bluuebunny/crossref_metadata_2025 huggingface dataset:
Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia
Authors: Jetani Hardikkumar , Navarro-Bailón Almudena , Maucher Marius , Frenz Silke , Verbruggen Christina , Yeguas Ana , Vidriales María Belén , González Marcos , Rial Saborido Judit , Kraus Sabrina , Mestermann Katrin , Thomas Simone , Bonig Halvard , Luu Maik , Monjezi Razieh , Mougiakakos Dimitrios , Sauer Markus , Einsele Hermann , Hudecek Michael
Published: July 2021

Acute myeloid leukemia (AML) is an attractive entity for the development of chimeric antigen receptor (CAR) T-cell immunotherapy because AML blasts are susceptible to T-cell–mediated elimination. Here, we introduce sialic acid–binding immunoglobulin-like lectin 6 (Siglec-6) as a novel target for CAR T cells in AML. We designed a Siglec-6–specific CAR with a targeting domain derived from the human monoclonal antibody JML-1. We found that Siglec-6 is commonly expressed on AML cell lines and primary AML blasts, including the subpopulation of AML stem cells. Treatment with Siglec-6 CAR T cells confers specific antileukemia reactivity that correlates with Siglec-6 expression in preclinical models, including induction of complete remission in a xenograft AML model in immunodeficient mice (NSG/U937). In addition, we confirmed Siglec-6 expression on transformed B cells in chronic lymphocytic leukemia (CLL), and specific anti-CLL reactivity of Siglec-6 CAR T cells in vitro. Of particular interest, we found that Siglec-6 is not detectable on normal hematopoietic stem and progenitor cells (HSPCs) and that treatment with Siglec-6 CAR T cells does not affect their viability and lineage differentiation in colony-formation assays. These data suggest that Siglec-6 CAR T-cell therapy may be used to effectively treat AML without the need for subsequent allogeneic hematopoietic stem cell transplantation. In mature normal hematopoietic cells, we detected Siglec-6 in a proportion of memory (and naïve) B cells and basophilic granulocytes, suggesting the potential for limited on-target/off-tumor reactivity. The lack of expression of Siglec-6 on normal HSPCs is a key to differentiating it from other Siglec family members (eg, Siglec-3 [CD33]) and other CAR target antigens (eg, CD123) that are under investigation in AML, and it warrants the clinical investigation of Siglec-6 CAR T-cell therapy.
Phase 1 study of ibrutinib and the CXCR4 antagonist ulocuplumab in CXCR4-mutated Waldenström macroglobulinemia
Authors: Treon Steven P. , Meid Kirsten , Hunter Zachary R. , Flynn Catherine A. , Sarosiek Shayna R. , Leventoff Carly R. , White Timothy P. , Cao Yang , Roccaro Aldo M. , Sacco Antonio , Demos Maria G. , Guerrera Maria Luisa , Kofides Amanda , Liu Xia , Xu Lian , Patterson Christopher J. , Munshi Manit , Tsakmaklis Nicholas , Yang Guang , Ghobrial Irene M. , Branagan Andrew R. , Castillo Jorge J.
Published: July 2021

MYD88 and CXCR4 mutations are common in Waldenström macroglobulinemia (WM). Mutated CXCR4 (CXCR4Mut) impacts BTK-inhibitor response. We conducted a phase 1 trial of the CXCR4-antagonist ulocuplumab with ibrutinib in this first-ever study to target CXCR4Mut in WM. Ibrutinib was initiated at 420 mg/d with cycle 1 and continued until intolerance or progression; ulocuplumab was given cycles 1 to 6, with a 3 + 3 dose-escalation design. Each cycle was 4 weeks. Thirteen symptomatic patients, of whom 9 were treatment-naive patients were enrolled. Twelve were evaluable for response. At best response, their median serum immunoglobulin M declined from 5574 to 1114 mg/dL; bone marrow disease decreased from 65% to 10%, and hemoglobin increased from 10.1 to 14.2 g/dL (P < .001). The major and VGPR response rates were 100% and 33%, respectively, with VGPRs observed at lower ulocuplumab dose cohorts. Median times to minor and major responses were 0.9 and 1.2 months, respectively. With a median follow-up of 22.4 months, the estimated 2-year progression-free survival was 90%. The most frequent recurring grade ≥2 adverse events included reversible thrombocytopenia, rash, and skin infections. Ulocuplumab dose-escalation did not impact adverse events. The study demonstrates the feasibility of combining a CXCR4-antagonist with ibrutinib and provides support for the development of CXCR4-antagonists for CXCR4Mut WM. This trial was registered at www.clinicaltrials.gov as #NCT03225716.
Ventilatory efficiency in athletes, asthma and obesity
Authors: Collins Sophie É. , Phillips Devin B. , Brotto Andrew R. , Rampuri Zahrah H. , Stickland Michael K.
Published: July 2021

