generation, and dynamic changes in morphology. Special attention is given to recent findings, including mitochondrial donut formation in osteoblasts, which actively generates mitochondrial-derived vesicles (MDVs), followed by extracellular secretion of small mitochondria and MDVs. We also discuss the therapeutic effects of targeting osteoblast mitochondria, highlighting their potential applications in improving bone health.
Modified dung beetle optimizer with multi-strategy for uncertain multi-modal transport path problem
Authors: Wu Jiang , Luo Qifang , Zhou Yongquan
Published: June 2024

Uncertain multi-modal transport path optimization (UMTPO) is a combined optimization non-deterministic polynomial-time hard problem. Its goal is to determine a path with the lowest total transportation cost and carbon emissions from the starting point to the destination. To effectively address this issue, this article proposes a modified dung beetle optimizer (DBO) to address it. DBO is a swarm-based metaheuristic optimization algorithm that has the features of a fast convergence rate and high solution accuracy. Despite this, the disadvantages of weak global exploration capability and falling easily into local optima exist. In this article, we propose a modified DBO called MSHDBO for function optimization and to solve the UMTPO problem. However, for the vast majority of metaheuristic algorithms, they are designed for continuous problems and cannot directly solve discrete problems. Therefore, this article employs a priority based encoding and decoding method to solve the UMTPO problem. To verify the performance and effectiveness of the MSHDBO algorithm, we compared it with other improved versions of the DBO algorithm used in the literature. We confirmed the excellent performance of MSHDBO using 41 benchmark test functions from the IEEE CEC 2017 test suite and IEEE CEC 2022 test suite. Additionally, we compared the MSHDBO algorithm with 10 other state-of-the-art metaheuristic optimization algorithms through a practical UMTPO problem. The experimental results indicated that the MSHDBO algorithm achieved very good performance when solving the UMTPO problem.
Feasibility and acceptability of a telehealth intervention for improving peer relationships for adolescents with neurofibromatosis type 1: a single-arm pilot study
Authors: Glad Danielle M , Pardej Sara K , Olszewski Ellen , Klein-Tasman Bonita P
Published: June 2024

Objective

Elevated rates of social difficulties are evident for children and adolescents with neurofibromatosis type 1 (NF1) but the effects of social skills interventions have not been investigated for this population. The Program for the Education and Enrichment of Relational Skills (PEERS®), a widely established social skills intervention in autism spectrum disorders with expansion to other conditions, was recently modified to be offered virtually. This study examined the feasibility and acceptability of this telehealth intervention.

Methods

27 adolescents with NF1 with social skills difficulties and at least 1 caregiver enrolled in the study. 19 of those participants (Mage = 14.21 years, SD = 1.63; 7 females; 79% White) completed PEERS® via telehealth in a single-arm pilot study. Dropout rates, attendance records, helpfulness of the curriculum topics and caregiver-reported acceptability, including ratings on the Treatment Acceptability Questionnaire, were examined.

Results

Low study drop out (30% of enrolled participants; 14% of participants who began the intervention) and high attendance rates were observed. Caregivers found sessions related to common, everyday interactions most helpful. Adolescents indicated sessions related to having get-togethers and social nuances (e.g., humor) as most helpful. Caregiver ratings indicated acceptability of the intervention.

Conclusions

This investigation supported the feasibility and acceptability of telehealth PEERS®, a social skills intervention program, among adolescents with NF1 and their caregivers based on attendance patterns as well as appraisal of the curriculum and telehealth modality.
Language-based machine perception: linguistic perspectives on the compilation of captioning datasets
Authors: Hekanaho Laura , Hirvonen Maija , Virtanen Tuomas
Published: June 2024

