Breakthrough Article Research Articles

The 2024 Nucleic Acids Research database issue and the online molecular biology database collection.

The 2024 Nucleic Acids Research database issue contains 180 papers from across biology and neighbouring disciplines. There are 90 papers reporting on new databases and 83 updates from resources previously published in the Issue. Updates from databases most recently published elsewhere account for a further seven. Nucleic acid databases include the new NAKB for structural information and updates from Genbank, ENA, GEO, Tarbase and JASPAR. The Issue's Breakthrough Article concerns NMPFamsDB for novel prokaryotic protein families and the AlphaFold Protein Structure Database has an important update. Metabolism is covered by updates from Reactome, Wikipathways and Metabolights. Microbes are covered by RefSeq, UNITE, SPIRE and P10K; viruses by ViralZone and PhageScope. Medically-oriented databases include the familiar COSMIC, Drugbank and TTD. Genomics-related resources include Ensembl, UCSC Genome Browser and Monarch. New arrivals cover plant imaging (OPIA and PlantPAD) and crop plants (SoyMD, TCOD and CropGS-Hub). The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Over the last year the NAR online Molecular Biology Database Collection has been updated, reviewing 1060 entries, adding 97 new resources and eliminating 388 discontinued URLs bringing the current total to 1959 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection.

The 2023 Nucleic Acids Research Database Issue contains 178 papers ranging across biology and related fields. There are 90 papers reporting on new databases and 82 updates from resources previously published in the Issue. Six more papers are updates from databases most recently published elsewhere. Major nucleic acid databases reporting updates include Genbank, ENA, ChIPBase, JASPAR, mirDIP and the Issue's first Breakthrough Article, NACDDB for Circular Dichroism data. Updates from BMRB and RCSB cover experimental protein structural data while AlphaFold 2 computational structure predictions feature widely. STRING and REBASE are stand-out updates in the signalling and enzymes section. Immunology-related databases include CEDAR, the second Breakthrough Article, for cancer epitopes and receptors alongside returning IPD-IMGT/HLA and the new PGG.MHC. Genomics-related resources include Ensembl, GWAS Central and UCSC Genome Browser. Major returning databases for drugs and their targets include Open Targets, DrugCentral, CTD and Pubchem. The EMPIAR image archive appears in the Issue for the first time. The entire database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, revisiting 463 entries, adding 92 new resources and eliminating 96 discontinued URLs so bringing the current total to 1764 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

Characteristics and Trends of Highly Cited Articles in Calcaneus Fracture Research.

Background:Despite significant effort expended toward exploring fracture patterns, surgical timing, surgical approaches, and possible implants within the calcaneus fracture literature, treatment is still fraught with complications and controversy. This study aims to conduct a citation analysis of the most cited articles related to calcaneus fractures to highlight the most historically influential articles, as well as the more recent breakthrough articles that are leading change within the field.Methods:A literature search was performed via Scopus on September 20, 2021 using the terms “(calcaneus OR calcaneal OR hindfoot) AND (fracture OR injury)” to search “article title, abstract, and keywords” of all primary and review articles. Search results were rigorously reviewed to ensure appropriateness for this study. The 50 highest total cited included articles were analyzed. Title, authors, journal, country of origin, institution, year of publication, citation variables (total citation count, total citation density, citation count from the last 5 years, and 5-year citation density), and level of evidence were collected for each article. One-way analysis of variance with post hoc testing was used to identify differences in citation variables and level of evidence. Pearson correlation was used to directly compare different citation variables.Results:The total citation count average was 178±33, with a total citation density average of 9±2. The year of publication for the 50 articles ranged from 1948 to 2014, with a median year of 1999. Roy W. Sanders was the most productive author in the field, authoring 6 articles and lead authoring 3. The most frequent level of evidence was IV with 19 articles. There was a strong correlation between total citation density and 5-year citation density. The article level of evidence showed no impact on the included measures of an article’s influence.Conclusion:This study successfully analyzes and presents the characteristics among the highest cited articles related to calcaneus fractures. The provided characterization of influential works and authors highlights trends, impactful findings, and future areas of focus within calcaneus fracture literature.Level of Evidence: Review Article.

