Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): A pragmatic trial of complex treatment for a complex disorder

Background Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the ‘real-world’ advantages and disadvantages of these medications. Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments (APTs). The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score, and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT). Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus APT, across 10 sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. In all, 482 participants were randomized to the study, and 364 completed the study. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants’ ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a second-generation antipsychotic with broad-spectrum activity in bipolar disorder, and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.
Draft Genome Sequence of Lactobacillus zeae KCTC 3804

ABSTRACT We announce the draft genome sequence of the type strain Lactobacillus zeae KCTC 3804 (3,110,326 bp, with a G+C content of 47.8%), which is one of the most prevalent lactic acid bacteria present during the processing of raw cow's milk. The genome consists of 113 large contigs (>100 bp). All of the contigs were assembled by Newbler Assembler 2.3 (454 Life Science).
Genome of a Novel Isolate of Paracoccus denitrificans Capable of Degrading N,N-Dimethylformamide

ABSTRACT The bacterial genus Paracoccus is comprised of metabolically versatile organisms having diverse degradative capabilities and potential industrial and environmental applications for bioremediation in particular. We report a de novo-assembled sequence and annotation of the genome of a novel isolate of Paracoccus denitrificans originally sourced from coal mine tailings in India. The isolate was capable of utilizing N,N-dimethylformamide (DMF) as a source of carbon and nitrogen and therefore holds potential for bioremediation and mineralization of industrial pollutants. The genome sequence and biological circuitry revealed thereupon will be invaluable in understanding the metabolic capabilities, functioning, and evolution of this important bacterial organism.
How well informed is the informed consent for cancer clinical trials?

Aims: The purpose of this study was to analyze the content of informed consent forms for clinical trials in medical oncology to assess readability, determine their completeness, and identify any shortcomings. Methods: Informed consent forms for Phase I–III studies that were conducted at two tertiary care cancer centers over a 3-year period were reviewed. Information pertaining to length of the informed consent form, research regimen/methods, treatment agent, potential risks, and benefits was extracted. The reading level was assessed by Flesch–Kincaid and Gunning-Fog index readability tests. Results: All of the 112 informed consent forms clearly stated the voluntary nature of participation. Nearly one half of the forms (51.8%) were of Phase I studies. The median length of informed consent form was 20 pages (range: 8–28). A detailed estimation of the frequency or intensity of risks (range: 3–8 pages) was provided. The average reading level of the informed consent forms was high (Flesch–Kincaid Grade Level of 9.8), which corresponds roughly to 10th-grade reading level. Less than 15% of all consent forms were written at the recommended eighth-grade reading level. A substantial number of forms did not report a potential risk to pregnant/lactating women (16.9%), mechanism of action of the investigational agent (34.8%), study schema (77.6%), a possibility of receiving sub-therapeutic dose (37%), or death (12.5%). Nearly one half of the forms (49.1%) stated clearly that individual participants may not benefit. Conclusion: Overall, these informed consent forms provided a detailed description of the trials in accordance to international guidelines. However, there remains room for improvement, particularly in areas of readability and document length.
Evacuation of dermoid cysts before excision

Purpose The aim of this work is to evaluate safety and efficacy of evacuation of dermoid cysts before excision. Patients and methods Twenty patients with orbital dermoid, 10 patients with external angular dermoid, seven patients with internal angular dermoid, and three patients with deep orbital dermoid were included in this study. The patients attended the outpatient clinic of Mansoura Ophthalmic Center from January 2011 to September 2011. All patients were operated by puncture of the cyst wall, aspiration of the contents with a suction device, and then complete removal of the cyst wall. Results Twenty patients were operated, 11 males (55%) and nine females (45%), mean age 6.8 (ranged from 2.5 to 27 years). There were three patients (15%) with deep orbital dermoid, 10 patients (50%) with external angular dermoid, and seven patients (35%) with internal angular dermoid. Patients with external and internal angular dermoid were operated through external and internal sub-brow incisions (85%); however, in patients with deep orbital dermoid (15%), they were located in the lacrimal fossa and were operated through lateral orbitotomy without a bone flap. All cases were excised successfully without postoperative recurrence. In one patient (5%), rupture had already occurred before surgery, and this patient developed postoperative recurrent orbital inflammation that responded to a local triamcinolone injection. Conclusion Evacuation of dermoid cyst before excision represents a safe and efficient technique.
A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety

Background/aims: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. Methods: “Reducing Suicidal Ideation Through Insomnia Treatment” is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. Results: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. Conclusion: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.
Global Transcription Profiles of the Nitrogen Stress Response Resulting in Heterocyst or Hormogonium Development in Nostoc punctiforme