Over the last decade, a plethora of training datasets have been compiled for use in language-based machine perception and in human-centered AI, alongside research regarding their compilation methods. From a primarily linguistic perspective, we add to these studies in two ways. First, we provide an overview of sixty-six training datasets used in automatic image, video, and audio captioning, examining their compilation methods with a metadata analysis. Second, we delve into the annotation process of crowdsourced datasets with an interest in understanding the linguistic factors that affect the form and content of the captions, such as contextualization and perspectivation. With a qualitative content analysis, we examine annotator instructions with a selection of eleven datasets. Drawing from various theoretical frameworks that help assess the effectiveness of the instructions, we discuss the visual and textual presentation of the instructions, as well as the perspective-guidance that is an essential part of the language instructions. While our analysis indicates that some standards in the formulation of instructions seem to have formed in the field, we also identified various reoccurring issues potentially hindering readability and comprehensibility of the instructions, and therefore, caption quality. To enhance readability, we emphasize the importance of text structure, organization of the information, consistent use of typographical cues, and clarity of language use. Last, engaging with previous research, we assess the compilation of both web-sourced and crowdsourced captioning datasets from various perspectives, discussing factors affecting the diversity of the datasets.
Pain Management in Staged Osseointegration Procedures: A Retrospective Study and Foundation for Future Optimization
Authors: McCarthy Margaret L , Ariizumi Ren M , Grajales Ana G , DeCicco Joseph , Forsberg Jonathan A , Watson Nora , Burch Robert H , Highland Krista B
Published: June 2024

Introduction

Osseointegration is an innovative procedure to attach an external prosthetic device directly to the skeleton. The technique has been shown to improve physical function and quality of life relative to conventional socket prosthetic devices. While much of the research in osseointegration has focused on functional outcomes, less is known regarding perioperative pain management. The purpose of this study was to describe perioperative and postoperative pain management approaches received by patients undergoing osseointegration procedures at a tertiary medical center.

Materials and Methods

This retrospective study was determined to be exempt from Institutional Review Board review by the Walter Reed National Military Medical Center Department of Research Programs. Perioperative and postoperative pain management approaches received by 41 patients who underwent 76 staged osseointegration procedures from 2016 to 2021 at Walter Reed National Military Medical Center were described.

Results

Pain management approaches included perioperative ketamine (51% stage I, 55% stage II), epidurals (76% stage I, 77% stage II) with a median of 3-4 days across stages, peripheral nerve catheters (27% stage I, 16% stage II), and/or single-shot peripheral nerve block (<10% across stages). The median morphine equivalent dose provided during surgery was 65 mg across both stages, with 56% and 54% of patients also requiring opioid medication in the post-anesthesia care unit. In 11 of 76 (15%) procedures, patients required an increase in the rate or concentration of epidural or peripheral nerve catheter infusion. In six (8%) unique recovery periods, patients experienced a dislodged catheter. In 27 of 76 (36%) unique recovery periods, patients experienced a significant increase in postoperative pain requiring acute pain service intervention in the form of catheter adjustment, intravenous pain medications, and/or the addition of intravenous patient-controlled analgesia. Adequate pain control was achieved with minimal epidural or peripheral nerve catheter trouble-shooting and a bolus for 24 patients (89% requiring intervention). Summed 24-hour pain scores (SPI24) did not vary across stages. SPI24 was positively correlated with opioid doses received. Patients with single, relative to multiple, limb amputations had similar SPI24 values (P > .05).

Conclusions

Variability in pain management requirements calls forth opportunities to optimize osseointegration analgesia care and future research. As osseointegration becomes more accessible, the need for optimizing pain management through patient-centered research becomes more salient.
Accurate estimate of the ESPRESSO fibre-injection losses inferred from integrated field-stabilization images
Authors: Schmidt Tobias M
Published: June 2024

Ground-based astronomy is unavoidably subject to the adverse effect of atmospheric turbulence, a.k.a. the seeing, which blurs the images and limits the achievable spatial resolution. For spectroscopic observations, it leads to slit or fibre-injection losses, since not all photons distributed over the extended seeing disc can be captured. These losses might have a very substantial impact on the overall efficiency of a spectrograph and are naturally highly variable. Assessing the fibre-injection losses requires accurate information about the image quality (IQ) delivered by the telescope to the instrument over the course of the observations, which, however, is often not directly available. ESPRESSO provides acquisition and field-stabilization images attached to the science data and thus offers the opportunity for a post-processing analysis. Here, we present a novel method to infer the IQ profile and fibre-injection losses from the integrated field-stabilization images, utilizing the spill-over light that does not get injected into the fibre. We validate these measurements against the IQ observed in the acquisition images and determine that our method delivers unbiased estimates with a scatter of 0.11 arcsec for the FWHM of the profile and $15~{{\ \rm per\ cent}}$ in terms of fibre-injection losses. This compares favourably to the estimates derived from either the differential image motion monitor or the telescope guide probe sensors and therefore represents a valuable tool to characterize the instrument efficiency and to correct raw spectra for fibre-injection losses.
Nebular dominated galaxies: insights into the stellar initial mass function at high redshift
Authors: Cameron Alex J , Katz Harley , Witten Callum , Saxena Aayush , Laporte Nicolas , Bunker Andrew J
Published: June 2024