A deep learning approach for identifying biomedical breakthrough discoveries using context analysis

Breakthrough research in scientific fields usually comes as a manifestation of major development and advancement. These advances build to an epiphany where new ways of thinking about a problem become possible. Identifying breakthrough research can be useful for cultivating and funding further innovation. This article presents a new method for identifying scientific breakthroughs from research papers based on cue words commonly associated with major advancements. We looked for specific terms signifying scientific breakthroughs in citing sentences to identify breakthrough articles. By setting a threshold for the number of citing sentences (“citances”) with breakthrough cue words that peer scholars often use when evaluating research, we identified articles containing breakthrough research. We call this approach the “others-evaluation” process. We then shortlisted candidates from the selected articles based on the authors’ evaluations of their own research, found in the abstracts. This we call the “self-evaluation” process. Combining the two approaches into a dual “others-self” evaluation process, we arrived at a sample of 237 potential breakthrough articles, most of which are recommended by the Faculty Opinions. Based on the breakthrough articles identified, using SVM, TextCNN, and BERT to train the models to identify abstracts with breakthrough evaluations. This automatic identification model can greatly simplify the process of others-self-evaluation process and promote identifying breakthrough research.

Extraordinary claims require extraordinary evidence in asserted mtDNA biparental inheritance

A breakthrough article published in PNAS by Luo et al. challenges a central dogma in biology which states that the mitochondrial DNA (mtDNA) in humans is inherited exclusively from the mother. We re-analyzed original FASTQ files and results reported by Luo et al. to investigate methodological issues (e.g. nuclear mitochondrial DNA or NUMTs, DNA rearrangements) that could lead to biological misinterpretations. A comprehensive analysis of their data reveals several methodological and analytical issues that must be carefully addressed before challenging the current paradigm. We first show that the probability of the findings described by the authors is extremely small (most likely below 10−37). The sequencing replicates from the same donors show aberrations in the variants detected that need further investigation to exclude contributions from other sources or methodological artifacts. Applying the principle of reductio ad absurdum, we demonstrate that the nuclear factor invoked by the authors to explain the phenomenon would need to be extraordinarily complex and precise to preclude linear accumulation of mtDNA lineages across generations, which would make the appearance of mixed haplotypes a much more frequent event in the population. We discuss alternate scenarios that explain findings of the same nature as reported by Luo et al., in the context of in-vitro fertilization and therapeutic mtDNA replacement ooplasmic transplantation.

The 27th annual Nucleic Acids Research database issue and molecular biology database collection.

The 2020 Nucleic Acids Research Database Issue contains 148 papers spanning molecular biology. They include 59 papers reporting on new databases and 79 covering recent changes to resources previously published in the issue. A further ten papers are updates on databases most recently published elsewhere. This issue contains three breakthrough articles: AntiBodies Chemically Defined (ABCD) curates antibody sequences and their cognate antigens; SCOP returns with a new schema and breaks away from a purely hierarchical structure; while the new Alliance of Genome Resources brings together a number of Model Organism databases to pool knowledge and tools. Major returning nucleic acid databases include miRDB and miRTarBase. Databases for protein sequence analysis include CDD, DisProt and ELM, alongside no fewer than four newcomers covering proteins involved in liquid–liquid phase separation. In metabolism and signaling, Pathway Commons, Reactome and Metabolights all contribute papers. PATRIC and MicroScope update in microbial genomes while human and model organism genomics resources include Ensembl, Ensembl genomes and UCSC Genome Browser. Immune-related proteins are covered by updates from IPD-IMGT/HLA and AFND, as well as newcomers VDJbase and OGRDB. Drug design is catered for by updates from the IUPHAR/BPS Guide to Pharmacology and the Therapeutic Target Database. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been revised, updating 305 entries, adding 65 new resources and eliminating 125 discontinued URLs; so bringing the current total to 1637 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

Peripheral neurons: Master regulators of skin and mucosal immune response.

The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro-immune interactions.

Innovations: Brave new worlds.

