bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances and future directions in ROS1 fusion-positive lung cancer
Authors: Boulanger Mary C , Schneider Jaime L , Lin Jessica J 
Published: August 2024

Abstract
ROS1 gene fusions are an established oncogenic driver comprising 1%-2% of non–small cell lung cancer (NSCLC). Successful targeting of ROS1 fusion oncoprotein with oral small-molecule tyrosine kinase inhibitors (TKIs) has revolutionized the treatment landscape of metastatic ROS1 fusion-positive (ROS1+) NSCLC and transformed outcomes for patients. The preferred Food and Drug Administration-approved first-line therapies include crizotinib, entrectinib, and repotrectinib, and currently, selection amongst these options requires consideration of the systemic and CNS efficacy, tolerability, and access to therapy. Of note, resistance to ROS1 TKIs invariably develops, limiting the clinical benefit of these agents and leading to disease relapse. Progress in understanding the molecular mechanisms of resistance has enabled the development of numerous next-generation ROS1 TKIs, which achieve broader coverage of ROS1 resistance mutations and superior CNS penetration than first-generation TKIs, as well as other therapeutic strategies to address TKI resistance. The approach to subsequent therapy depends on the pace and pattern of progressive disease on the initial ROS1 TKI and, if known, the mechanisms of TKI resistance. Herein, we describe a practical approach for the selection of initial and subsequent therapies for metastatic ROS1+ NSCLC based on these clinical considerations. Additionally, we explore the evolving evidence for the optimal treatment of earlier-stage, non–metastatic ROS1+ NSCLC, while, in parallel, highlighting future research directions with the goal of continuing to build on the tremendous progress in the management of ROS1+ NSCLC and ultimately improving the longevity and well-being of people living with this disease.
Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the “MOZART” prospective observational study
Authors: Schettini Francesco , Sirico Marianna , Loddo Marco , Williams Gareth H , Hardisty Keeda-Marie , Scorer Paul , Thatcher Robert , Rivera Pablo , Milani Manuela , Strina Carla , Ferrero Giuseppina , Ungari Marco , Bottin Cristina , Zanconati Fabrizio , de Manzini Nicolò , Aguggini Sergio , Tancredi Richard , Fiorio Elena , Fioravanti Antonio , Scaltriti Maurizio , Generali Daniele 
Published: August 2024

Abstract

Background
The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations’ type, frequency, actionability, and potential correlations with PD-L1 expression.

Methods
A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P &lt; .05.

Results
A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes.

Conclusions
We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical.
Arm symptom pattern among breast cancer survivors with and without lymphedema: a contemporaneous network analysis
Authors: Shen Aomei , Zhang Zhongning , Ye Jingming , Wang Yue , Zhao Hongmeng , Li Xin , Wu Peipei , Qiang Wanmin , Lu Qian 
Published: August 2024

Abstract

Background
Arm symptoms commonly endure in post-breast cancer period and persist into long-term survivorship. However, a knowledge gap existed regarding the interactions among these symptoms. This study aimed to construct symptom networks and visualize the interrelationships among arm symptoms in breast cancer survivors (BCS) both with and without lymphedema (LE).

Patients and Methods
We conducted a secondary analysis of 3 cross-sectional studies. All participants underwent arm circumference measurements and symptom assessment. We analyzed 17 symptoms with a prevalence &gt;15%, identifying clusters and covariates through exploratory factor and linear regression analysis. Contemporaneous networks were constructed with centrality indices calculated. Network comparison tests were performed.

Results
1116 cases without missing data were analyzed, revealing a 29.84% prevalence of LE. Axillary lymph node dissection [ALND] (vs sentinel lymph node biopsy [SLNB]), longer post-surgery duration, and radiotherapy significantly impacted overall symptom severity (P &lt; .001). “Lymphatic Stasis,” “Nerve Injury,” and “Movement Limitation” symptom clusters were identified. Core symptoms varied: tightness for total sample network, firmness for non-LE network, and tightness for LE network. LE survivors reported more prevalent and severe arm symptoms with stronger network connections than non-LE group (P = .010). No significant differences were observed among different subgroups of covariates (P &gt; .05). Network structures were significantly different between ALND and SLNB groups.

