bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life of refugees: a systematic review of studies using the WHOQOL-Bref instrument in general and clinical refugee populations in the community setting
Authors: Gagliardi Juliette , Brettschneider Christian , König Hans-Helmut
Published: June 2021

Purpose

To systematically review studies on HRQOL, measured by the WHOQOL-Bref instrument, of refugees in general and clinical populations who are settled in the community of the hosting country, and outline the differences in scores among the two population groups and across the four domains of WHOQOL-Bref (physical, psychological, social relationships and environment domain) as well as factors impacting those outcomes.

Methods

Several databases were systematically searched by using a broad search strategy. Additionally, a hand search for grey literature was performed. Studies had to comply with the following inclusion criteria: (a) population of refugees; (b) living in the community of the country of destination; (c) assessing HRQOL through the WHOQOL-Bref instrument.

Results

15 studies were identified and divided into two subgroups: (a) general population of refugees (b) clinical population of refugees, who were specifically selected for their mental status or because they had experienced relevant past traumas. Although we can outline common patterns among the two groups, in terms of domains scoring the highest and the lowest, heterogeneous values of HRQOL are observed across the studies included.

Conclusions

Individuals who were included in the clinical refugee group have a lower quality of life in respect to the general population of refugees. However, among the two groups different patterns can be outlined considering each domain of HRQOL: higher scores for the Physical and lower for the Environment domain when considering the general population of refugees and higher scores for the Environment and lower for the Psychological domain when referring to the clinical one. These lower scores are probably due to having a higher rate of mental distress and being more exposed to somatization, stigmatization and barriers to access the healthcare system of the hosting country.
Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy
Authors: Brignole Chiara , Bensa Veronica , Fonseca Nuno A. , Del Zotto Genny , Bruno Silvia , Cruz Ana F. , Malaguti Fabiana , Carlini Barbara , Morandi Fabio , Calarco Enzo , Perri Patrizia , Moura Vera , Emionite Laura , Cilli Michele , De Leonardis Francesco , Tondo Annalisa , Amoroso Loredana , Conte Massimo , Garaventa Alberto , Sementa Angela R. , Corrias Maria V. , Ponzoni Mirco , Moreira Joao N. , Pastorino Fabio
Published: June 2021

Background

Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB.

Methods

NB cell lines, Schwannian stroma-poor NB tumors and bone marrow (BM)-infiltrating NB cells were evaluated for the expression of cell surface NCL by Flow Cytometry, Imaging Flow Cytometry and Immunohistochemistry analyses. The cytotoxic activity of doxorubicin (DXR)-loaded nanocarriers decorated with the NCL-recognizing F3 peptide (T-DXR) was evaluated in terms of inhibition of NB cell proliferation and induction of cell death in vitro, whereas metastatic and orthotopic animal models of NB were used to examine their in vivo anti-tumor potential.

Results

NB cell lines, NB tumor cells (including patient-derived and Patient-Derived Xenografts-PDX) and 70% of BM-infiltrating NB cells show cell surface NCL expression. NCL staining was evident on both tumor and endothelial tumor cells in NB xenografts. F3 peptide-targeted nanoparticles, co-localizing with cell surface NCL, strongly associates with NB cells showing selective tumor cell internalization. T-DXR result significantly more effective, in terms of inhibition of cell proliferation and reduction of cell viability in vitro, and in terms of delay of tumor growth in all NB animal model tested, when compared to both control mice and those treated with the untargeted formulation.

Conclusions

Our findings demonstrate that NCL could represent an innovative therapeutic cellular target for NB.
Expression profiles and prognostic values of BolA family members in ovarian cancer
Authors: Zhu Mingyang , Xiao Shiqi
Published: June 2021

Background

The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer.

Methods

In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members’ involvement in OC by using gene set enrichment analysis.

Results

The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer.

Conclusion

In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.
A fatal toxic shock-like syndrome post COVID-19 infection in a child
Authors: Ajmi Houda , Besghaier Wissem , Kallala Wafa , Trabelsi Abdelhalim , Abroug Saoussan
Published: June 2021

Background

Children affected by Coronavirus disease 2019 (COVID-19) showed various manifestations. Some of them were severe cases presenting with multi-system inflammatory syndrome (MIS-C) causing multiple organ dysfunction.

Case presentation

We report the case of a 12-year-old girl with recent COVID-19 infection who presented with persistent fever, abdominal pain and other symptoms that meet the definition of MIS-C. She had lymphopenia and a high level of inflammatory markers. She was admitted to pediatric intensive care unit since she rapidly developed refractory catecholamine-resistant shock with multiple organ failure. Echocardiography showed a small pericardial effusion with a normal ejection fraction (Ejection Fraction = 60%) and no valvular or coronary lesions. The child showed no signs of improvement even after receiving intravenous immunoglobulin, fresh frozen plasma, high doses of Vasopressors and corticosteroid. His outcome was fatal.

