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The perception of meaningful patterns in random arrangements and unrelated events takes place in our everyday lives, coined apophenia, synchronicity, or the experience of meaningful coincidences. However, we do not know yet what predicts this phenomenon. To investigate this, we re-analyzed a combined data set of two daily diary studies with a total of N = 169 participants (mean age 29.95 years; 54 men). We investigated if positive or negative affect (PA, NA) predicts the number of meaningful coincidences on the following day (or vice versa). By means of a cross-lagged multilevel modelling approach (Bayesian estimation) we evaluated with which of two theoretical assumptions the data are more in line. First, if meaningful coincidences are facilitated by a broader and more flexible thinking style, PA should positively predict meaningful coincidences at the following day. However, if the experience of meaningful coincidences signifies a strategy to cope with negative feeling states, NA should predict the experience of meaningful coincidences during the following day. In favour of a more flexible thinking style, we found that PA predicted the number of perceived coincidences the following day. We did not find any effect for NA, and therefore, no evidence arguing for the coping mechanism hypothesis of meaningful coincidences.
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INTRODUCTION: Serendipitous findings are findings that were initially unsought but nevertheless contribute to the development of the discipline. This article reviews eight serendipitous findings in oto-rhino-laryngology important to its advancement. METHOD: The following serendipitous findings are discussed: the accidental discovery of the laryngeal mirror and indirect laryngoscopy by Garcia (1854), the invention of direct oesophagoscopy by Kußmaul (circa 1868), Czermák's (1863) development of diaphanoscopy, the unintentional emergence of bronchography from a clinical error made by Weingartner (1914), adenotomy by Meyer (1869), the discovery of the causes of unbalance related to the vestibular nerve by Flourens (1830), Bárány's (1914) finding that the semi-circular canal reflex is involved in equilibrium, and the relationship between gastroesophageal reflux and middle-ear infections by Poelmans and Feenstra (2002). DISCUSSION: Based on these case studies we conclude that serendipity, defined as the art of making an initially unsought find, does not always appear out of nowhere. Often the researcher is already wrestling with a problem for which the serendipitous finding provides a solution. Sometimes the serendipitous finding enables the application of a known solution to a new problem. And sometimes a serendipitous finding is not recognized as such or considered unimportant. Since observations tend to be theory-loaded, having appropriate background knowledge is a conditio sine qua non to elaborate an unanticipated observation.
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Otolaringología , Humanos , Otolaringología/historia , Historia del Siglo XIX , Historia del Siglo XX , Laringoscopía/historiaRESUMEN
Artificial intelligence (AI) is progressively spreading through the world of health, particularly in the field of oncology. AI offers new, exciting perspectives in drug development as toxicity and efficacy can be predicted from computer-designed active molecular structures. AI-based in silico clinical trials are still at their inception in oncology but their wider use is eagerly awaited as they should markedly reduce durations and costs. Health authorities cannot neglect this new paradigm in drug development and should take the requisite measures to include AI as a new pillar in conducting clinical research in oncology.
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Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day.
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Frutas , Plantas , Saccharomycetales , Ratas , Animales , Proteínas de Plantas/genética , MamíferosRESUMEN
The concept of serendipity or accidental discovery is typically discussed in the context of organizational research and development (RnD) through narratives involving 'renegade iconoclasts' laboring at the periphery. Recently, robust academic literature has emerged that grounds serendipity epistemologically. In the current work, this literature is introduced in the context of the typical activities of contemporary life science-focused RnD organizations. Practical patterns are described that can increase the likelihood of realizing accidental (serendipitous) RnD discoveries.
