bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S2 from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J.
Published: May 2023

Kaplan Meier plots depict the association between PSMA+ CTC enumeration and OS and PFS. The associations of PSMA+ CTC enumeration with overall survival (OS) and progression-free survival (PFS) were explored using the proportional hazard model. A) The median OS in months for CTC=0 (reference), CTC+ PSMA-CTC, CTC+ PSMA+CTC but heterogeneous (<100%), and CTC+ PSMA+ 100% (homogeneous), respectively, were 25.7 (95% CI=19.8-NR), 24.5 (95% CI=16.7-30.4),15.6 (95% CI=14.4-20.7), and 35.0 (95% CI=16.9-NA). Univariate hazard ratio (HR) was 1.3 (95% CI=0.7-2.6), 2.0 (95% CI=1.0-3.8) and 0.7; 95% CI = 0.2-2.1 for CTC+, PSMA-CTC, CTC+ PSMA CTC+ but heterogeneous (<100%), and CTC+ PSMA+ 100% (homogeneous) vs. CTC=0, respectively. B) The median PFS for CTC=0 (reference), CTC+, PSMA-CTC, CTC+ PSMA+ CTC but heterogeneous (<100%), and CTC+ PSMA+ 100%, respectively, were 7.6 (95% CI=6.7-16.5), 6.0 (95% CI=3.5-11.4),5.5 (95% CI=3.6-7.6), and 5.7 (95% CI=3.0-NA). Univariate HR was 1.4 (95% CI=0.8-2.6), 2.0 (95% CI=1.1-3.6) and 1.5; 95% CI = 0.7-3.6 for CTC+, PSMA-CTC, CTC+ PSMA+ CTC but heterogeneous (<100%), and CTC+ PSMA+ 100% (homogeneous) vs. CTC=0, respectively.
Supplementary Methods S1 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: May 2023

Correlative studies’ methodology
Supplementary Tables S1-S11 from Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma
Authors: Westin Jason R. , Locke Frederick L. , Dickinson Michael , Ghobadi Armin , Elsawy Mahmoud , van Meerten Tom , Miklos David B. , Ulrickson Matthew L. , Perales Miguel-Angel , Farooq Umar , Wannesson Luciano , Leslie Lori , Kersten Marie José , Jacobson Caron A. , Pagel John M. , Wulf Gerald , Johnston Patrick , Rapoport Aaron P. , Du Linqiu , Vardhanabhuti Saran , Filosto Simone , Shah Jina , Snider Julia T. , Cheng Paul , To Christina , Oluwole Olalekan O. , Sureda Anna
Published: May 2023

Tabulated data supporting ZUMA-7 elderly analysisSupplementary Table S1. Patient-reported outcomes instrumentsSupplementary Table S2. Axi-cel delivery and administration timeSupplementary Table S3. Summary of efficacy and safety outcomes in patients ≥65 years versus all patients in ZUMA-7Supplementary Table S4. Serious adverse events in at least 3 patients in patients ≥65 yearsSupplementary Table S5. Summary of cytopenias present on or after 90 days from initiation of definitive therapy on protocol in patients ≥65 yearsSupplementary Table S6. Deaths in axi-cel and SOC arms for patients ≥65 years (safety analysis set)Supplementary Table S7. Summary of serum analytes in patients <65 years versus ≥65 years in the axi-cel arm (N = 170)Supplementary Table S8. Most common adverse events, cytokine release syndrome, and neurologic events in patients ≥70 yearsSupplementary Table S9. Deaths in axi-cel and SOC arms for patients ≥70 years Supplementary Table S10. Baseline characteristics for quality-of-life analysis in patients ≥65 yearsSupplementary Table S11. Mixed model with repeated measures estimated difference in change from baseline forprespecified patient-reported outcomes measures (quality-of-life analysis set) in patients ≥65 years
Supplementary Figure S5 from Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma
Authors: Westin Jason R. , Locke Frederick L. , Dickinson Michael , Ghobadi Armin , Elsawy Mahmoud , van Meerten Tom , Miklos David B. , Ulrickson Matthew L. , Perales Miguel-Angel , Farooq Umar , Wannesson Luciano , Leslie Lori , Kersten Marie José , Jacobson Caron A. , Pagel John M. , Wulf Gerald , Johnston Patrick , Rapoport Aaron P. , Du Linqiu , Vardhanabhuti Saran , Filosto Simone , Shah Jina , Snider Julia T. , Cheng Paul , To Christina , Oluwole Olalekan O. , Sureda Anna
Published: May 2023

CAR T-cell levels in patients ≥65 years
Supplementary Figure S3 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: May 2023

