bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mediating Effect of the Perceived Professional Benefit of New Nurses in Cancer Hospitals on the Nursing Work Environment, Psychological Resilience, and Transition Shock: A Cross-Sectional Questionnaire Survey
Authors: Liu Lu , Lv Zhuoheng , Zhou Ye , Liu Man , Liu Yan
Published: August 2023

Aim. The aim of this study was to determine whether the relationship among the nursing work environment, psychological resilience, and transition shock was mediated by nurses’ perceived professional benefits and to explore the associations among these variables. Background. Nurses’ transition shock is an important factor in reducing the nursing staff turnover rate. Thus, clarifying the factors influencing nurses’ transition shock has become a priority. Methods. Cross-sectional research was used in this study. A total of 200 newly graduated Chinese nurses were recruited by convenience sampling in 2022 from three tertiary hospitals in Beijing, Tianjin, and Hebei. Data were collected through questionnaires and included demographic data in addition to the perceived professional benefit scale of nurses, the nursing work environment scale, the brief resilience scale, and the transition shock scale. The data were analysed using SPSS 25.0 and the SPSS PROCESS macro programme, Model 6. Results. The perceived professional benefit of new nurses, the nursing work environment, and psychological resilience directly influenced transition shock (

p
<
0.01

). The perceived professional benefit of new nurses mediated the relationship among the nursing work environment, psychological resilience, and transition shock (

p
<
0.01

). The final model’s mediating influence contributed 21.53% and 6.85% to the total influence. Conclusion. Nursing managers can improve nurses’ perceptions of professional benefits from psychological resilience and the nursing work environment to reduce the impact of transition from school to work for new nurses. Implications for Nursing Management. This study provides a reference for the development of intervention strategies and training programmes to assist new nurses in cancer hospitals in effectively navigating the transition into their careers. In the future, appropriate training methods should be used at the individual cognitive, psychological, and organizational levels to improve the physical and mental health of new nurses and their ability to provide high-quality patient care.
Table S8 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Supplementary Table 8 FGFR mutations
Table S6 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Supplementary Table 6 ROC formulae training and test
Table S5 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Supplementary Table 5 LOBICO data
Figure S2 from T Cell–intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: August 2023

Figure S2 shows Magnetically enriched CD3+ T cells were activated with 0.5 µg/mL αCD3/28 in the presence of TAK-981 or vehicle control for up to 96 h
Table S2 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Supplementary Table 2 pancancer clinical info
Figure S4 from S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: August 2023

Binding profile of the newly created CCR8 antibody
Supplementary Table S4 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: August 2023

Supplementary Table S4 shows the immunogenicity results
Supplementary Table S1 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: August 2023

Supplementary Table S1 shows the treatment-related adverse events
Supplementary Figure S2 from Safety and Tolerability of a Novel Anti-HER2 Antibody–Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham C.F. , Curigliano Giuseppe
Published: August 2023

Supplementary Figure S2 shows the duration of treatment including response and tumor type (the safety analysis set)
Data from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Abstract
As a result of tumor heterogeneity and solid cancers harboring multiple molecular defects, precision medicine platforms in oncology are most effective when both genetic and pharmacologic determinants of a tumor are evaluated. Expandable patient-derived xenograft (PDX) mouse tumor and corresponding PDX culture (PDXC) models recapitulate many of the biological and genetic characteristics of the original patient tumor, allowing for a comprehensive pharmacogenomic analysis. Here, the somatic mutations of 23 matched patient tumor and PDX samples encompassing four cancers were first evaluated using next-generation sequencing (NGS). 19 antitumor agents were evaluated across 78 patient-derived tumor cultures using clinically relevant drug exposures. A binarization threshold sensitivity classification determined in culture (PDXC) was used to identify tumors that best respond to drug in vivo (PDX). Using this sensitivity classification, logic models of DNA mutations were developed for 19 antitumor agents to predict drug response. We determined that the concordance of somatic mutations across patient and corresponding PDX samples increased as variant allele frequency increased. Notable individual PDXC responses to specific drugs, as well as lineage-specific drug responses were identified. Robust responses identified in PDXC were recapitulated in vivo in PDX-bearing mice and logic modeling determined somatic gene mutation(s) defining response to specific antitumor agents. In conclusion, combining NGS of primary patient tumors, high-throughput drug screen using clinically relevant doses, and logic modeling, can provide a platform for understanding response to therapeutic drugs targeting cancer.
Data from S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: August 2023