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Disciplinas de las Ciencias Biológicas , Proyectos de Investigación , ProbabilidadRESUMEN
Mary Dallman has left a legacy in neuroendocrinology, not only as the scientist who elaborated on new concepts such as rapid corticosteroid feedback pathways, but also as a role model, particularly for women who followed in her footsteps. In this contribution, I compare (i) the remarkable journey she made toward her position as the first female faculty member ever at the physiology department at USCF with that of generations after her; (ii) the contribution of our labs on rapid corticosteroid actions; and, (iii) finally, our experiences with unexpected findings for which one should always keep an open mind, a standpoint that was fervently advocated by Mary Dallman.
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Médicos , Estrés Psicológico , Humanos , FemeninoRESUMEN
The goal of this book is to provide a guide on modern day drug development in psychiatry. However, in order to understand current practices in drug development, it is important to first understand the history of psychiatry including early attempts at drug discovery and develoment. The early history of psychiatry is mired with the use of inhumane experimental treatments and the institutionalization of patients in asylums. Some of the earliest drugs used in these asylums were meant to sedate patients rather than treat underlying mental disorders. The earliest identified drugs treating mental disorders were born out of serendipitous discoveries which later led to their clinical effects being demonstrated through clinical trials and case studies. This is evident from the history of chlorpromazine, monoamine oxidase inhibitors, tricyclic antidepressants, lithium, and others. We discuss in detail about each of these psychotropic drugs, the events leading up to their discovery, and their role in formulating the biological basis of mental disorders including schizophrenia, depression, and bipolar disorder. Psychiatry, it seems has worked its way backwards from first identifying treatments before understanding the biological basis of mental disorders, in a sharp contrast to the other fields of medicine. With our growing understanding of the etiopathogenesis of mental disorders, drug development in psychiatry is evolving to develop treatments that target the underlying physiology of mental disorders.
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Psiquiatría , Esquizofrenia , Humanos , Psicotrópicos/uso terapéutico , Psicotrópicos/farmacología , Esquizofrenia/tratamiento farmacológico , Clorpromazina/uso terapéutico , Desarrollo de MedicamentosRESUMEN
Since the COVID-19 outbreak, people have been spending more time in the online world because of restrictions on face-to-face communication due to epidemic prevention controls. This has also brought the issue of Internet addiction, including the overuse and negative effects of short videos, to the forefront of attention. Past research has found that Internet addiction has a negative impact on well-being. However, there is a special concept of positive emotion called "serendipity" (). Serendipity provides a small, fleeting but positive experience, yet it is often associated with negative perceptions from an outside perspective. However, the relationship between short video addiction and serendipity is not yet known. Based on this, a theoretical model was developed in the context of the I-PACE model. To understand the relationship between short video addiction and serendipity among college students, in this study, we conducted snowball sampling and distributed online questionnaires using the Wenjuanxing platform. The target population of the questionnaire distribution was vocational college students in China, of whom 985 valid study participants responded, yielding a valid return rate of 82.1%. Of the respondents, 410 (41.6%) were male and 575 (58.4%) were female. The results were as follows: a. short video flow had a positive relationship with serendipity, a negative relationship with achievement motivation, and a positive effect on short video addiction; b. short video addiction had a positive effect on serendipity and a negative effect on achievement motivation; and c. serendipity had a negative impact on achievement motivation. This shows that short video addiction, like other Internet addictions, can have a negative impact on students' learning.
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By providing personalized suggestions to users, recommender systems have become essential to numerous online platforms. Collaborative filtering, particularly graph-based approaches using Graph Neural Networks (GNNs), have demonstrated great results in terms of recommendation accuracy. However, accuracy may not always be the most important criterion for evaluating recommender systems' performance, since beyond-accuracy aspects such as recommendation diversity, serendipity, and fairness can strongly influence user engagement and satisfaction. This review paper focuses on addressing these dimensions in GNN-based recommender systems, going beyond the conventional accuracy-centric perspective. We begin by reviewing recent developments in approaches that improve not only the accuracy-diversity trade-off but also promote serendipity, and fairness in GNN-based recommender systems. We discuss different stages of model development including data preprocessing, graph construction, embedding initialization, propagation layers, embedding fusion, score computation, and training methodologies. Furthermore, we present a look into the practical difficulties encountered in assuring diversity, serendipity, and fairness, while retaining high accuracy. Finally, we discuss potential future research directions for developing more robust GNN-based recommender systems that go beyond the unidimensional perspective of focusing solely on accuracy. This review aims to provide researchers and practitioners with an in-depth understanding of the multifaceted issues that arise when designing GNN-based recommender systems, setting our work apart by offering a comprehensive exploration of beyond-accuracy dimensions.
