The association between dietary intakes of methionine, choline and betaine and breast cancer risk: A systematic review and meta-analysis.

BACKGROUND AND AIM: This study evaluates the associations between dietary intakes and circulating blood levels of methionine, choline or betaine and breast cancer risk, which remains currently unclear. METHODS: Systematic searches for observational epidemiological studies were performed of the MEDLINE, Embase, and Web of Science databases through July, 2022. Two review authors independently screened titles and abstracts against the eligibility criteria at a first stage, and screened full texts of potentially eligible records at a second stage, followed by data extraction from qualified studies. Quality of evidence was assessed using the Newcastle-Ottawa scale quality assessment tool. Risk estimates were calculated using random-effects meta-analysis. RESULTS: In total, 21 studies were selected for qualitative analyses and 18 studies were included in the meta-analyses. Random-effects analysis combining prospective cohort (N = 8) or case-control studies (N = 10) showed little evidence of an association between dietary intake of methionine or betaine and the risk of breast cancer. However, inconclusive evidence for a significant inverse association between choline intake and breast cancer risk was found in case-control studies (odds ratio [OR] estimates for highest vs. lowest intakes = 0.38; 95 % CI: 0.16-0.86) but not in prospective cohort studies (hazard ratio [HR] estimates for highest vs. lowest intakes = 1.01; 95 % CI: 0.92-1.12). CONCLUSION: This study did not suggest an effect of dietary intake of methionine, choline, nor betaine on breast cancer risk, mainly due to the lack of precision of the combined risk estimates as few studies are available. To overcome this uncertainty, more well-designed studies with relevant individual-level covariates are needed.

Phyllodes tumour evidence gaps mapped from the 5th edition of the WHO classification of tumours of the breast.

AIMS: Breast phyllodes tumours (PTs) are a rare subset of fibroepithelial neoplasms categorised into benign, borderline, and malignant grades according to the World Health Organization (WHO) Classification of Tumours (WCTs). In this report, we developed an evidence gap map (EGM) based on the literature cited in the PT chapter of the 5th edition of the breast WCT in order to identify knowledge and research gaps in PT. METHODS: A framework was first established where the dimensions of the EGM were defined as categories of tumour descriptors, tumour types, and evidence levels. Citations were collected into a Microsoft Excel form and imported into EPPI-reviewer to produce the EGM. RESULTS: The EGM showed that the "Histopathology" and "Pathogenesis" sections contained the most citations, the majority being of low-level evidence. The highest number of citations considered of moderate-level evidence were found in the "Histopathology" section. There was no high-level evidence cited in this chapter. The "Localisation", "Aetiology", and "Staging" sections had the fewest citations. CONCLUSION: This EGM provides a visual representation of the cited literature in the PT chapter of the breast WCT, revealing the lack of high-level evidence citations. There is an uneven distribution of references, probably due to citation practices. Pockets of low-level evidence are highlighted, possibly related to referencing habits, lack of relevant research, or the belief that the information presented is standard accepted fact, without the need for specific citations. Future work needs to bridge evidence gaps and broaden citations beyond those in the latest WCT.

Machine learning computational tools to assist the performance of systematic reviews: A mapping review.

BACKGROUND: Within evidence-based practice (EBP), systematic reviews (SR) are considered the highest level of evidence in that they summarize the best available research and describe the progress in a determined field. Due its methodology, SR require significant time and resources to be performed; they also require repetitive steps that may introduce biases and human errors. Machine learning (ML) algorithms therefore present a promising alternative and a potential game changer to speed up and automate the SR process. This review aims to map the current availability of computational tools that use ML techniques to assist in the performance of SR, and to support authors in the selection of the right software for the performance of evidence synthesis. METHODS: The mapping review was based on comprehensive searches in electronic databases and software repositories to obtain relevant literature and records, followed by screening for eligibility based on titles, abstracts, and full text by two reviewers. The data extraction consisted of listing and extracting the name and basic characteristics of the included tools, for example a tool's applicability to the various SR stages, pricing options, open-source availability, and type of software. These tools were classified and graphically represented to facilitate the description of our findings. RESULTS: A total of 9653 studies and 585 records were obtained from the structured searches performed on selected bibliometric databases and software repositories respectively. After screening, a total of 119 descriptions from publications and records allowed us to identify 63 tools that assist the SR process using ML techniques. CONCLUSIONS: This review provides a high-quality map of currently available ML software to assist the performance of SR. ML algorithms are arguably one of the best techniques at present for the automation of SR. The most promising tools were easily accessible and included a high number of user-friendly features permitting the automation of SR and other kinds of evidence synthesis reviews.