Abstract
Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating Tregs is, therefore, expected to activate antitumor immunity without affecting immune homeostasis. We previously reported that selective Treg depletion targeted by a C-C motif chemokine receptor 8 (CCR8) resulted in induction of strong antitumor immunity without any obvious autoimmunity in mouse models. Thus, herein, we developed a novel humanized anti-CCR8 monoclonal antibody, S-531011, aimed as a cancer immunotherapy strategy for patients with cancer. S-531011 exclusively recognized human CCR8 among all chemokine receptors and showed potent antibody-dependent cell-mediated cytotoxicity activity toward CCR8+ cells and neutralization activity against CCR8-mediated signaling. We observed that S-531011 reduced tumor-infiltrating CCR8+ Tregs and induced potent antitumor activity in a tumor-bearing human-CCR8 knock-in mouse model. Moreover, combination therapy with S-531011 and anti-mouse programmed cell death 1 (PD-1) antibody strongly suppressed tumor growth compared with anti–PD-1 antibody alone with no observable adverse effects. S-531011 also depleted human tumor-infiltrating Tregs, but not Tregs derived from human peripheral blood mononuclear cells. These results suggest that S-531011 is a promising drug for inducing antitumor immunity without severe side effects in the clinical setting.
Supplementary Table S5 from Association and Prediction Utilizing Craniocaudal and Mediolateral Oblique View Digital Mammography and Long-Term Breast Cancer Risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Supplementary Table S5: Hazards ratio (95% Confidence Interval) for association inure-menopausal women between baseline risk factors and breast cancer risk utilizing MLOL-VPD
Supplementary Table S1 from Association and Prediction Utilizing Craniocaudal and Mediolateral Oblique View Digital Mammography and Long-Term Breast Cancer Risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Supplementary Table S1: Hazards ratio for association between baseline risk factors and breast cancer risk among postmenopausal women using CC-VPD only.
Supplementary Figure S6 from Association and Prediction Utilizing Craniocaudal and Mediolateral Oblique View Digital Mammography and Long-Term Breast Cancer Risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Supplementary Figure S6: The proportional hazards assumption is deemed reasonable by checking the Schoenfeld residuals plot for MLO-VPD.
Supplementary Figure S3 from Association and Prediction Utilizing Craniocaudal and Mediolateral Oblique View Digital Mammography and Long-Term Breast Cancer Risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Supplementary Figure S3: Pearson correlation separated by view and case control status.
Supplementary Figure S1 from Association and Prediction Utilizing Craniocaudal and Mediolateral Oblique View Digital Mammography and Long-Term Breast Cancer Risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Supplementary Figure S1: Cohort recruit and follow up chart.
Supplementary Materials and Methods from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

The details for the assays and image analysis are summarized in the Supplementary Materials and Methods.
Supplementary Figure 6 from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

Supplementary Figure 6. Posttreatment CD163 (by QIF) increase in three patients with concurrent increase in the CD163 transcripts. Representative images from a patient’s tumor tissue sample showing pre and post treatment (Durvalumab-Olaparib Arm) CD163 expression. Nuclei (blue), Cytokeratin (green), CD163 (yellow) and CSF1R (red).
Supplementary Figure 5 from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

Supplementary Figure 5. Map showing the distribution of mutations per gene per tumor. Light and dark purple, green and orange indicate pre- and post-treatment samples for patients treated with cisplatin and olaparib, olaparib and durvalumab and olaparib only, respectively. Blues correspond to samples before and after second biopsy/surgery for patients who did not receive treatment.
Supplementary Figure 2 from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