Supplementary Figure 3: Comparison of outcomes between patients treated with prior chemotherapy vs. not A) Progression-free survival and B) Overall survival comparison
Supplementary Figure S1 from Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma
Authors: Westin Jason R. , Locke Frederick L. , Dickinson Michael , Ghobadi Armin , Elsawy Mahmoud , van Meerten Tom , Miklos David B. , Ulrickson Matthew L. , Perales Miguel-Angel , Farooq Umar , Wannesson Luciano , Leslie Lori , Kersten Marie José , Jacobson Caron A. , Pagel John M. , Wulf Gerald , Johnston Patrick , Rapoport Aaron P. , Du Linqiu , Vardhanabhuti Saran , Filosto Simone , Shah Jina , Snider Julia T. , Cheng Paul , To Christina , Oluwole Olalekan O. , Sureda Anna
Published: May 2023

Event-free survival per central review and objective response rate in patients ≥70 years
Supplementary Figure S1 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: May 2023

Study Schema. This is a single-arm, phase II trial combining durvalumab and cetuximab in patients with recurrent/metastatic HNSCC. Patients received the loading dose of cetuximab followed by the addition of durvalumab with weekly cetuximab doses. CT scans were done every eight weeks. Blood draws for correlatives occurred at screening, after the loading dose of cetuximab, and after the first dose of durvalumab and cetuximab combined.Abbreviations: CT, computed tomography; POD, progression of disease
Supplementary Table S1 from Reversal of Lactate and PD-1–mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer
Authors: Chaudagar Kiranj , Hieromnimon Hanna M. , Khurana Rimpi , Labadie Brian , Hirz Taghreed , Mei Shenglin , Hasan Raisa , Shafran Jordan , Kelley Anne , Apostolov Eva , Al-Eryani Ghamdan , Harvey Kate , Rameshbabu Srikrishnan , Loyd Mayme , Bynoe Kaela , Drovetsky Catherine , Solanki Ani , Markiewicz Erica , Zamora Marta , Fan Xiaobing , Schürer Stephan , Swarbrick Alex , Sykes David B. , Patnaik Akash
Published: May 2023

Supplementary Table S1. ADT + PI3Ki + PD-1 antibody leads to TAM activation within TME of PTEN/p53-deficient prostate tumors.
Data from Immunologic Predictors for Clinical Responses during Immune Checkpoint Blockade in Patients with Myelodysplastic Syndromes
Authors: Lee Sung-Eun , Wang Feng , Grefe Maison , Trujillo-Ocampo Abel , Ruiz-Vasquez Wilfredo , Takahashi Koichi , Abbas Hussein A. , Borges Pamella , Antunes Dinler Amaral , Al-Atrash Gheath , Daver Naval , Molldrem Jeffrey J. , Futreal Andrew , Garcia-Manero Guillermo , Im Jin S.
Published: May 2023

AbstractPurpose:
The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).
Experimental Design:
Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.
Results:
Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape.
Conclusions:
Analysis of tumor–immune landscape in MDS during immunotherapy provides clinical response biomarkers.
Data from Quiescent Ovarian Cancer Cells Secrete Follistatin to Induce Chemotherapy Resistance in Surrounding Cells in Response to Chemotherapy
Authors: Cole Alexander J. , Panesso-Gómez Santiago , Shah Jaynish S. , Ebai Tonge , Jiang Qi , Gumusoglu-Acar Ece , Bello Maya G. , Vlad Anda , Modugno Francesmary , Edwards Robert P. , Buckanovich Ronald J.
Published: May 2023

AbstractPurpose:
We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence to increase ovarian cancer chemoresistance. The goal of this work was to better understand the mechanisms of NFATC4-driven ovarian cancer chemoresistance.
Experimental Design:
We used RNA sequencing to identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were used to assess impact of loss of FST function on cell proliferation and chemoresistance. ELISA was used to quantify FST induction in patient samples and in vitro in response to chemotherapy.
Results:
We found that NFATC4 upregulates FST mRNA and protein expression predominantly in quiescent cells and FST is further upregulated following chemotherapy treatment. FST acts in at least a paracrine manner to induce a p-ATF2–dependent quiescent phenotype and chemoresistance in non-quiescent cells. Consistent with this, CRISPR knockout (KO) of FST in ovarian cancer cells or antibody-mediated neutralization of FST sensitizes ovarian cancer cells to chemotherapy treatment. Similarly, CRISPR KO of FST in tumors increased chemotherapy-mediated tumor eradication in an otherwise chemotherapy-resistant tumor model. Suggesting a role for FST in chemoresistance in patients, FST protein in the abdominal fluid of patients with ovarian cancer significantly increases within 24 hours of chemotherapy exposure. FST levels decline to baseline levels in patients no longer receiving chemotherapy with no evidence of disease. Furthermore, elevated FST expression in patient tumors is correlated with poor progression-free, post–progression-free, and overall survival.
Conclusions:
FST is a novel therapeutic target to improve ovarian cancer response to chemotherapy and potentially reduce recurrence rates.
Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer
Authors: Schwartz Gary N. , Kaufman Peter A. , Giridhar Karthik V. , Marotti Jonathan D. , Chamberlin Mary D. , Arrick Bradley A. , Makari-Judson Grace , Goetz Matthew P. , Soucy Shannon M. , Kolling Fred , Demidenko Eugene , Miller Todd W.
Published: May 2023

Purpose:

Strategies to implement estrogen therapy for advanced estrogen receptor–positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17β-estradiol followed by estrogen deprivation can control tumor growth long-term.

