bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA019: Resolving the paradigm of the pre-existing resistance to targeted therapy, and the fitness costs associate with resistance: In vitro and theoretical evidence using an evolutionary game theoretic approach
Authors: Scott Jacob G.
Published: May 2022

Therapeutic strategies for tumor control have traditionally assumed that maximizing reduction in tumor volume correlates with clinical efficacy. Unfortunately, this rapid decrease in tumor burden is almost invariably followed by the emergence of therapeutic resistance. Evolutionary based treatment strategies attempt to delay resistance via judicious treatments that maintain a significant treatable subpopulation. While these strategies have shown promise in recent clinical trials, they often rely on biological conjecture and intuition to derive parameters. To bridge this gap, we recently developed an in vitro assay to directly measure the parameters of the underlying evolutionary game played between cancer cells under therapy. Using this assay we have subsequently directly observed competitive exclusion in non-small cell lung cancer cells – a necessary, but not sufficient condition for adaptive therapy. Intrinsic to this finding lies another advance: one which helps us settle the long standing paradox of pre-existing resistance and fitness costs associated with resistance mutations. In particular, if a cost of resistance exists, how can a less fit mutant persist in a population long enough for a treatment to be given to expose its increased fitness? To answer this, we show experimental and theoretical results that help explain this paradox which we posit submit should be generalizable outside cancer and applicable across the kingdoms of life where eco-evolutionary dynamics are at play.

Citation Format: Jacob G. Scott. Resolving the paradigm of the pre-existing resistance to targeted therapy, and the fitness costs associate with resistance: In vitro and theoretical evidence using an evolutionary game theoretic approach [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA019.
Abstract IA020: Dynamics of response and resistance to cancer therapy
Authors: Bozic Ivana
Published: May 2022

Despite the effectiveness of many cancer therapies in reducing tumor burden for significant amounts of time in a subset of patients, primary and acquired resistance to treatment remain one of the biggest challenges in the effort to cure cancer. Successful management, or prevention, of resistance requires deciphering the mechanisms by which it arises, and in particular whether it stems from pre-existing cell populations or arises de novo during therapy. Using evolutionary principles and mathematical techniques together with patient data, we aim to develop a precise mathematical understanding of the dynamics of response and resistance to various cancer therapies, including targeted therapies and immunotherapy. Our work shows that therapies that maximize the killing rate of cancer cells may not be optimal, and that instead the parameters determining the fraction of resistant cells and their growth rate have a larger effect on the long-term control of cancer.

Citation Format: Ivana Bozic. Dynamics of response and resistance to cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA020.
Abstract IA022: Exploiting immune surveillance to target colorectal cancer evolution and mutability
Authors: Bardelli Alberto
Published: May 2022

The emergence of drug resistance limits the efficacy of targeted therapies in human tumors. Strategies to prevent or overcome resistance are essential to design the next generation of clinical trials. The prevalent view is that resistance is a fait accompli: when treatment is initiated, cancers already contain drug-resistant mutant cells. Notably, bacteria exposed to antibiotics transiently increase their mutation rates (adaptive mutability) thus improving chances of survival. We studied colorectal cancer (CRC) to assess whether tumor cells similarly exploit adaptive mutability to evade therapeutic pressure. We found that EGFR and BRAF inhibition activates stress-induced mutagenesis through downregulation of MMR and HR DNA repair effectors, and concomitant up-regulation of error-prone polymerases in drug-tolerant persister cells resulting in increased mutation rates. Overcoming drug resistance, therefore, means considering as a target not “only” individual oncogenes but also the evolving nature of human tumors. One possibility is to unleash the ability of the immune system to recognize mutations induced by therapy. We tested this possibility in syngeneic mouse models of CRC. Our findings indicate that inactivation of DNA repair mechanisms and manipulation of mutational loads can trigger immune surveillance and prolonged therapeutic responses.

Citation Format: Alberto Bardelli. Exploiting immune surveillance to target colorectal cancer evolution and mutability [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA022.
Abstract IA025: Decoding breast cancer evolution with single cell genomics
Authors: Navin Nicholas
Published: May 2022

I will discuss our efforts to develop and apply single cell DNA sequencing technologies to study breast cancer progression and evolution. We have developed a method called Acoustic Cell Tagmentation (ACT) which can provide high-throughput single cell copy number profiling of hundreds of cells in parallel at single-molecule resolution. We have applied this approach to study copy number evolution in Triple-negative breast cancer, which has revealed a ‘transient instability’ model of early copy number evolution, after the acquisition of TP53 mutations and genome doubling. We have also developed a computational toolkit called CopyKit to analyze single cell DNA sequencing data, and applied it to study metastasis in breast and colon cancer, as well as the spatial organization of subclones in metastatic tumors. Collectively these studies and tools provide new insights into the evolution of chromosome aberrations in human tumors.