Conclusion

Pediatric patients affected by the new COVID-19 related syndrome may show severe life-threatening conditions similar to Kawasaki disease shock syndrome. Hypotension in these patients results from heart failure and the decreased cardiac output. We report a new severe clinical feature of SARS-CoV-2 infection in children in whom hypotension was the result of refractory vasoplegia.
Panarthropod tiptop/teashirt and spalt orthologs and their potential role as “trunk”-selector genes
Authors: Medina-Jiménez Brenda I. , Budd Graham E. , Janssen Ralf
Published: June 2021

Background

In the vinegar flyDrosophila melanogaster, the homeodomain containing transcription factor Teashirt (Tsh) appears to specify trunk identity in concert with the function of the Hox genes. While inDrosophilathere is a second gene closely related totsh, calledtiptop(tio), in other arthropods species only one copy exists (calledtio/tsh). The expression oftshandtio/tsh, respectively, is surprisingly similar among arthropods suggesting that its function as trunk selector gene may be conserved. Other research, for example on the beetleTribolium castaneum, questions even conservation of Tsh function among insects. The zinc-finger transcription factor Spalt (Sal) is involved in the regulation ofDrosophila tsh, but this regulatory interaction does not appear to be conserved inTriboliumeither. Whether the function and interaction oftshandsalas potential trunk-specifiers, however, is conserved is still unclear because comparative studies onsalexpression (except forTribolium) are lacking, and functional data are (if at all existing) restricted to Insecta.

Results

Here, we provide additional data on arthropodtshexpression, show the first data on onychophorantio/tshexpression, and provide a comprehensive investigation onsalexpression patterns in arthropods and an onychophoran.

Conclusions

Our data support the idea thattio/tshgenes are involved in the development of “trunk” segments by regulating limb development. Our data suggest further that the function of Sal is indeed unlikely to be conserved in trunk vs head development like inDrosophila, but early expression ofsalis in line with a potential homeotic function, at least in Arthropoda.
Development of a balanced scorecard as a strategic performance measurement system for clinical radiology as a cost center
Authors: Teichgräber Ulf , Sibbel Rainer , Heinrich Andreas , Güttler Felix
Published: June 2021

Objectives

To develop a goal-oriented indicator system based on the balanced scorecard (BSC) concept, which takes into account the perspectives of the referring physician and patient and emphasizes the focus on the internal processes of the radiology department.

Methods

Development of a BSC occurred in six steps: (Step 1) strengths/weaknesses and opportunities/risks (SWOT-) analysis of the radiology department, (Step 2) setting-specific objectives (model, core values, key objective) followed by the development of 4 perspectives, (Step 3) and definition of strategic issues oriented to the value-added chain of the processes of the radiology department. (Step 4) Creation of a “Strategy Map” with regard to the perspective and their cause–effect relationships. (Step 5) Development of an automated key performance indicator (KPI) cockpit for the monitoring, reporting, and management scorecard.

Results

A total of 10 success factors were identified using SWOT analysis. The core values include high quality in clinical, teaching, and research areas. The radiological value-added chain is composed of three processing steps. 1. registration, 2. examination, and 3. reading/X-ray demonstration. Three action programs were derived: 1. increase competency (e.g., specialist standard), 2. improve referring physician/patient satisfaction, 3. increase productivity. Daily process monitoring was added to the management cockpit as a monitoring scorecard. The scorecard comprises 18 KPIs and is automatically updated every month. The annual management scorecard comprises 10 KPIs.

Conclusions

The BSC makes it possible to implement a strategy for radiology that is strongly oriented toward the requirements of the referring physicians and the demands of patients.
Report on ammonoid soft tissue remains revealed by computed tomography
Authors: Hoffmann R. , Morón-Alfonso D. , Klug C. , Tanabe K.
Published: June 2021