Conclusion
Our study revealed arm symptoms pattern and interrelationships in BCS. Targeting core symptoms in assessment and intervention might be efficient for arm symptoms management. Future research is warranted to construct dynamic symptom networks in longitudinal data and investigate causal relationships among symptoms.
A cyclical marker system enables indefinite series of oligonucleotide-directed gene editing in Chlamydomonas reinhardtii
Authors: Ross Ian L , Le Hong Phuong , Budiman Sabar , Xiong Dake , Hemker Fritz , Millen Elizabeth A , Oey Melanie , Hankamer Ben 
Published: August 2024

Abstract
CRISPR/Cas9 gene editing in the model green alga Chlamydomonas reinhardtii relies on the use of selective marker genes to enrich for nonselectable target mutations. This becomes challenging when many sequential modifications are required in a single-cell line, as useful markers are limited. Here, we demonstrate a cyclical selection process which only requires a single marker gene to identify an almost infinite sequential series of CRISPR-based target gene modifications. We used the NIA1 (Nit1, NR; nitrate reductase) gene as the selectable marker in this study. In the forward stage of the cycle, a stop codon was engineered into the NIA1 gene at the CRISPR target location. Cells retaining the wild-type NIA1 gene were killed by chlorate, while NIA1 knockout mutants survived. In the reverse phase of the cycle, the stop codon engineered into the NIA1 gene during the forward phase was edited back to the wild-type sequence. Using nitrate as the sole nitrogen source, only the reverted wild-type cells survived. By using CRISPR to specifically deactivate and reactivate the NIA1 gene, a marker system was established that flipped back and forth between chlorate- and auxotrophic (nitrate)-based selection. This provided a scarless cyclical marker system that enabled an indefinite series of CRISPR edits in other, nonselectable genes. We demonstrate that this “Sequential CRISPR via Recycling Endogenous Auxotrophic Markers (SCREAM)” technology enables an essentially limitless series of genetic modifications to be introduced into a single-cell lineage of C. reinhardtii in a fast and efficient manner to complete complex genetic engineering.
Two serial filters control P2X7 cation selectivity, Ser342 in the central pore and lateral acidic residues at the cytoplasmic interface
Authors: Markwardt Fritz , Schön Eike Christian , Raycheva Mihaela , Malisetty Aparna , Hawro Yakoob Sanaria , Berthold Malte , Schmalzing Günther 
Published: August 2024

Abstract
The human P2X7 receptor (hP2X7R) is a homotrimeric cell surface receptor gated by extracellular ATP4− with two transmembrane helices per subunit, TM1 and TM2. A ring of three S342 residues, one from each pore-forming TM2 helix, located halfway across the membrane bilayer, functions to close and open the gate in the apo and ATP4−-bound open states, respectively. The hP2X7R is selective for small inorganic cations, but can also conduct larger organic cations such as Tris+. Here, we show by voltage-clamp electrophysiology in Xenopus laevis oocytes that mutation of S342 residues to positively charged lysines decreases the selectivity for Na+ over Tris+, but maintains cation selectivity. Deep in the membrane, laterally below the S342 ring are nine acidic residues arranged as an isosceles triangle consisting of residues E14, D352, and D356 on each side, which do not move significantly during gating. When the E14K mutation is combined with lysine substitutions of D352 and/or D356, cation selectivity is lost and permeation of the small anion Cl− is allowed. Lysine substitutions of S342 together with D352 or E14 plus D356 in the acidic triangle convert the hP2X7R mutant to a fully Cl−-selective ATP4−-gated receptor. We conclude that the ion selectivity of wild-type hP2X7R is determined by two sequential filters in one single pathway: (i) a primary size filter, S342, in the membrane center and (ii) three cation filters lateral to the channel axis, one per subunit interface, consisting of a total of nine acidic residues at the cytoplasmic interface.
Associations of physical activity levels with fatigue in people with inflammatory rheumatic diseases in the LIFT trial
Authors: Gray Stuart R , Montoye Alexander H K , Vondrasek Joseph D , Neph Sylvia , Siebert Stefan , Paul Lorna , Bachmair Eva M , Basu Neil 
Published: August 2024

Abstract

Objectives
The overall aim of the current study was to quantify physical activity levels in inflammatory rheumatic diseases (IRDs) and to explore their role in fatigue.

Methods
We conducted a secondary analysis of data from the Lessening the Impact of Fatigue in IRDs (LIFT) trial of the personalized exercise program (PEP) intervention for fatigue. Participants with IRDs were recruited from 2017 to 2019 and the current analysis used fatigue, measured by the Chalder Fatigue Scale (CFS) and the Fatigue Severity Scale (FSS), and accelerometer measured physical activity data collected at baseline and at the 6-month follow-up. Physical activity levels were quantified and associations with fatigue and effects of PEP investigated.

Results
Of the 337 included participants, 195 (68.4%) did not meet the current recommendations for moderate–vigorous physical activity (MVPA). In baseline cross-sectional analysis, many dimensions of physical activity were associated with fatigue. After mutual adjustment, overall physical activity (vector magnitude) was associated with CFS [−0.88 (95% CI −0.12, −1.64)] and distribution of time spent at different activity intensities was associated with FSS [−1.16 (95% CI −2.01, −0.31)]. Relative to usual care, PEP resulted in an increase in upright time, with trends for increases in step count and overall physical activity. People who increased overall physical activity (vector magnitude) more had greater improvements in CFS and FSS, while those who increased step count and MVPA more had greater improvements in FSS.

