bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study
Authors: Sada Ken-ei , Katayama Yu , Asano Yosuke , Hayashi Keigo , Miyawaki Yoshia , Ohashi Keiji , Katsuyama Eri , Katsuyama Takayuki , Takano-Narazaki Mariko , Matsumoto Yoshinori , Yoshimi Ryusuke , Shimojima Yasuhiro , Ohno Shigeru , Kajiyama Hiroshi , Ichinose Kunihiro , Sato Shuzo , Fujiwara Michio , Yajima Nobuyuki 
Published: September 2022

ObjectiveIt is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status.MethodsUsing data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5–20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index.ResultsGC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3).ConclusionEven in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual.
The mid-Cretaceous Peninsular Ranges orogeny: a new slant on Cordilleran tectonics? III: the orogenic foredeep
Authors: Hildebrand Robert S. , Bhattacharya Janok P. , Whalen Joseph B. 
Published: September 2022

The Cretaceous Western Interior Basin reflects the interplay between the North American craton and allochthonous terranes to the west. We divide the basinal stratigraphy into three successions, Aptian–Albian, Cenomanian–Turonian, and Santonian–Maastrichtian, each related to periods of deformation in the adjacent fold-thrust belt. Here we focus on the Cenomanian–Turonian succession, where progressive west to east uplift and fluvial incision of older Aptian–Albian sedimentary rocks (Cedar Mtn–San Pitch–Thermopolis–Skull Creek–Mannville) are interpreted as a migrating forebulge. Uplift was underway at 103 Ma in the west (Paddy–Blackleaf–Muddy sandstones) and propagated eastward throughout the trough by 99.5 Ma (Viking–Bow Island–Newcastle sandstones). The incised fluvial valleys were subsequently filled by swampy and shallow marine facies, then overlain by dark, marine Neogastroplites-bearing shale and associated bentonites of the 100–97.5 Ma Shell Creek–Mowry–Slater River–Goodrich–Shaftesbury–Westgate shales. The shales are characterized by a distinctive condensed horizon with abundant fish scales, teeth, and bones. They are interpreted as outer-trench slope deposits, with the overlying anoxic horizon representing a starved isochronous unit formed atop the slope deposits. The starved horizon is overlain by prodeltaic muddy clinoforms of easterly migrating clastic wedges (Trevor–Dunvegan–Frontier–Cintura–Mexcala) that can be traced 800 km atop the fish-scale hash and contain hinterland-derived 99–90 Ma detrital zircons. Although the Western Interior Basin has long been considered a retro-arc trough, the overall succession instead suggests that the Cretaceous–Turonian part represents a collisional foredeep created during the ∼100 Ma collision between the arc-bearing Peninsular Ranges composite terrane and North America. The accretion brought tyrannosaurids, pachycephalosaurs, snakes, and marsupials to North America.
Risk management planning on a volcanic island: fear and loathing in Ischia (Italy)
Authors: Tomasone Mario , Avvisati Gala , Cirillo Francesca , Colucci Orazio , Marotta Enrica , Fiorenza Elisa , Vertechi Enrico , Simonetti Biagio 
Published: September 2022

Abstract
The volcanic island of Ischia (southern Italy) represents an interesting challenge as far as both risk analysis and risk management planning (RMP) go; hence, it is detailed here as a study case. We analysed the strengths and weaknesses of the emergency plans brought forward following the August 2017 earthquake, elaborating and revising scientific information, and involving researchers and experts with very different competences and backgrounds (e.g. engineers, architects, geologists, volcanologists, sociologists and information science experts). In particular, the historical evolution of the emergency plans prior to this event was recollected; the social context, on the basis of both literature and new statistical results, was analysed; and the guidelines proposed and/or implemented in other similar contexts in the world were examined. This work analyses and discusses the results, and proposes models that are universally applicable. Indeed, the key factors necessary for a 3E (Effective, Efficient and Effectual) RMP have been identified and described. These factors must characterize the RMP of the island of Ischia – and, in general, of any volcanic island – in order to be able to manage the occurrence of an emergency in the best possible way.
Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis
Authors: Tabata Junya , Nakaoku Takashi , Araki Mitsugu , Yoshino Ryunosuke , Kohsaka Shinji , Otsuka Ayaka , Ikegami Masachika , Ui Ayako , Kanno Shin-ichiro , Miyoshi Keiko , Matsumoto Shigeyuki , Sagae Yukari , Yasui Akira , Sekijima Masakazu , Mano Hiroyuki , Okuno Yasushi , Okamoto Aikou , Kohno Takashi 
Published: September 2022