Patients and Methods:

Postmenopausal women with advanced ER+/HER2− breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17β-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations.

Results:

Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%–63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%–37.9%). One patient experienced a grade 3 adverse event related to 17β-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17β-estradiol/AI therapy. The only two patients to experience objective responses to initial 17β-estradiol had tumor ESR1 mutations.

Conclusions:

Alternating 17β-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17β-estradiol differs according to ESR1 mutation status.
FIGURE 6 from Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans
Authors: Oh Wonkyung , Kim Alyssa Min Jung , Dhawan Deepika , Kirkham Perry M. , Ostafe Raluca , Franco Jackeline , Aryal Uma K. , Carnahan Robert H. , Patsekin Valery , Robinson J. Paul , Knapp Deborah W. , Lim Seung-Oe
Published: May 2023

Pharmacokinetic analysis of 12C chimeric antibody in laboratory dogs. A, Schematic diagram of ELISA for pharamacokinetic analysis. The concentration of the 12C chimeric antibody was measured in the 2 mg/kg (B) or 5 mg/kg (C) 12C antibody-treated dogs’ serum.
FIGURE 2 from Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans
Authors: Oh Wonkyung , Kim Alyssa Min Jung , Dhawan Deepika , Kirkham Perry M. , Ostafe Raluca , Franco Jackeline , Aryal Uma K. , Carnahan Robert H. , Patsekin Valery , Robinson J. Paul , Knapp Deborah W. , Lim Seung-Oe
Published: May 2023

The high-throughput screening of therapeutic antibodies. A, Schematic diagram of the cPD-L1 antibody binding assay. BT549 cells expressing cPD-L1 were seeded on 96-well or 384-well plates. cPD-L1 antibodies (from hybridomas) and Alexa Fluor 488–conjugated anti-mouse IgG Fc-specific secondary antibody were added, and then green fluorescence signal was measured to quantify the amount of bound PD-L1 antibody by IncuCyte S3. B, A representative result of the cPD-L1 antibody binding assay. Kinetic graphs from each well of a 96-well plate showing quantitative binding of cPD-L1 antibodies on BT549 cells expressing cPD-L1 at 6-hour time intervals. The positive clones are highlighted in red (A2, I6, and I11). C, Representative images (at 18 hours) of cPD-L1 antibody binding. Green fluorescent merged images of cPD-L1–expressing cells are shown. D, Schematic diagram of the cPD-L1/cPD-1 blockade assay. BT549 cells expressing cPD-L1 were seeded on 96-well or 384-well plates. cPD-1-human IgG Fc (hFc) protein, Alexa Fluor 488–conjugated anti-human IgG Fc-specific secondary antibody and/or cPD-L1 antibody were added, and then green fluorescence signal was measured to quantify the amount of bound PD-1 protein by IncuCyte S3. E, A representative result of the cPD-L1/cPD-1 blockade assay. Kinetic graphs from each well of a 96-well plate showing quantitative binding of cPD-1 protein on BT549 cells expressing cPD-L1 at 3-hour intervals after the addition of cPD-L1 antibodies. The positive clones that blocked the interaction of cPD-L1/cPD-1 proteins are highlighted in red (A4 and B8). F, Representative images (at 18 hours) of the cPD-L1/cPD-1 blockade. Green fluorescent merged images of cPD-L1–expressing cells are shown. Note the lack of fluorescence due to the antibody binding to PD-L1 and blocking the interaction with cPD-1.
FIGURE 1 from Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans
Authors: Oh Wonkyung , Kim Alyssa Min Jung , Dhawan Deepika , Kirkham Perry M. , Ostafe Raluca , Franco Jackeline , Aryal Uma K. , Carnahan Robert H. , Patsekin Valery , Robinson J. Paul , Knapp Deborah W. , Lim Seung-Oe
Published: May 2023