We identify a low-metallicity ($12+\log ({\rm O}/{\rm H})=7.59$) Ly $\alpha$-emitting galaxy at $z=5.943$ with evidence of a strong Balmer jump, arising from nebular continuum. While Balmer jumps are sometimes observed in low-redshift star-forming galaxies, this galaxy also exhibits a steep turnover in the UV continuum. Such turnovers are typically attributed to absorption by a damped Ly $\alpha$ system (DLA); however, the shape of the turnover and the high observed Ly $\alpha$ escape fraction ($f_{\rm esc,Ly\alpha }~\sim 27~{{\ \rm per\ cent}}$) is also consistent with strong nebular two-photon continuum emission. Modelling the UV turnover with a DLA requires extreme column densities ($N_{\rm HI}\,\,\gt\,\, 10^{23}$ cm$^{-2}$), and simultaneously explaining the high $f_{\rm esc,Ly\alpha }$ requires a fine-tuned geometry. In contrast, modelling the spectrum as primarily nebular provides a good fit to both the continuum and emission lines, motivating scenarios in which (a) we are observing only nebular emission or (b) the ionizing source is powering extreme nebular emission that outshines the stellar emission. The nebular-only scenario could arise if the ionizing source has ‘turned off’ more recently than the recombination time-scale ($\sim$1000 yr), hence we may be catching the object at a very specific time. Alternatively, hot stars with $T_{\rm eff}\gtrsim 10^5$ K (e.g. Wolf–Rayet or low-metallicity massive stars) produce enough ionizing photons such that the two-photon emission becomes visible. While several stellar SEDs from the literature fit the observed spectrum well, the hot-star scenario requires that the number of $\gtrsim 50~{\rm M}_\odot$ stars relative to $\sim 5\!-\!50~{\rm M}_\odot$ stars is significantly higher than predicted by typical stellar initial mass functions (IMFs). The identification of more galaxies with similar spectra may provide evidence for a top-heavy IMF at high redshift.
Reconsidering the dynamical states of galaxy clusters using PCA and UMAP
Authors: Haggar Roan , De Luca Federico , De Petris Marco , Sazonova Elizaveta , Taylor James E , Knebe Alexander , Gray Meghan E , Pearce Frazer R , Contreras-Santos Ana , Cui Weiguang , Kuchner Ulrike , Mostoghiu Paun Robert A , Power Chris
Published: June 2024

Numerous metrics exist to quantify the dynamical state of galaxy clusters, both observationally and within simulations. Many of these correlate strongly with one another, but it is not clear whether all of these measures probe the same intrinsic properties. In this work, we use two different statistical approaches – principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) – to investigate which dynamical properties of a cluster are in fact the best descriptors of its dynamical state. We use measurements taken directly from The Three Hundred suite of galaxy cluster simulations, as well as morphological properties calculated using mock X-ray and SZ maps of the same simulated clusters. We find that four descriptions of dynamical state naturally arise, and although correlations exist between these, a given cluster can be ‘dynamically relaxed’ according to all, none, or some of these four descriptions. These results demonstrate that it is highly important for future observational and theoretical studies to consider in which sense clusters are dynamically relaxed. Cluster dynamical states are complex and multidimensional, and so it is not meaningful to classify them simply as ‘relaxed’ and ‘unrelaxed’ based on a single linear scale.
Disordered sequences of transcription factors regulate genomic binding by integrating diverse sequence grammars and interaction types
Authors: Hurieva Bohdana , Kumar Divya Krishna , Morag Rotem , Lupo Offir , Carmi Miri , Barkai Naama , Jonas Felix
Published: June 2024