During submaximal exercise, minute ventilation (V′E) increases in proportion to metabolic rate (i.e.carbon dioxide production (V′CO2)) to maintain arterial blood gas homeostasis. The ratioV′E/V′CO2, commonly termed ventilatory efficiency, is a useful tool to evaluate exercise responses in healthy individuals and patients with chronic disease. Emerging research has shown abnormal ventilatory responses to exercise (either elevated or bluntedV′E/V′CO2) in some chronic respiratory and cardiovascular conditions. This review will briefly provide an overview of the physiology of ventilatory efficiency, before describing the ventilatory responses to exercise in healthy trained endurance athletes, patients with asthma, and patients with obesity. During submaximal exercise, theV′E/V′CO2response is generally normal in endurance-trained individuals, patients with asthma and patients with obesity. However, in endurance-trained individuals, asthmatics who demonstrate exercise induced-bronchoconstriction, and morbidly obese individuals, theV′E/V′CO2can be blunted at maximal exercise, likely because of mechanical ventilatory constraint.
Impact of ageing and pregnancy on the minute ventilation/carbon dioxide production response to exercise
Authors: Schaeffer Michele R. , Guenette Jordan A. , Jensen Dennis
Published: July 2021

Ventilatory efficiency can be evaluated using the relationship between minute ventilation (V′E) and the rate of CO2production (V′CO2). In accordance with the modified alveolar ventilation equation, this relationship is determined by changes in dead space volume (VD) and/or the arterial CO2tension (PaCO2) equilibrium point. In this review, we summarise the physiological factors that may account for normative ageing and pregnancy induced increases inV′E/V′CO2during exercise. Evidence suggests that age-related increases inVDand pregnancy-related decreases in thePaCO2equilibrium point are mechanistically linked to the increasedV′E/V′CO2during exercise. Importantly, the resultant increase inV′E/V′CO2(ratio or slope), with normal ageing or pregnancy, remains below the critical threshold for prognostic indication in cardiopulmonary disease, is not associated with increased risk of adverse health outcomes, and does not affect the respiratory system's ability to fulfil its primary role of eliminating CO2and maintaining arterial oxygen saturation during exercise.
Update on molecular pathology and role of liquid biopsy in nonsmall cell lung cancer
Authors: Abdayem Pamela , Planchard David
Published: July 2021

Personalised medicine, an essential component of modern thoracic oncology, has been evolving continuously ever since the discovery of the epidermal growth factor receptor and its tyrosine kinase inhibitors. Today, screening for driver alterations in patients with advanced lung adenocarcinoma as well as those with squamous cell carcinoma and no/little history of smoking is mandatory. Multiplex molecular platforms are preferred to sequential molecular testing since they are less time- and tissue-consuming. In this review, we present the latest updates on the nine most common actionable driver alterations in nonsmall cell lung cancer. Liquid biopsy, a simple noninvasive technique that uses different analytes, mostly circulating tumour DNA, is an appealing tool that is used in thoracic oncology to identify driver alterations including resistance mutations. Additional roles are being evaluated in clinical trials and include monitoring the response to treatment, screening for lung cancer in high-risk patients and early detection of relapse in the adjuvant setting. In addition, liquid biopsy is being tested in immune-oncology as a prognostic, predictive and pharmacodynamic tool. The major limitation of plasma-based assays remains their low sensitivity when compared to tissue-based assays. Ensuring the clinical validity and utility of liquid biopsy will definitely optimise cancer care.
Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description
Authors: Steiner Timothy J. , Jensen Rigmor , Katsarava Zaza , Stovner Lars Jacob , Uluduz Derya , Adarmouch Latifa , Al Jumah Mohammed , Al Khathaami Ali M. , Ashina Messoud , Braschinsky Mark , Broner Susan , Eliasson Jon H. , Gil-Gouveia Raquel , Gómez-Galván Juan B. , Gudmundsson Larus S. , Herekar Akbar A. , Kawatu Nfwama , Kissani Najib , Kulkarni Girish Baburao , Lebedeva Elena R. , Leonardi Matilde , Linde Mattias , Luvsannorov Otgonbayar , Maiga Youssoufa , Milanov Ivan , Mitsikostas Dimos D. , Musayev Teymur , Olesen Jes , Osipova Vera , Paemeleire Koen , Peres Mario F. P. , Quispe Guiovanna , Rao Girish N. , Risal Ajay , de la Torre Elena Ruiz , Saylor Deanna , Togha Mansoureh , Yu Sheng-Yuan , Zebenigus Mehila , Zewde Yared Zenebe , Zidverc-Trajković Jasna , Tinelli Michela ,   on behalf of Lifting The Burden: the Global Campaign against Headache
Published: July 2021

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles.