Conclusion
Increasing physical activity is important for fatigue management in people with IRDs and further work is needed to optimize PEPs to target the symptoms and impact of fatigue.

Trial registration
ClinicalTrials.gov (http://clinicaltrials.gov), NCT03248518.
Computational forms for binary particle interactions at different levels of anisotropy
Authors: Everett Christopher N , Cotter Garret 
Published: August 2024

ABSTRACT
Particle interactions are key elements of many dynamical systems. In the context of systems described by a Boltzmann equation, such interactions may be described by a collision integral, a multidimensional integral over the momentum-phase space of the interaction. This integral is often simplified by assuming isotropic particle distributions; however, such an assumption places constraints on the dynamics of the system. This paper presents computational forms of the collision integral for relativistic, binary interactions at three levels of anisotropy, including a novel form in the isotropic case. All these forms are split into two parts, an absorption and an emission spectrum, which may be pre-calculated via numerical integration for simulation purposes. We demonstrate the use of these forms by comparison with the analytically integrated, isotropic emission spectrum of electron–positron annihilation, which are shown to agree to numerical precision. The emission spectrum is then further extended to axisymmetric particle distributions, where two-dimensional spectral maps can be generated to provide new insight.
Techno-nationalism to collaborative technology sovereignty
Authors: Lee Jeong-Dong , Kim Hanbin , Si Saerom , Lee Saangkeub 
Published: August 2024

Abstract
The current geopolitical instability has driven global policy frameworks to prioritize economic security. This shift has intensified the debate on technology sovereignty among developed countries, due to concerns over supply chain disruptions and competition for future technologies. However, equating technology sovereignty with techno-nationalism should be avoided. Techno-nationalism can lead to unrealistic goals of domestically possessing all necessary technologies, resulting in protectionism. Given the complex and interconnected nature of technological development, no single country can control all component technologies. This study proposes a concept of collaborative technology sovereignty, promoting openness in technology development and acquisition. Policies should focus on creating systems for sharing technologies with like-minded countries while securing critical technologies. Lessons from existing policies are essential for expanding this collaborative approach and establishing strategies for collaborative technology sovereignty.
State Complicity: Settler Colonialism, Multisided Violence, and Missing and Murdered Indigenous Women and Girls in Canada
Authors: García-Del Moral Paulina 
Published: August 2024

Abstract
This article theorizes and analyzes the Canadian state’s complicity in the crisis of missing and murdered Indigenous women and girls (MMIWG) in terms of the acts of omission (inaction) and commission (action) of the police and courts. Building on the intersectional perspective of Indigenous and antiracist feminist scholarship on MMIWG, I argue that these acts of omission and commission are rooted in a context of “multisided violence” that is colonial in nature: state action and inaction reproduce and normalize the conditions in which Indigenous women and girls can be murdered with impunity. I analyze reports by Indigenous and feminist civil society organizations as part of their transnational advocacy to compel the Canadian state to address MMIWG. I show that state acts of omission and commission are intertwined and reinforce each other through a pattern of inconsistent, deficient, and contradictory institutional responses to violence against Indigenous women and girls.
Building a future for phage-based technologies—a thought leadership approach to accelerating progress in the UK
Authors: Hodges Francesca E , Smith Darren L 
Published: August 2024

Abstract
Antimicrobial resistance is a global issue that threatens our ability to effectively manage and treat bacteria in the context of human health, animal health, and the environment. Bacteriophages provide a viable and necessary alternative to existing antimicrobials. Recognizing the extensive expertise and existing infrastructure that can support phage development in the UK, the Phage Innovation Network (PIN) was established with the aim of catalysing progress in this area. Through comprehensive consultation with the phage community and wider stakeholders, the PIN has carried out a variety of activities to address key issues that are considered to be preventative for the development and use of phage-based technologies in the UK. The successful outcomes of these activities demonstrate how this thought leadership approach has been effective in increasing engagement, delivering solutions, and supporting progress of the phage sector in the UK.
Live and carcass production traits for progeny of an F1 USDA Prime—Yield Grade 1 carcass clone sire compared to progeny of popular beef terminal sires
Authors: Francis Forest L , Grimes Becca B , Hawkins Dean E , Lust David G , McEvers Trent J , Tennant Travis C , Veneklasen Gregg O , Abraham Jason M , Gleghorn Justin F , Lawrence Ty E 
Published: August 2024