Intrinsically disordered regions (IDRs) guide transcription factors (TFs) to their genomic binding sites, raising the question of how structure-lacking regions encode for complex binding patterns. We investigated this using the TF Gln3, revealing sets of IDR-embedded determinants that direct Gln3 binding to respective groups of functionally related promoters, and enable tuning binding preferences between environmental conditions, phospho-mimicking mutations, and orthologs. Through targeted mutations, we defined the role of short linear motifs (SLiMs) and co-binding TFs (Hap2) in stabilizing Gln3 at respiration-chain promoters, while providing evidence that Gln3 binding at nitrogen-associated promoters is encoded by the IDR amino-acid composition, independent of SLiMs or co-binding TFs. Therefore, despite their apparent simplicity, TF IDRs can direct and regulate complex genomic binding patterns through a combination of SLiM-mediated and composition-encoded interactions.
A treasure trove of 1034 actinomycete genomes
Authors: Jørgensen Tue Sparholt , Mohite Omkar S , Sterndorff Eva B , Alvarez-Arevalo Maria , Blin Kai , Booth Thomas J , Charusanti Pep , Faurdal David , Hansen Troels Ø , Nuhamunada Matin , Mourched Anna-Sophie , Palsson Bernhard Ø , Weber Tilmann
Published: June 2024

Filamentous Actinobacteria, recently renamed Actinomycetia, are the most prolific source of microbial bioactive natural products. Studies on biosynthetic gene clusters benefit from or require chromosome-level assemblies. Here, we provide DNA sequences from >1000 isolates: 881 complete genomes and 153 near-complete genomes, representing 28 genera and 389 species, including 244 likely novel species. All genomes are from filamentous isolates of the class Actinomycetia from the NBC culture collection. The largest genus is Streptomyces with 886 genomes including 742 complete assemblies. We use this data to show that analysis of complete genomes can bring biological understanding not previously derived from more fragmented sequences or less systematic datasets. We document the central and structured location of core genes and distal location of specialized metabolite biosynthetic gene clusters and duplicate core genes on the linear Streptomyces chromosome, and analyze the content and length of the terminal inverted repeats which are characteristic for Streptomyces. We then analyze the diversity of trans-AT polyketide synthase biosynthetic gene clusters, which encodes the machinery of a biotechnologically highly interesting compound class. These insights have both ecological and biotechnological implications in understanding the importance of high quality genomic resources and the complex role synteny plays in Actinomycetia biology.
Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2′-deoxyguanosine
Authors: Gao Shijun , Tahara Yuki , Kool Eric T , Greenberg Marc M
Published: June 2024

Formamidopyrimidine (Fapy•dG) is a major lesion arising from oxidation of dG that is produced from a common chemical precursor of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OxodGuo). In human cells, replication of single-stranded shuttle vectors containing Fapy•dG is more mutagenic than 8-OxodGuo. Here, we present the first data regarding promoter dependent RNA polymerase II bypass of Fapy•dG. 8-OxodGuo bypass was examined side-by-side. Experiments were carried out using double-stranded shuttle vectors in HeLa cell nuclear lysates and in HEK 293T cells. The lesions do not significantly block transcriptional bypass efficiency. Less than 2% adenosine incorporation occurred in cells when the lesions were base paired with dC. Inhibiting base excision repair in HEK 293T cells significantly increased adenosine incorporation, particularly from Fapy•dG:dC bypass which yielded ∼25% adenosine incorporation. No effect was detected upon transcriptional bypass of either lesion in nucleotide excision repair deficient cells. Transcriptional mutagenesis was significantly higher when shuttle vectors containing dA opposite one of the lesions were employed. For Fapy•dG:dA bypass, adenosine incorporation was greater than 85%; whereas 8-OxodGuo:dA yielded >20% point mutations. The combination of more frequent replication mistakes and greater error-prone Pol II bypass suggest that Fapy•dG is more mutagenic than 8-OxodGuo.
Differential impact of quiescent non-coding loci on chromatin entropy
Authors: Wu Peiyao , Yao Mina , Wang Wei
Published: June 2024

Non-coding regions of the human genome are important for functional regulations, but their mechanisms remain elusive. We used machine learning to guide a CRISPR screening on hubs (i.e. non-coding loci forming many 3D contacts) and significantly increased the discovery rate of hubs essential for cell growth. We found no clear genetic or epigenetic differences between essential and nonessential hubs, but we observed that some neighboring hubs in the linear genome have distinct spatial contacts and opposite effects on cell growth. One such pair in an epigenetically quiescent region showed different impacts on gene expression, chromatin accessibility and chromatin organization. We also found that deleting the essential hub altered the genetic network activity and increased the entropy of chromatin accessibility, more severe than that caused by deletion of the nonessential hub, suggesting that they are critical for maintaining an ordered chromatin structure. Our study reveals new insights into the system-level roles of non-coding regions in the human genome.
PBOX-sRNA-seq uncovers novel features of miRNA modification and identifies selected 5′-tRNA fragments bearing 2′-O-modification
Authors: Chen Susu , Cai Yuchen , Yang Huiru , Zhang Bin , Li Ning , Ren Guodong
Published: June 2024