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Although network management tasks are highly automated using big data and artificial intelligence technologies, when an unforeseen cybersecurity problem or fault scenario occurs, administrators sometimes directly analyze system data to make a heuristic decision. However, a wide variety of information is required to address complex cybersecurity risks, whereas current systems are focused on narrowing the candidates of information. In this study, we propose a multiagent-based data presentation mechanism (MADPM) that consists of agents operating data-processing tools that store and analyze network data. Agents in MADPM interact with other agents to form data-processing sequences. In this process, we design not only the composition of the sequence according to requirements, but also a mechanism to expand it to enable multifaceted analysis that supports heuristic reasoning. We tested five case studies in the prototype system implemented in an experimental network. The results indicated that the multifaceted presentation of data can support administrators more than the selected single-faceted optimal presentation. The final outcome of our proposed approach is the provision of a multifaceted and cross-system data presentation for heuristic inference in network management tasks.
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Inteligencia Artificial , Seguridad Computacional , Macrodatos , Heurística , Solución de ProblemasRESUMEN
With campuses opening up and stimulating interactions among different campus users more and more, we aim to identify the characteristics of successful meeting places (locations) on campus. These can help practitioners such as campus managers and directors to further optimize their campus to facilitate unplanned or serendipitous meetings between academic staff and companies. A survey on three Dutch campuses, including questions on both services and locations, was analyzed both spatially and statistically using principal component (PC) and regression analysis. Four PCs were found for services (Relax, Network, Proximity and Availability) and three PCs were found for locations (Aesthetics, Cleaned and Indoor Environment). Personal characteristics as explanatory variables were not significant or only had very small effect sizes, indicating that a campus' design does not need to be tailored to certain user groups but can be effective for all. The pattern of successful locations is discussed, including the variables in each PC. These PCs provide a framework for practitioners who want to improve their campus' design to further facilitate unplanned meetings, thus contributing to cooperation between campus users, hopefully leading to further innovation.
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Universidades , Humanos , Encuestas y CuestionariosRESUMEN
Although salmonellosis, an infectious disease, is a significant global healthcare burden, there are no Salmonella-specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a Salmonella deglycase responsible for fructose-asparagine catabolism, is a viable drug target, we initiated experimental and computational efforts to identify inhibitors of FraB. To this end, our recent high-throughput screening initiative yielded almost exclusively uncompetitive inhibitors of FraB. In parallel with this advance, we report here how a separate structural and computational biology investigation of FrlB, a FraB paralog, led to the serendipitous discovery that 2-deoxy-6-phosphogluconate is a competitive inhibitor of FraB (KI ~ 3 µM). However, this compound was ineffective in inhibiting the growth of Salmonella in a liquid culture. In addition to poor uptake, cellular metabolic transformations by a Salmonella dehydrogenase and different phosphatases likely undermined the efficacy of 2-deoxy-6-phosphogluconate in live-cell assays. These insights inform our ongoing efforts to synthesize non-hydrolyzable/-metabolizable analogs of 2-deoxy-6-phosphogluconate. We showcase our findings largely to (re)emphasize the role of serendipity and the importance of multi-pronged approaches in drug discovery.