Findings of ammonoid soft tissues are extremely rare compared to the rich fossil record of ammonoid conchs ranging from the Late Devonian to the Cretaceous/Paleogene boundary. Here, we apply the computed-tomography approach to detect ammonoid soft tissue remains in well-preserved fossils from the Early Cretaceous (early Albian) of NE-Germany ofProleymeriella. The ammonites were found in glauconitic–phosphatic sandstone boulders. Analyses of the high-resolution Ct-data revealed the presence of cameral sheets, the siphuncular tube wall, and the siphuncle itself. The siphuncle is a long, segmented soft tissue that begins at the rear end of the body chamber and comprises blood vessels. Chemical analyses using energy-dispersive spectroscopy (EDS) showed that all preserved soft tissues were phosphatized and are now composed of fluorapatite. The same holds true for preserved shell remains that locally show the nacreous microstructure. We provide a short description of these soft tissue remains and briefly discuss the taphonomic pathway.
Target arterial PO2 according to the underlying pathology: a mini-review of the available data in mechanically ventilated patients
Authors: Demiselle Julien , Calzia Enrico , Hartmann Clair , Messerer David Alexander Christian , Asfar Pierre , Radermacher Peter , Datzmann Thomas
Published: June 2021

There is an ongoing discussion whether hyperoxia, i.e. ventilation with high inspiratory O2 concentrations (FIO2), and the consecutive hyperoxaemia, i.e. supraphysiological arterial O2 tensions (PaO2), have a place during the acute management of circulatory shock. This concept is based on experimental evidence that hyperoxaemia may contribute to the compensation of the imbalance between O2 supply and requirements. However, despite still being common practice, its use is limited due to possible oxygen toxicity resulting from the increased formation of reactive oxygen species (ROS) limits, especially under conditions of ischaemia/reperfusion. Several studies have reported that there is a U-shaped relation between PaO2 and mortality/morbidity in ICU patients. Interestingly, these mostly retrospective studies found that the lowest mortality coincided with PaO2 ~ 150 mmHg during the first 24 h of ICU stay, i.e. supraphysiological PaO2 levels. Most of the recent large-scale retrospective analyses studied general ICU populations, but there are major differences according to the underlying pathology studied as well as whether medical or surgical patients are concerned. Therefore, as far as possible from the data reported, we focus on the need of mechanical ventilation as well as the distinction between the absence or presence of circulatory shock. There seems to be no ideal target PaO2 except for avoiding prolonged exposure (> 24 h) to either hypoxaemia (PaO2 < 55–60 mmHg) or supraphysiological (PaO2 > 100 mmHg). Moreover, the need for mechanical ventilation, absence or presence of circulatory shock and/or the aetiology of tissue dysoxia, i.e. whether it is mainly due to impaired macro- and/or microcirculatory O2 transport and/or disturbed cellular O2 utilization, may determine whether any degree of hyperoxaemia causes deleterious side effects.
Individualization of PEEP and tidal volume in ARDS patients with electrical impedance tomography: a pilot feasibility study
Authors: Becher Tobias , Buchholz Valerie , Hassel Daniel , Meinel Timo , Schädler Dirk , Frerichs Inéz , Weiler Norbert
Published: June 2021

Background

In mechanically ventilated patients with acute respiratory distress syndrome (ARDS), electrical impedance tomography (EIT) provides information on alveolar cycling and overdistension as well as assessment of recruitability at the bedside. We developed a protocol for individualization of positive end-expiratory pressure (PEEP) and tidal volume (VT) utilizing EIT-derived information on recruitability, overdistension and alveolar cycling. The aim of this study was to assess whether the EIT-based protocol allows individualization of ventilator settings without causing lung overdistension, and to evaluate its effects on respiratory system compliance, oxygenation and alveolar cycling.

Methods

20 patients with ARDS were included. Initially, patients were ventilated according to the recommendations of the ARDS Network with a VT of 6 ml per kg predicted body weight and PEEP adjusted according to the lower PEEP/FiO2 table. Subsequently, ventilator settings were adjusted according to the EIT-based protocol once every 30 min for a duration of 4 h. To assess global overdistension, we determined whether lung stress and strain remained below 27 mbar and 2.0, respectively.

Results

Prospective optimization of mechanical ventilation with EIT led to higher PEEP levels (16.5 [14–18] mbar vs. 10 [8–10] mbar before optimization; p = 0.0001) and similar VT (5.7 ± 0.92 ml/kg vs. 5.8 ± 0.47 ml/kg before optimization; p = 0.96). Global lung stress remained below 27 mbar in all patients and global strain below 2.0 in 19 out of 20 patients. Compliance remained similar, while oxygenation was significantly improved and alveolar cycling was reduced after EIT-based optimization.

Conclusions

Adjustment of PEEP and VT using the EIT-based protocol led to individualization of ventilator settings with improved oxygenation and reduced alveolar cycling without promoting global overdistension.