Citation Format: Nicholas Navin. Decoding breast cancer evolution with single cell genomics [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA025.
Abstract PR013: Oct4 and Sox2 induce cellular transition of glioma stem cells to an immune suppressive, regulatory T cell-like state
Authors: Johnson Amanda , Korleski Jack , Laterra John , Lopez-Bertoni Hernando
Published: May 2022

Solid malignancies, including GBM, contain small subsets of cells that display stem-like properties (i.e. glioma stem cells or GSCs) and act as key determinants of therapeutic resistance and tumor recurrence. Mechanisms of GSC immune escape are considered fundamental to clinical GBM growth and recurrence. GBM cells escape antitumor immunity by modifying the tumor microenvironment by secreting immune-suppressive factors and recruiting anti-inflammatory/pro-oncogenic cells (e.g. T-regulatory cells, M2-like macrophages). However, whether subsets of GSCs can mimic T-reg-like functions by expressing proteins associated with T-reg immune-suppression remains unknown. Single-cell RNA sequencing analysis of GBM neurospheres revealed a previously unrecognized Oct4/Sox2high/FOXP3− cell subpopulation with high expression of TGFb1, CD39, CD73, PD-L1, and Galectin-1, a gene expression fingerprint typically associated with T-reg cells and their immune suppressive functions within the tumor microenvironment. Bioinformatics analysis of public databases shows that the above-mentioned genes are enriched in the mesenchymal GBM subtype and highly correlated with CD44 and TGFb type II receptor (TGFBR2) expression in both clinical GBM and primary GSCs. Mechanistically, Oct4 and Sox2 were found to directly induce TGFBR2 transcription concurrent with chromatin architectural changes (i.e. heterochromatin-to-euchromatin transition) involving the TGFBR2 gene. Transgenic TGFBR2 expression increased neurosphere cell growth capacity, upregulated expression of T-reg-like effector genes and enriched for CD44+ GSCs. Functionally, neurospheres expressing transgenic Oct4/Sox2 or transgenic TGFBR2 possess increased immunosuppressive capacity, and pharmacological inhibition of TGFBR2 depleted CD44+ GSCs and reduced immunosuppression in T-cell co-cultures. Taken together, we show that reprogramming events initiated by Oct4 and Sox2 induce a CD44+/FOX3P− GSC cell subset with a T-reg-like immunosuppressive transcriptional profile via a TGFBR2-dependent mechanism. This research provides the first description of such neoplastic cells in any malignancy and has high potential translational impact since targeting these tumor cell subsets and their immunosuppressive mechanisms may be critical to the successful development of GBM immunotherapies.

Citation Format: Amanda Johnson, Jack Korleski, John Laterra, Hernando Lopez-Bertoni. Oct4 and Sox2 induce cellular transition of glioma stem cells to an immune suppressive, regulatory T cell-like state [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr PR013.
Cardiac Penetrating Injury with Complete Heart Block: A Case Report
Authors: Tannouri Lamiz , Aljanaahi Salwa Younis , Noori Omar Qais Muhammed , Muhammed Khalifa
Published: May 2022

The development of heart block following cardiac penetrating injury is rare, and only few cases can be found in the literature. This uncommon healthcare emergency has shown to be a medical challenge for healthcare personnel, and it manifests very high mortality rates of 80–90% among its victims. The pre-hospital management and transport time for these cases are vital and can dictate the possible outcome for the victim. In this article, we present the first case ever reported in the Gulf Region about complete heart block as a consequence of penetrating chest injury. Our patient was a 35-year-old male who had a stab wound on the right side of chest wall and who developed complete heart block in the Emergency Department (ED) as a result of the injury. Patient was rapidly diagnosed and managed in ED and then was shifted to the operating theater for immediate surgical repair. However, despite anatomical correction during the surgery he remained hypotensive and bradycardic. When a hemodynamic stability was achieved, he was then placed on a temporary pacemaker and later on a permanent pacemaker by the cardiology team.
Retrospective Investigation of Cranial Volume and Cephalic Index in Patients with Nonsyndromic Sagittal Synostosis Operated by Total Vault Remodeling
Authors: Goetzinger Maximilian , Verius Michael , Eder Robert , Laimer Ilse , Rasse Michael
Published: May 2022

Background: Premature fusion of cranial sutures affects skull development and leads to head deformity. Intracranial pressure increase and brain growth restriction can occur in untreated craniosynostosis. Operative treatment aims to achieve an immediate and long-lasting correction of skull shape that is close to the average and to prevent or release possible increased intracranial pressure by increasing the intracranial volume (ICV) or normalizing the ICV if it is already below the standards. This study was designed to evaluate the effect of a total calvarial reconstruction on skull development in patients with nonsyndromic sagittal synostosis. Material and Methods: The study population included 19 male and 5 female patients with isolated nonsyndromic sagittal suture synostosis. During the operation, temporarily fixed prebent metal plates provided an intraoperative reference for the desired cranial expansion gain of height and shortening. Preoperative and postoperative ICVs and cephalic indices were measured on computed tomography datasets using the software program ImageJ and were compared with one another and with normative data. Results: The male population presented with a preoperative mean ICV of 863.3 cm³. A postoperative mean ICV increase of 243.5 cm³ (p < 0.001) and a further ICV enlargement (p < 0.001) was measured. The mean CI changed from 71.0% preoperatively to 75.4% postoperatively (p = 0.002) and decreased insignificantly in the follow-up (p = 0.546). The female population had a preoperative mean ICV of 804.9 cm³. Postoperatively, the mean ICV increased by 211.1 cm³ (p = 0.043) and also increased in the follow-up (p = 0.043). Their mean CI values increased from 66.5% preoperatively to 72.8% (p = 0.043) postoperatively and decreased insignificantly in the follow-up (p = 0.345). Conclusion: This method of total vault remodeling provides reliable ICV increase and improvement in length and width of skull proportions beyond the immediate postoperative period together with an ICV increase.
Surgical Timing in Patients With Infective Endocarditis and With Intracranial Hemorrhage: A Systematic Review and Meta‐Analysis
Authors: Musleh Rita , Schlattmann Peter , Caldonazo Túlio , Kirov Hristo , Witte Otto W. , Doenst Torsten , Günther Albrecht , Diab Mahmoud
Published: May 2022

Background

Intracranial hemorrhage (ICH) is one of the main causes for lack of surgery in patients with infective endocarditis (IE), despite the presence of surgical indications. We aimed to evaluate the impact of early surgery in patients with IE and with ICH on postoperative neurological deterioration and all‐cause mortality and to elucidate the risk of 30‐day mortality in patients who were denied surgery.

Methods and Results

Three libraries (MEDLINE, EMBASE, and Cochrane Library) were assessed. The primary outcome was all‐cause mortality, and the secondary outcome was neurological deterioration. Inverse variance method and random model were performed. We identified 16 studies including 355 patients. Nine studies examined the impact of surgical timing (early versus late) and were included in the meta‐analysis. Only one study examined the fate of patients with IE and with ICH who were treated conservatively despite having an indication for cardiac surgery, showing higher mortality rates than those who underwent surgery (11.8% versus 2.5%). We found no significant association between early surgery, regardless of its definition, and a higher mortality (odds ratio [OR], 1.69; 95% CI, 0.95–3.02). Early surgery was associated with higher risk for neurological deterioration (OR, 2.00; 95% CI, 1.10–3.65).

Conclusions

Cardiac surgery for IE within 30 days of ICH was not associated with higher mortality, but with an increased rate of neurological deterioration. The 30‐day mortality in patients with IE and with ICH who were denied surgery has not yet been sufficiently investigated. This patient group should be analyzed in future studies in more detail.
London Fog: A Century of Pollution and Mortality, 1866–1965
Authors: Hanlon W. Walker
Published: May 2022

This study draws on London’s long experience with air pollution in order to improve our understanding of the overall effects of pollution exposure and how and why these effects evolve as locations develop. I compare uniquely detailed new mortality data covering 1866 to 1965 to the timing of London’s famous fog events, which trapped emissions in the city. I show that air pollution was a major contributor to mortality in London over this period and that it interacted strongly with specific infectious diseases. As a consequence of this interaction, reductions in the infectious disease burden substantially altered the health costs of pollution.
Luciogobius punctilineatus n. sp., a new earthworm goby from southern Japan
Authors: KOREEDA REO , MOTOMURA HIROYUKI
Published: May 2022

Luciogobius punctilineatus n. sp. is described on the basis of 21 type specimens from Kyushu, and the Koshiki and Osumi Islands, southern Japan. It is also found in Kochi Prefecture (Shikoku) and Amami-oshima island (Ryukyu Islands), Japan, confirmed by examination of non-type specimens. The genus Luciogobius includes 15 valid and several undescribed species, and most of them inhabit interstitial spaces of stones and gravel in the intertidal zone. The new species is characterized by the following combination of characters: total second dorsal-fin rays 10–12 (modally 11); total anal-fin rays 12–14 (13); pectoral-fin rays 8–12 (10); vertebrae 16–18 + 22–24 = 39–42 (17 + 23 = 40); pectoral-fin posterior margin slightly concave; pelvic fins united, forming a ventral disc; snout relatively short, length 3.1–4.3% of SL; anus to anal-fin origin (AAA) distance twice body depth at anus, 11.4–16.9% of SL; snout length less than 34.7% of AAA distance; pre-anus length less than 85.5% of pre-anal-fin length; single poorly defined black longitudinal line along mid-lateral body region from behind pectoral fin to caudal-fin base, indistinct anteriorly (line embedded, visible through semi-transparent muscle tissue in fresh or live specimens); black spots forming a single longitudinal row on mid-lateral body surface from behind pectoral fin to caudal-fin base (more distinct in preserved specimens).
Description of the new genus Tarsobaenus and three new species from Costa Rica (Coleoptera: Cleridae: Clerinae: Hydnocerini)
Authors: LEAVENGOOD JOHN M. JR. , PINKERTON MORGAN G. , RIFKIND JACQUES
Published: May 2022

The new genus Tarsobaenus and three new species—Tarsobaenus letourneauae, T. piper and T. hansoni—are described from Costa Rica. Tarsobaenus is distinguished by the broad, subulate form of the plical excavation along the elytral suture, the lower margin of which is modified into a broad flattened flange; serrulate apical elytral margins; and the conspicuously large, shiny body. Two of the species are associates of Piper plants and their pharaoh ant symbionts. We provide a key to the three species of Tarsobaenus.
Real-world effectiveness after initiating fremanezumab treatment in US patients with episodic and chronic migraine or difficult-to-treat migraine
Authors: Driessen Maurice T. , Cohen Joshua M. , Thompson Stephen F. , Patterson-Lomba Oscar , Seminerio Michael J. , Carr Karen , Totev Todor I. , Sun Rochelle , Yim Erica , Mu Fan , Ayyagari Rajeev
Published: May 2022

Background

Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings.

Methods

This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]).

Results

Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively.

Conclusions

In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).
Folic acid-conjugated magnetic triblock copolymer nanoparticles for dual targeted delivery of 5-fluorouracil to colon cancer cells
Authors: Mirzaghavami Parvin Sadat , Khoei Samideh , Khoee Sepideh , Shirvalilou Sakine
Published: May 2022

Background

In the current study, folic acid-conjugated PEG-PCL-PEG triblock copolymer were synthesized and loaded with 5-fluorouracil and magnetite nanoparticles (5-FU-SPION-PEG-PCL-PEG-FA) for targeted delivery of drug to HT29 human colon cancer cells and CT26 mouse colon cancer model. The nanoparticles were synthesized and characterized by nuclear magnetic resonance spectroscopy (NMR) and transmission electron microscopy (TEM). The cellular uptake of nanoparticles was assessed in vitro (on HUVEC and HT29) and in vivo (on CT26 colon tumor tissues). The cytotoxic effect of nanoparticles was assessed on human colon cell lines (HT29, Caco-2, HTC116, and SW480) and normal HUVEC cells. In addition, antitumor effects of nanoparticles were investigated based on tumor volume, survival time and protein expression of Bax and Bcl-2 on CT26 tumor-bearing BALB/c mice.

Results

Characterization of nanoparticles showed 5-FU-SPION-PEG-PCL-PEG-FA (5-FU-NPs-FA) nanoparticles had spherical shape with hydrodynamic diameter of 85 nm. The drug-release profile exhibited sustained pH-responsive release with cumulative release reaching approximately 23% after 24 h. Cellular uptake studies revealed that HT29 cancer cells absorb higher amount of 5-FU-NPs-FA as compared to HUVEC normal cells (P < 0.05). In addition, 5-FU-NPs-FA was found to be more antitumor efficient in comparison to free 5-FU based on Bax/Bcl2 ratio, survival rate of tumoral mouse and inhibitory tumor volume (P < 0.05).