The field of cytopathology, from fine-needle aspiration to computer-assisted screening, has always attracted innovators and creative thinkers. Technology touches every aspect of our world and our cytopathology practice. Opportunities and challenges both are in abundant supply. In this new “Innovations” section, we will highlight the latest developments in technology, social media, and informatics to keep readers up to date. Social media has added new layers of interaction and networking capabilities to our field. The pathology and cytopathology communities have harnessed the power of these technologies to build stronger professional networks, share and discuss the latest research findings, and even conduct multi-institutional research studies. Social media platforms make the world smaller, enabling education and collaborations across continents. Journal clubs now can involve participants from across the country. Twitter chats regarding topics such as the Milan System, ancillary testing in cytology, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) flatten hierarchies and allow unprecedented real-time access to experts in the field (Fig. 1). Our recent #CytoChat on the topic of NIFTP featured a real-time discussion of practice patterns, the sharing of useful articles, and expert input from Drs. Faquin and Rossi. This chat drew greater than 60 participants from around the world, garnering greater than 1 million potential impressions. Not sure how to get started with social media? A previously published article provides an overview of what social media can do for you, and how to get started.1 To make sure you do not miss out, follow Cancer Cytopathology on Facebook (https://www.facebook.com/CancerCytopath) and Twitter (https://twitter.com/CancerCytopath). The complexity of workflows and the need to meet quality assurance mandates have precipitated the computerization of the cytology laboratory to improve effectiveness and efficiency. As an early adopter of pathology informatics and its data management principle, the cytology laboratory has in some ways defined how data are collected, accessed, and analyzed. Another area of informatics to which cytology has made early contributions is digital pathology. Ironically, although one of the first successful implementations of digital pathology was the automation of the Papanicolaou test, progress in this realm of informatics has been delayed due to the unique challenges present in cytologic specimens and the use of whole-slide imaging (WSI). Nevertheless, computational progress and improved imaging technology have allowed pathology informatics to enter a period of rapid growth and innovation. Using improved WSI technology and z-stacking modalities to overcome the challenges of digitizing 3-dimensional cytologic material, leading investigators in the field of cytopathology have begun to exploit the advantages offered by digital pathology over traditional microscopy. To that end, this new and exciting section of Cancer Cytopathology will focus on highlighting innovative applications of pathology informatics in the cytology laboratory, including the use of traditional statistical tools and advanced deep-learning approaches for data mining and visualization. In an effort to increase visibility, we also will showcase how digital pathology continues to revolutionize the clinical practice of cytology through the application of WSI in telecytology for rapid on-site evaluation, remote consultation, and digital image analysis for diagnostic testing. To kick off this issue of Cancer Cytopathology, we would like to congratulate Dr. Louis J. Vaickus from Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, for winning this year's Young Investigator Challenge (Fig. 2). His work explored the development of a hybrid deep-learning and morphometric algorithm for the analysis of urine cytology specimens.2 This breakthrough article presents the framework for a system that can automate the Paris System for Urine Cytopathology reliably, with the potential to increase the efficiency of digital screening for urine WSI. Xiaoyin “Sara” Jiang, MD, is an associate professor of pathology at Duke University in Durham, North Carolina, and the associate director of the Duke BioRepository and Precision Pathology Center. Her areas of research and expertise are cytopathology and surgical pathology of the head and neck and endocrine systems, with particular interest in thyroid nodules, ultrasound-guided fine-needle aspiration, and novel applications of social media for medical professionals. Emilio Madrigal, DO, is a Cuban-born anatomic and clinical pathologist specializing in cytopathology and clinical informatics at the Massachusetts General Hospital in Boston, Massachusetts. He has special interests in salivary gland cytology and machine intelligence–powered digital image analysis. Dr. Madrigal received his Doctor of Osteopathic Medicine from Rowan University in Glassboro, New Jersey and has been certified by the American Board of Pathology in anatomic and clinical pathology and cytopathology.

Binding or Hydrolysis? How Does the Strigolactone Receptor Work?

The strigolactone (SL) receptor in plants is unusual in that it both binds and hydrolyses SL molecules. Landmark studies had proposed that a product of hydrolysis irreversibly binds the receptor and then activates signalling. However, recent breakthrough articles (Seto et al. Nat. Commun. 2019;10:191 and Shabek et al. Nature 2018;563:652-656) have revealed a new model based on inhibition of hydrolysis by protein conformation.

The 26th annual Nucleic Acids Research database issue and Molecular Biology Database Collection.