The concomitant cloning of RNA degradation products is a major concern in standard small RNA-sequencing practices. This not only complicates the characterization of bona fide sRNAs but also hampers cross-batch experimental replicability and sometimes even results in library construction failure. Given that all types of plant canonical small RNAs possess the 3′ end 2′-O-methylation modification, a new small RNA sequencing (sRNA-seq) method, designated as PBOX-sRNA-seq, has been developed specifically to capture this modification. PBOX-sRNA-seq, as its name implies, relies on the sequential treatment of RNA samples with phenylboronic acid-polyacrylamide gel electrophoresis (PBA-PAGE) and sodium periodate (NaIO4) oxidation, before sRNA library construction and sequencing. PBOX-sRNA-seq outperformed separate treatments (i.e. PBA-PAGE only or NaIO4 only) in terms of the depletion of unmethylated RNA species and capture 2′-O-modified sRNAs with extra-high purity. Using PBOX-sRNA-seq, we discovered that nascent miRNA-5p/-3p duplexes may undergo mono-cytidylation/uridylation before 2′-O-methylation. We also identified two highly conserved types of 5′-tRNA fragments (tRF) bearing HEN1-independent 2′-O modification (mainly the 13-nt tRF-5aAla and the 26-nt tRF-5bGly). We believe that PBOX-sRNA-seq is powerful for both qualitative and quantitative analyses of sRNAs in plants and piRNAs in animals.
Tracking rivalry with neural rhythms: multivariate SSVEPs reveal perception during binocular rivalry
Authors: Laukkonen Ruben E , Lewis-Healey Evan , Ghigliotti Luca , Daneshtalab Nasim , Lageman Jet , Slagter Heleen A
Published: June 2024

The contents of awareness can substantially change without any modification to the external world. Such effects are exemplified in binocular rivalry, where a different stimulus is presented to each eye causing instability in perception. This phenomenon has made binocular rivalry a quintessential method for studying consciousness and the necessary neural correlates for awareness. However, to conduct research on binocular rivalry usually requires self-reports of changes in percept, which can produce confounds and exclude states and contexts where self-reports are undesirable or unreliable. Here, we use a novel multivariate spatial filter dubbed ‘Rhythmic Entrainment Source Separation’ to extract steady state visual evoked potentials from electroencephalography data. We show that this method can be used to quantify the perceptual switch-rate of participants during binocular rivalry and therefore may be valuable in experimental contexts where self-reports are methodologically problematic or impossible, particularly as an adjunct. Our analyses also reveal that ‘no-report’ conditions may affect the deployment of attention and thereby neural correlates, another important consideration for consciousness research.
Validation of the graded prognostic assessment and recursive partitioning analysis as prognostic tools using a modern cohort of patients with brain metastases
Authors: Sperber Jacob , Yoo Seeley , Owolo Edwin , Dalton Tara , Zachem Tanner J , Johnson Eli , Herndon James E , Nguyen Annee D , Hockenberry Harrison , Bishop Brandon , Abu-Bonsrah Nancy , Cook Steven H , Fecci Peter E , Sperduto Paul W , Johnson Margaret O , Erickson Melissa M , Goodwin C Rory
Published: June 2024

Background

Prognostic indices for patients with brain metastases (BM) are needed to individualize treatment and stratify clinical trials. Two frequently used tools to estimate survival in patients with BM are the recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA). Given recent advances in therapies and improved survival for patients with BM, this study aims to validate and analyze these 2 models in a modern cohort.

Methods

Patients diagnosed with BM were identified via our institution’s Tumor Board meetings. Data were retrospectively collected from the date of diagnosis with BM. The concordance of the RPA and GPA was calculated using Harrell’s C index. A Cox proportional hazards model with backwards elimination was used to generate a parsimonious model predictive of survival.

