Current research status and emerging trends in wheat: An integrated scientometric analysis based on ploidy uncovers hidden footprints in the scientific landscape.

Wheat, a highly versatile staple crop cultivated extensively for its grains on a global scale, is poised to experience increased demand to sustain the burgeoning population, owing to its superior nutritional potential. Modern wheat, a hexaploid species, has evolved through the introgression of numerous preceding ploidies, including Einkorn, Emmer, Aegilops, and others, each possessing distinct qualitative and quantitative traits. Scientometric and topical analyses serve as effective tools to quantitatively evaluate scientific research by measuring the knowledge expressed in scientific publications and keywords. Thus, comprehending the research status regarding wheat domestication events within primary, secondary, and tertiary gene pools is paramount for enhancing wheat production. In this study, we analyze data retrieved from PubMed to elucidate the research status and identify bottlenecks across different ploidy of genomic pools of wheat. The publication trends on wheat have experienced exponential growth over the past three decades, with China emerging as a leading center for publications. In contrast to the publication frequency observed in hexaploid common wheat, scholarly output concerning Einkorn and Aegilops is approximately tenfold lesser, with emmer trailing behind at three times fewer publications. This discrepancy underscores the prioritization of expedited research initiatives targeting these species, aimed at elucidating latent biological characteristics and optimizing their breeding capabilities. Keywords such as "stress," "GWAS," and "gene" are prominent, reflecting the challenges posed by climatic factors on wheat production and their mitigation through molecular breeding and gene manipulation. Notably, the keyword "einkorn" highlights its potential as a donor for fine-tuning traits related to wheat adaptation processes and quality, crucial for modern wheat's survivability under adverse climates. Conversely, higher publication rates on emmer are primarily associated with Italy, possibly due to its favorable Mediterranean climate for tetraploid wheat. Keywords like "Pasta" and "Ochratoxin, DON" are prevalent, with the former being derived from durum wheat and the latter being reported in higher amounts in durum compared to other wheat species, rendering it less suitable for consumption. Enriched keywords such as "genome" and "resistance" underscore the critical characteristics of Aegilops. Other significant keywords like "Aceria tosichella" possibly indicate multiple stages of resistance conferred by Aegilops, while the presence of the grain softness protein "puroindoline" enhances its acceptability for donation by Aegilops. Spelt, a close relative of common wheat, exhibits a research trend with thousands of annual publications and enriched keywords such as "stress" and "yield" reflect the current scientific emphasis on wheat research. Furthermore, hierarchical keywords like "bio-control" and "celiac disease" merit consideration for future research on hexaploid wheat.

Survey Research Among Neurosurgeons: A Bibliometric Review of the Characteristics, Quality, and Citation Predictors of the Top 50 Most-Influential Publications in the Neurosurgical Literature.

Survey research enables the gathering of information on individual perspectives in a large cohort. It can be epidemiological, attitude or knowledge focussed. Assessment of survey studies sampling neurosurgeons is currently lacking in the literature. This study aimed to highlight the characteristics, quality, and citation predictors of the most influential survey research studies published in the neurosurgical literature. Using PubMed and Google Scholar, the 50 most cited survey research publications were identified and reviewed. Data relating to the characteristics of the articles, participants and questionnaires were retrieved. The studies' quality and citation patterns were assessed. The median articles' age and publishing journal impact factor (IF) were 15.5 years and 2.82, respectively. Thirty-two (64%) articles were first authored by researchers from the USA while 28(56%) studies were focussed on specific disease management. The median number of participants and response rates were 222 and 51%, respectively. A full version of the questionnaire was provided in 18 (36%) articles. Only four (8%) articles reported validation of the questionnaire. The overall quality of reporting of the surveys was considered fair (based on good grading in five parameters, fair grading in one parameter, and poor grading in four parameters). The median citation number was 111. The citation analysis showed that the participant number, article age (≥15.5 years), and questionnaire category (surgical complications) were significant predictors of citation numbers. The citation rates were not influenced by the response rates or the journal's IF. In conclusion, high-impact survey publications in the neurosurgical literature were moderately cited and of fair quality. Their citation numbers were not affected by response rates but were positively influenced by the publication age, number of participants, and by novel data or the questions raised in the survey category. Surveys are valuable forms of research that require extensive planning, time, and effort in order to produce meaningful results. Increasing awareness of the factors that could affect citations may be useful to those who wish to undertake survey research.