Understanding the use of evidence in the WHO Classification of Tumours: a protocol for an evidence gap map of the classification of tumours of the lung.

INTRODUCTION: There are gaps in the evidence base of tumour classification despite being essential for cancer diagnosis, treatment and patient care. The WHO in charge of the production of an updated international classification, the WHO Classification of Tumours (WCT), aims to adapt evidence gap map (EGM) methodology to inform future editions of the WCT, by providing a visual summary of the existing evidence. METHODS AND ANALYSIS: Bibliographical references used in the WCT fifth edition of Tumours of the Lung (Thoracic Tumours volume) will be used as search results of a literature search. A descriptive analysis of the cited evidence for tumour types and descriptors will be drafted and plotted in EPPI-Reviewer to develop a visual evidence map. The resulting EGM will reflect the number of cited studies in the size of the spheres, and the level of evidence by applying a four-colour code (red=low level evidence, orange=moderate level, green=high level and blue=unclassifiable). Overview of the findings will be provided in narrative form and a report will discuss the overall stage of cited research in the WCT and will include analysis of gaps, under-researched categories of tumour descriptors and pockets of low-level evidence. ETHICS AND DISSEMINATION: No ethics approval will be required as this is a study of previously published material. Findings of the EGM will be published and used to guide editors, stakeholders and researchers for future research planning and related decision-making, especially for the development of future editions of the WCT. PROSPERO REGISTRATION NUMBER: CRD42022302327.

Global frequency and epidemiological profile of electronic cigarette users: a systematic review.

OBJECTIVE: Electronic cigarette (e-cigarette) use is growing significantly worldwide, especially among young people. This product has been associated with renormalizing smoking and hindering quit attempts in smokers. Moreover, among nonsmokers, it can lead to subsequent cigarette smoking and nicotine dependence. The present study aimed to assess the epidemiological profile of e-cigarette users worldwide. STUDY DESIGN: A systematic review was performed using 3 main electronic databases (Medline/PubMed, SCOPUS, and EMBASE). Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the MAStARI critical appraisal instrument. RESULTS: From 4,496 records, 43 were included. Among the 1,238,392 participants, 132,786 (10.72%) were e-cigarette users. The age range with the highest percentage of e-cigarette users was 18-24 years old, with 40,989 (30.86%) males, 34,875 (26.26%) females, and 33.6% being current cigarette smokers. The highest prevalence of users was 52.88% in Croatia and 49.62% in New Zealand. Other possible correlations were observed with e-cigarette use, such as a high level of education. CONCLUSION: Overall, e-cigarette users tended to be male young adults with a higher level of education. The highest prevalence of use was found in Croatia. This systematic review provides valuable information to improve the development of appropriate intervention strategies targeting e-cigarette users for more accurate anti-smoking actions.

Clinical predictors of malignant transformation and recurrence in oral potentially malignant disorders: A systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral potentially malignant disorders (OPMDs) (actinic cheilitis [AC], oral leukoplakia [OL], and proliferative verrucous leukoplakia [PVL]). STUDY DESIGN: We selected studies that included clinical features and risk factors (age, sex, site, size, appearance, alcohol intake, tobacco use, and sun exposure) of OL, PVL, and AC associated with recurrence and/or MT. RESULTS: Based on the meta-analysis results, non-homogeneous OL appears to have a 4.53 times higher chance of recurrence after treatment. We also found 6.52 higher chances of MT of non-homogeneous OL. Another clinical feature related to higher MT chances is the location (floor of the mouth and tongue has 4.48 higher chances) and the size (OL with >200 mm2 in size has 4.10 higher chances of MT). Regarding habits, nonsmoking patients with OL have a 3.20 higher chance of MT. The only clinical feature related to higher chances of MT in patients with PVL was sex (females have a 2.50 higher chance of MT). CONCLUSIONS: Our study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD.

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review.