Conclusions

The results suggested that 5-FU-NPs-FA could be considered as promising sustained drug delivery platform for in vitro and in vivo conditions, which may provide selective treatment of tumor cancer cells.

Graphical Abstarct
Taxonomy and SSU rRNA gene-based phylogeny of two new Euplotes species from China: E. chongmingensis n. sp. and E. paramieti n. sp. (Protista, Ciliophora)
Authors: Han Kun , Pan Hongbo , Jiang Jiamei
Published: May 2022

Background

The genus Euplotes Ehrenberg, 1830, one of the most complicated and confused taxa, contains about 160 nominal species. It was once proposed to be divided into four genera, two of which were proved to be non-monophyletic. At least 19 new species have been discovered in the past decade, implying that there is a large undiscovered diversity of this genus.

Results

The morphology of two new freshwater euplotid ciliates, Euplotes chongmingensis n. sp. and E. paramieti n. sp., isolated from Shanghai, China, were investigated using live observations, protargol staining, and Chatton-Lwoff silver staining method. Euplotes chongmingensis is characterized by its small size (40–50 × 25–35 μm), about 24 adoral membranelles, 10 frontoventral cirri, two marginal and two caudal cirri, eight dorsolateral kineties with 11–16 dikinetids in the mid-dorsolateral kinety and a double type of silverline system. Euplotes paramieti n. sp. is 180–220 × 110–155 μm in vivo and strongly resembles E. amieti but having a difference of 57 bp in their SSU rRNA gene sequences. Phylogenetic analyses based on SSU rRNA gene sequence data were used to determine the systematic positions of these new taxa.

Conclusions

The description of two new freshwater taxa and their SSU rRNA gene sequences improve knowledge of biodiversity and enrich the database of euplotids. Furthermore, it offers a reliable reference for environmental monitoring and resource investigations.
An antisense Alu transposon insertion/deletion polymorphism of ALDH1A1 may functionally associate with Parkinson’s disease
Authors: Fan Hui-Hui , Zheng Jing , Huang Xiao-Ya , Wu Ke-Yun , Cui Lei , Dong Hao-Jia , Wang Zhen , Zhang Xiong , Zhu Jian-Hong
Published: May 2022

Background

Aldehyde dehydrogenase 1 (encoded by ALDH1A1) has been shown to protect against Parkinson’s disease (PD) by reducing toxic metabolites of dopamine. We herein revealed an antisense Alu element insertion/deletion polymorphism in intron 4 of ALDH1A1, and hypothesized that it might play a role in PD. 

Methods

A Han Chinese cohort comprising 488 PD patients and 515 controls was recruited to validate the Alu insertion/deletion polymorphism following a previous study of tag-single nucleotide polymorphisms, where rs7043217 was shown to be significantly associated with PD. Functional analyses of the Alu element insertion were performed.

Results

The Alu element of ALDH1A1 was identified to be a variant of Yb8 subfamily and termed as Yb8c4. The antisense Yb8c4 insertion/deletion polymorphism (named asYb8c4ins and asYb8c4del, respectively) appeared to be in a complete linkage disequilibrium with rs7043217 and was validated to be significantly associated with PD susceptibility with asYb8c4ins serving as a risk allele (P = 0.030, OR = 1.224, 95% CI = 1.020–1.470). Multiple functional analyses including ALDH1A1 mRNA expression in blood cells of carriers, and reporters of EGFP and luciferase showed that the asYb8c4ins had a suppressive activity on gene transcription. Mechanistic explorations suggested that the asYb8c4ins induced no changes in CpG methylation and mRNA splicing of ALDH1A1 and appeared no binding of transcription factors.

Conclusions

Our results consolidate an involvement of ALDH1 in PD pathogenesis. The asYb8c4 polymorphism may be a functional output of its linkage disequilibrium-linked single nucleotide polymorphisms.
Clinical prediction models for diagnosis of COVID-19 among adult patients: a validation and agreement study
Authors: Dardenne Nadia , Locquet Médéa , Diep Anh Nguyet , Gilbert Allison , Delrez Sophie , Beaudart Charlotte , Brabant Christian , Ghuysen Alexandre , Donneau Anne-Françoise , Bruyère Olivier
Published: May 2022

Background

Since the beginning of the pandemic, hospitals have been constantly overcrowded, with several observed waves of infected cases and hospitalisations. To avoid as much as possible this situation, efficient tools to facilitate the diagnosis of COVID-19 are needed.