PubMed Retrieval with RAG Techniques.

This study explores the application of Retriever-Augmented Generation (RAG) in enhancing medical information retrieval from the PubMed database. By integrating RAG with Large Language Models (LLMs), we aim to improve the accuracy and relevance of medical information provided to healthcare professionals. Our evaluation on a labeled dataset of 1,000 queries demonstrates promising results in answer relevance, while highlighting areas for improvement in groundedness and context relevance.

[One more step in the quality of 'Farmacéuticos Comunitarios': indexing]. / Un paso más en la calidad de 'Farmacéuticos Comunitarios': indexación.

The reason for existence of a scientific journal is to disseminate knowledge of science. The objective is a continuous improvement in the quality of what is published and an increase in the number of readers. In this sense, the impact factor is an indicator that helps us visualize the improvement in the quality of our journal. To improve this impact factor, indexing in the most used databases is very important.Farmacéuticos Comunitarios is indexed in several index journals but we were missing the most used ones. In this last year we have requested indexing in the most important ones, SCOPUS and Medline. In November we received SCOPUS approval and are close to getting it on Medline. In September we were approved by the editorial criteria and in December by the scientists. We only need the technical criteria to be able to appear in Medline and in its online version PubMed. We are working on it and it is very likely that within a year we will be indexed in PubMed.

The evolution of plasticity in the neuroscientific literature during the second half of the twentieth century to the present.

In the neurosciences, concepts play an important role in the conception and direction of research. Among the theoretical notions and direction of research, plasticity stands out because of the multiple ways in which scientists use it to describe and interpret how the nervous system changes and adapts to different requirements. The occurrence of different conceptualizations of plasticity in the scientific literature during the second half of the twentieth century and up to the present was investigated using bibliometric methods. Throughout the period analyzed, synaptic plasticity has remained the dominant conceptualization of plasticity. However, scientists have continued to introduce novel plasticity concepts reflecting the scientific advances they have made in understanding the dynamic nature of the nervous system. The conceptual evolution of plasticity documents that the view of the adult nervous system as immutable has been replaced by an understanding of the nervous system as capable of lifelong change and adaptation.

MEDLINE citation tool accuracy: an analysis in two platforms.

Background: Libraries provide access to databases with auto-cite features embedded into the services; however, the accuracy of these auto-cite buttons is not very high in humanities and social sciences databases. Case Presentation: This case compares two biomedical databases, Ovid MEDLINE and PubMed, to see if either is reliable enough to confidently recommend to students for use when writing papers. A total of 60 citations were assessed, 30 citations from each citation generator, based on the top 30 articles in PubMed from 2010 to 2020. Conclusions: Error rates were higher in Ovid MEDLINE than PubMed but neither database platform provided error-free references. The auto-cite tools were not reliable. Zero of the 60 citations examined were 100% correct. Librarians should continue to advise students not to rely solely upon citation generators in these biomedical databases.

Insufficient compliance of the German Therapeutic Products Advertising Act in product catalogues of online pharmacies.