Supplementary Figure 2. Differentially expressed signatures in Responders relative to no-Responders. Response is based on physical examination, pathology or imaging. Responders had higher scores in Inflammatory Chemokines and Exhausted CD8 Signatures, as well as PD-1, Cytotoxicity and CD45. The significance (p-value, P and adjusted p-value, Padj) is represented relative to Fold Change (FC) in the x-axis.
FIGURE 3 from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

Baseline (up) and after treatment (down) images in Patient A (Cisplatin-Olaparib arm) and B (Olaparib arm), respectively, showing dramatic tumor volumetric decrease. Both patients had SD on imaging based on RECIST. Representative immunofluorescence (IF) images at baseline (up) and after treatment (down), highlighting changes in Ki67 (red), PD-L1 (white), STING (magenta) in tumor. Nuclei (blue) and cytokeratin (green) are also shown. A posttreatment decrease in Ki-67 (measured by QIF) was noticed in both patients.
FIGURE 2 from Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer
Authors: Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios , Kyrodimos Efthymios , Delides Alexander , Giotakis Evangelos , Papadimitriou Nikolaos G. , Panayiotides Ioannis G. , Perisanidis Christos , Fernandez Aileen I. , Xirou Vasiliki , Poulios Christos , Gagari Eleni , Yaghoobi Vesal , Gavrielatou Niki , Shafi Saba , Aung Thazin Nwe , Kougioumtzopoulou Andromachi , Kouloulias Vassilis , Palialexis Konstantinos , Gkolfinopoulos Stavros , Strati Areti , Lianidou Evi , Fountzilas George , Rimm David L. , Foukas Periklis G. , Psyrri Amanda
Published: August 2023

A, Waterfall plot of Ki67 change (measured by QIF) compared with pretreatment values. B, Comparison of Ki67 distribution assessed by QIF pretreatment and posttreatment/second biopsy or surgery within study groups. Wilcoxon matched pairs signed-rank P values were calculated for each treatment group; Cisplatin-Olaparib (C-O), P = 0.266; Olaparib (O), P = 0.004; Control, P = 0.875; Durvalumab-Olaparib (D-O), P = 0.461.
False-Negative Testing for FIP1L1::PDGFRA by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay
Authors: Pongdee Thanai , Berry Alexis , Wetzler Lauren , Sun Xiaoping , Thumm Lauren , Yoon Pryscilla , Kuang Fei Li , Makiya Michelle , Constantine Gregory , Khoury Paneez , Rheinbay Esther , Lane Andrew A , Maric Irina , Klion Amy D.
Published: August 2023

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.
Integrative Role of the SALL4 Gene: From Thalidomide Embryopathy to Genetic Defects of the Upper Limb, Internal Organs, Cerebral Midline, and Pituitary
Authors: Kodytková Aneta , Dušátková Petra , Amaratunga Shenali Anne , Plachý Lukáš , Průhová Štěpánka , Lebl Jan
Published: August 2023