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BACKGROUND: Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson's disease, gabapentin for restless legs ). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures. SUMMARY: James Parkinson's observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson's disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced tremor. Both the discoveries of the anterior limbic subthalamic nucleus as a DBS target for OCD and the medial forebrain bundle as a DBS target for depression occurred by chance. Hamani and Lozano observed memory flashbacks in a patient who was undergoing DBS for obesity, which led to the discovery of the fornix as a potential DBS target for Alzheimer's disease. KEY MESSAGES: In the history of functional neurosurgery, serendipity and observations have resulted in discoveries of several procedures, brain targets for lesioning or DBS as well as new clinical surgical indications. In this era of neuromodulation, this technology should be exquisite in allowing potential serendipitous discoveries, provided that clinicians remain both observant and prepared.
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Neurocirugia , Observación , Estimulación Encefálica Profunda , Historia del Siglo XX , Humanos , Neurocirugia/historia , Enfermedad de Parkinson/cirugía , Psicocirugía , Accidente Cerebrovascular/cirugía , Temblor/cirugíaRESUMEN
The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature. In its original meaning (Walpole), serendipity refers to discoveries made through a combination of accidents and sagacity. We have implemented an operational definition of serendipity based on finding something unexpected or unintended, regardless of the systematic process that led to the accidental observation, and we have established four different patterns of serendipitous attributability. In this paper, we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs, tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic, "atypical" or "second generation" antidepressants. The discovery of the antidepressant properties of imipramine and iproniazid, the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors, respectively, fits the mixed type II pattern; initial serendipitous discoveries (imipramine was an antipsychotic and iproniazid was an anti-tuberculosis agent) led secondarily to non-serendipitous discoveries. But the other components of these two families of drugs were developed specifically as antidepressants, modifying the chemical structure of the series leaders, thereby allowing all of them to be included in the type IV pattern, characterized by the complete absence of serendipity. Among the heterocyclic drugs, mianserin (originally developed as an antihistamine) also falls into the type II pattern.
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Previous studies on the follow-up effect of serendipity mostly focused on the positive effects and less on the negative effects. Therefore, the purpose of this article is to investigate the negative effect of serendipity on the purchase intention of unexpected products. To verify all hypotheses in this article, we used online and offline survey data in China. Three experimental results showed that serendipity contains a certain degree of uncertainty, which will cause consumers' perceived risk and decrease the purchase intention of unexpected products. Perceived risk plays a mediating role in the effect of serendipity on the purchase intention of unexpected products. Moreover, regulatory focus moderates the effect of serendipity on purchase intention of unexpected products. Specifically, for prevention-focused individuals, the negative effect of serendipity on the purchase intention of unexpected products is strengthened. For promotion-focused individuals, the negative effect of serendipity on the purchase intention of unexpected products is weakened. This article augments the understanding of the negative effects of serendipity and provides theoretical guidance and support for the management practice of marketers.
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HemoglobinA1c (HbA1c) is used to diagnose Diabetes mellitus and monitor glycemic control over the previous eight to twelve weeks in diabetic patients. Detection of HbA1c by cation exchange-high performance liquid chromatography (CE-HPLC) gives a chromatogram by which abnormal hemoglobin variants are also picked up. Some of these may interfere with HbA1c values affecting clinical management. Due to increased inter-state migration as well as medical tourism, there is a high possibility of finding various hemoglobin variants in any part of India. We did a prospective analysis over 1.5 years, of the hemoglobin variants detected during all the HbA1c runs. The HbA1c was tested on Bio-Rad D10 dual HbA2/F/A1c platform, which uses the CE-HPLC method. Every chromatogram was carefully studied to look for unknown peaks. The samples showing unknown peaks >6% were re-run in extended HbA2/F mode to categorize the hemoglobin variants. We had 9595 HbA1c samples, of which 70 cases showed a variant window. There were 40 males and 30 females, age ranging from 28 to 76 years. The different hemoglobin variants detected were HbD, HbE and HbS in heterozygous state, high HbF (with a differential diagnosis of HPFH heterozygous and delta-beta thalassemia heterozygous), HbE homozygous, HbQ heterozygous and HbJ heterozygous. We conclude that in the process of monitoring glycemic control using HbA1c, we can also pick-up hemoglobin variants. Hence, it is essential to review HbA1c graphs, so that the diagnosis of hemoglobin variants is not missed and the HbA1c reported is reliable.