The importance of ordering drugs from online pharmacies in Germany is increasing constantly. At the same time, there are many online pharmacies that try to increase their own market share through advertising. In Germany, the advertising of drugs is regulated by the Therapeutic Products Advertising Act (Heilmittelwerbegesetz (HWG)) and must therefore also be complied with by online pharmacies in their product catalogues. One important purpose of the HWG is to protect consumers by ensuring that they are presented with all necessary medical-pharmacological information about the advertised product. This paper examines the implementation of as well as the compliance with Section 4 of the HWG in the product catalogues of two online pharmacies. For this purpose, the spring/summer catalogue of 2023 was considered in the allergy, cold and gastrointestinal tract categories, resulting in the inclusion of 143 drugs from online pharmacy 1 (OP1) and 102 drugs from online pharmacy 2 (OP2) for the analysis. The information on the drugs was taken from the respective catalogue and the pharmaceutical index 'Gelbe Liste', collected in tabular form and was encoded. Subsequently, the required mandatory information according to Section 4 was checked by comparing the collected information with the information from the package leaflet. The analysis revealed that both catalogues insufficiently complied with Section 4 of the HWG. OP1 complied with 75% of the mandatory information required under Section 4 of the HWG and OP2 with 64%. In the OP1 catalogue, there is no indication for 6% of the drugs and no specification for 29% of the traditionally registered drugs. In addition, the mandatory notice on risks and adverse effects in the OP1 catalogue is not presented in a consumer-friendly way. In the OP2 catalogue, further concerns about the compliance with the HWG were raised due to the missing indication for 17% of the drugs, no warning for 64% of the ethanol-containing drugs and no active ingredient for 31% of the monopreparations. The insufficient compliance with the HWG in the product catalogues of OP1 and OP2 means that consumer protection as a stated objective of the HWG cannot be guaranteed. Advertising for drugs should only be possible under the condition that the content of the advertisement complies with the HWG. Insufficient compliance, as in the product catalogue of OP1 and OP2, should be prohibited as it directly contradicts the law's objective.

Representation of Social Determinants of Health terminology in medical subject headings: impact of added terms.

OBJECTIVES: To enhance and evaluate the quality of PubMed search results for Social Determinants of Health (SDoH) through the addition of new SDoH terms to Medical Subject Headings (MeSH). MATERIALS AND METHODS: High priority SDoH terms and definitions were collated from authoritative sources, curated based on publication frequencies, and refined by subject matter experts. Descriptive analyses were used to investigate how PubMed search details and best match results were affected by the addition of SDoH concepts to MeSH. Three information retrieval metrics (Precision, Recall, and F measure) were used to quantitatively assess the accuracy of PubMed search results. Pre- and post-update documents were clustered into topic areas using a Natural Language Processing pipeline, and SDoH relevancy assessed. RESULTS: Addition of 35 SDoH terms to MeSH resulted in more accurate algorithmic translations of search terms and more reliable best match results. The Precision, Recall, and F measures of post-update results were significantly higher than those of pre-update results. The percentage of retrieved publications belonging to SDoH clusters was significantly greater in the post- than pre-update searches. DISCUSSION: This evaluation confirms that inclusion of new SDoH terms in MeSH can lead to qualitative and quantitative enhancements in PubMed search retrievals. It demonstrates the methodology for and impact of suggesting new terms for MeSH indexing. It provides a foundation for future efforts across behavioral and social science research (BSSR) domains. CONCLUSION: Improving the representation of BSSR terminology in MeSH can improve PubMed search results, thereby enhancing the ability of investigators and clinicians to build and utilize a cumulative BSSR knowledge base.

Telemedicine Applications for Cancer Rehabilitation: Scoping Review.