Working flow chart for production and validation of the cPD-L1 antibody. A, Immunization of antigen, cPD-L1 protein. B, Establishment of hybridomas (over 2,000 clones). C, Evaluation of the cPD-L1 specific antibody by the live cell–based antibody binding assay. D, Therapeutic antibody selection by cPD-L1/cPD-1 blockade assay. E,In vivo validation of therapeutic efficacy of cPD-L1 antibodies in the caninized PD-L1 mice. F, Production of the cPD-L1 chimeric antibody. G, Validation of the cPD-L1 chimeric antibody. H, Initial safety profile and PK analysis. PK, pharmacokinetic.
Employment Formalization in Indonesia: Role of Parents’ Employment Mobility Toward Children’s Employment Mobility
Authors: Ruslan Kadir , Sukma Weni Lidya
Published: May 2023

This study aims to analyze the impact of parents’ employment status mobility on the children’s employment status mobility. In doing so, we applied a two-stage multinomial logistic regression model. In this research, employment status mobility refers to a mobility status from informal to formal jobs and vice versa. Using data from the Indonesian Family Life Survey (IFLS) for the period 2007 and 2014, the profile of the Indonesian workforce was dominated by stayers. The estimation results of multinomial logistic regression indicate that only fathers’ employment status mobility has a significant effect on the children’s employment status mobility, where fathers who are stayers and experiencing upward mobility will provide greater opportunities for their children to be stayers and fewer opportunities to experience downward mobility. Moreover, the employment status mobility of mothers does not have a significant impact on their children’s employment mobility. Our study points out the pivotal role of fathers in influencing employment formalization in Indonesia. Our findings could be valuable inputs for policy-making regarding employment formalization in Indonesia.
Validação de indicadores de qualidade do cuidado cirúrgico no Sistema Único de Saúde
Authors: Caldas Anna Cláudia Sales Gomes , Araújo Rafael Santiago de , Medeiros Paulo José , Freitas Marise Reis de , Aledo Victoriano Soria , Gama Zenewton André da Silva
Published: May 2023

OBJETIVO: Validar um conjunto de indicadores para monitoramento da qualidade dos procedimentos cirúrgicos no Sistema Único de Saúde (SUS). MÉTODOS: Estudo de validação desenvolvido em 5 etapas: 1) revisão de literatura; 2) priorização de indicadores; 3) validação de conteúdo dos indicadores por método de consenso RAND/UCLA; 4) estudo piloto para análise da confiabilidade; e 5) desenvolvimento de instrutivo para tabulação dos indicadores de resultado para monitoramento via sistemas de informações oficiais. RESULTADOS: A partir da revisão de literatura, foram identificados 217 indicadores de qualidade cirúrgica. Os indicadores excluídos foram: indicadores baseados em evidências científicas inferiores a 1A, similares, específicos, que correspondiam a eventos sentinelas; e aqueles que não se aplicavam ao contexto do SUS. Foram submetidos ao consenso de especialistas 26 indicadores com alto nível de evidência científica. Foram validados 22 indicadores, dos quais 14 indicadores de processo e 8 indicadores de resultado com índice de validação de conteúdo ≥80%. Dos indicadores de processo validados, 6 foram considerados confiáveis substancialmente (Coeficiente de Kappa entre 0,6 e 0,8; p < 0,05) e 2 tiveram confiabilidade quase perfeita (coeficiente de Kappa > 0,8, p < 0,05), quando analisada a concordância interavaliador. Foi possível mensurar e estabelecer mecanismo de tabulação para TabWin para 7 indicadores de resultado. CONCLUSÃO: O estudo contribui com o desenvolvimento de um conjunto de indicadores cirúrgicos potencialmente eficazes para o monitoramento da qualidade do cuidado e segurança do paciente nos serviços hospitalares do SUS.
Association Between Postresuscitation 12‐Lead ECG Features and Early Mortality After Out‐of‐Hospital Cardiac Arrest: A Post Hoc Subanalysis of the PEACE Study
Authors: Gentile Francesca Romana , Baldi Enrico , Klersy Catherine , Schnaubelt Sebastian , Caputo Maria Luce , Clodi Christian , Bruno Jolie , Compagnoni Sara , Fasolino Alessandro , Benvenuti Claudio , Domanovits Hans , Burkart Roman , Primi Roberto , Ruzicka Gerhard , Holzer Michael , Auricchio Angelo , Savastano Simone
Published: May 2023

Background

Once the return of spontaneous circulation after out‐of‐hospital cardiac arrest is achieved, a 12‐lead ECG is strongly recommended to identify candidates for urgent coronary angiography. ECG has no apparent role in mortality risk stratification. We aimed to assess whether ECG features could be associated with 30‐day survival in patients with out‐of‐hospital cardiac arrest.