Background: The thalidomide disaster resulted in tremendous congenital malformations in more than 10,000 children in the late 1950s and early 1960s. Summary: Although numerous putative mechanisms were proposed to explain thalidomide teratogenicity, it was confirmed only recently that thalidomide, rather its derivative 5-hydroxythalidomide (5HT) in a complex with the cereblon protein, interferes with early embryonic transcriptional regulation. 5HT induces selective degradation of SALL4, a principal transcriptional factor of early embryogenesis. Genetic syndromes caused by pathogenic variants of the SALL4 gene phenocopy thalidomide embryopathy with congenital malformations ranging from phocomelia, reduced radial ray, to defects of the heart, kidneys, ear, eye, and possibly cerebral midline and pituitary. SALL4 interacts with TBX5 and a handful of other transcriptional regulators and downregulates the Sonic hedgehog signaling pathway. Cranial midline defects, microcephaly, and short stature due to growth hormone deficiency have been occasionally reported in children carrying SALL4 pathogenic variants associated with generalized stunting of growth rather than just the loss of height attributable to the shortening of leg bones in many children with thalidomide embryopathy. Key Messages: Thus, SALL4 joins the candidate gene list for monogenic syndromic pituitary insufficiency. In this review, we summarize the journey from the thalidomide disaster through the functions of the SALL4 gene to its link to the hormonal regulation of growth.
Underlying Dentin Shadows (ICDAS 4) in Occlusal Surface of Permanent Teeth Have Low Progression Rate after 1–2 Years
Authors: Marquezan Patricia Kolling , Alves Luana Severo , Comim Letícia Donato , Zenkner Julio Eduardo do Amaral
Published: August 2023

The aim of this prospective cohort study was to assess the radiographic progression of underlying dentin shadows (UDS) on the occlusal surfaces of permanent posterior teeth of adolescents and young adults over 1–2 years and to identify possible risk factors. A total of 149 UDS lesions (from 101 individuals) were included at baseline. Each participant had to present at least one UDS to be considered eligible for the study. Data collection included the application of a questionnaire, clinical examination, and bilateral bitewing radiographs, performed at baseline and after 1–2 years. The association between possible predictors and UDS progression (defined radiographically as an increase in the radiographic score from baseline to follow-up) was assessed using Weibull regression models. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated. A total of 81 individuals (mean age: 24.0, standard deviation: 8.03) were reexamined after 1–2 years (742 occlusal surfaces, of which 118 were UDS). The overall progression rate was 8.6% after 1–2 years, being 12.6% for UDS without baseline radiolucency and 20% for UDS with baseline radiolucency. The risk analysis showed that UDS without radiolucency at baseline had a similar likelihood of progression (adjusted HR = 1.71, 95% CI = 0.68–4.32, p = 0.26) while UDS with radiolucency at baseline were more likely to progress (adjusted HR = 2.96, 95% CI = 1.06–8.26, p = 0.04) than the reference category (sound occlusal surfaces without radiolucency). These estimates were adjusted for caries prevalence, tooth type, and arch. This study showed low progression rates of UDS after 1–2 years. The presence of radiolucency at baseline was found to predict UDS progression.
Patienten-Arzt-Interaktion: Effektive Gesprächsführung bei fortgeschrittenen Krebserkrankungen
Authors: Witt Claudia M.
Published: August 2023