The 2019 Nucleic Acids Research (NAR) Database Issue contains 168 papers spanning molecular biology. Among them, 64 are new and another 92 are updates describing resources that appeared in the Issue previously. The remaining 12 are updates on databases most recently published elsewhere. This Issue contains two Breakthrough articles, on the Virtual Metabolic Human (VMH) database which links human and gut microbiota metabolism with diet and disease, and Vibrism DB, a database of mouse brain anatomy and gene (co-)expression with sophisticated visualization and session sharing. Major returning nucleic acid databases include RNAcentral, miRBase and LncRNA2Target. Protein sequence databases include UniProtKB, InterPro and Pfam, while wwPDB and RCSB cover protein structure. STRING and KEGG update in the section on metabolism and pathways. Microbial genomes are covered by IMG/M and resources for human and model organism genomics include Ensembl, UCSC Genome Browser, GENCODE and Flybase. Genomic variation and disease are well-covered by GWAS Catalog, PopHumanScan, OMIM and COSMIC, CADD being another major newcomer. Major new proteomics resources reporting here include iProX and jPOSTdb. The entire database issue is freely available online on the NAR website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, reviewing 506 entries, adding 66 new resources and eliminating 147 discontinued URLs, bringing the current total to 1613 databases. It is available at http://www.oxfordjournals.org/nar/database/c.

The promise of complementarity: Using the methods of foresight for health workforce planning.

Health workforce planning aims to meet a health system's needs with a sustainable and fit-for-purpose workforce, although its efficacy is reduced in conditions of uncertainty. This PhD breakthrough article offers foresight as a means of addressing this uncertainty and models its complementarity in the context of the health workforce planning problem. The article summarises the findings of a two-case multi-phase mixed method study that incorporates actor analysis, scenario development and policy Delphi. This reveals a few dominant actors of considerable influence who are in conflict over a few critical workforce issues. Using these to augment normative scenarios, developed from existing clinically developed model of care visions, a number of exploratory alternative descriptions of future workforce situations are produced for each case. Their analysis reveals that these scenarios are a reasonable facsimile of plausible futures, though some are favoured over others. Policy directions to support these favoured aspects can also be identified. This novel approach offers workforce planners and policy makers some guidance on the use of complimentary data, methods to overcome the limitations of conventional workforce forecasting and a framework for exploring the complexities and ambiguities of a health workforce's evolution.

Identifying potential “breakthrough” publications using refined citation analyses: Three related explorative approaches

The article presents three advanced citation‐based methods used to detect potential breakthrough articles among very highly cited articles. We approach the detection of such articles from three different perspectives in order to provide different typologies of breakthrough articles. In all three cases we use the hierarchical classification of scientific publications developed at CWTS based on direct citation relationships. We assume that such contextualized articles focus on similar research interests. We utilize the characteristics scores and scales (CSS) approach to partition citation distributions and implement a specific filtering algorithm to sort out potential highly‐cited “followers,” articles not considered breakthroughs. After invoking thresholds and filtering, three methods are explored: A very exclusive one where only the highest cited article in a micro‐cluster is considered as a potential breakthrough article (M1); as well as two conceptually different methods, one that detects potential breakthrough articles among the 2% highest cited articles according to CSS (M2a), and finally a more restrictive version where, in addition to the CSS 2% filter, knowledge diffusion is also considered (M2b). The advance citation‐based methods are explored and evaluated using validated publication sets linked to different Danish funding instruments including centers of excellence.

Eyes wide open: reader and author responsibility in understanding the limits of peer review.

'Medical science can only flourish in a free society and dies under totalitarian repression.' (1) Peer review post-publication is relatively easy to define: when the world decides the importance of publication. Peer review pre-publication is what the scientific community frequently means when using the term 'peer review'. But what it is it? Few will agree on an exact definition; generally speaking, it refers to an independent, third party scrutiny of a manuscript by scientific experts (called peers) who advise on its suitability for publication. Peer review is expensive; although reviewers are unpaid, the cost in time is enormous and it is slow. There is often little agreement among reviewers about whether an article should be published and peer review can be a lottery. Often referred to as a quality assurance process, there are many examples of when peer review failed. Many will be aware of Woo-Suk Hwang's shocking stem cell research misconduct at Seoul National University. (2) Science famously published two breakthrough articles that were found subsequently to be completely fabricated and this happened in spite of peer review. Science is not unique in making this error. However, love it or hate it, peer review, for the present time at least, is here to stay. In this article, Philippa Benson, Managing Editor of Science Advances (the first open access journal of the American Association for the Advancement of Science), discusses the merits of peer review. Dr Benson has extensive experience in the publishing world and was Executive Director of PJB Consulting, a not-for-profit organisation supporting clients on issues related to converting to full electronic publishing workflows as well as challenges working with international authors and publishers. Her clients included the Public Library of Science journals, the American Society for Nutrition and the de Beaumont Foundation. She recently co-authored a book, What Editors Want: An Author's Guide to Scientific Journal Publishing (University of Chicago Press), which helps readers understand and navigate the publishing process in high impact science and technical journals. Her master's and doctorate degrees are from Carnegie Mellon University. JYOTI SHAH Commissioning Editor