Methods and Results

All the post‐return of spontaneous circulation ECGs from January 2015 to December 2018 in 3 European centers (Pavia, Lugano, and Vienna) were collected. Prehospital data were collected according to the Utstein style. A total of 370 ECGs were collected: 287 men (77.6%) with a median age of 62 years (interquartile range, 53–70 years). After correction for the return of spontaneous circulation‐to‐ECG time, age >62 years (hazard ratio [HR], 1.78 [95% CI, 1.21–2.61];
P
=0.003), female sex (HR, 1.5 [95% CI, 1.05–2.13];
P
=0.025), QRS wider than 120 ms (HR, 1.64 [95% CI, 1.43–1.87];
P
<0.001), the presence of a Brugada pattern (HR, 1.49 [95% CI, 1.39–1.59];
P
<0.001), and the presence of ST‐segment elevation in >1 segment (HR, 1.75 [95% CI, 1.59–1.93];
P
<0.001) were independently associated with 30‐day mortality. A score ranging from 0 to 26 was created, and by dividing the population into 3 tertiles, 3 classes of risk were found with significantly different survival rate at 30 days (score 0–4, 73%; score 5–7, 66%; score 8–26, 45%).

Conclusions

The post‐return of spontaneous circulation ECG can identify patients who are at high risk of mortality after out‐of‐hospital cardiac arrest earlier than other forms of prognostication. This provides important risk stratification possibilities in postcardiac arrest care that could help to direct treatments and improve outcomes in patients with out‐of‐hospital cardiac arrest.
Association Between Spotty Calcification in Nonstenosing Extracranial Carotid Artery Plaque and Ipsilateral Ischemic Stroke
Authors: Homssi Moayad , Vora Amar , Zhang Cenai , Baradaran Hediyeh , Kamel Hooman , Gupta Ajay
Published: May 2023

Background

Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with <50% luminal stenosis of the extracranial carotid arteries.

Methods and Results

We used data from the CAESAR (Cornell Acute Stroke Academic Registry), a prospective registry of all patients with acute ischemic stroke admitted to our institution. We included patients who met criteria for cryptogenic stroke and underwent computed tomography angiography and brain magnetic resonance imaging. Patients with extracranial carotid artery stenosis ≥50% and patients with posterior or bilateral anterior circulation infarcts were excluded. We examined the carotid bifurcations for spotty calcifications, defined as ≥1 contiguous regions of luminal calcification ≤3 mm along the long axis of the vessel. We also measured low‐density plaque and maximum plaque thickness. The eligible cohort consisted of 117 patients with a mean age of 66.7±1.65 years with a median National Institute of Health Stroke Scale stroke at the time of arrival of 6 (range, 3–13). The number of spotty calcifications present within a low‐density plaque was significantly associated with ipsilateral infarction (0.3±0.8 versus 0.1±0.4,
P
=0.02). Maximum plaque thickness was also significantly associated with ipsilateral infarction (1.4 mm ±1.5 versus 1.0 mm ±1.1,
P
=0.004).

Conclusions

Spotty calcifications associated with low‐density plaque and maximum plaque thickness were associated with ipsilateral ischemic stroke in patients with nonstenotic carotid atherosclerosis, suggesting a role as imaging markers of high‐risk plaque.
Cost Implications of Left Atrial Appendage Occlusion During Cardiac Surgery: A Cost Analysis of the LAAOS III Trial
Authors: Eqbal Adam , Tong Wesley , Lamy Andre , Belley‐Cote Emilie , Paparella Domenico , Bogachev‐Prokophiev Alexander , Royse Alistair G. , Reents Wilko , Devereaux P. J. , Brady Katheryn , Vincent Jessica , Connolly Stuart J. , Whitlock Richard P. ,   the LAAOS III Investigators
Published: May 2023

Background

The LAAOS III (Left Atrial Appendage Occlusion Study) clinical trial demonstrated that concomitant left atrial appendage (LAA) occlusion leads to a lower risk of ischemic stroke or systemic embolism compared with no occlusion in participants with atrial fibrillation and a CHA
2
DS
2
‐VASc score of ≥2 undergoing cardiac surgery for another indication. We report the cost implications of concomitant LAA occlusion during cardiac surgery.

Methods and Results

Using LAAOS III data, we compared the costs (in US dollars) associated with LAA occlusion to no occlusion from the perspective of the Centers for Medicare and Medicaid Services. We calculated the average cost per participant during the trial by applying Medicare reimbursement costs to cardiovascular events for all trial participants. We conducted sensitivity analyses, varying the cost of stroke ±25% and occlusion technique use. Cost neutrality was defined as a mean cost difference within ±5% of the cost per participant in the no‐occlusion group. Total study cost per participant was $3878 in the LAA occlusion group and $4490 in the no‐occlusion group, a mean difference of −$612 (95% CI, −$1276 to $45). The main drivers of cost savings were fewer stroke events during the trial (mean difference of −$1021). In sensitivity analyses, LAA occlusion was cost saving for suture and stapler techniques but more expensive with closure device.