Trial registrationThis study was registered at clinicaltrials.gov (NCT02703012) on March 9, 2016 before including the first patient.
Unsupervised outlier detection in multidimensional data
Authors: ur Rehman Atiq , Belhaouari Samir Brahim
Published: June 2021

Detection and removal of outliers in a dataset is a fundamental preprocessing task without which the analysis of the data can be misleading. Furthermore, the existence of anomalies in the data can heavily degrade the performance of machine learning algorithms. In order to detect the anomalies in a dataset in an unsupervised manner, some novel statistical techniques are proposed in this paper. The proposed techniques are based on statistical methods considering data compactness and other properties. The newly proposed ideas are found efficient in terms of performance, ease of implementation, and computational complexity. Furthermore, two proposed techniques presented in this paper use transformation of data to a unidimensional distance space to detect the outliers, so irrespective of the data’s high dimensions, the techniques remain computationally inexpensive and feasible. Comprehensive performance analysis of the proposed anomaly detection schemes is presented in the paper, and the newly proposed schemes are found better than the state-of-the-art methods when tested on several benchmark datasets.
A field guide for aging passerine nestlings using growth data and predictive modeling
Authors: Sanchez Audrey A. , Bartlow Andrew W. , Chan Allison M. , Fair Jeanne M. , Skinner Aaron A. , Hutchins Kelly , Musgrave Maria A. , Phillips Emily M. , Thompson Brent E. , Hathcock Charles D.
Published: June 2021

Background

Accurate nestling age is valuable for studies on nesting strategies, productivity, and impacts on reproductive success. Most aging guides consist of descriptions and photographs that are time consuming to read and subjective to interpret. The Western Bluebird (Sialia mexicana) is a secondary cavity-nesting passerine that nests in coniferous and open deciduous forests. Nest box programs for cavity-nesting species have provided suitable nesting locations and opportunities for data collection on nestling growth and development.

Methods

We developed models for predicting the age of Western Bluebird nestlings from morphometric measurements using model training and validation. These were developed for mass, tarsus, and two different culmen measurements.

Results

Our models were accurate to within less than a day, and each model worked best for a specific age range. The mass and tarsus models can be used to estimate the ages of Western Bluebird nestlings 0–10 days old and were accurate to within 0.5 days for mass and 0.7 days for tarsus. The culmen models can be used to estimate ages of nestlings 0–15 days old and were also accurate to within less than a day. The daily mean, minimum, and maximum values of each morphometric measurement are provided and can be used in the field for accurate nestling age estimations in real time.

Conclusions

The model training and validation procedures used here demonstrate that this method can create aging models that are highly accurate. The methods can be applied to any passerine species provided sufficient nestling morphometric data are available.
Natural forests in New Zealand – a large terrestrial carbon pool in a national state of equilibrium
Authors: Paul Thomas , Kimberley Mark O. , Beets Peter N.
Published: June 2021

Background

Natural forests cover approximately 29% of New Zealand’s landmass and represent a large terrestrial carbon pool. In 2002 New Zealand implemented its first representative plot-based natural forest inventory to assess carbon stocks and stock changes in these mostly undisturbed old-growth forests. Although previous studies have provided estimates of biomass or carbon stocks, these were either not fully representative or lacked data from important pools such as dead wood (coarse woody debris). The current analysis provides the most complete estimates of carbon stocks and stock changes in natural forests in New Zealand.

Results

We present estimates of per hectare carbon stocks and stock changes in live and dead organic matter pools excluding soil carbon based on the first two measurement cycles of the New Zealand Natural Forest Inventory carried out from 2002 to 2014. These show that New Zealand’s natural forests are in balance and are neither a carbon source nor a carbon sink. The average total carbon stock was 227.0 ± 14.4 tC·ha− 1(95% C.I.) and did not change significantly in the 7.7 years between measurements with the net annual change estimated to be 0.03 ± 0.18 tC·ha− 1·yr− 1. There was a wide variation in carbon stocks between forest groups. Regenerating forest had an averaged carbon stock of only 53.6 ± 9.4 tC·ha− 1but had a significant sequestration rate of 0.63 ± 0.25 tC·ha− 1·yr− 1, while tall forest had an average carbon stock of 252.4 ± 15.5 tC·ha− 1, but its sequestration rate did not differ significantly from zero (− 0.06 ± 0.20 tC·ha− 1·yr− 1). The forest alliance with the largest average carbon stock in above and below ground live and dead organic matter pools was silver beech-red beech-kamahi forest carrying 360.5 ± 34.6 tC·ha− 1. Dead wood and litter comprised 27% of the total carbon stock.