Importance: There are few robust evaluations of disease-specific question prompt sheets (QPS) in patient-physician communication among patients with advanced cancer. Objective: To compare the patient perception of helpfulness, global evaluation, and preference for the QPS vs a general information sheet (GIS), and to examine the effect of the QPS on participants' anxiety, participants' speaking time, number of questions asked, and length of the clinical encounter. Design, setting, and participants: This controlled, double-blind randomized clinical trial was conducted at an outpatient palliative and supportive care clinic in a cancer center in the US. Eligible patients were 18 years or older, had a cancer diagnosis, and were undergoing their first outpatient consultation visit with a palliative care physician from September 1, 2017, to May 31, 2019. Data analysis used a modified intention-to-treat design. Data were analyzed from May 18 to June 27, 2022. Intervention: QPS, a 25-item list of questions developed by expert palliative care clinicians using a Delphi process and tested among ambulatory advanced cancer patients. The control was GIS, generic information material given routinely to patients seen at the supportive care clinic. Main outcomes and measures: The main outcome was patient perception of helpfulness. Secondary outcomes included global evaluation and preference of QPS compared with GIS immediately after the encounter. Results: A total of 130 patients (mean [SD] age, 58.6 [13.3] years; 79 [60.8%] female) were randomized to receive either QPS (67 patients [51.5%]) or GIS (63 patients [48.5%]). Patients considered QPS and GIS equally helpful, with no statistically significant difference (mean [SD] helpfulness score, 7.2 [2.3] points vs 7.1 [2.7] points; P = .79). The QPS group, compared with the GIS group, had a higher global positive view of the material (mean [SD] global perception score, 7.1 [1.3] vs 6.5 [1.7]; P = .03) and felt it prompted them more to generate new questions (mean [SD] rating, 7.0 [2.9] vs 5.3 [3.5]; P = .005). Of 47 patients asked their preference between the items, more participants preferred the QPS to the GIS in communicating with their physicians (24 patients [51.1%] vs 7 patients [14.9%]; P = .01) at the 4-week follow-up. No significant differences between the QPS and GIS groups were observed regarding participant anxiety, speaking time, number of questions asked, or consultation length (eg, mean [SD] anxiety rating, 2.3 [3.7] vs 1.6 [2.7]; P = .19). Conclusions and relevance: In this randomized clinical trial, participants perceived both QPS and GIS as equally helpful, but they had a more positive global view of and preferred the QPS. QPS facilitated generation of new questions without increasing patient anxiety nor prolonging the consultation. The findings provide support for increased adoption and integration of QPS into routine oncologic care. Trial registration: ClinicalTrials.gov Identifier: NCT03287492.
Ovarialkarzinom: Antikörper-Wirkstoff-Konjugat übertrifft bisherige Ansprechraten beim platinresistenten Ovarialkarzinom
Authors: Pölcher Martin
Published: August 2023

Purpose: Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC. Methods: SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point. Results: One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively. Conclusion: MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.
Prostatakarzinom: Wie eine gezielte Strahlentherapie bei biochemischem Rezidiv das Leben nach der Operation beeinflusst
Authors: Bahlburg Henning
Published: August 2023

Objective: Radical prostatectomy reduces mortality among patients with localized prostate cancer, however up to 35% of patients will experience biochemical recurrence, often treated with salvage radiotherapy. The objective of the study was to investigate long-term effects of salvage radiotherapy. Methods: A prospective, controlled, non-randomized trial at 14 Swedish center's including 4,003 patients scheduled for radical prostatectomy 2008-2011. A target trial emulation approach was used to identify eligible patients that was treated with salvage radiotherapy. The control group received no salvage radiotherapy. Outcomes were assessed by patient questionnaires on ordinal scales and statistical group comparisons were made using ordered logit regression with adjustment for baseline outcome and confounding factors. The primary endpoints were bowel, urinary and sexual function and bothering due to dysfunction at 8 years. Results: Eleven percent (330/3,139) of the analyzed study population received salvage radiotherapy. Fecal leakage, leakage of mucus and hematochezia were more common after receiving salvage radiotherapy compared with the control group; 4.5% versus 2.6% odds ratio (95% confidence interval [CI]): (1.90 [1.38; 2.62]), 6.8% versus 1.5% 4.14 (2.98; 5.76) and 8.6% versus 1.2% 4.14 (2.98; 5.76), respectively. Urinary incontinence, erectile dysfunction and hematuria were more common after receiving salvage radiotherapy, 34% versus 23% 2.23 (2.65; 3.00), 65% versus 57% 1.65 (1.18; 2.29) and 16% versus 1.6% 11.17 (5.68; 21.99), respectively. Conclusion: Salvage radiotherapy was associated with increased risk for fecal leakage, hematochezia, urinary incontinence and hematuria. Our results emphasize the importance of selecting patients for salvage radiotherapy to avoid overtreatment and to give high quality pre-treatment information to ensure patients' preparedness for late side-effects.Copyright (c) 2023 Stefan Carlsson, David Bock, Anna Lantz, Eva Angenete, Katarina Koss Modig, Jonas Hugosson, Anders Bjartell, Gunnar Steineck, Peter Wiklund, Eva Haglind
As palavras do opositor político: o ‘discurso representado’ como expressão da opinião
Authors: Domínguez Patrícia
Published: August 2023