Conclusions

Concomitant LAA occlusion was cost saving for participants in LAAOS III. Our findings support concomitant LAA occlusion as an economically dominant strategy for patients with atrial fibrillation and a CHA
2
DS
2
‐VASc score of ≥2 undergoing cardiac surgery.
The Importance of Being Constrained: Dealing with Infeasible Solutions in Differential Evolution and Beyond
Authors: Kononova Anna V. , Vermetten Diederick , Caraffini Fabio , Mitran Madalina-A. , Zaharie Daniela
Published: May 2023

We argue that results produced by a heuristic optimisation algorithm cannot be considered reproducible unless the algorithm fully specifies what should be done with solutions generated outside the domain, even in the case of simple bound constraints. Currently, in the field of heuristic optimisation, such specification is rarely mentioned or investigated due to the assumed triviality or insignificance of this question. Here, we demonstrate that, at least in algorithms based on Differential Evolution, this choice induces notably different behaviours in terms of performance, disruptiveness, and population diversity. This is shown theoretically (where possible) for standard Differential Evolution in the absence of selection pressure and experimentally for the standard and state-of-the-art Differential Evolution variants, on a special test function and the BBOB benchmarking suite, respectively. Moreover, we demonstrate that the importance of this choice quickly grows with problem dimensionality. Differential Evolution is not at all special in this regard—there is no reason to presume that other heuristic optimisers are not equally affected by the aforementioned algorithmic choice. Thus, we urge the heuristic optimisation community to formalise and adopt the idea of a new algorithmic component in heuristic optimisers, which we refer to as the strategy of dealing with infeasible solutions. This component needs to be consistently: (a) specified in algorithmic descriptions to guarantee reproducibility of results, (b) studied to better understand its impact on an algorithm's performance in a wider sense (i.e., convergence time, robustness, etc.), and (c) included in the (automatic) design of algorithms. All of these should be done even for problems with bound constraints.
Conductance-Based Phenomenological Nonspiking Model: A Dimensionless and Simple Model That Reliably Predicts the Effects of Conductance Variations on Nonspiking Neuronal Dynamics
Authors: Naudin Loïs , Raison-Aubry Laetitia , Buhry Laure
Published: May 2023

The modeling of single neurons has proven to be an indispensable tool in deciphering the mechanisms underlying neural dynamics and signal processing. In that sense, two types of single-neuron models are extensively used: the conductance-based models (CBMs) and the so-called phenomenological models, which are often opposed in their objectives and their use. Indeed, the first type aims to describe the biophysical properties of the neuron cell membrane that underlie the evolution of its potential, while the second one describes the macroscopic behavior of the neuron without taking into account all of its underlying physiological processes. Therefore, CBMs are often used to study “low-level” functions of neural systems, while phenomenological models are limited to the description of “high-level” functions. In this letter, we develop a numerical procedure to endow a dimensionless and simple phenomenological nonspiking model with the capability to describe the effect of conductance variations on nonspiking neuronal dynamics with high accuracy. The procedure allows determining a relationship between the dimensionless parameters of the phenomenological model and the maximal conductances of CBMs. In this way, the simple model combines the biological plausibility of CBMs with the high computational efficiency of phenomenological models, and thus may serve as a building block for studying both high-level and low-level functions of nonspiking neural networks. We also demonstrate this capability in an abstract neural network inspired by the retina and C. elegans networks, two important nonspiking nervous tissues.
Dynamic Modeling of Spike Count Data With Conway-Maxwell Poisson Variability
Authors: Wei Ganchao , Stevenson Ian H.
Published: May 2023

In many areas of the brain, neural spiking activity covaries with features of the external world, such as sensory stimuli or an animal's movement. Experimental findings suggest that the variability of neural activity changes over time and may provide information about the external world beyond the information provided by the average neural activity. To flexibly track time-varying neural response properties, we developed a dynamic model with Conway-Maxwell Poisson (CMP) observations. The CMP distribution can flexibly describe firing patterns that are both under- and overdispersed relative to the Poisson distribution. Here we track parameters of the CMP distribution as they vary over time. Using simulations, we show that a normal approximation can accurately track dynamics in state vectors for both the centering and shape parameters (λ and ν). We then fit our model to neural data from neurons in primary visual cortex, “place cells” in the hippocampus, and a speed-tuned neuron in the anterior pretectal nucleus. We find that this method outperforms previous dynamic models based on the Poisson distribution. The dynamic CMP model provides a flexible framework for tracking time-varying non-Poisson count data and may also have applications beyond neuroscience.
Hodophilus pseudoglabripes (Clavariaceae, Agaricales), a new species from Thailand
Authors: TANG SONGMING , LV TONG , HE JUN , YU FENGMING , LUO HONGMEI , LI SHUHONG
Published: May 2023