Conclusions

New Zealand’s Natural Forest Inventory provides estimates of carbon stocks including estimates for difficult to measure pools such as dead wood and roots. It also provides estimates of uncertainties including effects of model prediction error and sampling variation between plots. Importantly it shows that on a national level New Zealand’s natural forests are in balance. Nevertheless, this is a nationally important carbon pool that requires continuous monitoring to identify potential negative or positive changes.
Numerical study for optimal design of soil nailed embankment slopes
Authors: Derghoum Rabah , Meksaouine Mohamed
Published: June 2021

This paper presents a set of new required programmes written in format data using the built-in programming FISH language available in three-dimensional Fast Lagrangian Analysis of Continua software (FLAC3D). These script data files were developed, to overcome difficulties noted during the nailed slope stability prediction. They established to analyse stability of general embankment slope cases under various soil nailing parameters design. To deal with 3D finite difference analysis results in terms of the factor of safety (FOS) and critical slip surface, both 2D finite difference and limit equilibrium (LEM) methods are also conducted. A comparison of the 3D and 2D results indicates that 2D analyses underestimate seriously stability predictions, notably in terms of the FOS. Therefore, it was concluded that, 3D analysis should be used as an alternative to the 2D analyses, even though it requires more time. Some useful conclusions are obtained from this work, which provides a good practice guidance for real life scenarios.
Hydration status, body composition, and anxiety status in aeronautical military personnel from Spain: a cross-sectional study
Authors: Carretero-Krug Alejandra , Úbeda Natalia , Velasco Carlos , Medina-Font Juan , Laguna Trinidad Trujillo , Varela-Moreiras Gregorio , Montero Ana
Published: June 2021

Background

An adequate hydration status is critical to ensure efficiency during mental and physical activities. Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.

Methods

A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.

Results

Of the total sample, 81% met the hydration criteria (urine color = well hydrated, water balance ≥ 0 ml, and total water intake/weight ≥ 35 ml/kg), and 19% did not meet the hydration criteria (urine color = not sufficiently hydrated or dehydrated, water balance < 0 ml, and total water intake/weight < 35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status (score = 4 vs. 3, P = 0.026), weight [(84.7 ± 10.5) vs. (80.5 ± 10.2) kg], body mass index [(26.3 ± 3.1) vs. (25.2 ± 2.8)]kg/m2, body fat [(22.3 ± 5.6) vs. (18.3 ± 6.5)] %, urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat (P = 0.004), but no relation was found with age, comorbidities, or medications.

Furthermore, total water intake/weight was positively correlated with percentage of body water (r = 0.357, P = 0.000) and negatively with body fat (kg) (r = − 0.427, P = 0.000), percentage of body fat (r = − 0.405, P = 0.000), and waist/hip ratio (r = − 0.223, P = 0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat (P = 0.001) and percentage of body water content (P = 0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.

Conclusions

These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.
Evaluation indicators for open-source software: a review
Authors: Zhao Yuhang , Liang Ruigang , Chen Xiang , Zou Jing
Published: June 2021

In recent years, the widespread applications of open-source software (OSS) have brought great convenience for software developers. However, it is always facing unavoidable security risks, such as open-source code defects and security vulnerabilities. To find out the OSS risks in time, we carry out an empirical study to identify the indicators for evaluating the OSS. To achieve a comprehensive understanding of the OSS assessment, we collect 56 papers from prestigious academic venues (such as IEEE Xplore, ACM Digital Library, DBLP, and Google Scholar) in the past 21 years. During the process of the investigation, we first identify the main concerns for selecting OSS and distill five types of commonly used indicators to assess OSS. We then conduct a comparative analysis to discuss how these indicators are used in each surveyed study and their differences. Moreover, we further undertake a correlation analysis between these indicators and uncover 13 confirmed conclusions and four cases with controversy occurring in these studies. Finally, we discuss several possible applications of these conclusions, which are insightful for the research on OSS and software supply chain.
Systematic Review of Cancer Research Output From Africa, With Zambia as an Example
Authors: Kayamba Violet , Mutale Wilbroad , Cassell Holly , Heimburger Douglas Corbett , Shu Xiao-Ou
Published: June 2021

PURPOSE

Cancer occurrence is increasing in Africa, although research has lagged. The objective of this review was to analyze cancer research outputs from Africa, with a particular focus on Zambia.

METHODS

We searched PubMed for published cancer-related articles from African countries. All articles reporting on cancer in Africa were considered. We conducted analyses to explore correlations between cancer research output and total population, gross domestic product, and new cancer cases recorded in 2020. For Zambia articles, we also analyzed cancer types and time trends.