High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.

The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.

It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.
Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre
Authors: Grall Maximilien , Daviet Florence , Chiche Noémie Jourde , Provot François , Presne Claire , Coindre Jean-Philippe , Pouteil-Noble Claire , Karras Alexandre , Guerrot Dominique , François Arnaud , Benhamou Ygal , Veyradier Agnès , Frémeaux-Bacchi Véronique , Coppo Paul , Grangé Steven
Published: July 2021

Background

Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).

Methods

This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016.

Results

Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group.

Conclusions

These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.
An integrated primary care workforce planning toolkit at the regional level (part 2): quantitative tools compiled for decision-makers in Toronto, Canada
Authors: Simkin Sarah , Chamberland-Rowe Caroline , Bourgeault Ivy Lynn
Published: July 2021

Background

Health workforce planning capability at a regional level is increasingly necessary to ensure that the healthcare needs of defined local populations can be met by the health workforce. In 2016, a regional health authority in Toronto, Canada, identified a need for more robust health workforce planning infrastructure and processes. The goal of this project was to develop an evidence-informed toolkit for integrated, multi-professional, needs-based primary care workforce planning for the region. This article presents the quantitative component of the workforce planning toolkit and describes the process followed to develop this tool.

Methods

We conducted an environmental scan to identify datasets addressing population health need and profession-specific health workforce supply that could contribute to quantitative health workforce modelling. We assessed these sources of data for comprehensiveness, quality, and availability. We also developed a quantitative health workforce planning model to assess the alignment of regional service requirements with the service capacity of the workforce.

Results

The quantitative model developed as part of the toolkit includes components relating to both population health need and health workforce supply. Different modules were developed to capture the information and address local issues impacting delivery and planning of primary care health services in Toronto.

Conclusions

A quantitative health workforce planning model is a necessary component of any health workforce planning toolkit. In combination with qualitative tools, it supports integrated, multi-professional, needs-based primary care workforce planning. This type of planning presents an opportunity to address inequities in access and outcome for regional populations.
A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus
Authors: Hariharan Prashant , Sondheimer Jeffrey , Petroj Alexandra , Gluski Jacob , Jea Andrew , Whitehead William E. , Sood Sandeep , Ham Steven D. , Rocque Brandon G. , Marupudi Neena I. , McAllister James P. , Limbrick David , Del Bigio Marc R. , Harris Carolyn A.
Published: July 2021

Background

Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors.

Methods

343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry.

Results

61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p < 0.02). Mean length of time of implantation of occluded VCs, 33.22 months was greater than for non-occluded VCs, 23.8 months (p = 0.02). Patients with myelomeningocele had a greater probability of having an occluded VC (p = 0.0426). VCs with occlusions had greater numbers of macrophages and astrocytes in comparison to non-occluded VCs (p < 0.01). Microglia comprised only 2–6% of the VC-obstructing tissue aggregates. Histologic analysis showed choroid plexus occlusion in 24%, vascularized glial tissue occlusion in 24%, prevalent lymphocytic inflammation in 29%, and foreign body giant cell reactions in 5% and no ependyma.

Conclusion

Our data show that age of the first surgery and length of time a VC is implanted are factors that influence the degree of VC obstruction. The tissue aggregates obstructing VCs are composed predominantly of astrocytes and macrophages; microglia have a relatively small presence.
Image analysis for the automatic phenotyping of Orobanche cumana tubercles on sunflower roots
Authors: Le Ru A. , Ibarcq G. , Boniface M.- C. , Baussart A. , Muños S. , Chabaud M.
Published: July 2021

Background

The parasitic plant Orobanche cumana is one of the most important threats to sunflower crops in Europe. Resistant sunflower varieties have been developed, but new O. cumana races have evolved and have overcome introgressed resistance genes, leading to the recurrent need for new resistance methods. Screening for resistance requires the phenotyping of thousands of sunflower plants to various O. cumana races. Most phenotyping experiments have been performed in fields at the later stage of the interaction, requiring time and space. A rapid phenotyping screening method under controlled conditions would need less space and would allow screening for resistance of many sunflower genotypes. Our study proposes a phenotyping tool for the sunflower/O. cumana interaction under controlled conditions through image analysis for broomrape tubercle analysis at early stages of the interaction.