Objective

To evaluate and compare prediction models to diagnose COVID-19 identified in a systematic review published recently using performance indicators such as discrimination and calibration measures.

Methods

A total of 1618 adult patients present at two Emergency Department triage centers and for whom qRT-PCR tests had been performed were included in this study. Six previously published models were reconstructed and assessed using diagnostic tests as sensitivity (Se) and negative predictive value (NPV), discrimination (Area Under the Roc Curve (AUROC)) and calibration measures. Agreement was also measured between them using Kappa’s coefficient and IntraClass Correlation Coefficient (ICC). A sensitivity analysis has been conducted by waves of patients.

Results

Among the 6 selected models, those based only on symptoms and/or risk exposure were found to be less efficient than those based on biological parameters and/or radiological examination with smallest AUROC values (< 0.80). However, all models showed good calibration and values above > 0.75 for Se and NPV but poor agreement (Kappa and ICC < 0.5) between them. The results of the first wave were similar to those of the second wave.

Conclusion

Although quite acceptable and similar results were found between all models, the importance of radiological examination was also emphasized, making it difficult to find an appropriate triage system to classify patients at risk for COVID-19.
Symptoms of post-traumatic stress and associations with sexual behaviour and PrEP preferences among young people in South Africa, Uganda and Zimbabwe
Authors: Webb Emily L. , Dietrich Janan J. , Ssemata Andrew S. , Nematadzira Teacler G. , Hornschuh Stefanie , Kakande Ayoub , Tshabalala Gugulethu , Muhumuza Richard , Mutonyi Gertrude , Atujuna Millicent , Bere Tarisai , Bekker Linda-Gail , Abas Melanie A. , Weiss Helen A. , Seeley Janet , Stranix-Chibanda Lynda , Fox Julie ,   for the CHAPS Study Team
Published: May 2022

Background

It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP.

Methods

Young people without HIV, aged 13–24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety.

Results

Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05–4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04–1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08–1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex.

Conclusions

Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP.
Feasibility and thematic analysis of narrative visualization materials with physical activity monitoring among breast cancer survivors
Authors: Bentley Jason R. , Yu Xiaoying , Karmarkar Amol M. , Downer Brian , Prochaska John , Lyons Elizabeth J.
Published: May 2022

Background

Breast cancer survivors have a unique risk for negative health outcomes. Engaging in routine physical activity (PA) can reduce these risks. However, PA levels are low among this population. Narrative visualization (NV) is a technique that uses drawings, photographs, and text to contextualize data, which may increase integrated regulation, or motivation related to personal values and identity. A PA intervention targeting breast cancer survivors using an NV strategy may improve PA behavior. The purpose of this study was to determine whether scrapbooking activities could successfully be used as an NV strategy for older (55+) breast cancer survivors.

Methods

Breast cancer survivors were given workbooks, wearable electronic activity monitors, instant cameras, and art supplies including a variety of stickers (e.g., emojis, affirmations). Participants were instructed to use these materials for 7 days. The workbook pages prompted participants to re-draw their daily activity graphs from the wearable’s mobile app, then annotate them with text, photographs, stickers, etc. to reflect what the data meant to them. Hybrid thematic analysis was used to analyze the photographs, drawings, and written content to identify emergent themes. Content analysis was also used to investigate use of stickers and photographs.

Results

Of the 20 consented women (mean age 67 ± 5 years, 45% non-Hispanic white), 3 participants were lost to follow-up or unable to complete the procedures. The NV procedures were successfully utilized by the remaining 17 participants, who collectively used 945 stickers over 7 days, most of which were emojis. Emojis were both positively and negatively valanced. Participants took a mean of 9 photos over 7 days and completed workbook questions regarding current PA and PA goals. Themes within the photos included family, specific locations, everyday objects, religion, and friends. Themes within the written portions of the workbook included family, chores and obligations, health, personal reflection, hobbies, and shopping.

Conclusions

The materials provided allowed breast cancer survivors to successfully use NV techniques to reflect on their PA data and behavior. These techniques show promise for promoting integrated regulation in activity monitoring interventions.