Results

Our study consisted of 206 patients diagnosed with BM between 2010 and 2019. The RPA had a prediction performance characterized by Harrell’s C index of 0.588. The DS-GPA demonstrated a Harrell’s C index of 0.630. A Cox proportional hazards model assessing the effect of age, presence of lung, or liver metastases, and Eastern Cooperative Oncology Group (ECOG) performance status score of 3/4 on survival yielded a Harrell’s C index of 0.616. Revising the analysis with an uncategorized ECOG demonstrated a C index of 0.648.

Conclusions

We found that the performance of the RPA remains unchanged from previous validation studies a decade earlier. The DS-GPA outperformed the RPA in predicting overall survival in our modern cohort. Analyzing variables shared by the RPA and DS-GPA produced a model that performed analogously to the DS-GPA.
Lewis-base ligand-reshaped interfacial hydrogen-bond network boosts CO2 electrolysis
Authors: Ge Wangxin , Tao Haolan , Dong Lei , Fan Yu , Niu Yanpu , Zhu Yihua , Lian Cheng , Liu Honglai , Jiang Hongliang , Li Chunzhong
Published: June 2024

Both the catalyst and electrolyte strongly impact the performance of CO2 electrolysis. Despite substantial progress in catalysts, it remains highly challenging to tailor electrolyte compositions and understand their functions at the catalyst interface. Here, we report that the ethylenediaminetetraacetic acid (EDTA) and its analogs, featuring strong Lewis acid-base interaction with metal cations, are selected as electrolyte additives to reshape the catalyst-electrolyte interface for promoting CO2 electrolysis. Mechanistic studies reveal that EDTA molecules are dynamically assembled toward interface regions in response to bias potential due to strong Lewis acid-base interaction of EDTA4–-K+. As a result, the original hydrogen-bond network among interfacial H2O is disrupted, and a hydrogen-bond gap layer at the electrified interface is established. The EDTA-reshaped K+ solvation structure promotes the protonation of *CO2 to *COOH and suppressing *H2O dissociation to *H, thereby boosting the co-electrolysis of CO2 and H2O toward carbon-based products. In particular, when 5 mM of EDTA is added into the electrolytes, the Faradaic efficiency of CO on the commercial Ag nanoparticle catalyst is increased from 57.0% to 90.0% at an industry-relevant current density of 500 mA cm−2. More importantly, the Lewis-base ligand-reshaped interface allows a range of catalysts (Ag, Zn, Pd, Bi, Sn, and Cu) to deliver substantially increased selectivity of carbon-based products in both H-type and flow-type electrolysis cells.
The Impact of New Jersey’s 2020 E-cigarette Flavor Ban on E-cigarette, Cigarette, and Cigar Sales in New Jersey
Authors: Hrywna Mary , Teotia Arjun , Miller Lo Erin , Giovenco Daniel P , Delnevo Cristine D
Published: June 2024

Introduction

On April 20, 2020, New Jersey (NJ) implemented a comprehensive ban on the sale of flavored e-cigarettes. This study compares sales of e-cigarettes, cigarettes, and cigars before and after the law.

Aims and Methods

Data were biweekly retailer scanner sales in NJ convenience stores for e-cigarettes, cigarettes, and cigars between August 2019 and December 2020. We used Joinpoint regression to assess sales trends for cigarettes (non-menthol and menthol), cigars (unflavored and flavored), and e-cigarettes (unflavored, fruit or sweet or concept flavor, and menthol flavor) in the 36 weeks before and 36 weeks after a statewide ban on flavored e-cigarettes.

Results

Flavored e-cigarette sales, not including menthol, significantly decreased over the study period while menthol e-cigarette sales significantly increased until the e-cigarette flavor ban took effect, after which these sales rapidly declined through May 2020, then slowed. Unflavored e-cigarette sales declined through September 2019, then grew modestly until the flavored e-cigarette ban, after which sales significantly increased. Flavored cigar sales increased between March and May 2020, then declined; non-flavored cigar sales increased between mid-February and early July 2020, then declined. Cigarette sales were decreasing before the flavored e-cigarette ban but after, significantly increased until June 2020. Overall, there was no significant trend in the average biweekly percent change for cigarette sales.

Conclusions

Flavored e-cigarette sales were declining prior to the ban but the pace of the decline accelerated following federal and state restrictions on flavored e-cigarette sales, then slowed by the second half of 2020, with a brief period of increased cigarette and cigar sales immediately following the ban.