Results

We optimized the phenotyping of sunflower/O. cumana interactions by using rhizotrons (transparent Plexiglas boxes) in a growth chamber to control culture conditions and Orobanche inoculum. We used a Raspberry Pi computer with a picamera for acquiring images of inoculated sunflower roots 3 weeks post inoculation. We set up a macro using ImageJ free software for the automatic counting of the number of tubercles. This phenotyping tool was named RhizOSun. We evaluated five sunflower genotypes inoculated with two O. cumana races and showed that automatic counting of the number of tubercles using RhizOSun was highly correlated with manual time-consuming counting and could be efficiently used for screening sunflower genotypes at the tubercle stage.

Conclusion

This method is rapid, accurate and low-cost. It allows rapid imaging of numerous rhizotrons over time, and it enables image tracking of all the data with time kinetics. This paves the way toward automatization of phenotyping in rhizotrons that could be used for other root phenotyping, such as symbiotic nodules on legumes.
Management of chronic knee pain caused by postsurgical or posttraumatic neuroma of the infrapatellar branch of the saphenous nerve
Authors: Regev G. J. , Ben Shabat D. , Khashan M. , Ofir D. , Salame K. , Shapira Y. , Kedem R. , Lidar Z. , Rochkind S.
Published: July 2021

Purpose

Injury to the infrapatellar branch of the saphenous nerve (IBSN) is a relatively common complication after knee surgery, which can interfere with patient satisfaction and functional outcome. In some cases, injury to the IBSN can lead to formation of a painful neuroma. The purpose of this study was to report the results of surgical treatment in a series of patients with IBSN painful neuroma.

Methods

We retrospectively identified 37 patients who underwent resection of IBSN painful neuroma at our institution, after failure of non-operative treatment for a minimum of 6 months. Injury to the IBSN resulted from prior orthopedic surgery, vascular surgery, tumor resection, trauma, or infection. Leg pain and health-related quality of life were measured using the numeric rating scale (NRS) and EuroQol 5 dimensions (EQ-5D) questionnaire, respectively. Clinically meaningful improvement in leg pain was defined as reduction in NRS by at least 3 points. Predictors of favorable and unfavorable surgical outcome were investigated using multivariable logistic regression analysis.

Results

Patient-reported leg pain, health-related quality of life, and overall satisfaction with the surgical outcome were obtained at 94 ± 52.9 months after neuroma surgery. Postoperative patient-reported outcomes were available for 25 patients (68% of the cohort), of whom 20 patients (80.0%) reported improvement in leg pain, 17 patients (68.0%) reported clinically meaningful improvement in leg pain, and 17 patients (68%) reported improvement in health-related quality of life. The average NRS pain score improved from 9.43 ± 1.34 to 5.12 ± 3.33 (p < 0.01) and the average EQ-5D functional score improved from 10.48 ± 2.33 to 7.84 ± 2.19 (p < 0.01). Overall patient reported satisfaction with the surgical outcome was good to excellent for 18 patients (72.0%). Older age, multiple prior orthopedic knee surgeries, and failed prior attempts to resect an IBSN neuroma were associated with non-favorable surgical outcome.

Conclusion

We conclude that surgical intervention is efficacious for appropriately selected patients suffering from IBSN painful neuroma.
Mobilisation of emergency services for chemical incidents in Sweden - a multi-agency focus group study
Authors: Westman Anton , Saveman Britt-Inger , Björnstig Ulf , Hylander Johan , Gyllencreutz Lina
Published: July 2021

Background

In chemical incidents, infrequent but potentially disastrous, the World Health Organization calls for inter-organizational coordination of actors involved. Multi-organizational studies of chemical response capacities are scarce. We aimed to describe chemical incident experiences and perceptions of Swedish fire and rescue services, emergency medical services, police services, and emergency dispatch services personnel.

Methods

Eight emergency service organizations in two distinct and dissimilar regions in Sweden participated in one organization-specific focus group interview each. The total number of respondents was 25 (7 females and 18 males). A qualitative inductive content analysis was performed.

Results

Three types of information processing were derived as emerging during acute-phase chemical incident mobilization: Unspecified (a caller communicating with an emergency medical dispatcher), specified (each emergency service obtaining organization-specific expert information), and aligned (continually updated information from the scene condensed and disseminated back to all parties at the scene). Improvable shortcomings were identified, e.g. randomness (unspecified information processing), inter-organizational reticence (specified information processing), and downprioritizing central information transmission while saving lives (aligned information processing).