Abstract
The cloning of beef carcasses that grade United States Department of Agriculture (USDA) Prime—yield grade (YG) 1 (P1) has produced a sire that ranked well against high-performing bulls from multiple breeds. An F1 (P1 × P1 - first generation offspring) sire would ideally outperform its high-performing parents. A terminal sire study was conducted comparing progeny of an F1 (P1 × P1) sire (AxG1) against progeny (heifers and steers) of four high-performing sires of varying breeds {P1 (ALPHA); Angus; Simmental; Angus × Simmental}. Production traits included morbidity and mortality frequencies, weaning weight, feedlot arrival weight, and days on feed; carcass traits included frequency of abscessed liver and lung health, quality grade and YG parameters, total carcass value (US$), and carcass value per hundredweight (CWT [45.4 kg]; US$). A completely randomized experimental design was used; data were analyzed using a mixed model with a fixed effect of sire and random effects of harvest date, sex, and pen. AxG1 sired heifers had the highest (P &lt; 0.01) marbling score, the highest (P &lt; 0.01) carcass value per CWT, and numerically had the lowest calculated YG and highest frequency of YG one carcass. Steers sired by AxG1 had the least (P = 0.05) backfat, lowest (P &lt; 0.01) calculated YG, highest (P &lt; 0.01) marbling score, highest (P &lt; 0.01) frequency of USDA Prime carcasses, the greatest (P &lt; 0.03) total carcass value, and greatest (P &lt; 0.01) carcass value per CWT. Collectively, AxG1 steer and heifer carcasses exhibited the least 12th rib fat thickness and lowest USDA YG in addition to the largest longissimus muscle area, highest marbling score, and greatest frequency of USDA Prime. These data suggest that AxG1 performed comparably to other high-performing industry terminal sires in carcass quality and YG outcomes.
Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation
Authors: Kranidioti Eleftheria , Ricaño-Ponce Isis , Antonakos Nikolaos , Kyriazopoulou Evdoxia , Kotsaki Antigone , Tsangaris Iraklis , Markopoulou Dimitra , Rovina Nikoleta , Antoniadou Eleni , Koutsodimitropoulos Ioannis , Dalekos George N. , Vlachogianni Glykeria , Akinosoglou Karolina , Koulouras Vasilios , Komnos Apostolos , Kontopoulou Theano , Dimopoulos George , Netea Mihai G. , Kumar Vinod , Giamarellos-Bourboulis Evangelos J. 
Published: August 2024

OBJECTIVE:
To investigate the metabolomic profiles associated with different immune activation states in sepsis patients.

DESIGN:
Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study.

SETTING:
Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation.

PATIENTS OR SUBJECTS:
Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia.

INTERVENTIONS:
During our comparison, we did not perform any intervention.

MEASUREMENTS AND MAIN RESULTS:
Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites.

CONCLUSIONS:
Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.
Evaluation of the Implementation of a Day-Treatment Program for Executive Functioning for Individuals With Traumatic Brain Injury in Rehabilitation Settings Using the Consolidated Framework for Implementation Research
Authors: Kajankova Maria , Tsaousides Theodore , Dudek Emily , Ashman Teresa 
Published: August 2024

Objective:
To identify barriers and facilitators to implementation of a cognitive rehabilitation intervention (Short-Term Executive Plus [STEP]) into routine clinical practice using the Consolidated Framework for Implementation Research (CFIR) by comparing high (HI) and low implementation (LI) sites.

Setting:
Qualitative interviews conducted with professionals who work with people who have sustained brain injuries at various rehabilitations sites across the United States.

Participants:
Seven sites completed training, consultation, and agreed to implement STEP.

Design:
Retrospective qualitative study.

Main Measure(s):
Qualitative interview developed for the purposes of this study and the CFIR for evaluation of implementation efforts and identification of barriers and facilitators.

Results:
Out of 7 sites, 6 completed interviews. Out of the 39 CFIR constructs, 4 distinguished between HI and LI sites. Four distinguishing factors included evidence strength and quality, needs and resources of those served by the organization, leadership engagement, and engaging champions. Five common factors were identified (4 positive and 1 negative) across HI and LI sites, which may reflect aspects of implementation that could inform future implementation efforts. Ten inconclusive factors were identified, having both a positive and a negative influence on implementation.

Conclusions:
While there were several factors that were viewed positively by all sites, only 4 factors made a difference in implementation outcomes. These distinguishing factors can help inform future implementation efforts, highlighting a need for strong evidence supporting an intervention, a match between the intervention and the needs of the population served, engaging those in leadership and decision-making roles and ensuring their buy-in, and having a strong champion directly involved in implementation. In addition, taking a closer look at common and inconclusive factors may enable us to identify areas in which the implementation efforts could be strengthened.