Este trabalho tem como objetivo analisar como o locutor político recorre à citação de palavras do opositor para transmitir a própria ideologia. Para tal, o locutor manifesta a sua subjetividade através de vários recursos linguísticos. O nosso quadro teórico apoia-se em conceitos enunciativos como “discurso representado” (Rabatel, 2003) e “Ponto De Vista” (Rabatel, 1998). Os aspectos ideológicos são abordados de acordo com a proposta sociolinguística de Thompson (1990) sobre os modos de operação da ideologia. A metodologia centra-se na análise linguística de excertos retirados de três discursos políticos proferidos na ONU. Assim, o objetivo do estudo é caracterizar a inscrição linguística da subjetividade presente na amostra. Com base nos resultados, demonstramos como a citação permite ao locutor introduzir dois pontos de vista contraditórios, assumindo um certo grau de responsabilidade perante as palavras convocadas através de “verbos de processo mental” (Rabatel, 2003), que veiculam opiniões e emoções.
O gênero memorial em contexto acadêmico: memoriais de formação e memoriais acadêmicos em comparação
Authors: Netto Mônica Inês de Castro , Silva Fátima
Published: August 2023

O principal objetivo deste trabalho é fazer uma análise de memoriais produzidos em contexto acadêmico em função de três variáveis: condições de produção, plano de texto e marcadores discursivos. O corpus é constituído por 30 memoriais, sendo 15 de estudantes de dois cursos de especialização e 15 de candidatos a concursos para entrada na carreira docente em variadas áreas do conhecimento. A metodologia de análise é mista e apresenta as seguintes etapas: a) análise das condições de produção; b) análise do plano de texto de cada um dos tipos de memoriais; c) análise dos marcadores discursivos mais frequentes em cada um dos tipos de memoriais; d) comparação dos dois grupos de memoriais em relação às variáveis em análise; e) discussão dos resultados. Os resultados evidenciam diferenças ao nível do plano textual e da conexão marcada através do uso de marcadores discursivos nos dois grupos de memoriais.
“O homem tem a razão ou a razão tem o homem?”: A relação entre o saber mediato (entendimento) e o saber imediato (crença) na filosofia de F. H. Jacobi
Authors: Martone Juliana Ferraci
Published: August 2023

O intuito deste texto é mostrar a diferença entre duas concepções de razão para F. H. Jacobi. Por um lado, a razão especulativa, mediata como sinônimo de entendimento, por outro uma razão imediata e reveladora como sinônimo de crença. As duas faculdades exprimem dois lados opostos, mas indissociáveis do homem: sensível e suprassensível, condicionado e incondicionado. Jacobi procura mostrar como é impossível um saber intelectual do suprassensível (uma filosofia natural do suprassensível), buscado sobretudo pelas filosofias que se pretendem sistemáticas, aqui representadas pelo monismo (filosofias de um único princípio). Jacobi, ao contrário, mostrará que de fato há um saber do suprassensível, mas este não passa pelo entendimento.
Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation
Authors: Dobner Stephan , Pilgrim Thomas , Hagemeyer Daniel , Heg Dik , Lanz Jonas , Reusser Nicole , Gräni Christoph , Afshar‐Oromieh Ali , Rominger Axel , Langhammer Bettina , Reineke David , Windecker Stephan , Stortecky Stefan
Published: August 2023

Background

The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR‐CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR‐CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR‐CM undergoing transcatheter aortic valve implantation.

Methods and Results

Prospective screening for ATTR‐CM with Technetium
99
‐3,3‐diphosphono‐1,2‐propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium
99
‐3,3‐diphosphono‐1,2‐propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR‐CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5;
P
=0.001), male sex (82.4% versus 57.7%;
P
=0.005), and prior carpal tunnel surgery (17.6% versus 4.3%;
P
=0.007) were associated with coexisting ATTR‐CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%;
P
<0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8;
P
<0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m
2
;
P
<0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6;
P
<0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5;
P
=0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04–12.53]; stroke: HR, 0.46 [95% CI, 0.03–7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69–3.43]) and 1‐year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37–2.96]; stroke: HR, 0.34 [95% CI, 0.02–5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67–3.34]) were similar between groups.