BACKGROUND: Cancer is a significant public health issue worldwide. Treatments such as surgery, chemotherapy, and radiation therapy often cause psychological and physiological side effects, affecting patients' ability to function and their quality of life (QoL). Physical activity is crucial to cancer rehabilitation, improving physical function and QoL and reducing cancer-related fatigue. However, many patients face barriers to accessing cancer rehabilitation due to socioeconomic factors, transportation issues, and time constraints. Telerehabilitation can potentially overcome these barriers by delivering rehabilitation remotely. OBJECTIVE: The aim of the study is to identify how telemedicine is used for the rehabilitation of patients with cancer. METHODS: This scoping review followed recognized frameworks. We conducted an electronic literature search on PubMed for studies published between January 2015 and May 2023. Inclusion criteria were studies reporting physical therapy telerehabilitation interventions for patients with cancer, including randomized and nonrandomized controlled trials, feasibility studies, and usability studies. In total, 21 studies met the criteria and were included in the final review. RESULTS: Our search yielded 37 papers, with 21 included in the final review. Randomized controlled trials comprised 47% (n=10) of the studies, with feasibility studies at 33% (n=7) and usability studies at 19% (n=4). Sample sizes were typically 50 or fewer participants in 57% (n=12) of the reports. Participants were generally aged 65 years or younger (n=17, 81%), with a balanced gender distribution. Organ-specific cancers were the focus of 66% (n=14) of the papers, while 28% (n=6) included patients who were in the posttreatment period. Web-based systems were the most used technology (n=13, 61%), followed by phone call or SMS text messaging-based systems (n=9, 42%) and mobile apps (n=5, 23%). Exercise programs were mainly home based (n=19, 90%) and included aerobic (n=19, 90%), resistance (n=13, 61%), and flexibility training (n=7, 33%). Outcomes included improvements in functional capacity, cognitive functioning, and QoL (n=10, 47%); reductions in pain and hospital length of stay; and enhancements in fatigue, physical and emotional well-being, and anxiety. Positive effects on feasibility (n=3, 14%), acceptability (n=8, 38%), and cost-effectiveness (n=2, 9%) were also noted. Functional outcomes were frequently assessed (n=19, 71%) with tools like the 6-minute walk test and grip strength tests. CONCLUSIONS: Telerehabilitation for patients with cancer is beneficial and feasible, with diverse approaches in study design, technologies, exercises, and outcomes. Future research should focus on developing standardized methodologies, incorporating objective measures, and exploring emerging technologies like virtual reality, wearable or noncontact sensors, and artificial intelligence to optimize telerehabilitation interventions. Addressing these areas can enhance clinical practice and improve outcomes for remote rehabilitation with patients.

A bibliometric analysis of the research outcome of the Faculty of Medicine, University of Khartoum 2019-2023.

Using two databases, this bibliometric analysis was done for the papers published by the Faculty of Medicine, University of Khartoum (FMUK), from 2019 to 2023. Data were extracted from SCImago for all Sudan, and from PubMed for the publications by FMUK and its associated research centres, the Institute of Endemic Diseases, and the Mycetoma Research Center. The analysis of publications included the count and type of publications, the journals, and national and international collaboration assessment. The publications from FMUK show improvement over time in number and quality, a growth that is significantly influenced by national and international collaboration. These partnerships have proven to be a key driver of FMUK's research output, together with the valuable contributions of the specialized research institutions. However, there is room for improvement in the research output by increasing institutional capacity to support research and scientific communication. The Sudanese Journal of Paediatrics is an example where open access has a positive impact by allowing peripheral journals to be established despite the constraints.

Assessing the impact of history of medicine research: A scientometric and altmetric analysis.

Background and Aims: After conducting a comprehensive literature search of two medical electronic databases, PubMed and Embase, as well as two citation databases, Web of Science Core Collections (WoS) and Scopus, we aimed to conduct an Altmetric and Scientometric analysis of the History of Medicine literature in medical research. Methods: The following software tools were used for analyzing the retrieved records from PubMed and Embase databases and conducting a collaboration analysis to identify the countries involved in scientific medical papers, as well as clustering keywords to reveal the trend of History of Medicine research for the future. These software tools (VOSviewer 1.6.18 and Spss 16) allowed the researchers to visualize bibliometric networks, perform statistical analysis, and identify patterns and trends in the data. Results: Our analysis revealed 53,771 records from PubMed and 54,405 records from EMBASE databases retrieved in the field of History of Medicine by 105,286 contributed authors in WoS. We identified 157 countries that collaborated on scientific medical papers. By clustering 59,995 keywords, we were able to reveal the trend of History of Medicine research for the future. Our findings showed a positive association between traditional bibliometrics and social media metrics such as the Altmetric Attention Score in the History of Medicine literature (p < 0.05). Conclusion: Sharing research findings of articles in social scientific networks will increase the visibility of scientific works in History of Medicine research, which is one of the most important factors influencing the citation of articles. Additionally, our overview of the literature in the medical field allowed us to identify and examine gaps in the History of Medicine research.