Implications

NJ’s 2020 statewide e-cigarette flavor ban offered the opportunity to observe how sales of e-cigarette, cigarette, and cigar products shifted after the change. The effect of the state law, at least in the short-term, was decreased sales of flavored e-cigarettes and increased sales of unflavored e-cigarettes. Research on long-term policy effects is needed.
Longitudinal Association Between Harm Perceptions and Tobacco Behaviors Among Adults Who Smoke Cigarettes: Differential Associations Across Age Groups Using the PATH Study
Authors: Weiger Caitlin V , Wackowski Olivia A , Bover Manderski Michelle T , Villanti Andrea C , Chen-Sankey Julia
Published: June 2024

Introduction

The relationship between e-cigarette and cigarette harm perceptions and tobacco behaviors may vary by age. We examined longitudinal associations of harm perceptions with tobacco use behaviors among adults who smoke cigarettes.

Aims and Methods

Data were from Waves 4 (2016–2018) and 5 (2018–2019) of the Population Assessment of Tobacco and Health survey. Weighted multivariable logistic regressions identified independent associations between relative and absolute e-cigarette and cigarette harm perceptions at baseline and continued smoking, dual use, complete switching, and quit intention at follow-up, stratified by age (young adults [YAs] 18–24, middle-aged adults [MAs] 25–44, and older adults [OAs] ≥45) among U.S. adults who smoke (n = 8231).

Results

Perceiving e-cigarettes as less harmful than cigarettes was associated with higher odds of complete switching from cigarettes to e-cigarettes (adjusted odds ratio [aOR] overall: 1.52; MAs: 1.68). Perceiving e-cigarettes as very/extremely harmful was associated with lower odds of dual use (overall aOR: 0.75; MAs: 0.72) and higher odds of quit intention (aOR OAs: 1.34). Perceiving cigarettes as very/extremely harmful was associated with lower odds of continued smoking (overall aOR: 0.69; MAs: 0.76; OAs: 0.53), and higher odds of complete switching (overall aOR: 1.65; MAs: 1.86) and quit intention (overall aOR: 1.58; MAs: 1.42; OAs: 1.80). No findings reached significance for YAs.

Discussion

E-cigarette relative and absolute harm perceptions were associated with different tobacco behaviors by age. Low cigarette harm perceptions were similarly associated with continued smoking and lower quit intentions in MAs and OAs. Future research should explore what beliefs inform these perceptions and age-related differences.

Implications

The associations between harm perceptions and subsequent tobacco behaviors differed by age among adults who smoke. This study adds that low relative harm perceptions of e-cigarettes can promote complete switching among MAs who smoke. High absolute harm perceptions of e-cigarettes may deter dual use among MAs. Additionally, high absolute harm perceptions of cigarettes may reduce smoking and increase cigarette smoking quit intentions among MAs and OAs. Future research is needed to understand the beliefs that support harm perceptions among different age groups, why their effects differ by age, and what factors influence YAs’ tobacco use behaviors.
Topography of mutational signatures in non-small cell lung cancer: emerging concepts, clinical applications, and limitations
Authors: Jayakrishnan Ritujith , Kwiatkowski David J , Rose Michal G , Nassar Amin H
Published: June 2024

The genome of a cell is continuously battered by a plethora of exogenous and endogenous processes that can lead to damaged DNA. Repair mechanisms correct this damage most of the time, but failure to do so leaves mutations. Mutations do not occur in random manner, but rather typically follow a more or less specific pattern due to known or imputed mutational processes. Mutational signature analysis is the process by which the predominant mutational process can be inferred for a cancer and can be used in several contexts to study both the genesis of cancer and its response to therapy. Recent pan-cancer genomic efforts such as “The Cancer Genome Atlas” have identified numerous mutational signatures that can be categorized into single base substitutions, doublet base substitutions, or small insertions/deletions. Understanding these mutational signatures as they occur in non-small lung cancer could improve efforts at prevention, predict treatment response to personalized treatments, and guide the development of therapies targeting tumor evolution. For non-small cell lung cancer, several mutational signatures have been identified that correlate with exposures such as tobacco smoking and radon and can also reflect endogenous processes such as aging, APOBEC activity, and loss of mismatch repair. Herein, we provide an overview of the current knowledge of mutational signatures in non-small lung cancer.
HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains
Authors: Zhu Xiaolin , Chan Emily , Turski Michelle L , Mendez Carlos Espinosa , Hsu Sarah C , Kumar Vipul , Shipp Chase , Jindal Tanya , Chang Kevin , Onodera Courtney , Devine W Patrick , Grenert James P , Stohr Bradley A , Ding Chien-Kuang Cornelia , Stachler Matthew D , Quigley David A , Feng Felix Y , Chu Carissa E , Porten Sima P , Chou Jonathan , Friedlander Terence W , Koshkin Vadim S
Published: June 2024