RESULTS

A total of 48,487 cancer-related publications from Africa were identified, with nearly half coming from Egypt (13,372; 28%) and South Africa (9,393; 19%). Cancer research output correlated significantly with country population (Spearman's correlation coefficient 0.74; P < .001) and the number of new cancer cases recorded in 2020 (Spearman's correlation coefficient 0.77; P < .001). Standardized by population size, Western Sahara (0.576), Seychelles (0.244), Tunisia (0.239), South Africa (0.158), and Egypt (0.131) had the highest overall output per 1,000 population. A total of 244 publications were from Zambia; the most studied cancers were cervical (25%), Kaposi sarcoma (24%), and breast (10%). Although an increase in cancer research output from Zambia was noted, only 33% of publications were first or last authored by Zambians. The major limitation of this review is that the evaluation was based on a single electronic database, PubMed.

CONCLUSION

Cancer research output from Africa is very low, with many of the publications concentrated in a few countries. There is an urgent need to invest in both human resources and infrastructure to increase cancer research output from African countries, particularly in less populous countries.
Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study
Authors: Zheng Huyong , Jiang Hui , Hu Shaoyan , Liao Ning , Shen Diying , Tian Xin , Hao Guoping , Jin Runming , Li Jianxin , Fang Yongjun , Ju Xiuli , Liu Ansheng , Wang Ningling , Zhai Xiaowen , Zhu Jiashi , Hu Qun , Li Limin , Liu Wei , Sun Lirong , Wang Li , Dai Yunpeng , Feng Xiaoqin , Li Fu , Liang Hui , Luo Xinhui , Yan Mei , Yin Qingning , Chen Yan , Han Yueqin , Qu Lijun , Tao Yanling , Gao Hui , He Zhixu , Lin Limin , Luo Jixia , Pan Kaili , Zhang Jingrong , Zhang Rong , Zhou Min , Zhang Yuanyuan , Wang Linya , Zhang Ruidong , Xiao Peifang , Ling Yayun , Peng Xiaoxia , Peng Yaguang , Wang Tianyou ,   for the Chinese Children's Leukemia Group
Published: June 2021

PURPOSE

Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes.

METHODS

We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years.

RESULTS

We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment.

CONCLUSION

Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.
Changes in ctDNA levels after MIBG therapy in patients with relapsed or refractory neuroblastoma.
Authors: Campbell Kevin M. , Klega Kelly S. , Shulman David Stephen , Tsao-Wei Denice D. , Groshen Susan G. , Goodarzian Fariba , Berkovich Rachel , Shimada Hiroyuki , Marachelian Araz , Villablanca Judith , Park Julie R. , Granger Meaghan , Matthay Katherine K. , Crompton Brian D. , DuBois Steven G.
Published: June 2021

10012

Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]
Dalpiciclib versus placebo plus fulvestrant in HR+/HER2- advanced breast cancer that relapsed or progressed on previous endocrine therapy (DAWNA-1): A multicenter, randomized, phase 3 study.
Authors: Xu Binghe , Zhang Qingyuan , Zhang Pin , Hu Xichun , Li Wei , Tong Zhongsheng , Sun Tao , Teng Yuee , Wu Xinhong , Ouyang Quchang , Yan Xi , Cheng Jing , Liu Qiang , Feng Jifeng , Wang Xiaojia , Zhu Xiaoyu , Wu Fei , Zhang Xiao , Zou Jianjun
Published: June 2021