Hodophilus pseudoglabripes, a new species with a strong earthy odor, was found in forests dominated by Castanopsis (Fagaceae) in northern Thailand. This species is introduced with microscopic and macroscopic descriptions and colour photographs. Phylogenetic affinities were determined based on a combination of internal transcribed spacers (ITS) and large subunit (nrLSU) of the nuclear ribosomal DNA (rDNA). The new species was placed in Hodophilus, within an independent clade comprising the other two species from Asia, H. glabripes and H. indicus. This is the first report of the genus Hodophilus in Thailand. An updated key to all members of the genus Hodophilus is also provided.
Erratum: Bouman, R.W., Keβler, P.J.A., Telford, I.R.H., Bruhl, J.J., Strijk, J.S., Saunders, R.M.K., Esser, H.-J., Falcón-Hidalgo, B. & van Welzen, P.C. (2022) A revised phylogenetic classification of tribe Phyllantheae (Phyllanthaceae). Phytotaxa 540: 1–100
Authors: BOUMAN RODERICK W. , KEBLER PAUL J.A. , TELFORD IAN R.H. , BRUHL JEREMY J. , STRIJK JOERI S. , SAUNDERS RICHARD M.K. , ESSER HANS-JOACHIM , FALCÓN-HIDALGO BANESSA , VAN WELZEN PETER C.
Published: May 2023

N/A
Blood-saving dissection with monopolar tungsten needle electrodes and Teflon-coated spatula electrodes in tumor orthopedics
Authors: Puetzler Jan , Steinbicker Andrea Ulrike , Santel Jana , Deventer Niklas , Jahn Michael , Zarbock Alexander , Gosheger Georg , Schulze Martin , Jenke Dana Janina
Published: May 2023

Introduction

Resection of musculoskeletal tumors and reconstruction with tumor endoprostheses often results in blood loss requiring transfusion of blood products. We assessed the blood-saving potential of using monopolar tungsten needle electrodes and polytetrafluoroethylene (PTFE)-coated spatula electrodes (intervention) compared with conventional dissection with sharp instruments and coagulation with uncoated steel electrodes (control).

Methods

We retrospectively analyzed data of 132 patients (79 interventions, 53 controls) undergoing surgery by one single experienced surgeon in our tertiary referral center between 2012 and 2021.

Results

Intraoperative blood loss in the intervention group was reduced by 29% [median (IQR): 700 (400–1200) vs 500 (200–700) ml; p = 0.0043]. Postoperative wound drainage decreased by 41% [median (IQR): 1230 (668–2041) vs 730 (450–1354) ml; p = 0.0080]. Additionally, patients in need of PRBCs during surgery declined from 43% to 15% (23/53 vs 12/79; p = 0.0005), while the transfusion rate after surgery did not change notably. The number of patients in need of revision surgery due to wound healing disorders was low in both groups (control group: 4/53 vs intervention group: 4/79). Only one patient in the control group and two patients in the intervention group underwent revision surgery due to hemorrhage. Baseline characteristics were similar between groups (sex, Charlson Comorbidity score, tumor entity).

Conclusion

Dissection with tungsten needle electrodes and PTFE-coated spatula electrodes appears an effective surgical blood-saving measure without increased risk of wound healing disorders.

Level of evidence

III, retrospective comparative study.

Clinical trial registration. The study was registered at ClinicalTrials.gov. Identifier: NCT05164809.
Paediatric procedural sedation and analgesia in a South African emergency centre: a single-centre, descriptive study
Authors: Dunn Cornelle , Cloete Philip , Saunders Colleen , Evans Katya
Published: May 2023

Background

Procedural sedation and analgesia are considered a core competency in emergency medicine as patients present to the emergency centre on an unscheduled basis, often with complex complaints that necessitate emergent management. Previous evidence has consistently shown that procedural sedation and analgesia in the emergency centre in the paediatric population, even the very young, are safe if appropriate monitoring is performed and appropriate medications are used. The aim of the study was to describe the indications for procedural sedation and analgesia, the fasting status of paediatric patients undergoing procedural sedation and analgesia and the complications observed during procedural sedation and analgesia in the paediatric population at a single emergency centre in Cape Town, South Africa.

Methods

A retrospective, descriptive study was conducted at Mitchells Plain Hospital, a district-level hospital situated in Mitchells Plain, Cape Town. All paediatric patients younger than 13 years of age who presented to the emergency centre and received procedural sedation and analgesia during the study period (December 2020–April 2021) were included in the study. Data was extracted from a standardised form, and simple descriptive statistics were used.