The discovery of the brain lymphatic system

Not required

Clinical Male Infertility and Assisted Reproduction

The current issue of Journal of Andrology is designated as a Special Issue on Clinical Male Infertility and Assisted Reproduction. The opportunity to create a Special Issue developed because of a high number of quality papers that were recently accepted for publication. Highlighting these papers with a Special Issue is an opportunity to capitalize on the purposeful goal of the Journal to solicit high quality papers in basic and clinical Andrology, emphasizing genetic aspects of Andrology and assisted reproduction. Encompassed in the focus on clinical genetics, we have included manuscripts in this issue that examine the relationship between varicocele and DNA integrity (Enciso et al) as well as varicoceles and sperm aneuploidy (Baccetti et al). Although DNA integrity and sperm aneuploidy appear more common in men with varicoceles, it is not clear whether it is the physical condition of varicocele, or merely poor sperm production that result in these sperm DNA abnormalities. Different approaches to evaluation of sperm DNA integrity were compared in a paper from the Utah group (Chohan et al). This is an important topic because of increasing attention being drawn to DNA integrity and its ability to detect male factor contributions to infertility. Other studies on clinical genetics included a report on the frequency of androgen receptor mutations in Indian men (Singh et al) and further investigation of the genetic anomalies that are present in men with globozoospermia (Christensen et al). This article is complemented by the paper from Emilia et al, also investigating chromosome abnormalities in men with large heads or multiple tails. Too often, treatment of patients with globozoospermia and other phenotypically-identifiable conditions is undertaken using assisted reproduction without any consideration of the potential underlying genetic anomalies. A study from Chen et al reported on the inverse relationship between sperm apoptosis and sperm motility in infertile men. Kovacic reported on the value of pentoxifylline stimulation prior to use of sperm for assisted reproduction, a useful clinical tool to help identify viable sperm among a population of immotile spermatozoa. Several articles examined technical issues relating to sperm retrieval and assisted reproduction. Given the increasing role of andrologists in assisted reproduction, these articles are worthy of note. Hauser et al compared sperm extraction (TESE) with testicular aspiration, and Wald et al reported on outcomes using frozen or fresh testicular sperm from men with nonobstructive azoospermia used for ICSI. The discussions from Androlog outline a current area of controversy regarding the relative value of assisted reproduction versus specific treatment of male infertility (vasectomy reversal). Nistal et al described five patients with Wolffian-derived intratesticular abnormalities; given the increased potential for detection of small and benign lesions within the testis, a greater understanding of rare intratesticular lesions is worthwhile. More information on alpha-glucosidase activity in human semen was presented by Schill et al. Whereas clinical evaluation of glucosidase activity is not a standard in the United States, its application in Europe is far more common. Other insight into clinical topics is provided in the articles by Shafik et al and Corona et al describing specific aspects of ejaculatory and sexual function. Haugen et al described the characteristics of semen parameters in a group of fertile men from Norway. Amory et al provide further information on the use of oral androgen supplementation (testosterone in oil) in combination with 5-alpha reductase inhibitors. Such a combination provides promise as treatment of men with androgen deficiency, enhancing circulating testosterone levels while limiting their effects on the prostate. A breakthrough article is included in this Special Issue, outlining the important antifertility effects of DDT on men. Although DDT is not used in the United States any longer, effects on fertility may still be seen in other countries, particularly in Africa where it is still in use, and concern about its metabolic products may exist long after popular use is stopped (De Jager et al). Taken together, these articles reflect an increase in the high quality articles that we have been receiving at the Journal—we hope our readers agree with our reviewers and the editors in their appraisal of these articles.