Conclusions

Coexisting ATTR‐CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri‐interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation.

REGISTRATION

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT04061213.
Profiling Daily Life Performance Recovery in the Early Subacute Phase After Stroke Using a Graphical Modeling Approach
Authors: Veerbeek Janne M. , Hutter Clemens , Ottiger Beatrice , Micheletti Soel , Riedi Simone , Bianchi Enrico , Maaijwee Noortje , Vanbellingen Tim , Nyffeler Thomas
Published: August 2023

Background

Laboratory‐based assessments have shown that stroke recovery is heterogeneous between patients and affected domains such as motor and language function. However, laboratory‐based assessments are not ecologically valid and do not necessarily reflect patients' daily life performance. Therefore, we aimed to give an innovative view on stroke recovery by profiling daily life performance recovery across domains in patients with early subacute stroke and determine their interrelatedness, taking stroke localization into account.

Methods and Results

Daily life performance was observed at neurorehabilitation admission and weekly thereafter until discharge, using a scale containing 7 daily life domains. Graphical modeling was applied to investigate the conditional independence between recovery of these domains depending on stroke localization. There were 592 patients analyzed. Four clusters of interrelated domains were identified within the first 6 weeks poststroke. The first cluster included recovery in learning and applying knowledge, general tasks and demands, and domestic life. The second cluster comprised recovery in self‐care and general tasks and demands. The third cluster included recovery in mobility and self‐care; it incorporated interpersonal interactions and relationships in left supratentorial stroke, and learning and applying knowledge in right supratentorial stroke. The final cluster included only communication recovery.

Conclusions

Daily life recovery dynamics early poststroke show that although impairments in body functions are anatomically determined, their impact on performance is comparable. Second, some, but by no means all, domains show an interrelated recovery. Domains requiring cognitive abilities are especially interrelated and seem to be essential for concomitant recovery in mobility and domestic life.
Association Between Prekallikrein and Stroke: A Mendelian Randomization Study
Authors: Wang Yinan , Jia Yiming , Xu Qingyun , Yang Pinni , Sun Lulu , Liu Yi , Chang Xinyue , He Yu , Shi Mengyao , Guo Daoxia , Zhang Yonghong , Zhu Zhengbao
Published: August 2023

Background

High plasma prekallikrein was reported to be associated with increased risks of stroke, but the causality for these associations remains unclear. We aimed to investigate the associations of genetically predicted plasma prekallikrein concentrations with all‐cause stroke, ischemic stroke, 3 ischemic stroke subtypes, and intracerebral hemorrhage (ICH) using a 2‐sample Mendelian randomization approach.

Methods and Results

Seven independent prekallikrein‐related single‐nucleotide polymorphisms were identified as genetic instruments for prekallikrein based on a genome‐wide association study with 1000 European individuals. The summary statistics for all‐cause stroke, ischemic stroke, and ischemic stroke subtypes were obtained from the Multiancestry Genome‐wide Association Study of Stroke Consortium with 40 585 cases and 406 111 controls of European ancestry. The summary statistics for ICH were obtained from the ISGC (International Stroke Genetics Consortium) with 1545 ICH cases and 1481 controls of European ancestry. In the main analysis, the inverse‐variance weighted method was applied to estimate the associations of plasma prekallikrein concentrations with all‐cause stroke, ischemic stroke, ischemic stroke subtypes, and ICH. Genetically predicted high plasma prekallikrein levels were significantly associated with elevated risks of all‐cause stroke (odds ratio [OR] per SD increase, 1.04 [95% CI, 1.02–1.06];
P
=5.44×10
−5
), ischemic stroke (OR per SD increase, 1.05 [95% CI, 1.03–1.07];
P
=1.42×10
−5
), cardioembolic stroke (OR per SD increase, 1.08 [95% CI, 1.03–1.12];
P
=3.75×10
−4
), and small vessel stroke (OR per SD increase, 1.11 [95% CI, 1.06–1.17];
P
=3.02×10
−5
). However, no significant associations were observed for genetically predicted prekallikrein concentrations with large artery stroke and ICH.