BACKGROUND: It remains uncertain whether Kaposi sarcoma (KS) is a true neoplasm, in that it regresses after removal of the stimulus to growth (as HHV8) when immunosuppression is reduced. We aimed to summarize the available evidence on somatic mutations and clonality within KS to assess whether KS is a neoplasm or not. METHODS: Medline and Web of Science were searched until September 2020 for articles on clonality or mutation in KS. Search strings were supervised by expert librarians, and two researchers independently performed study selection and data extraction. An adapted version of the QUADAS2 tool was used for methodological quality appraisal. RESULTS: Of 3077 identified records, 20 publications reported on relevant outcomes and were eligible for qualitative synthesis. Five studies reported on clonality, 10 studies reported on various mutations, and 5 studies reported on chromosomal aberrations in KS. All studies were descriptive and were judged to have a high risk of bias. There was considerable heterogeneity of results with respect to clonality, mutation and cytogenetic abnormalities as well as in terms of types of lesions and patient characteristics. CONCLUSIONS: While KS certainly produces tumours, the knowledge is currently insufficient to determine whether KS is a clonal neoplasm (sarcoma), or simply an aggressive reactive virus-driven lesion.

The International Collaboration for Cancer Classification and Research.

Gaps in the translation of research findings to clinical management have been recognized for decades. They exist for the diagnosis as well as the management of cancer. The international standards for cancer diagnosis are contained within the World Health Organization (WHO) Classification of Tumours, published by the International Agency for Research on Cancer (IARC) and known worldwide as the WHO Blue Books. In addition to their relevance to individual patients, these volumes provide a valuable contribution to cancer research and surveillance, fulfilling an important role in scientific evidence synthesis and international standard setting. However, the multidimensional nature of cancer classification, the way in which the WHO Classification of Tumours is constructed, and the scientific information overload in the field pose important challenges for the translation of research findings to tumour classification and hence cancer diagnosis. To help address these challenges, we have established the International Collaboration for Cancer Classification and Research (IC3 R) to provide a forum for the coordination of efforts in evidence generation, standard setting and best practice recommendations in the field of tumour classification. The first IC3 R meeting, held in Lyon, France, in February 2019, gathered representatives of major institutions involved in tumour classification and related fields to identify and discuss translational challenges in data comparability, standard setting, quality management, evidence evaluation and copyright, as well as to develop a collaborative plan for addressing these challenges.

Closing the gap between training needs and training provision in addiction medicine.

Substance use disorders pose a significant global social and economic burden. Although effective interventions exist, treatment coverage remains limited. The lack of an adequately trained workforce is one of the prominent reasons. Recent initiatives have been taken worldwide to improve training, but further efforts are required to build curricula that are internationally applicable. We believe that the training needs of professionals in the area have not yet been explored in sufficient detail. We propose that a peer-led survey to assess those needs, using a standardised structured tool, would help to overcome this deficiency. The findings from such a survey could be used to develop a core set of competencies which is sufficiently flexible in its implementation to address the specific needs of the wide range of professionals working in addiction medicine worldwide.

What Are the Self-Assessed Training Needs of Early Career Professionals in Addiction Medicine? A BEME Focused Review.

This article was migrated. The article was marked as recommended. Background: Substance use disorders represent a significant social and economic burden globally. Accurate diagnosis and treatment by early career professionals in addiction medicine (ECPAM) falls short, in part, due to a lack of training programmes targeting this career stage. Prior research has highlighted the need to assess the specific training needs of ECPAM. Therefore, this focused review assessed self-reported training needs of ECPAM. Methods: Medical and medical education databases (Medline, EMBASE, CINAHL, ERIC, PSYCHInfo, BEI, and AEI) were searched to June 2018 for studies reporting self-reported training needs of ECPAM (trained at most five years before assessment occurred). Retrieved citations were screened for eligibility; two independent researchers reviewed included studies, assessed quality and extracted data. Experts reviewed study findings. Results: Of 1364 identified records, three cross-sectional studies were included, originating from China, USA and England. All studies surveyed ECPAM using self-reported questionnaires, with one study including face-to-face interviews. Participants included residents, physicians and social workers. All studies had a low risk of bias, and reported a wide range of training needs including rehabilitation, relapse prevention, buprenorphine treatment and risk assessment. Conclusions: There is little evidence for and substantial heterogeneity of training needs of ECPAM found in this review, particularly at the level of skills and knowledge. Study quality varies greatly. ECPAM training needs assessments are a priority.