Prospect Theory and Mean-Variance Analysis

The experimental results of prospect theory (PT) reveal suggest that investors make decisions based on change of wealth rather than total wealth, that preferences are S-shaped with a risk-seeking segment, and that probabilities are subjectively distorted. This article shows that while PT’s findings are in sharp contradiction to the foundations of mean-variance (MV) analysis, counterintuitively, when diversification between assets is allowed, the MV and PT-efficient sets almost coincide. Thus one can employ the MV optimization algorithm to construct PTefficient portfolios. The Markowitz (1952a)-Tobin (1958) mean-variance (MV) rule is probably the most popular investment decision rule under uncertainty in economics and in finance, and it is widely employed by both academics and practitioners. The strength of the MV analysis is that in the case of normal return distributions the choice of any expected utility maximizing risk-averse individual will be according to the MV rule. 1 The MV framework is the foundation of the Sharpe (1964)-Lintner (1965) capital asset pricing model (CAPM), which is a cornerstone of modern finance. Moreover, the MV framework provides a very important practical procedure for the construction of efficient portfolios. While standard economic theory and, in particular, MV analysis assume expected utility maximization and risk aversion, in a breakthrough article Kahneman and Tversky (1979) show that the actual behavior of individuals systematically and consistently violates these

Patients with negative skin tests

The aim of this article is to present and discuss the clinical problem of systemic anaphylaxis to Hymenoptera venoms in patients without detectable immunoglobulin E, as it appears in recent literature. Reported at variable frequency in large series of patients undergoing evaluation, systemic anaphylaxis was previously considered to reflect lost sensitization or to involve non-immunoglobulin E mediated mechanisms. Sporadic case-reports drew attention to the fact that severe or even fatal reactions may occur in patients with negative skin tests. A breakthrough article by Golden et al., who performed deliberate stings on skin test negative venom anaphylaxis patients, demonstrated that clinical sensitivity was still present in a subset of these subjects and pointed out to the limitations of present diagnostic methods or reagents. New immunobiochemical methods and highly specific recombinant allergens--when all clinically relevant Hymenoptera venom allergens have been identified, cloned, sequenced and expressed in the proper system--are anticipated to increase the diagnostic yield. Non-specific mechanisms causing anaphylactoid reactions will probably explain some enigmatic, skin test negative radioallergosorbent test negative cases in the future. Occult mastocytosis, predisposing patients to anaphylactoid reactions, has been reported with increasing frequency among skin test negative patients. Lastly, other causes mimicking venom anaphylaxis may on rare occasions contribute to the problem. With the present understanding of venom allergy, the practising clinician is not infrequently faced with the dilemma of the skin test negative patient. Once other identifiable causes have been carefully ruled out, referral to a specialized center for deliberate sting-challenges appears in selected cases to be a medically appropriate and ethically justified management approach.

Beyond our pages

Beyond our pages

JAGS and the Geriatrics Renaissance.

JAGS and the Geriatrics Renaissance.

The German bourgeois club as a political and social structure in the late nineteenth and early twentieth centuries

The German voluntary association (hereafter in German the Verein, or Vereine in the plural) played an important role in the evolution of German society in the later nineteenth century and in the first third of the twentieth. This sort of association (or male bourgeois club) was a cornerstone of European Enlighenment society at the end of the eighteenth century, of the liberal society of the Vormärz, and of the German political parties in the years 1848–1849. Furthermore, the Verein was one of the main characteristics in the rise and hegemony of German bourgeoisie in the second half of the nineteenth century, and one of the cornerstones of local society as it developed in Germany towards the end of the 1890s.Research into the German Vereine is very advanced. To this day, historical research continues to benefit from Thomas Nipperdeys' breakthrough article concerning the importance of the Vereine in the rise of bourgeois-liberal society prior to 1848. Otto Dann, Wolfgang Hardtwig, and Dieter Düding have expanded our knowledge concerning the importance of the Vereine for the rise of bourgeois nationalism and liberalism before 1848. Regional studies have also emphasized these aspects during the Vormärz period and after.Folklorist-anthropological research is indebted to Hermann Bausinger's article on the importance of the connection between the Vereine and the development of German folklore. Similarly, Max Weber paved the way for the sociological research on the Vereine that has flourished since the 1860s, led by sociologists such as Hans Jürgen Siewert and Gerhard Wurzbacher. These are the two dominant streams in current research of the Vereine, although it is beyond the scope of this article to explore them here.