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.
Fertility in young-onset colorectal patients with cancer: a review
Authors: Jiang Qiuping , Hua Hongmei
Published: June 2024

Although the overall incidence and mortality of colorectal cancer have declined, diagnosed cases of young-onset colorectal cancer have increased significantly. Concerns about future fertility are second only to concerns about survival and may significantly affect the quality of life of young cancer survivors. Fertility preservation is an important issue in young-onset colorectal patients with cancer undergoing oncotherapy. Here, we discussed the effects of different treatments on fertility, common options for fertility preservation, factors affecting fertility preservation and improvement measures, and the relationship between fertility and pregnancy outcomes in young-onset colorectal patients with cancer.
Optimization of implementation strategies using the Multiphase Optimization STratgey (MOST) framework: Practical guidance using the factorial design
Authors: Szeszulski Jacob , Guastaferro Kate
Published: June 2024

The Multiphase Optimization STrategy (MOST) is a framework that uses three phases—preparation, optimization, and evaluation—to develop multicomponent interventions that achieve intervention EASE by strategically balancing Effectiveness, Affordability, Scalability, and Efficiency. In implementation science, optimization of the intervention requires focus on the implementation strategies—things that we do to deliver the intervention—and implementation outcomes. MOST has been primarily used to optimize the components of the intervention related to behavioral or health outcomes. However, innovative opportunities to optimize discrete (i.e. single strategy) and multifaceted (i.e. multiple strategies) implementation strategies exist and can be done independently, or in conjunction with, intervention optimization. This article details four scenarios where the MOST framework and the factorial design can be used in the optimization of implementation strategies: (i) the development of new multifaceted implementation strategies; (ii) evaluating interactions between program components and a discrete or multifaceted implementation strategies; (iii) evaluating the independent effects of several discrete strategies that have been previously evaluated as a multifaceted implementation strategy; and (iv) modification of a discrete or multifaceted implementation strategy for the local context. We supply hypothetical school-based physical activity examples to illustrate these four scenarios, and we provide hypothetical data that can help readers make informed decisions derived from their trial data. This manuscript offers a blueprint for implementation scientists such that not only is the field using MOST to optimize the effectiveness of an intervention on a behavioral or health outcome, but also that the implementation of that intervention is optimized.
Efficacy of Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Authors: Qureshi Zaheer , Jamil Abdur , Fatima Eeshal , Altaf Faryal , Siddique Rimsha
Published: June 2024

Objectives:

Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2– breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety.

Methods:

Adhering to “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2– advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis.

Results:

Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P = 0.005; I
2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P = 0.11; I
2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I
2 = 61%).

Conclusion:

SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2– advanced breast cancer.
Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD
Authors: Wang Dan , Baghoomian Ania , Zhang Zhengyi , Cui Ya , Whang Emily C. , Li Xiang , Fraga Josue , Spellman Rachel Ariana , Dong Tien S. , Li Wei , Gupta Arpana , Benhammou Jihane N. , Sallam Tamer
Published: June 2024

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most common liver disease worldwide. The progression to fibrosis, occurring against a backdrop of hepatic steatosis and inflammation, critically determines liver-related morbidity and mortality. Inflammatory processes contribute to various stages of MAFLD and thought to instigate hepatic fibrosis. For this reason, targeting inflammation has been heavily nominated as a strategy to mitigate liver fibrosis. Lipopolysaccharide binding protein (LBP) is a secreted protein that plays an established role in innate immune responses. Here, using adoptive transfer studies and tissue-specific deletion models we show that hepatocytes are the dominant contributors to circulating LBP. In a murine model of MAFLD, hepatocyte-specific deletion of LBP restrained hepatic inflammation and improved liver function abnormalities, but not measures of fibrosis. Human studies, including genetic evidence, corroborate an important role for LBP in hepatic inflammation with minimal impact on fibrosis. Collectively, our data argues against the idea that targeting hepatic inflammation is a viable approach to reducing fibrosis.