A Bibliometric Analysis of Clinical Trials on Salivary Biomarkers for Mental Health (2003-2024).

Mental health conditions, such as depression, anxiety, and stress-related disorders, are often difficult to diagnose and monitor using traditional methods. Salivary biomarkers offer a promising alternative due to their non-invasive nature, ease of collection, and the potential to reflect real-time physiological changes associated with mental health. This bibliometric analysis examines 95 clinical trials on stress biomarkers for mental health, published between 2003 and 2024. The field is characterized by extensive collaboration and global participation, involving 593 authors and publications across 73 journals. Despite a consistent annual publication rate, notable increases in 2011, 2014, and 2018 indicate growing research interest. The United States leads in research output, followed by Australia, Germany, and Japan, with Psychoneuroendocrinology being the most prominent journal. Co-occurrence analysis identified nine research clusters, suggesting diverse directions such as the impact of stress-related hormones, circadian rhythms, mindfulness, various therapies, aging, psychological adaptation mechanisms, exercise therapy, anxiety disorders, and the autonomic nervous system on salivary biomarkers. Key terms such as "biomarkers/metabolism," AND "hydrocortisone/metabolism," AND "saliva/metabolism" were central, with significant activity from 2012 to 2018. This analysis highlights a growing focus on the metabolic processes and therapeutic applications of salivary biomarkers in mental health. This bibliometric analysis calls attention to the promising potential of salivary biomarkers to revolutionize mental health diagnostics and treatment through non-invasive methods, fostering interdisciplinary research, technological advancements, and global health improvements.

Update on IJTLD OPEN: the future is open.

The launch of IJTLD OPEN, which is fully compliant with Plan S, has extended our author base and allowed readers worldwide to access the content for free. PubMed Central (PMC) has recently approved the journal for indexing (including indexing by PubMed), which will further improve visibility and access. Because authors retain copyright they can use their articles without restriction (e.g., to post on free digital repositories), helping to further disseminate their research. All these factors help to ensure that IJTLD OPEN has maximum reach and impact. However, we recognise that fees for open access may present a barrier for authors based in low- to middle-income countries. We call on the international community to ensure funding support for open access is broadly available, with equal opportunity for researchers worldwide.

The landscape of biomedical research.

The number of publications in biomedicine and life sciences has grown so much that it is difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here, we present a two-dimensional (2D) map of the entire corpus of biomedical literature, based on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we used the large language model PubMedBERT, combined with t-SNE tailored to handle samples of this size. We used our map to study the emergence of the COVID-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, the distribution of gender imbalance in academic authorship, and the distribution of retracted paper mill articles. Furthermore, we present an interactive website that allows easy exploration and will enable further insights and facilitate future research.

COVID-19 Pandemic and Impact on Research Publications in Critical Care.