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Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual's resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term promise beyond use against infection. Multiple clinical trials and research studies in cancer patients have reported favourable outcomes with AZB as well as an optimal safety and tolerability profile. The findings raise the possibility of direct antitumor properties. This literature review analyses the novel mechanisms that mediate the AZB direct anticancer effects. Overall, the evidence suggests that AZB has the hallmark of an agent that could be used to support existing cancer treatments at different stages of disease.
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La idea del encuentro con el amor destinado, anhelado, perdido, es uno de los mitos del amor romántico que hunde sus raíces en el Banquete de Platón. La alienación y luego la separación, fundante del sujeto está en la base de esta ilusión perdida. Soy yo en el Otro y el Otro en mí, en un espejismo eterno, ahora ofrecido como un gadget de la industria biotecnológica. El avance de la genética nos produce ese estado de vértigo y asombro (Ansermet, 2019) que nos deja al borde del estado confusional. La promesa del encuentro con mi familia genética, la posibilidad de construir el árbol genealógico genético, el estudio prenupcial del mapeo genético de mi prometido y finalmente, el screening cromosómico de mi futuro hijo/a son actualmente prácticas cada vez más accesibles y extendidas. Las planetarias bases de datos genéticas se hayan en un imparable crecimiento inundando nubes bioinformáticas con bases de nucleótidos humanos. Si todo puede ser dicho por la ciencia y mi destino está encerrado en el ADN, que lugar queda para la verdad subjetiva, el deseo o el encuentro con las diferencias. La única salida a esta maquinaria de desciframiento genético parece ser la serendipia, que en el amor y en la ciencia dejan abierto el terreno al azar del encuentro con la causa.
The idea of encountering love destined, longed for, lost, is one of the myths of romantic love that has its roots in Plato's Banquet. Alienation and then separation, the foundation of the subject, is at the base of this lost illusion. It is me in the Other and the Other in me, in an eternal mirage, now offered as a gadget for the biotechnology industry. The advancement of genetics produces us that state of vertigo and amazement (Ansermet, 2019) that leaves us on the edge of a confusional state. The promise of meeting my genetic family, the possibility of building the genetic family tree, the prenuptial study of the genetic mapping of my fiancé and finally, the chromosome screening of my future child are currently increasingly accessible and widespread practices. The planetary genetic databases are in an unstoppable growth flooding bioinformatic clouds with human nucleotide bases. If everything can be said by science and my destiny is locked in DNA, what place is there for subjective truth, desire or the encounter with differences. The only way out of this machinery of genetic decipherment seems to be serendipity, which in love and in science leaves open the chance field of the encounter with the cause.
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Humanos , Biotecnología , Amor , Filosofía , Humanos , ADN , GenéticaRESUMEN
Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Descubrimiento de Drogas , Reposicionamiento de Medicamentos/métodos , Animales , Biología Computacional , Femenino , HumanosRESUMEN
This Essay highlights the complex issue of twinning in science publications. Historical accounts present cases where two scientists focused on the same problem and came up with the same solution following different paths. This has changed in the present day. The concurrent publication of rather similar research papers from different groups has increased in frequency since 2010. In the past, twinning in research publications was serendipitous, and there was a healthy competition among teams working on similar projects. Today, twinning has become more frequent. This can be attributed to the urge of researchers to have publications on popular topics, the tendency to base research programs on popular keywords, and funding agencies preferentially supporting certain areas of research. With vast amounts of literature being generated, editorial offices and referees may not be able to find these twins very easily. As we inch away from human ingenuity towards artificial intelligence, twinning may become even more frequent.