Conclusions

The flow of information may be improved by automation, public education, revised dispatcher education, and use of technical resources in the field. Future studies should independently assess these mechanism’s degree of impact on mobilisation of emergency services in chemical incidents.
Trends in clinical trial registration in sub-Saharan Africa between 2010 and 2020: a cross-sectional review of three clinical trial registries
Authors: Edem Bassey , Onwuchekwa Chukwuemeka , Wariri Oghenebrume , Nkereuwem Esin , Nkereuwem Oluwatosin O. , Williams Victor
Published: July 2021

Objective

Prospective registration of clinical trials is an ethical, scientific, and legal requirement that serves several functions, including minimising research wastage and publication bias. Sub-Saharan Africa (SSA) is increasingly hosting clinical trials over the past few years, and there is limited literature on trends in clinical trial registration and reporting in SSA. Therefore, we set out to determine the trends in clinical trials registered in SSA countries between 2010 and July 2020.

Methods

A cross-sectional study design was used to describe the type of clinical trials that are conducted in SSA from 1 January 2010 to 31 July 2020. The registries searched were ClinicalTrials.gov (CTG), the Pan African Clinical Trials Register (PACTR), and the International Standard Randomized Controlled Trial Number (ISRCTN). Data were extracted into Excel and imported into STATA for descriptive analysis.

Results

CTG had the highest number of registered trials at 2622, followed by PACTR with 1501 and ISRCTN with 507 trials. Trials were observed to increase gradually from 2010 and peaked at 2018–2019. Randomised trials were the commonest type, accounting for at least 80% across the three registries. Phase three trials investigating drugs targeted at infections/infestations were the majority. Few completed trials had their results posted: 58% in ISRCTN and 16.5% in CTG, thus suggesting reporting bias.

Conclusion

Despite the gradual increase in clinical trials registered during the period, recent trends suggest a drop in the number of trials registered across the region. Strengthening national and regional regulatory capacity will improve clinical trial registration and minimise reporting bias in completed clinical trials.
Role of Plasmodium berghei ookinete surface and oocyst capsule protein, a novel oocyst capsule-associated protein, in ookinete motility
Authors: Nakayama Kazuhiko , Kimura Yuta , Kitahara Yu , Soga Akira , Haraguchi Asako , Hakozaki Jun , Sugiyama Makoto , Kusakisako Kodai , Fukumoto Shinya , Ikadai Hiromi
Published: July 2021

Background

Plasmodium sp., which causes malaria, must first develop in mosquitoes before being transmitted. Upon ingesting infected blood, gametes form in the mosquito lumen, followed by fertilization and differentiation of the resulting zygotes into motile ookinetes. Within 24 h of blood ingestion, these ookinetes traverse mosquito epithelial cells and lodge below the midgut basal lamina, where they differentiate into sessile oocysts that are protected by a capsule.

Methods

We identified an ookinete surface and oocyst capsule protein (OSCP) that is involved in ookinete motility as well as oocyst capsule formation.

Results

We found that knockout of OSCP in parasite decreases ookinete gliding motility and gradually reduces the number of oocysts. On day 15 after blood ingestion, the oocyst wall was significantly thinner. Moreover, adding anti-OSCP antibodies decreased the gliding speed of wild-type ookinetes in vitro. Adding anti-OSCP antibodies to an infected blood meal also resulted in decreased oocyst formation.

Conclusion

These findings may be useful for the development of a transmission-blocking tool for malaria.

Graphical abstract
Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer
Authors: Feng Li-yuan , Yan Bing-bing , Huang Yong-zhi , Li Li
Published: July 2021

Background

Primary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients.

Methods

In this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan–Meier.

Results

In advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60–97.00%, 46.40–89.30% and 0.774–0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression.

Conclusions

As a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.
First discovery of nautilids from the Albian–Cenomanian succession of the Koppeh Dagh Basin, NE Iran
Authors: Sharifi Javad , Tajika Amane , Mohammadabadi Alireza , Tabari Abkuh Mohammad Hossein
Published: July 2021