1002

Background: Dalpiciclib (SHR6390), a novel CDK4/6 inhibitor, as monotherapy has demonstrated tolerability and preliminary antitumor activity in pretreated HR+/HER2− advanced breast cancer (ABC). Here we evaluated dalpiciclib with fulvestrant in ABC. Methods: In this randomized, double-blind, phase 3 trial, patients (pts) with HR+/HER2− locally advanced or metastatic breast cancer who had relapsed or progressed on previous endocrine therapy were enrolled. Eligible pts were randomized 2:1 to receive dalpiciclib (dalp; 150 mg po qd, d1-21, q4w) or placebo (PBO) with fulvestrant (fulv; 500 mg im, cycle 1 d1, d15, then d1 q4w). The primary endpoint was investigator (INV)-assessed PFS. As of Nov. 15, 2020, 162 (71.4% of total projected) events of disease progression or death had occurred and a preplanned interim analysis was done. The corresponding superiority boundary was 1-sided P = 0.0080 (Lan-DeMets [O’Brien-Fleming] boundary). Results: Overall, 361 pts were randomized to receive dalp-fulv (n = 241) or PBO-fulv (n = 120). With a median follow-up of 10.5 mo, dalp-fulv significantly improved INV-assessed PFS versus PBO-fulv (median, 15.7 [95% CI 11.1-NR] vs 7.2 [95% CI 5.6-9.2] mo; HR, 0.42 [95% CI 0.31-0.58]; P < 0.0001). PFS per IRC were consistent with INV assessment (Table). The benefit of dalpiciclib extended beyond initial study treatment based on time to first subsequent chemotherapy (TFSCT; HR, 0.47 [95% CI 0.32-0.69]; P < 0.0001). OS data were not mature with a total of 25 deaths documented. Median duration of exposure was 9.4 (IQR, 4.3-11.4) mo with dalpiciclib and 9.9 (4.7-11.9) mo with fulvestrant in the dalp-fulv group and was 6.1 (3.7-11.0) mo with fulvestrant in the PBO-fulv group. The most common (incidence ≥3%) grade 3 or 4 AEs with dalp-fulv were neutropenia (84.2%; vs 0% with PBO-fulv) and leukopenia (62.1%; vs 0%). Treatment discontinuation due to AE was reported for 2.5% of pts with dalp-fulv vs 3.3% with PBO-fulv. The incidence of SAE was 5.8% with dalp-fulv vs 6.7% with PBO-fulv. Conclusions: The study met its primary endpoint, demonstrating that dalpiciclib plus fulvestrant significantly improved PFS versus placebo plus fulvestrant, with a manageable safety profile. Our findings support dalpiciclib plus fulvestrant as a new treatment option in pts with HR+/HER2- ABC who relapsed or progressed on endocrine therapy. Clinical trial information: NCT03927456 .[Table: see text]
Predicting response to chemotherapy in neuroblastoma using deep learning: A report from the International Neuroblastoma Risk Group.
Authors: Ramesh Siddhi , Michael Diana , Liu Liu , Feinberg Nicholas , Granger Meaghan , Naranjo Arlene , Cohn Susan Lerner , Volchenboum Samuel Louis , Mayampurath Anoop , Applebaum Mark A.
Published: June 2021

10039

Background: Metaiodobenzylguanidine (MIBG) scans are a radionucleotide imaging modality used to evaluate neuroblastoma stage at diagnosis and also determine disease response following therapy. Curie scoring is used to semi-quantitatively assess disease burden from an MIBG scan on a scale from none (0) to widespread throughout the body (30). While a Curie score ≤2 after six cycles of induction chemotherapy has been shown to be prognostic of outcome, there is no established correlation between diagnostic Curie score and outcome. Deep learning models, such as convolutional neural networks (CNN), have been shown to learn generalizable patterns within images for successful classification of metastases and detection of multiple adult cancers. We hypothesized a CNN could be developed to predict response to induction chemotherapy, a proxy for outcome, using diagnostic MIBG scans. Methods: DICOM MIBG scans and associated clinical data from a Children’s Oncology Group (COG) pilot study for children diagnosed with high-risk neuroblastoma (ANBL12P1; NCT1798004) were deidentified and linked to clinical data by the Pediatric Cancer Data Commons and obtained from the International Neuroblastoma Risk Group Data Commons. Patients were defined as having a poor response to induction chemotherapy if their Curie score after four cycles of induction chemotherapy was ≥2. An independent external validation cohort was comprised of 29 images from 26 high-risk patients treated at the University of Chicago with clinically-annotated diagnostic and post-cycle six induction DICOM MIBG scans. The CNN was trained using 2D whole body MIBG scans obtained at diagnosis. We developed the CNN using a transfer learning approach using the Xception architecture as the base layer. Hyperparameter optimization was performed using an 80%-20% train-validation strategy. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). Results: Among 146 patients with high-risk neuroblastoma enrolled on ANBL12P1, 104 had available diagnostic and end-induction MIBG scans. There were no differences in clinical or biological characteristics between included and excluded patients. The base model CNN was able to predict which patients had a poor response to induction chemotherapy with an AUROC of 0.72 in the validation set from the ANBL12P1 cohort. Additionally, the CNN was able to predict patient response to therapy with an AUROC of 0.64 in an independent external dataset from University of Chicago. Conclusions: Our study suggests it is feasible to apply machine learning of diagnostic MIBG scans to predict response to chemotherapy for high-risk neuroblastoma patients. Given these promising results, further work to improve AUROC and performance within larger datasets is ongoing.
Treatment-related side effects and views about dosage assessment to sustain quality of life: Results of an advocate-led survey of patients with metastatic breast cancer (MBC).
Authors: Loeser Anne L , Peppercorn Jeffrey M. , Burkard Mark E. , Kalinsky Kevin , Rugo Hope S. , Bardia Aditya
Published: June 2021