Abstract

Distinguishing oncogenic mutations from variants of unknown significance (VUS) is critical for precision cancer medicine. Here, computational modeling of 71,756 RET variants for positive selection together with functional assays of 110 representative variants identified a three-dimensional cluster of VUSs carried by multiple human cancers that cause amino acid substitutions in the calmodulin-like motif (CaLM) of RET. Molecular dynamics simulations indicated that CaLM mutations decrease interactions between Ca2+ and its surrounding residues and induce conformational distortion of the RET cysteine-rich domain containing the CaLM. RET-CaLM mutations caused ligand-independent constitutive activation of RET kinase by homodimerization mediated by illegitimate disulfide bond formation. RET-CaLM mutants possessed oncogenic and tumorigenic activities that could be suppressed by tyrosine kinase inhibitors targeting RET. This study identifies calcium-binding ablating mutations as a novel type of oncogenic mutation of RET and indicates that in silico–driven annotation of VUSs of druggable oncogenes is a promising strategy to identify targetable driver mutations.

Significance:
Comprehensive proteogenomic and in silico analyses of a vast number of VUSs identify a novel set of oncogenic and druggable mutations in the well-characterized RET oncogene.
Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial
Authors: Albanell Joan , Pérez-García José Manuel , Gil-Gil Miguel , Curigliano Giuseppe , Ruíz-Borrego Manuel , Comerma Laura , Gibert Joan , Bellet Meritxell , Bermejo Begoña , Calvo Lourdes , de la Haba Juan , Espinosa Enrique , Minisini Alessandro Marco , Quiroga Vanesa , Santaballa Bertran Ana , Mina Leonardo , Bellosillo Beatriz , Rojo Federico , Menéndez Silvia , Sampayo-Cordero Miguel , Popa Crina , Malfettone Andrea , Cortés Javier , Llombart-Cussac Antonio 
Published: September 2022

Abstract

Purpose:
To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC).

Patients and Methods:
The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis.

Results:
Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6–53.2; P &lt; 0.001] and 13.0% of tumors (95% CI, 5.2–27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71–282.9; P = 0.018).

Conclusions:
Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials.
Mass Cytometry Reveals Classical Monocytes, NK Cells, and ICOS+ CD4+ T Cells Associated with Pembrolizumab Efficacy in Patients with Lung Cancer
Authors: Rochigneux Philippe , Lisberg Aaron , Garcia Alejandro , Granjeaud Samuel , Madroszyk Anne , Fattori Stéphane , Gonçalves Anthony , Devillier Raynier , Maby Pauline , Salem Nassim , Gorvel Laurent , Chanez Brice , Gukasyan Jaklin , Carroll James , Goldman Jonathan , Chretien Anne Sophie , Olive Daniel , Garon Edward B. 
Published: September 2022

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of non–small cell lung cancer (NSCLC), but predictive biomarkers of their efficacy are imperfect. The primary objective is to evaluate circulating immune predictors of pembrolizumab efficacy in patients with advanced NSCLC.

Experimental Design:
We used high-dimensional mass cytometry (CyTOF) in baseline blood samples of patients with advanced NSCLC treated with pembrolizumab. CyTOF data were analyzed by machine-learning algorithms (Citrus, tSNE) and confirmed by manual gating followed by principal component analysis (between-group analysis).

Results:
We analyzed 27 patients from the seminal KEYNOTE-001 study (median follow-up of 60.6 months). We demonstrate that blood baseline frequencies of classical monocytes, natural killer (NK) cells, and ICOS+ CD4+ T cells are significantly associated with improved objective response rates, progression-free survival, and overall survival (OS). In addition, we report that a baseline immune peripheral score combining these three populations strongly predicts pembrolizumab efficacy (OS: HR = 0.25; 95% confidence interval = 0.12–0.51; P &lt; 0.0001).

Conclusions:
As this immune monitoring is easy in routine practice, we anticipate our findings may improve prediction of ICI benefit in patients with advanced NSCLC.
JAZF1: A Metabolic Regulator of Sensitivity to a Polyamine-Targeted Therapy
Authors: Rosario Spencer R. , Jacobi Justine J. , Long Mark D. , Affronti Hayley C. , Rowsam Aryn M. , Smiraglia Dominic J. 
Published: September 2022

Abstract

Identifying and leveraging unique points of metabolic dysregulation in different disease settings is vital for safe and effective incorporation of metabolism-targeted therapies in the clinic. In addition, it has been shown identification of master metabolic transcriptional regulators (MMTR) of individual metabolic pathways, and how they relate to the disease in question, may offer the key to understanding therapeutic response. In prostate cancer, we have previously demonstrated polyamine biosynthesis and the methionine cycle were targetable metabolic vulnerabilities. However, the MMTRs of these pathways, and how they affect treatment, have yet to be explored. We sought to characterize differential sensitivity of prostate cancer to polyamine- and methionine-targeted therapies by identifying novel MMTRs. We began by developing a gene signature from patient samples, which can predict response to metabolic therapy, and further uncovered a MMTR, JAZF1. We characterized the effects of JAZF1 overexpression on prostate cancer cells, basally and in the context of treatment, by assessing mRNA levels, proliferation, colony formation capability, and key metabolic processes. Lastly, we confirmed the relevance of our findings in large publicly available cohorts of prostate cancer patient samples. We demonstrated differential sensitivity to polyamine and methionine therapies and identified JAZF1 as a MMTR of this response.