The Aitamir Formation, situated in the Koppeh Dagh Basin in the northeast of Iran, is known for its well-exposed Albian-to-Cenomanian succession. Although geologists previously documented a number of macro- and microfossils, no nautilids had been discovered until now to our knowledge. Here, we present lower Albian and middle Cenomanian nautilids from the Koppeh Dagh Basin for the first time. This discovery is also the first record of Cretaceous nautilids from Iran. We identified the specimens asEutrephoceras clementianum(d’Orbigny 1840),E.sublaevigatum(d’Orbigny 1850),E.bouchardianum(d’Orbigny 1840) andEutrephocerassp. These specimens occur in horizons situated between several ammonite-bearing levels, which allowed us to more precisely constrain age estimates for the recovered nautilid specimens.E.clementianumcould not be dated precisely but likely comes from between late Aptian ammonite indexHypacanthoplites uhligiand middle AlbianHoplites(Hoplites)baylei.E. sublaevigatumoccurs just above the late Albian ammonitesMariella bergeriandSemenoviceras michalskiiand below theMantelliceras mantelliZone. At the upper part of the section,E.bouchardianumandEutrephocerassp. were collected from lower Albian beds, which correspond to theMantelliceras mantelliandMantelliceras dixoniizones. These new findings contribute to our knowledge of the geographical distribution and stratigraphic range of Albian–Cenomanian nautilid species.
Circulating miR-146a as a possible candidate biomarker in the indeterminate phase of Chagas disease
Authors: Ballinas-Verdugo Martha Alicia , Jiménez-Ortega Rogelio Frank , Martínez-Martínez Eduardo , Rivas Nancy , Contreras-López Erick Abraham , Carbó Roxana , Sánchez Fausto , Bojalil Rafael , Márquez-Velasco Ricardo , Sánchez-Muñoz Fausto , Alejandre-Aguilar Ricardo
Published: July 2021

Background

Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction.

Results

Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated.

Conclusions

The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.
Dietary intake and food behaviours of Senegalese adolescent girls
Authors: Giguère-Johnson Madélie , Ward Stéphanie , Ndéné Ndiaye Aminata , Galibois Isabelle , Blaney Sonia
Published: July 2021

Background

Malnutrition is a public health concern in low- and middle-income countries. In Senegal, 35% of adolescent girls are undernourished and 56% are anemic.

Methods

This study assessed the dietary intake of 14–18-year-old adolescent girls in Dakar, Senegal. Specifically, the study 1) assessed their intake in energy, fibre, macro- and micronutrients, 2) described the types and the quality of the foods they consume, and 3) assessed some of their eating behaviours. Dietary intake was measured using three non-consecutive 24-h recalls from 136 adolescent girls attending two colleges. Energy and nutrient intakes were measured and compared to recommendations. Foods were classified by food group and by whether they were healthy or unhealthy. Adolescents’ daily intake (g) of fruits and vegetables, as well as the proportion of girls who ate breakfast and who consumed three meals a day were calculated.

Results

Sodium intake was high, while fibre intake was low. On average, 40% of the adolescents’ total energy intake came from fats. Mean intakes of zinc and calcium were higher on the weekend than on weekdays, while the opposite was observed for sodium. Eighty-three percent of adolescents had an inadequate intake of iron and 99% were at risk of calcium deficiency. Approximately 60% of the foods consumed were classified as healthy, however, the majority came from grains.

Conclusions

Adolescent nutrition deserves attention given the poor quality of their dietary intake which may put them at risk of malnutrition and chronic diseases. These findings may be used to help improve programs targeting Senegalese adolescent girls’ nutrition.
A guide to do randomized controlled trials in the field of otolaryngology
Authors: Zamzam Sameh M. , Abdel-Aziz Mosaad , Atef Ahmed , Abdel-Naseer Usama , Hamoda Mostafa , Salah Mohamed , Dewidar Hazem , Elsharkawy Louay , Abdelmalek Mena E.
Published: July 2021

Background

Randomized controlled trials (RCTs) are prospective comparative studies in which study groups are allocated randomly to intervention or serve as controls. RCT is the mainstay to achieve evidence in the literature in clinical research. A RCT is the main research design to study the effect of an intervention and the only way to confirm the value of a new treatment.

Main body

RCT also gives the way to generate meta-analyses and systematic reviews giving a stronger evidence for clinical practice. Evidence-based medicine (EBM) is crucial for safe, effective, and standardized patient care. Although there is an agreement on the importance of performing RCT, it can be challenging to do it efficiently including different aspects like study design, funding, randomization, blinding, follow-up, data analysis, statistics, generalization of results, and reporting of quality of the studies.

Conclusion

In this article, we gave a comprehensive review for RCT in otolaryngology discussing their importance, advantages, and drawbacks, types, steps, challenges, reporting their quality and their prevalence in the literature.
CBCT image artefacts generated by implants located inside the field of view or in the exomass
Authors: Demirturk Kocasarac Husniye , Koenig Lisa J , Ustaoglu Gulbahar , Oliveira Matheus Lima , Freitas Deborah Queiroz
Published: July 2021

Objectives:

To compare artefacts in cone-beam computed tomography (CBCT) arising from implants of different materials located either inside the field of view (FOV) or in the exomass, and to test different image-acquisition parameters to reduce them.