Anemia en el primer control de gestantes en un centro de salud de Lima, Perú y su relación con el estado nutricional pregestacional / Anemia at the first prenatal visit in a health center in Lima, Peru, and its relationship with the pregestational nutritional status

Objetivo: Determinar la frecuencia de anemia en gestantes y su relación con el estado nutricional pregestacional. Materiales y métodos: Estudio descriptivo, observacional, transversal y retrospectivo, realizado en el Servicio de Obstetricia y Nutrición del Centro de Salud del distrito de Santiago de Surco entre el 1 de julio de 2015 y el 31 julio de 2016.Se revisaron 455 historias clínicas materno-perinatales (HCMP) del servicio de Obstetricia del Centro de Salud de Surco de las que se seleccionaron 93 que cumplian los criterios de inclusión. Se utilizó estadística descriptiva.Resultados: El 11,8 % de gestantes presentaron anemia. La hemoglobina promedio en las gestantes fue 12,2 ± 1,06 g/dl. El 58,5 % tenía índice de masa corporal (IMC) pregestacional normal y también una mayor frecuencia de anemia (10,7 %). Se observó que los casos de anemia son más frecuentes en los dos primeros trimestres, con un promedio de 4,8 %, y disminuyen en el tercer trimestre (2,2 %). Conclusiones: La mayor frecuencia de anemia en mujeres embarazadas se presentó en el grupo con IMC pregestacional normal. Los niveles de hemoglobina disminuyen de acuerdo a la edad de la madre y aumentan conforme a la edad gestacional.

Objective: To determine the frequency of anemia in pregnant women and its relationship with the pregestational nutritional status.Materials and methods: A descriptive, observational, cross-sectional and retrospective study was carried out in the Obstetrics and Nutrition Department of the Centro de Salud de Surco between July 1, 2015 and July 31, 2016. Four hundred fifty-five (455) maternal perinatal medical records (HCMP) from the Obstetrics Department of the Centro de Salud de Surco were reviewed, out of which 93 met the inclusion criteria and were selected. Descriptive statistics was used.Results:Eleven point eight percent (11.8 %) of the pregnant women presented anemia. The average hemoglobin level in the aforementioned women was 12.2 ± 1.06 g/dl. Fifty-eight point five percent (58.5 %) had a normal pregestational body mass index (BMI) and the highest frequency of anemia (10.7 %). It was observed that cases of anemia were more frequent in the first two quarters of pregnancy, reaching on average 4.8 %, and decreased in the third quarter (2.2 %).Conclusions: The highest frequency of anemia in pregnant women occurred in the normal pregestational BMI group. Hemoglobin levels decrease according to the age of the mother and increase according to the gestational age.

Interferometric nanoimmunosensor for label-free and real-time monitoring of Irgarol 1051 in seawater.

An interferometric nanobiosensor for the specific and label-free detection of the pollutant Irgarol 1051 directly in seawater has been settled. Due to the low molecular weight of Irgarol pollutant and its expected low concentration in seawater, the sensor is based on a competitive inhibition immunoassay. Parameters as surface biofunctionalization, concentration of the selective antibody and regeneration conditions have been carefully evaluated. The optimized immunosensor shows a limit of detection of only 3 ng/L, well below the 16 ng/L set by the EU as the maximum allowable concentration in seawater. It can properly operate during 30 assay-regeneration cycles using the same sensor biosurface and with a time-to-result of only 20 min for each cycle. Moreover, the interferometric nanosensor is able to directly detect low concentrations of Irgarol 1051 in seawater without requiring sample pre-treatments and without showing any background signal due to sea matrix effect.

Nanophotonic label-free biosensors for environmental monitoring.

The field of environmental monitoring has experienced a substantial progress in the last years but still the on-site control of contaminants is an elusive problem. In addition, the growing number of pollutant sources is accompanied by an increasing need of having efficient early warning systems. Several years ago biosensor devices emerged as promising environmental monitoring tools, but their level of miniaturization and their fully operation outside the laboratory prevented their use on-site. In the last period, nanophotonic biosensors based on evanescent sensing have emerged as an outstanding choice for portable point-of-care diagnosis thanks to their capability, among others, of miniaturization, multiplexing, label-free detection and integration in lab-on-chip platforms. This review covers the most relevant nanophotonic biosensors which have been proposed (including interferometric waveguides, grating-couplers, microcavity resonators, photonic crystals and localized surface plasmon resonance sensors) and their recent application for environmental surveillance.

The Disulfide Bond Cys255-Cys279 in the Immunoglobulin-Like Domain of Anthrax Toxin Receptor 2 Is Required for Membrane Insertion of Anthrax Protective Antigen Pore.

Anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, pH-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. We previously reported that reduction of the disulfide bonds in the immunoglobulin-like (Ig) domain of the anthrax toxin receptor 2 (ANTXR2) inhibited the function of the protective antigen (PA) pore. In the present study, the disulfide linkage in the Ig domain was identified as Cys255-Cys279 and Cys230-Cys315. Specific disulfide bond deletion mutants were achieved by replacing Cys residues with Ala residues. Deletion of the disulfide bond C255-C279, but not C230-C315, inhibited the PA pore-induced release of the fluorescence dyes from the liposomes, suggesting that C255-C279 is essential for PA pore function. Furthermore, we found that deletion of C255-C279 did not affect PA prepore-to-pore conversion, but inhibited PA pore membrane insertion by trapping the PA membrane-inserting loops in proteinaceous hydrophobic pockets. Fluorescence spectra of Trp59, a residue adjacent to the PA-binding motif in von Willebrand factor A (VWA) domain of ANTXR2, showed that deletion of C255-C279 resulted in a significant conformational change on the receptor ectodomain. The disulfide deletion-induced conformational change on the VWA domain was further confirmed by single-particle 3D reconstruction of the negatively stained PA-receptor heptameric complexes. Together, the biochemical and structural data obtained in this study provides a mechanistic insight into the role of the receptor disulfide bond C255-C279 in anthrax toxin action. Manipulation of the redox states of the receptor, specifically targeting to C255-C279, may become a novel strategy to treat anthrax.

Colecistitis aguda enfisematosa / Emphysematous cholecystitis

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Pediatric formulation issues identified in Paediatric Investigation Plans.

Since the European Paediatric Regulation was introduced in 2007, companies developing new medicinal products or new indications/routes of administration/pharmaceutical forms are obliged to present age-appropriate formulations for the pediatric population within a Paediatric Investigation Plan (PIP) to the European Medicines Agency. Our review highlights a number of discrepancies between what is proposed by applicants and what is considered acceptable by regulators, taking a sample of PIP applications assessed by a specialized Formulation Working Group (FWG) of the Paediatric Committee in 2009. This Working Group assessed 43% of the total number of validated PIP applications during that year. Ninety-two percent of the formulations assessed raised at least one issue, mainly relating to excipients, appropriateness of the route of administration or pharmaceutical form, dosing accuracy and patient's acceptability. A stronger focus on all these aspects, considering the targeted age range, the severity of the disease and the treatment duration, could streamline the development process.

Presence and composition of cathinone derivatives in drug samples taken from a drug test service in Spain (2010-2012).

OBJECTIVE: The aim of this study was to describe the presence and composition of cathinone derivatives (CDs) in drug samples analyzed at a Drug Testing Service. MATERIAL AND METHODS: Data provided by the Drug Testing Service at Energy Control (a Spanish organization working in risk reduction among recreational drug users) were obtained from samples delivered as, or containing CDs, between January 2010 and June 2012. Specimens were identified by combining thin layer chromatography and gas chromatography associated with mass spectrometry. RESULTS: Two hundred and thirty-seven (3.8%) of the 6199 samples were delivered as, or contained CDs. 22 different CDs were detected, alone or in different combinations. Methylone (24.9%), mephedrone (24.5%), 4-methylethcathinone (9.28%), and methylenedioxypyrovalerone (6.8%) were the most common CDs. These substances were also found in 80 (1.3%) of 6042 samples delivered allegedly containing drugs different from CDs (such as 3,4-methylenedioxy-N-methylamphetamine (MDMA), amphetamines, ketamine…). CONCLUSIONS: Cathinone derivatives were markedly present in the Spanish drug market during the studied period. There is no evidence to conclude that use of CDs will become widespread or relevant for public health, but the phenomenon must be followed, as the potential risks of these new drugs of abuse are substantial.