Implications:
We have shown JAZF1 can alter sensitivity of cells and its expression can segregate patient populations into those that do, or do not highly express polyamine genes, leading to better prediction of response to a polyamine targeting therapy.
Why Do Some Post-Tropical Cyclones Impact Europe?
Authors: Sainsbury Elliott M. , Schiemann Reinhard K. H. , Hodges Kevin I. , Baker Alexander J. , Shaffrey Len C. , Bhatia Kieran T. 
Published: September 2022

Abstract
Post-tropical cyclones (PTCs) can bring high winds and extreme precipitation to Europe. Although the structure and intensity of observed Europe-impacting PTCs has been investigated in previous studies, a quantitative understanding of the factors important for PTCs to reach Europe has not been established. By tracking and identifying the full life cycle of tropical cyclones (TCs) in the ERA5 reanalysis, we investigate why some PTCs impact Europe and why others do not, using a composite analysis. We show that PTCs that impact Europe are typically ∼4–6 m s−1 stronger at their lifetime maximum intensity and throughout the extratropical transition process. They are also twice as likely to reintensify in the midlatitudes. During ET, the Europe-impacting PTCs interact more strongly with an upstream upper-level trough in a significantly more baroclinic environment. The Europe-impacting PTCs are steered on a more poleward trajectory across a midlatitude jet streak. It is during the crossing of the jet that these cyclones often undergo their reintensification. Using contingency table analysis, TC lifetime maximum intensity, and whether post-ET reintensification occurs are shown to be significantly associated with the odds that a PTC reaches Europe. This supports our composite analysis and further indicates that TC intensity and reintensification both modulate the likelihood that a PTC will impact Europe.

Significance Statement
Some post-tropical cyclones (PTCs) reach Europe, often associated with extreme precipitation and high winds. It is currently unclear what factors allow this to occur. In this study, we track cyclones in two reanalyses using a feature tracking scheme and identify the PTCs by matching (in space and time) reanalysis tracks with observed tracks. Using a composite analysis, we show that 1) tropical cyclones (TCs) that are more intense, and 2) TCs that reintensify after extratropical transition, are more likely to reach Europe. TCs that reintensify interact strongly with an upper-level upstream trough and cross a midlatitude jet streak. Reintensification occurs as the cyclones cross this jet streak.
Patient Safety/Quality Improvement Primer, Part IV: Psychological Safety—Drivers to Outcomes and Well‐being
Authors: Jamal Nausheen , Young VyVy N. , Shapiro Jo , Brenner Michael J. , Schmalbach Cecelia E. 
Published: September 2022

AbstractPsychological safety is the concept that an individual feels comfortable asking questions, voicing ideas or concerns, and taking risks without undue fear of humiliation or criticism. In health care, psychological safety is associated with improved patient safety outcomes, increased clinician engagement, and greater creativity. A culture of psychological safety is imperative for physician well‐being and satisfaction, which in turn directly affect delivery of care. For health care professionals, psychological safety creates an environment conducive to trust and openness, enabling the team to focus on high‐quality care. In contrast, unprofessional behavior reduces psychological safety and threatens the culture of the organization. This patient safety/quality improvement primer considers the barriers and facilitators to psychological safety in health care; outlines principles for creating a psychologically safe environment; and presents strategies for managing conflict, microaggressions, and lapses in professionalism. Individuals and organizations share the responsibility of promoting psychological safety through proactive policies, conflict management, interventions for microaggressions, and cultivation of emotional intelligence.
Assessment and Correlation of Dactyloscopy, Cheiloscopy, and Rugoscopy Among Individuals With Different Skeletal Malocclusion—A Cross-Sectional Study
Authors: Sapasetty Sirisha , Gandikota Chandrasekhar 
Published: September 2022