Trial registration

This study was funded by the National Cancer Institute (R21CA218543) beginning July 1, 2018.
Factors associated with serum CA125 level in women without ovarian cancer in the United States: a population-based study
Authors: Hu Xiao , Zhang Jingzhou , Cao Yu
Published: May 2022

Background

Cancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States.

Methods

Participants were identified from the National Health and Nutrition Examination Survey 2001–2002. Linear and logistic regression models were applied.

Results

Higher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (− 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5–10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression.

Conclusions

Results suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients’ CA125 levels.
The biallelic novel pathogenic variants in AGL gene in a chinese patient with glycogen storage disease type III
Authors: Wang Jing , Yu Yuping , Cai Chunquan , Zhi Xiufang , Zhang Ying , Zhao Yu , Shu Jianbo
Published: May 2022

Background

Glycogen storage disease type III (GSD III) is a rare autosomal recessive glycogenolysis disorder due to AGL gene variants, characterized by hepatomegaly, fasting hypoglycemia, hyperlipidemia, elevated hepatic transaminases, growth retardation, progressive myopathy, and cardiomyopathy. However, it is not easy to make a definite diagnosis in early stage of disease only based on the clinical phenotype and imageology due to its clinical heterogeneity.

Case presentation

We report a two-year-old girl with GSD III from a nonconsanguineous Chinese family, who presented with hepatomegaly, fasting hypoglycemia, hyperlipidemia, elevated levels of transaminases. Accordingly, Sanger sequencing, whole‑exome sequencing of family trios, and qRT-PCR was performed, which revealed that the patient carried the compound heterogeneous variants, a novel frameshift mutation c.597delG (p. Q199Hfs*2) and a novel large gene fragment deletion of the entire exon 13 in AGL gene. The deletion of AGL was inherited from the proband’s father and the c.597delG variant was from the mother.

Conclusions

In this study, we identified two novel variants c.597delG (p. Q199Hfs*2) and deletion of the entire exon 13 in AGL in a Chinese GSD III patient. We extend the mutation spectrum of AGL. We suggest that high-throughput sequencing technology can detect and screen pathogenic variant, which is a scientific basis about genetic counseling and clinical diagnosis.
Syrian national growth references for children and adolescents aged 2–20 years
Authors: Zamlout Ali , Alwannous Kamal , Kahila Ali , Yaseen Majd , Albadish Raneem , Aleid Morhaf , Hamzah Karina , Monther Mahmoud , Akkari Oudai , Hasan Amah , Hasan Manal , Khallouf Ammar , Obied Amjad , Schmidt Amna , Deeb Sara , Deeb Orwa , Eldin Judie Jalal , Ojaily Nour , Taifour Mohammad , Ghanem Qusai , Kabalan Younes , Alrstom Ali , Alhalabi Marwan
Published: May 2022

Background

During the past three decades, growth charts have become one of the principal tools for monitoring anthropometric development in individuals and populations as well. Growth references by the CDC and other countries have been widely used in our hospitals and healthcare units for clinical assessment of children’s development. The apparent overestimation and underestimation of many children's anthropometrics indicated the need to construct our own references. The objective of this study is to establish the national growth references for the Syrian population 2–20-year-old.

Methods

A multicenter cross-sectional sample of 13,548 subjects, aged 2–20 years, were recruited from various kindergartens, schools, and universities across the Syrian Arab Republic between February and May-2019. Response variables (stature, weight, and BMI) were fitted against age using P-splines and three empirical distributions: Box-Cox T, Box-Cox Power Exponential, and Box-Cox Cole and Green. Residuals diagnostic Q-tests and worm plots were used to check the validity of fitted models.

Results

Box-Cox T provided the best fit for stature-for-age, whereas Box-Cox Power Exponential provided the best fit for weight-for-age and BMI-for-age. Residuals diagnostics revealed adequate models fitting. BMI cutoffs revealed an increased prevalence of obesity (4.5% and 3.66%) and overweight (20.1% and 19.54%), for boys and girls respectively, in our population.

Conclusions

Growth charts are available for use now in our hospitals and healthcare units. For 0–2-year-old children, we recommend using the World Health Organization’s standards.
Racism in healthcare: a scoping review
Authors: Hamed Sarah , Bradby Hannah , Ahlberg Beth Maina , Thapar-Björkert Suruchi
Published: May 2022

Background

Racism constitutes a barrier towards achieving equitable healthcare as documented in research showing unequal processes of delivering, accessing, and receiving healthcare across countries and healthcare indicators. This review summarizes studies examining how racism is discussed and produced in the process of delivering, accessing and receiving healthcare across various national contexts.