OBJECTIVES: The COVID-19 pandemic precipitated a significant transformation of scientific journals. Our aim was to determine how critical care (CC) journals and their impact may have evolved during the COVID-19 pandemic. We hypothesized that the impact, as measured by citations and publications, from the field of CC would increase. DESIGN: Observational study of journal publications, citations, and retractions status. SETTING: All work was done electronically and retrospectively. SUBJECTS: The top 18 CC journals broadly concerning CC, and the top 5 most productive CC journals on the SCImago list. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the top 18 CC journals and specifically Critical Care Medicine (CCM), time series analysis was used to estimate the trends of total citations, citations per publication, and publications per year by using the best-fit curve. We used PubMed and Retraction Watch to determine the number of COVID-19 publications and retractions. The average total citations and citations per publication for all journals was an upward quadratic trend with inflection points in 2020, whereas publications per year spiked in 2020 before returning to prepandemic values in 2021. For CCM total publications trend downward while total citations and citations per publication generally trend up from 2017 onward. CCM had the lowest percentage of COVID-related publications (15.7%) during the pandemic and no reported retractions. Two COVID-19 retractions were noted in our top five journals. CONCLUSIONS: Citation activity across top CC journals underwent a dramatic increase during the COVID-19 pandemic without significant retraction data. These trends suggest that the impact of CC has grown significantly since the onset of COVID-19 while maintaining adherence to a high-quality peer-review process.

What happened to my Index Medicus?

From its first printing in 1879 to when publication ceased in 2004, the Index Medicus had proved invaluable for persons wishing to conduct healthcare-related research. With the loss of this resource and the rapid expansion of alternative, online sources, it is vital that persons understand how to appropriately search for and use this information. The purpose of this review is to outline the information sources available, discuss how to use current search technology to best obtain relevant information while minimizing nonproductive references, and give the author's opinion on the reliability of the various informational sources available. Topics to be discussed will include Medical Subject Headings and PICO searches and sources ranging from the National Library of Medicine and Cochrane Reviews to Wikipedia and other sites, such as associations and commercial interest sites.

Writing and publishing papers in academic radiology: Why it needs to be more than a box checked for promotion.

An ongoing challenge in academic radiology is balancing the need to read the scans and generate relative value units (RVUs) with the need to ensure academic leadership and the consistent production of impactful publications. Indeed, the tripartite mission of academic radiology (i.e. clinical care, research, and teaching) does not lend itself to obvious answers in an era when institutions and departments are increasingly focused on RVU generation. Even the minority of radiologists who are interested in pursuing the academic mission and accept academic jobs are likely to find their time increasingly squeezed by massive volumes of scans to read and the priority placed on RVU generation. There are often no incentives for impactful academic work, leading to a decreasing relative number of manuscript submissions from U.S.-based researchers. With the lack of external incentivization for publication, writing and publishing papers must instead be driven by intrinsic enjoyment and a sense of accomplishment. The ability to think of an idea, to get a group of co-authors together, to acquire the data and/or put together the idea into a form that is ready for final publication, and to see that process through to the end is rewarded only by personal satisfaction. Perhaps, in the era of RVU generation, publishing papers in a form of defiance of a system that is hampering the academic mission.

Quantum dots: The trailblazers of early detection.

Considering the robust awareness of early detection among oral clinicians and patients the increasing imposition of better methods for screening of oral precancerous/cancerous lesions has become imperative. Although histopathology has been considered the indispensable gold standard, it has its pros and cons, as sometimes the diagnosis is compromised with the variabilities subject to the histopathologist under concern. In the realm of oral healthcare, one pioneering trailblazer is making waves, which are 'quantum dots'. Quantum dots are poised to transform the landscape of oral precancer and cancer screening. These nano-sized semiconductor particles possess extraordinary properties that set them apart from conventional detection methods. Their ability to emit distinct wavelengths of light when excited makes them ideal candidates for early detection. The keywords were pitched in and the research literature from the last 15 years (2008-2022) was extirpated to find out the information that existed, the discrepancies and the void left for upcoming research. Its nature and ingenuity have given rise to a transformative approach that holds the potential to redefine the future of oral healthcare. With each breakthrough, we edge closer to a world where the early detection of oral precancerous/cancerous lesions becomes the norm rather than the exception.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis.

PURPOSE: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. MATERIALS AND METHODS: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. RESULTS: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). CONCLUSION: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase.