Microfluidics for in vitro fertilization: from science to clinical validation.

Clinicians' Guide to New Tools and Features of PubMed

Study question Is Microfluidic Sperm Sorting (MFSS) an efficient and safe, advanced sperm processing intervention in assisted reproduction cycles (ART)? Summary answer MFSS seemed to be non-inferior, efficient and safe, advanced sperm processing intervention in comparison to DDG sperm processing technique in assisted reproduction cycles. What is known already MFSS is an advanced sperm selection technique that has been introduced recently in the field of assisted reproduction (ART). This new technique is still undergoing validation. Efficacy of MFSS in enhancing embryo development and reproductive outcomes is still under evaluation. Safety of pregnancy and health of the off-springs resulting from MFSS technique is still elusive and needs further validation. Study design, size, duration This study is retrospective data analysis of ART cycles with use of MFSS at our fertility clinic between 2017-2023. Study group- MFSS (n = 1805) and Control group - (DDG) sperm processing technique (n = 2005) were evaluated. Only self-gamete cycles with no PGT-A(Pre-Implantation-Genetic-Testing-Aneuploidy) with female age<37yrs were considered for this study. Male partner’s had sperm count above 5millions/ml (Only fresh ejaculated semen was considered for this study). Only singleton pregnancies were considered for this study, multiple gestation’s were excluded. Participants/materials, setting, methods For MFSS we used ZYMOT device (ZyMōt Multi (850µL) Sperm Separation Device) and DDG was done as per clinic’s standard protocol (SOP). Informed consent obtained from all participants recruited in MFSS group after discussing its limited clinical validation. ICSI was the choice of insemination for all cases, extended blastocyst culture with freeze all policy was adopted. All patients underwent Frozen Embryo Replacement (FET) Cycle with two blastocysts which showed 100% survival post warming. Main results and the role of chance Outcomes measured: Implantation Rate (IR), Miscarriage Rate (MR), Live Birth rate (LBR), Incidence of Placental diseases like PIH(Pregnancy-Induced-Hypertension), IUGR (intra-Uterine-Growth-restriction), Pre-Term Deliveries (we considered only singleton pregnancies), Incidence of Low birth weight(<2.5kgs) (LBW), NICU admission and incidence of congenital anomalies. Following were the outcomes between MFSS and DDG groups respectively: IR: 48% Vs 45% (p = 0.2766) MR: 6% Vs 8% (p = 0.6425) LBR: 52% vs 42% (p = 1.0000) PIH: 0.31% Vs 0.51% IUGR: 0% Vs 0% Pre-Term Deliveries: 0.42% Vs 0.25% LBW: 0.63% Vs 0.94% (p = 1.0000) NICU admissions: 5.46% Vs 3.79% (p = 0.6517) Congenital Anomalies: 0.73% Vs 0.25% (p = 0.8992) Chi-square test was used for statistical analysis and p value was non-significant in all categories tested. Outcomes with MFSS seemed comparable and non-inferior to DDG sperm processing technique. Data from this study is assuring that MFSS, a newer advanced sperm processing technique is offering comparable and efficient reproductive outcomes. Limitations, reasons for caution Retrospective data evaluation. Small sample size in each group. Higher incidence of congenital anomalies in MF groups needs further evaluation. Wider implications of the findings Microfluidics sperm sorting holds trans-formative potential for ART, offering a safer,efficient,and patient-friendly approach to sperm processing as a significant advancement in reproductive medicine. However its efficiency in enhancing embryo development and reproductive outcomes along with the safety of pregnancy and health of the off-springs still elusive and needs further validation. Trial registration number No

Nearsighted? farsighted? pragmatic? idealistic? “Charting a Course for the 21st Century”: the National Library of Medicine's long-range plan, 2006–2016

Background Our immune system is composed of an innate (germ-line encoded) and adaptive (acquired) arm. It involves specialized hematopoietic cells but also cell-intrinsic (non-hematopoietic) mechanisms, antigen-specific receptors (T and B cell receptors/immunoglobulins), microbial sensors (pattern recognition receptors), and a complex network of signaling molecules that cooperatively work together to prevent or control infection by invading microorganisms via a variety of effector mechanisms. Both innate and adaptive immune defense mechanisms are tightly regulated, to avoid potentially harmful consequences such as tissue damage to the host, and to maintain tolerance to self as well as to harmless foreign antigens. An imbalance or insufficiency of these immune defense and regulatory mechanisms becomes apparent as clinical disease, either in the form of symptomatic infections (in which case the host immune defense was insufficient to prevent or control infection, dysregulated, or even deficient), or during ...

In 2000, the National Center for Biotechnology Information at the National Library of Medicine (NLM) created PubMed Central (PMC) to serve as a free digital archive for biomedical and life sciences journal literature [1]. In 2005, researchers who received National Institutes of Health (NIH) funding were given the option to voluntarily submit their manuscripts to PMC. Three years later, in 2008, the NIH public access policy was implemented, which required that authors who publish articles based on NIH-funded research must submit the final, peer-reviewed manuscripts to PMC [2, 3]. This requirement ensures free public access to the results of federally funded research. NLM assumed that most NIH-funded research would have a health or life sciences focus and therefore would be published in journals that are in scope for the NLM collection. However, following the inception of this program, it soon became evident that some of the author manuscripts submitted through the NIH Manuscript Submission (NIHMS) system were published in journals that did not meet the guidelines for inclusion in the NLM collection, as defined by the Collection Development Manual of the National Library of Medicine, fourth edition (CDM) [4]. When manuscripts are submitted to PMC through the NIHMS, a record must exist in the NLM integrated library system (ILS) for the corresponding journal for the manuscript to be added to PMC. If no record exists, the cataloging section creates a new record for the journal title. Following record creation, selection and acquisition section staff review the title for possible selection. If a journal is selected, NLM will order it in print, if available, and edit the record in the catalog to indicate that it has been selected. A link is also included for electronic access, if available. If a journal does not meet NLM collection development criteria—due to subject, coverage, or an insufficient number of articles from which selectors can make a judgment—the title is not selected or, in the latter case, the decision may be deferred until the journal publishes more articles. NLM will preserve and make available the individual manuscript through PMC, whether or not the journal is selected for the collection. In October 2009, a project was undertaken to analyze the journals that were not selected for the NLM collection to determine if any notable patterns could be discerned among them. Through this project, the selection and acquisition section hoped to confirm that it was appropriate that NLM did not have the journals in question, identify titles that should be reviewed for the collection, develop holdings language to identify journals that did not meet NLM guidelines, and assemble overall data to help NLM plan and manage the new workflow.

The paper is an expanded version of the 2007 Joseph Leiter National Library of Medicine (NLM)/Medical Library Association Lecture presented at MLA '07, the Medical Library Association annual meeting in Philadelphia in May 2007. It presents an historical accounting of four major pieces of legislation, beginning with the NLM Act of 1956 up through the creation of the National Center for Biotechnology Information. The transition from the United States Armed Forces Medical Library to the United States National Library of Medicine in 1956 was a major turning point in NLM's history, scope, and direction. The succeeding landmark legislative achievements--namely, the 1965 Medical Library Assistance Act, the 1968 Joint Resolution forming the Lister Hill National Center for Biomedical Communications, and the 1988 authorization for the National Center for Biotechnology Information--transformed the library into a major biomedical communications institution and a leader and supporter of an effective national network of libraries of medicine. The leaders of the library and its major advocates--including Dr. Michael DeBakey, Senator Lister Hill, and Senator Claude Pepper-together contributed to the creation of the modern NLM.

Mol Syst Biol. 1: 2005.0021 What determines a gene's evolutionary rate? In particular, does it depend solely on functional constraints imposed on the structure of the encoded protein or are there higher‐level factors related to the selection at the organismal level? These questions seem to be among the most fundamental ones in biology because comprehensive answers will reveal the nature of the links between genome evolution and the phenotypes of organisms. A recent study by Wall et al (2005) proves more convincingly than ever before that systemic determinants of gene evolution rate do exist, and an intriguing paper by Fraser (2005) sheds light on some of the underlying mechanisms. However, a recent report by Coulomb et al (2005) issues an important warning by showing that some of the intuitively plausible connections discovered by Systems Biology may be due to biases in the data. Nearly 30 years ago, Wilson et al (1977) put forward a general proposition that may be called the rate‐dispensability conjecture—the evolutionary rate should be a function of, firstly, the constraints on the function of the given gene (protein) and, secondly, the ‘importance’ (fitness effect of knockout or dispensability) of the gene for the organism: R i = f(P i )f(Q i ) ( R i is the rate of evolution of the given protein, P i is the probability that a substitution is compatible with the function of this protein, and Q i is the probability that the organism survives and reproduces without this protein). The prediction, thus, is that essential (indispensable) genes, on average, should evolve slower than nonessential genes. This conjecture generally follows from Kimura's neutral theory of evolution but is nontrivial given the broad variance of structural–functional constraints on proteins, regardless of their dispensability; in principle, this variance could …

The sequencing of the human genome, the identification of common single-nucleotide polymorphisms (SNPs) and haplotype blocks, and advances in microarray technology have enabled the study of complex diseases at a level of detail not previously imaginable. These have aided in the design and analyses of association and linkage studies of many complex diseases including cardiovascular disease. Recent technological advances have enabled the undertaking of large-scale genome-wide association studies (GWAS) that can assay hundreds of thousands of polymorphic sites on hundreds to thousands of individuals to find genomic regions associated with disease. Although results from these experiments enable the identification of smaller regions of association compared with previous studies, as with all linkage and association studies, there is the need for the further investigation of regions of interest for the causal genes or variants. The purpose of this review is to present a detailed demonstration as to how publicly available resources can be used to easily guide more detailed research into genomic regions of interest identified in linkage and association study data. Large-scale projects, such as the Human Genome Sequencing project,1,2 have generated large volumes and varieties of annotated genomic data necessitating the development of Internet-based tools to organize and make practically available these public data. One important tool in human disease research is the web-based graphical genome browsers that use the human genome sequence as the framework on which to organize genomic annotations, providing various ways for researchers to view and extract important information. Currently, there are 3 human genome browsers that have been developed for public use: (1) the National Center for Biotechnology Information (NCBI) Map Viewer3; (2) the University of California Santa Cruz (UCSC) Genome Browser4; and (3) the European Bioinformatics Institute’s Ensembl system.5 Although these genome browsers share common features and …

Internet provides access to large amounts of information quickly, provides a flexible learning platform, and is easily accessible from anywhere, especially with new technologies. Web-based search engines and bibliographic databases, have already become part of a doctor's everyday life. However, even well-published researchers often fail to appreciate the background knowledge required to conduct a good literature search on the internet. Using the right techniques can improve the ability to search for relevant information This chapter briefly outlines the internet for information resources such as Google, Google Scholar, PubMed, Cochrane for orthopedic surgeons. Also the subsequent sections of the chapter offers combining search engines tips and tricks for a best search that orthopedic surgeons can use to improve their use of web-based information and learning resources. Introduction The impact of the internet on orthopedics and traumatology has been revolutionary. Compared with traditional education instruments, the Internet offers numerous advantages. It provides access to large amounts of information quickly, provides a flexible learning platform, and is easily accessible from anywhere, especially with new technologies. Furthermore, instruction is enhanced with audiovisual material and easily updated and modified to suit changing learning needs. Web-based search engines and bibliographic databases, such as Google, Google Scholar and PubMed, have already become part of a doctor's everyday life. However, many doctors do not know the best ways to maximize their efficacy, and some doctors are still not using them at all. Sinkov et al. reported that a majority of orthopedic surgeons (79%) use the internet for at least some of their continuing learning(Sinkov et al. 2004), but the study also reported that attending orthopedic surgeons do not use the internet as often as orthopedic residents do, suggesting a learning gap. Surprisingly even well-published researchers often fail to appreciate the background knowledge required to conduct a good literature search on the internet. Using the right techniques can improve the ability to search for relevant information; without them, however, internet literature searches can become time-consuming and even misleading. A study that examined how using PubMed and Google contributed to physicians’ diagnostic skill showed that some physicians actually made the correct diagnosis earlier in the investigation and then incorrectly changed their diagnoses after conducting an internet search about their decision.(Falagas et al. 2009) (Fig.1) This chapter briefly outlines the internet as an information resource for orthopedic surgeons and offers some simple techniques that orthopedic surgeons can use to improve their use of webbased information and learning resources. Databases & search engines Electronic databases provide an index of multiple journals, and include citations, abstracts, and sometimes a link to the full text. They are updated with newly published articles. Many are useful in the practice of orthopedic surgery. For instance, they can help surgeons keep track of new findings in the field or search for specific information on specific techniques or outcomes. The databases can be classified based on their field (medicine, nursing, etc.) and can be searched via specialized search engines (Table 1). Pubmed (National Library of Medicine Database) The National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) developed PubMed as part of the Entrez retrieval system.(National Center for Biotechnology Information) At time of publication, PubMed provides access to approximately 23 million citations. This includes the content in the NLM’s database of biomedical journals listed in MEDLINE, life science journals, and relevant online books. Most material includes indexed citations and abstracts, with some full-text available. Pubmed is updated Tuesday through Saturday and is freely available to anyone with an internet connection. Academic institutions can link their electronic subscriptions to PubMed offering their users enhanced access to full-text articles. Pubmed provides a free NCBI account, “My NCBI” allows users to store keyword and MESH searches. When new results match the keyword and/or MESH search specifications, users are emailed automatically. Researchers can specific how often they wish to receive search alerts. (Fig.2)

1National Center for Biotechnology Information (NCBI), National Library of Medicine (NLM), National Institutes of Health (NIH), Bethesda, MD, USA aCorresponding author: Zhiyong Lu, Ph.D., FACMI, Senior Investigator & Deputy Director for Literature Search, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA, Tel: 301-594-7089, E-mail: [email protected]

Environmental MicrobiologyVolume 7, Issue 4 p. 453-458 On the bottom of the deep blue sea Michael Y. Galperin, Corresponding Author Michael Y. Galperin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. *E-mail: [email protected]; Tel. (+1) 301 435 5910; Fax: (+1) 301 435 7794.Search for more papers by this author Michael Y. Galperin, Corresponding Author Michael Y. Galperin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. *E-mail: [email protected]; Tel. (+1) 301 435 5910; Fax: (+1) 301 435 7794.Search for more papers by this author First published: 06 April 2005 https://doi.org/10.1111/j.1462-2920.2005.00812.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume7, Issue4April 2005Pages 453-458 RelatedInformation

Environmental MicrobiologyVolume 7, Issue 8 p. 1061-1064 To finish or not to finish? Michael Y. Galperin, Michael Y. Galperin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.Search for more papers by this author Michael Y. Galperin, Michael Y. Galperin National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.Search for more papers by this author First published: 06 July 2005 https://doi.org/10.1111/j.1462-2920.2005.00879.xCitations: 1 E-mail [email protected]; Tel. (+1) 301 435 5910; Fax (+1) 301 435 7794. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume7, Issue8August 2005Pages 1061-1064 RelatedInformation

The National Center for Biotechnology Information (NCBI) is a division of the National Library of Medicine (NLM) at the National Institutes of Health (NIH). Furthermore it is a big system of bioinformatics, advancing science and health by providing access to biomedical and genomic information. It provides researchers with a variety of biology databases, data retrieval resources, data analysis resources and so on which are of great importance. This paper summarizes the common functions of NCBI to help make fully use of NCBI for biology research.

For unbiased judgement of the effectiveness of medications or non-pharmaceutical therapies, controlled clinical trials are the most important elements in deciding whether an intervention does more good than harm. Often undervalued, but increasingly used under the concept of evidence-based medicine, trial results are of utmost importance as the basis of decision-making in health care. As controlled trials are one of the main sources of medical knowledge, it is essential that results of completed trials and information about ongoing ones are available to all those professionally involved in health research and health care as well as to patients. Public access to trial information is essential from various perspectives. First of all, research is a cumulative process, the unbiased synthesis of which is particularly important in order to summarize existing knowledge about a specific problem. Systematic reviews need to have complete information about ongoing and completed trials: the widespread phenomenon of not publishing trials with negative or disappointing results can seriously distort perceptions of the effectiveness of medical interventions (1). Knowledge of unreported trials may help to reduce the detrimental effects of this publication bias. Next, reliable information about trials is necessary to identify evidence gaps and thus indicate where further trials are needed. Planning of new trials has to be based on knowledge gained from previous ones, and information about similar trials is necessary to avoid duplication of effort and to ensure optimal use of resources. Prioritization of research programmes is dependent on complete knowledge of the evidence from trials. Finally, it is particularly important for patients and doctors to be able to obtain support to find trials suitable for participation. Patients and consumers of health care need access to information about trial results to allow them to make an informed choice. Participants in clinical trials expect the results to be made fully available to future patients; this is stipulated in the contract when they agree to participate in a trial, with its associated risks of not receiving the optimal treatment or experiencing adverse events. Underreporting of trial results is thus unacceptable from an ethical point of view and should be overcome by publicly accessible registers (2). In view of these convincing arguments which have been put forward for more than 30 years (3, 4), it is surprising that no system has yet been developed that allows systematic access to information about past or current clinical trials. Various local as well as publicly accessible registers have been set up over the past decade. For example, the United States National Institutes of Health, through the National Library of Medicine (5) and the National Cancer Institute, have developed publicly available web sites that facilitate searching for clinical trials (6, 7). In Europe, the European Science Foundation published a policy briefing that strongly recommends registration of controlled trials (8, 9) and urged its members to introduce registration. However, all these registers are of limited use as they cover only specific geographical regions or medical specialties and are not mandatory. …

Advances in science depend on researchers being able to reproduce the findings of their peers, thus providing a solid platform from which to move forward with new lines of scientific inquiry. Yet for a variety of reasons, irreproducibility appears to be a growing problem in experimental research. Now funding agencies and research journals are crafting guidelines to ensure that published studies are well designed, well reported, and better able to generate reproducible results. © Jim Frazier Media reports have singled out a number of egregious cases of irreproducibility, including reports published in Nature earlier this year indicating that adult stem cells would become pluripotent if submerged in a mild acid bath.1,2 The findings were widely criticized after scientists were unable to reproduce the results in their own laboratories.3 Subsequently, the first author agreed to retract the reports.4 In another widely publicized example, the biopharmaceutical company Amgen claimed it could reproduce just 6 of 53 studies that were considered landmarks in basic cancer research, despite close cooperation with the original scientists to make sure the same experimental protocols were used.5 Experts blame the irreproducibility problem on a number of factors, including inadequate reporting of the methods used in published research studies. Mounting evidence links poor methods descriptions with overstated findings,6,7,8,9,10 but in other cases faulty conclusions can be attributed to poor study design. In particular, inadequate randomization and blinding can introduce biases that render a study incapable of accurately testing its thesis.11 Irreproducibility is especially problematic if it plagues findings that lead to human clinical trials or to regulations and policies that could affect public health. One such instance was documented by researchers at the National Institute of Neurological Disorders and Stroke (NINDS), who discovered that patients with amyotrophic lateral sclerosis had been enrolled in a clinical trial founded on inadequate preclinical data. According to NINDS director Story Landis, the patients weren’t doing nearly as well as hoped on the test treatment, a broad-spectrum antibiotic called minocycline. When NINDS researchers took a closer look at the preclinical studies upon which the trial was predicated, they found the authors had not reported whether the studies were randomized or blinded. Furthermore, the work was done using small numbers of animals. “That was a wake-up call,” Landis says. “Human clinical trials need to be based on solid preclinical findings.”