Method

The PRISMA guidelines for scoping reviews were followed and databases were searched for peer reviewed empirical articles in English across national contexts. No starting date limitation was applied for this review. The end date was December 1, 2020. The review scoped 213 articles. The results were summarized, coded and thematically categorized in regards to the aim.

Results

The review yielded the following categories: healthcare users’ experiences of racism in healthcare; healthcare staff’s experiences of racism; healthcare staff’s racial attitudes and beliefs; effects of racism in healthcare on various treatment choices; healthcare staff’s reflections on racism in healthcare and; antiracist training in healthcare. Racialized minorities experience inadequate healthcare and being dismissed in healthcare interactions. Experiences of racism are associated with lack of trust and delay in seeking healthcare. Racialized minority healthcare staff experience racism in their workplace from healthcare users and colleagues and lack of organizational support in managing racism. Research on healthcare staff’s racial attitudes and beliefs demonstrate a range of negative stereotypes regarding racialized minority healthcare users who are viewed as difficult. Research on implicit racial bias illustrates that healthcare staff exhibit racial bias in favor of majority group. Healthcare staff’s racial bias may influence medical decisions negatively. Studies examining healthcare staff’s reflections on racism and antiracist training show that healthcare staff tend to construct healthcare as impartial and that healthcare staff do not readily discuss racism in their workplace.

Conclusions

The USA dominates the research. It is imperative that research covers other geo-political contexts. Research on racism in healthcare is mainly descriptive, atheoretical, uses racial categories uncritically and tends to ignore racialization processes making it difficult to conceptualize racism. Sociological research on racism could inform research on racism as it theoretically explains racism’s structural embeddedness, which could aid in tackling racism to provide good quality care.
A comparison of peer change agent selection methods: Evidence from a high-school based suicide preventive intervention
Authors: Pickering Trevor A. , Wyman Peter A. , Valente Thomas W.
Published: May 2022

Background

Peer-led interventions for adolescents are effective at accelerating behavioral change. The Sources of Strength suicide preventive program trains student peer change agents (peer leaders) in secondary schools to deliver prevention messaging and conduct activities that increase mental health coping mechanisms. The program currently has school staff select peer leaders. This study examined potential for more efficient program diffusion if peer leaders had been chosen under network-informed selection methods.

Methods

Baseline assessments were collected from 5,746 students at 20 schools. Of these, 429 were selected by adults as peer leaders who delivered intervention content through the school year. We created theoretical alternate peer leader sets based on social network characteristics: opinion leadership, centrality metrics, and key players. Because these sets were theoretical, we examined the concordance of these sets with the actual adult-selected peer leaders sets and correlated this metric with diffusion of intervention modalities (i.e., presentation, media, communication, activity) after the first year.

Results

The sets of adult-selected peer leaders were 13.3%—22.7% similar to theoretical sets chosen by other sociometric methods. The use of friendship network metrics produced peer leader sets that were more white and younger than the general student population; the Key Players method produced more representative peer leader sets. Peer opinion leaders were older and more white than the general population. Schools whose selected peer leaders had higher overlap with theoretical ones had greater diffusion of intervention media and peer communication.

Conclusions

The use of network information in school-based peer-led interventions can help create more systematized peer leader selection processes. To reach at-risk students, delivery of an indirect message, such as through a poster or video, may be required. A hybrid approach where a combination of visible, respected opinion leaders, along with strategically-placed key players within the network, may provide the greatest potential for intervention diffusion.
Neighbors’ use of water and sanitation facilities can affect children’s health: a cohort study in Mozambique using a spatial approach
Authors: Grau-Pujol Berta , Cano Jorge , Marti-Soler Helena , Casellas Aina , Giorgi Emanuele , Nhacolo Ariel , Saute Francisco , Giné Ricard , Quintó Llorenç , Sacoor Charfudin , Muñoz Jose
Published: May 2022

Background

Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection – community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children’s morbidity and mortality using recorded health data.

Methods

We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012–2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality.

Results

Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition.

Conclusion

Household and neighbors’ access to improve water and sanitation can affect children’s health. Accounting for household WASH and herd protection in interventions’ evaluation could foster stakeholders’ investment and improve WASH related diseases control.

Graphical Abstract

Distribution of main water and sanitation facilities used during study period.