Results

A total of 113 patients (69% male) were included: 13 infants (< 1 year of age), 47 young children (1–5 years of age) and 53 older children (5–13 years of age). There was only 1 (0.9%) complication documented, which was vomiting and did not require admission. The majority of patients received ketamine (96.5%). The standardised procedural sedation and analgesia form was completed in 49.1% of cases. Indications included burns debridement (11.5%), suturing (17.7%), fracture reduction (23.9%), lumbar punctures (31.9%) and others (15.0%). The indications for procedural sedation and analgesia varied between the different age groups. The majority of patients in this study did not have their fasting status documented (68.1%), and 18.6% were not appropriately fasted as per American Society of Anaesthesiology guidelines. Despite this, there was an extremely low rate of documented complications of 0.9%.

Conclusion

The study findings are in accordance with previous international literature reporting low complication rates. Although fasting status was unknown in the majority of patients, there was an extremely low rate of documented complications and no interventions required. Safe, timely procedural sedation and analgesia with minimal pain and unnecessary suffering can become the norm in emergency medicine practice in South Africa.
A systematic review of biologically-informed deep learning models for cancer: fundamental trends for encoding and interpreting oncology data
Authors: Wysocka Magdalena , Wysocki Oskar , Zufferey Marie , Landers Dónal , Freitas André
Published: May 2023

Background

There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings.

Methods

This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. It focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental properties in the biomedical domain. For this, we retrieved and analyzed 42 studies focusing on emerging architectural and methodological advances, the encoding of biological domain knowledge and the integration of explainability methods.

Results

We discuss the recent evolutionary arch of DL models in the direction of integrating prior biological relational and network knowledge to support better generalisation (e.g. pathways or Protein-Protein-Interaction networks) and interpretability. This represents a fundamental functional shift towards models which can integrate mechanistic and statistical inference aspects. We introduce a concept of bio-centric interpretability and according to its taxonomy, we discuss representational methodologies for the integration of domain prior knowledge in such models.

Conclusions

The paper provides a critical outlook into contemporary methods for explainability and interpretability used in DL for cancer. The analysis points in the direction of a convergence between encoding prior knowledge and improved interpretability. We introduce bio-centric interpretability which is an important step towards formalisation of biological interpretability of DL models and developing methods that are less problem- or application-specific.
Postoperative glucocorticoids in patients with acute type A aortic dissection (GLAD): study protocol for a prospective, single-center, randomized controlled trial
Authors: Deng Yi-zhi , Luo Ming-hao , Luo Jing-chao , Li Jia-kun , Chen Jia-qi , Zhang Yi-jie , Hou Jun-yi , Su Ying , Tu Guo-wei , Luo Zhe
Published: May 2023

Background

Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking.

Methods

This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline.

Discussion

The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery.

Trial registration

This study has been registered on ClinicalTrials.gov (NCT04734418).
The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS
Authors: Zhu Yongjun , Wu Weixin , Qiao Liangliang , Ji Jingfen , Duan Lunxi , Gong Longlong , Ren Dandan , Li Feifei , Wei Lihui , Pan Ke
Published: May 2023

Background

Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein–Barr-virus-positive (EBV+) GC with microsatellite stability (MSS).

Methods

A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients.

Results

We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity.

Conclusion

In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.
Angiotensin receptor blockers might be protective against hepatic steatosis after liver transplantation
Authors: Eshraghian Ahad , Taghavi Alireza , Nikoupour Hamed , Nikeghbalian Saman , Malek-Hosseini Seyed Ali
Published: May 2023

Background

Hepatic steatosis is an increasing complication in liver transplant recipients. Currently, there is no pharmacologic therapy for treatment of hepatic steatosis after liver transplantation. The aim of this study was to determine the association between use of angiotensin receptor blockers (ARB) and hepatic steatosis in liver transplant recipients.

Methods

We conducted a case-control analysis on data from Shiraz Liver Transplant Registry. Liver transplant recipients with and without hepatic steatosis were compared for risk factors including use of ARB.

Results

A total of 103 liver transplant recipients were included in the study. Thirty five patients treated with ARB and 68 patients (66%) did not receive these medications. In univariate analysis, ARB use (P = 0.002), serum triglyceride (P = 0.006), weight after liver transplantation (P = 0.011) and etiology of liver disease (P = 0.008) were associated with hepatic steatosis after liver transplantation. In multivariate regression analysis, ARB use was associated with lower likelihood of hepatic steatosis in liver transplant recipients (OR = 0.303, 95% CI: 0.117–0.784; P = 0.014). Mean duration of ARB use (P = 0.024) and mean cumulative daily dose of ARB (P = 0.015) were significantly lower in patients with hepatic steatosis.

Conclusion

Our study showed that ARB use was associated with reduced incidence of hepatic steatosis in liver transplant recipients.