Background and Objectives A probable association between dermatoglyphics and malocclusions related to skeletal discrepancy may exist as dermal ridges, and craniofacial structures develop from the same embryonic tissues during the same embryonic period. The study aims to assess and correlate the pattern of fingerprints, lip prints, and palatal rugae in individuals with malocclusions related to skeletal discrepancy. Materials and Methods The 180 samples collected in the study were divided into 3 groups based on cephalometric analysis into class I, II, and III malocclusion. The fingerprints, lip prints, and palatal rugae patterns were obtained for each participant and pattern analysis was done. Results Class I malocclusion with no skeletal discrepancy showed a statistically significant difference in the loop fingerprint patterns on all fingers except the first finger on the right and left hand, branched lip pattern, and straight palatal rugae pattern in primary rugae 1 and 4. Class II malocclusion related to skeletal discrepancy showed a statistically significant difference in the loop pattern on all fingers except in the fourth finger of the right hand which showed a whorl pattern, branched lip pattern, and straight palatal rugae pattern in primary rugae 1, 4, and 5. Class III malocclusion related to skeletal discrepancy showed a statistically significant difference in the loop pattern on all fingers except in the fourth finger of the right hand which showed an absence of arch pattern, vertical lip print pattern, and straight palatal rugae pattern in primary rugae 1. Conclusion Dermatoglyphics analysis can be used to indicate developing malocclusions related to skeletal discrepancies. at an early age, thereby aiding the development of treatment aiming to establish favorable occlusion. Prospective and various ethnic and racial-based studies would be valuable for the establishment of dermatoglyphic markers of malocclusion.
Association of Pectus Excavatum With Ventricular Remodelling and Mitral Valve Abnormalities in Marfan Syndrome
Authors: Abdulmonem L Hashem Dalia , Chan Victor Siang Hua , Hanneman Kate , Wald Rachel M. , Thavendiranathan Paaladinesh , Ouzounian Maral , Oechslin Erwin , Karur Gauri R. 
Published: September 2022

Background: Marfan syndrome (MFS) is an inherited connective tissue disorder. Pectus excavatum (PEX) is common in MFS. The purpose was to evaluate the association of PEX with cardiovascular manifestations of MFS, biventricular size and function. Methods: MFS adults undergoing cardiac MRI were retrospectively evaluated. Exclusion criteria were incomplete cardiac MRI, significant artifacts, co-existent ischaemic or congenital heart disease. Haller Index (HI) ≥3.25 classified patients as PEX positive (PEX+) and PEX negative (PEX−). Cardiac MRI analysis included assessment of mitral valve prolapse (MVP), mitral annular disjunction (MAD), biventricular volumetry and aortic dimensions. Results: 212 MFS patients were included, 76 PEX+ and 136 PEX− (HI 8.3 ± 15.2 vs 2.3 ± 0.5, P < .001). PEX+ were younger (33.4 ± 12.0 vs 38.1 ± 14.3 years, P = .02) and similar in sex distribution (55% vs 63% male, P = .26) compared to PEX−. MVP and MAD were more frequent in PEX+ vs PEX− (43/76 [57%] vs 37/136 [27%], P < .001; 44/76 [58%] vs 50/136[37%], P = .003, respectively). PEX+ had higher right ventricular end-diastolic and end-systolic volumes (RVEDVi 92 ± 17mL/m2 vs 84 ± 22mL/m2, P = .04; RVESVi 44 ± 10 mL/m2 vs 39 ± 14 mL/m2, P = .02), lower RV ejection fraction (RVEF 52 ± 5% vs 55 ± 6%, P = .01) compared to PEX−. Left ventricular (LV) volumes, LVEF and aortic dimensions were similar. Conclusion: MFS adults with PEX have higher frequency of cardiac manifestations including MV abnormalities, increased RV volumes and lower RVEF compared to those without PEX. Awareness of this association is important for all radiologists who interpret aortic CT or MRI, where HI can be easily measured. PEX in MFS may suggest more severe disease expression necessitating careful screening for MV abnormalities and outcomes surveillance.
Carlevale intraocular lens opacification after Descemet stripping automated endothelial keratoplasty
Authors: Coco Giulia , Ferrara Mariantonia , Borgia Alfredo , Romano Davide , Romano Vito 
Published: September 2022

Purpose To report a case of sutureless scleral-fixated (SSF) Carlevale intraocular lens (IOL) opacification following Descemet stripping automated endothelial keratoplasty (DSAEK) surgery. Methods An 82-year-old man underwent combined SSF Carlevale IOL implant and DSAEK surgery for aphakic endothelial decompensation. Surgery was uneventful, while the postoperative period was complicated by multiple graft detachments requiring re-bubbling. After four re-bubbling procedures, the corneal graft attached and cleared over time. Results 29 months after combined SSF IOL implant and DSAEK surgery, the patient presented with decreased vision due to IOL opacification affecting the visual axis. Conclusion Although combined SSF IOL and DSAEK surgery is an overall safe and effective procedure for aphakic endothelial decompensation, risk of IOL opacification due to anterior chamber air injection is higher when using hydrophilic IOLs and in cases requiring multiple re-bubbling, therefore, intraocular lens material should be chosen after considering the risks and benefits.