Conclusions

This Mendelian randomization study found that genetically predicted high plasma prekallikrein concentrations were associated with increased risks of all‐cause stroke, ischemic stroke, cardioembolic stroke, and small vessel stroke, indicating that prekallikrein might have a critical role in the development of stroke.
Real‐World Evidence on Disparities on the Initiation of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome
Authors: Yildirim Mustafa , Mueller‐Hennessen Matthias , Milles Barbara Ruth , Biener Moritz , Hund Hauke , Frey Norbert , Giannitsis Evangelos , Salbach Christian
Published: August 2023

Background

Management of patients with non–ST‐segment–elevation acute coronary syndrome (NSTE‐ACS) is based on 2020 European Society of Cardiology guidelines, which recommend the preferential use of prasugrel over ticagrelor. Because the selection of the respective P
2
Y
12
inhibitor has to consider label restrictions, we sought to evaluate the proportion of patients qualifying for either ticagrelor or prasugrel and reasons for noneligibility in an unselected cohort of patients with acute coronary syndrome.

Methods and Results

In this retrospective observational study, patients with ST‐segment–elevation myocardial infarction (STEMI) or NSTE‐ACS presenting consecutively during a 24‐month period were enrolled. The eligibility of patients for a dual antiplatelet therapy option was assessed retrospectively. A total of 1502 patients had confirmed acute coronary syndrome (287 STEMI and 1215 NSTE‐ACS). Eligibility for ticagrelor and full‐dose prasugrel differed significantly for STEMI and NSTE‐ACS (93% versus 51%,
P
<0.0001 versus 80% versus 31%,
P
<0.0001). Eligibility remained significantly lower (STEMI 78% versus NSTE‐ACS 52%) if low‐dose prasugrel was considered. Patients eligible for full‐dose prasugrel had lower ischemic risk per GRACE (Global Registry of Acute Coronary Events) score (109 points [90–129 points] versus 121 points [98–146 points],
P
<0.0001) and lower bleeding risk (14 points [13–15 points] versus 20 points [12–29 points],
P
<0.0001) per PRECISE‐DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score.

Conclusions

In real life, eligibility for prasugrel in patients requiring dual antiplatelet therapy is considerably lower than for ticagrelor, even in a cohort with high rates of coronary angiography and percutaneous coronary interventions. The recommended use of prasugrel over ticagrelor in current acute coronary syndrome guidelines contrasts with our observations of a substantial disparity on the eligibility. This important aspect has not received appropriate attention yet.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05774431.
Toward stability of dynamic FC estimates in neuroimaging and electrophysiology: Solutions and limits
Authors: Alonso Sonsoles , Vidaurre Diego
Published: August 2023

Time-varying functional connectivity (FC) methods are used to map the spatiotemporal organization of brain activity. However, their estimation can be unstable, in the sense that different runs of the inference may yield different solutions. But to draw meaningful relations to behavior, estimates must be robust and reproducible. Here, we propose two solutions using the hidden Markov model (HMM) as a descriptive model of time-varying FC. The first, best ranked HMM, involves running the inference multiple times and selecting the best model based on a quantitative measure combining fitness and model complexity. The second, hierarchical-clustered HMM, generates stable cluster state time series by applying hierarchical clustering to the state time series obtained from multiple runs. Experimental results on fMRI and magnetoencephalography data demonstrate that these approaches substantially improve the stability of time-varying FC estimations. Overall, hierarchical-clustered HMM is preferred when the inference variability is high, while the best ranked HMM performs better otherwise.