Methods:

CBCT scans of a human mandible prepared with either a titanium, titanium–zirconium, or zirconia implant were acquired with the Planmeca ProMax utilizing FOV sizes of 8 × 5 cm and 4 × 5 cm, which placed the implant inside the FOV (8 × 5 cm) or in the exomass (4 × 5 cm). The scanning parameters considered three conditions of metal artefact reduction (MAR), disabled, low, and high, and 2 kVp levels (80 and 90). The standard deviation (SD) of grey values of regions of interest was obtained. The effects of implant material, implant position, MAR condition, kVp level, and their interactions were evaluated by Analysis of Variance (α = 5%).

Results:

The zirconia implant produced the highest SD values (more heterogeneous grey values, corresponding to greater artefact expression), followed by titanium–zirconium, and titanium. In general, implants in the exomass produced images with higher SD values than implants inside the FOV. MAR was effective in decreasing SD values, especially from the zirconia implant, only when the implant was inside the FOV. Images with 80 kVp had higher SD values than those with 90 kVp, regardless of the other factors (p < 0.05).

Conclusions:

Implants in the exomass lead to greater artefact expression than when they are inside the FOV. Special attention should be paid to scanning parameters that reduce metal-related artefacts, such as MAR activation and increasing kVp. This is especially important with a zirconia implant inside the FOV.
Effect of coping strategies on acute stress during the COVID–19 pandemic in Greece
Authors: Strongylaki Nefeli Paraskevi , Pilafas Georgios , Dermati Anastasia , Menti Despina , Lyrakos Georgios
Published: July 2021

Background: The psychological impact of quarantine, due to the SARS COVID-19 outbreak, was examined with a specific focus on the relationship between 7 coping strategies: (i) active coping, (ii) positive reframing, (iii) acceptance, (iv) use of emotional support, (v) religion, (vi) substance use and (vii) self-blame and acute stress. This study aimed to identify specifically which of those coping strategies could increase or decrease acute stress levels.Method and Material: The data collection took place during the lockdown and was performed using online surveys. The finale sample size reached up to 1154 Greek adults (age M= 40.51). Two adapted and translated scales were used to measure the variables of interest, including: Brief-COPE questionnaire as well as Acute Stress Disorder Scale (ASDS).Results: “Active coping”, “acceptance”, “positive reframing” and “emotional support”, four of the coping strategies examined, that were found to be significantly associated with stress reduction. Meanwhile, “religion”, “self-blame” and “substance use” were not associated with stress reduction. Conclusions: This study initially provides an insight of acute stress and effective coping strategies associated with the quarantine period during the COVID – 19 pandemic in Greece. The outcome of this study equip support for the expected inflation of the mental health issues stemmed from the unusual stressors, and urge clinicians, mental health providers, and public agencies to assemble, in an attempt to make possible the widespread implementation of more effective and beneficial coping strategies.
«Το αθλητικό ιδεώδες στην ποίηση: ταύτιση κάλλους και αγαθού»
Authors: Τριπόδης Νικόλαος
Published: July 2021

Eιδικό Τεύχος: Πρακτικά Προγράμματος «Το αθλητικό ιδεώδες στην ποίηση: ταύτιση κάλλους και αγαθού»
Just Art. Documentary poetics and justice
Authors: Toth Naomi
Published: July 2021

Introduction
Parragirls Past, Present: Unlocking Memories of Institutional ‘Care’: Witnessing and Creative Reparation in the Aftermath of Parramatta Girls Home
Authors: Toth Naomi , Hibberd Lily
Published: July 2021

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‘The Quarrel with Ourselves’. An Interview with Marjorie Perloff
Authors: Toth Naomi , Perloff Marjorie
Published: July 2021

Interview
Notes Towards an Exilic Co-existence
Authors: Radhakrishnan R.
Published: July 2021

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Double burden of malnutrition among school-aged children and adolescents: evidence from a community-based cross-sectional survey in two Nigerian States
Authors: Adeomi Adeleye , Fatusi Adesegun , Klipstein-Grobusch Kerstin
Published: July 2021

Background: Double burden of malnutrition (DBM) is the co-existence of overweight/obesity and undernutrition. Rising prevalence rates of childhood overweight/obesity in Nigeria have been reported, whilst undernutrition continues to be prevalent. This study aimed to estimate the prevalence and distribution of underweight, stunting, thinness, overweight/obesity, and DBM among school-aged children and adolescents in two Nigerian States.

Methods: This was a community-based cross-sectional study carried out in Osun and Gombe States. A total of 1,200 children aged 6 – 19 years were recruited using multi-stage sampling technique. Weight, height and data on demographic, socio-economic, household/family characteristics of the children were collected using structured interviewer administered questionnaires. Nutritional status was calculated using the WHO 2007 reference values using BMI-for-age (thinness, overweight/obesity), height-for-age (stunting) and weight-for-age (underweight). DBM was described at the population and individual levels.