1005

Background: Metastatic breast cancer (MBC) is generally incurable and the majority of patients with MBC will remain on treatment indefinitely. Patients usually begin each new treatment at the Recommended Starting Dose (RSD) on the FDA-approved label based on results from clinical trials. However, patients’ ability to tolerate the RSD in the real-world may differ from the clinical trial setting. While the importance of patient reported outcomes is recognized, understanding tolerability from the patient’s perspective is lacking and patients’ willingness to discuss individualized doses for MBC therapy has not been evaluated. Methods: Patient advocates from the Patient-Centered Dosing Initiative distributed a confidential online survey to patients with MBC via social media groups, organizational newsletters, and online support forums. The survey was developed by patients and medical oncologists to ascertain the prevalence and impact of patients’ treatment-related side effects, quality of patient-physician communication, management of side effects, and interest in alternative approaches to the RSD when a new treatment is initiated or adverse side effects are experienced. Results: 1,221 patients with MBC completed the survey within 15 days. The median number of lines of MBC therapy was 2.5 (range 1 - ≥5) and 46% (n = 564) of patients received their MBC diagnosis within two years of taking the survey. 86% (n = 1,051) reported experiencing at least one significant treatment-related side effect, and of these, 20% (n = 213) visited the Emergency Room/hospital and 43% (n = 454) missed at least one treatment. 98% (n = 1,026) of patients with side effects discussed them with their doctors and 82% (n = 838) were helped by their physicians. The most common (non-exclusive) mitigation strategies were dosage reductions (66%, n = 556) and prescription medications (59%, n = 494). Of the 556 patients given a dosage reduction, 83% (n = 459) reported feeling better. Notably, 92% (n = 1,127) of patients expressed willingness to discuss alternative dosing options with their physicians based upon their personal characteristics and individual preferences. Conclusions: Given that 86% of patients with MBC experienced at least one significant treatment-related side effect and 83% improved after dosage reduction, innovative dosage-related strategies are warranted to sustain Quality of Life. Patient-physician discussions in which the patient’s physical attributes and circumstances are periodically assessed may determine the right dose for the patient upon treatment initiation and afterwards, and the vast majority of patients would be receptive to such discussions.
The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130.
Authors: Emens Leisha A. , Goldstein Leonard D , Schmid Peter , Rugo Hope S. , Adams Sylvia , Barrios Carlos H. , Schneeweiss Andreas , Dieras Veronique , Iwata Hiroji , Chang Ching-Wei , Koeppen Hartmut , Chui Stephen Y. , Loi Sherene , Molinero Luciana
Published: June 2021

1006

Background: IMpassion130 was the first randomized phase 3 study to show clinical benefit of cancer immunotherapy (CIT) in untreated PD-L1+ mTNBC. Enhanced A + nP efficacy vs placebo (P) + nP was seen in pts with a richer immune TME but was confined to PD-L1 IC+ pts (PD-L1–expressing immune cells on ≥1% of tumor area; Emens JNCI 2021). While TNBC molecular subtyping and CD8 localization are prognostic in early TNBC, it is unknown whether these features are associated with CIT benefit in mTNBC. This exploratory analysis aimed to identify TME components associated with A + nP efficacy in IMpassion130. Methods: IHC was used to assess PD-L1 status (VENTANA SP142) and immune phenotypes (inflamed/excluded/desert per CD8 stromal/intratumoral localization; Mariathasan Nature 2018). RNA-seq was used for molecular subtyping (Burstein CCR 2015) and pathway analyses (MSigDB Hallmark). Cox regression was used to compare PFS/OS between A + nP vs P + nP, adjusted for prior taxanes, liver mets. Results: Sample classification and PD-L1 distribution are shown (Table). Improved PFS with A + nP vs P + nP was seen in PD-L1 IC+ inflamed and excluded tumors, but improved OS was limited to PD-L1 IC+ inflamed tumors. PD-L1 IC+ basal-like immune activated (BLIA) and immune suppressed (BLIS) subgroups derived PFS benefit, but OS benefit was limited to PD-L1 IC+ BLIA subgroups. In PD-L1 IC+ pts, pathway analysis identified proliferation/DNA damage repair (basal-like tumor features) and angiogenesis/ER response (higher in luminal androgen receptor [LAR]/ mesenchymal [MES] tumors) were associated with improved and reduced PFS, respectively. Conclusions: PD-L1 IC+ immune-inflamed tumors and PD-L1 IC+ BLIA tumors show highest CIT sensitivity, and LAR tumors may be resistant to CIT. These data warrant further study and validation. Clinical trial information: NCT02425891 .[Table: see text]