Results: The mean age of the respondents was 11.6 ± 3.8 years. The overall prevalence rate of stunting was 34.9%, underweight was 13.5%, thinness was 10.3% and overweight/obese was 11.4% and 4.0% had individual level DBM, which typifies the DBM at individual and population levels. These rates differed significantly across demographic, socio-economic and household/family characteristics (p < 0.05). Gombe State, which is in the Northern part of Nigeria, had significantly higher burden of stunted, underweight and thin children than Osun State, while Osun State, in the Southern part of Nigeria, had a significantly higher burden of overweight/obesity.

Conclusions: The study found evidence of DBM both at population and individual levels. The overall prevalence rates of stunting, underweight, thinness and overweight/obesity in this study were high, and they differed significantly across the demographic, socio-economic and household/family characteristics. There is the need for government and all other stakeholders to design nutritional educational programmes that will target both under- and over-nutrition among older children in the different contexts.
Screening for postoperative complications by continuous monitoring: protocol for the Biobeat-Postop cohort study
Authors: Paternot Alexis , Aegerter Philippe , Martin Aurélie , Ouattara Jonathan , Ma Sabrina , Adjavon Sherifa , Trillat Bernard , Alfonsi Pascal , Fischler Marc , Le Guen Morgan
Published: July 2021

Background: Postoperative hypotension associated with postoperative morbidity and early mortality has been studied previously. Hypertension and other hemodynamic, respiratory, and temperature abnormalities have comparatively understudied during the first postoperative days.

Methods: This bi-centre observational cohort study will include 114 adult patients undergoing non-cardiac surgery hospitalized on an unmonitored general care floor and wearing a multi-signal wearable sensor, allowing remote monitoring (Biobeat Technologies Ltd, Petah Tikva, Israel). The study will cover the first 72 hours after discharge of the patient from the post-anaesthesia care unit. Several thresholds will be used for each variable (arterial pressure, heart rate, respiratory rate, oxygen saturation, and skin temperature). Data obtained using the sensor will be compared to data obtained during the routine nurse follow-up. The primary outcome is hemodynamic abnormality. The secondary outcomes are postoperative respiratory and temperature abnormalities, artefacts and blank/null outputs from the wearable device, postoperative complications, and finally, the ease of use of the device. We hypothesize that remote monitoring will detect abnormalities in vital signs more often or more quickly than the detection by nurses’ routine surveillance.

Discussion: A demonstration of the ability of wireless sensors to outperform standard monitoring techniques paves the way for the creation of a loop which includes this monitoring mode, the automated creation of alerts, and the sending of these alerts to caregivers.

Trial registration: ClinicalTrials.gov, NCT04585178. Registered on October 14, 2020
The future of public health policymaking after COVID-19: a qualitative systematic review of lessons from Health in All Policies
Authors: Cairney Paul , St Denny Emily , Mitchell Heather
Published: July 2021

Background: ‘Health in All Policies’ (HiAP) describes the pursuit of health equity. It has five main elements: treat health as a human right; identify evidence of the ‘social determinants’ of health inequalities, recognise that most powers to affect health are not held by health departments, promote intersectoral policymaking and collaboration inside and outside of government, and generate political will. Studies describe its potential but bemoan a major implementation gap. Some HiAP scholars learn from policymaking research how to understand this gap, but the use of policy theories is patchy. In that context, our guiding research question is:How does HiAP research use policy theory to understand policymaking?It allows us to zoom-out to survey the field and zoom-in to identify: the assumed and actual causes of policy change, and transferable lessons to HiAP scholars and advocates.

Methods: Our qualitative systematic review (two phases, 2018 and 2020) identified 4972 HiAP articles. Of these, 113 journal articles (research and commentary) provide a non-trivial reference to policymaking (at least one reference to a policymaking concept). We use the 113 articles to produce a general HiAP narrative and explore how the relatively theory-informed articles enhance it.

Results: Most articles focus on policy analysis (identifying policy problems and solutions) rather than policy theory (explaining policymaking dynamics). They report a disappointing gap between HiAP expectations and policy outcomes. Theory-informed articles contribute to a HiAP playbook to close that gap or a programme theory to design and evaluate HiAP in new ways.  

Conclusions: Few HiAP articles use policy theories for their intended purpose. Policy theories provide lessons to aid critical reflection on power, political dilemmas, and policymaking context. HiAP scholars seek more instrumental lessons, potentially at the cost of effective advocacy and research.