ABSTRACT The filamentous cyanobacterium Nostoc punctiforme differentiates from vegetative cells into three distinct cell types, heterocysts, hormogonia, and akinetes, in response to different stimuli. Cultures growing with ammonium can be induced to form hormogonia or heterocysts upon removal of the combined nitrogen. A DNA microarray consisting of 94% of the open reading frames predicted from the 9.059-Mb N. punctiforme genome was used to generate a global transcription data set consisting of seven time points over a 24-h period of nitrogen deprivation, which results in heterocyst formation. This data set was compared to a similarly generated data set of nitrogen-starved N. punctiforme resulting in hormogonium formation that had previously been published (E. L. Campbell, H. Christman, and J. C. Meeks, J. Bacteriol. 190:7382-7391, 2008). The transition from vegetative cells to either heterocysts or hormogonia resulted in rapid and sustained expression of genes required for utilization of alternate nitrogen sources. Overall, 1,036 and 1,762 genes were found to be differentially transcribed during the heterocyst and hormogonium time courses, respectively, as analyzed with the Bayesian user-friendly software for analyzing time series microarray experiments (BATS). Successive transcription of heterocyst regulatory, structural, and functional genes occurred over the 24 h required to form a functional heterocyst. During hormogonium differentiation, some heterocyst structural and functional genes were upregulated, while the heterocyst master regulator hetR was downregulated. There are commonalities in differential expression between cells bound for differentiation into heterocysts or hormogonia, yet the two paths are distinguished by their developmentally specific transcription profiles.
Genome Sequence of Sphingobium yanoikuyae XLDN2-5, an Efficient Carbazole-Degrading Strain

ABSTRACT Sphingobium yanoikuyae XLDN2-5 is an efficient carbazole-degrading strain. Carbazole-degrading genes are accompanied on both sides by two copies of IS6100 elements. Here, we describe the draft genome sequence of strain XLDN2-5, which may provide important clues as to how it recruited exogenous genes to establish pathways to degrade the xenobiotics.
Genome Sequence of the Thermophilic Strain Bacillus coagulans XZL4, an Efficient Pentose-Utilizing Producer of Chemicals

ABSTRACT Bacillus coagulans XZL4 is an efficient pentose-utilizing producer of important platform compounds, such as l-lactic acid, 2,3-butanediol, and acetoin. Here we present a 2.8-Mb assembly of its genome. Simple and efficient carbohydrate metabolism systems, especially the transketolase/transaldolase pathway, make it possible to convert pentose sugars to products at high levels.
Joint transmitter- and receiver-based friendly jamming in a MIMO wiretap interference network

We consider an interference network tapped by external eavesdropper(s) in which each legitimate transmit-receive pair conceals its communications by using joint transmit-based friendly jamming (TxFJ) and receiver-based friendly jamming (RxFJ). Specifically, TxFJ is realized at the transmit side using MIMO precoding while RxFJ is achieved at the receiver side of each link by leveraging the state-of-the-art self-interference-suppression techniques (allowing a radio to cancel the self-interference effect of its transmit signal). We show that with a careful power allocation between the information signal and TxFJ at the transmit side of each link, the corresponding receiver is able decide on using RxFJ independent of any multi-user interference factor. This ability sets the receivers free from having to measure multi-user interference at eavesdropper(s). With every link following such strategy, we model this interaction as a non-cooperative game. We derive sufficient conditions under which the game admits a unique Nash equilibrium. We then propose a robust version of the game that requires only statistical knowledge of eavesdropping channel.
Genome Sequence of Bifidobacterium breve DPC 6330, a Strain Isolated from the Human Intestine

ABSTRACT The draft genome of Bifidobacterium breve DPC 6330, isolated from an elderly patient, was determined. B. breve DPC 6330 was previously identified to synthesize the beneficial metabolite conjugated linoleic acid from free linoleic acid. The sequence will allow identification and characterization of the genetic determinants of its putative beneficial properties.
FAce MOUSe: A novel human-machine interface for controlling the position of a laparoscope

Robotic laparoscope positioners are now expected as assisting devices for solo surgery among endoscopic surgeons. In such robotic systems, the human-machine (surgeon-robot) interface is of paramount importance because it is the means by which the surgeon communicates with and controls the robotic camera assistant. We have designed a novel human-machine interface, called "FAce MOUSe", for controlling the position of a laparoscope. The proposed human interface is an image-based system which tracks the surgeon's facial motions robustly in real time and does not require the use of any body-contact devices, such as head-mounted sensing devices. The surgeon can easily and precisely control the motion of the laparoscope by simply making the appropriate face gesture, without hand or foot switches or voice input. Based on the FAce MOUSe interface, we have developed a new robotic laparoscope positioning system for solo surgery. Our system allows nonintrusive, nonverbal, hands off and feet off laparoscope operations, which seem more convenient for the surgeon. To evaluate the performance of the proposed system and its applicability in clinical use, we set up an in vivo experiment, in which the surgeon used the system to perform a laparoscopic cholecystectomy on a pig.
Draft Genome Sequence of Streptomyces sp. Strain Wigar10, Isolated from a Surface-Sterilized Garlic Bulb

ABSTRACT Streptomyces sp. strain Wigar10 was isolated from a surface-sterilized garlic bulb (Allium sativum var. Purple Stripe). Its genome encodes several novel secondary metabolite biosynthetic gene clusters and provides a genetic basis for further investigation of this strain's chemical biology and potential for interaction with its garlic host.
A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network

Background: Adaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory-phase adaptive clinical trials within an emergency clinical trials network and to build a model to guide future development of adaptive clinical trials. Methods: We used an ethnographic, qualitative approach to evaluate key stakeholders’ views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials and completed a Strengths–Weaknesses–Opportunities–Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders’ responses to develop a conceptual model. Results: Four major overarching themes emerged during the analysis of stakeholders’ responses to questioning: the perceived statistical complexity of adaptive clinical trials and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials. Conclusion: The Adaptive Design Development Model illustrates how statistical complexity, time, communication, and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings.
Effect of Periodontal Pathogens on the Metatranscriptome of a Healthy Multispecies Biofilm Model

ABSTRACT Oral bacterial biofilms are highly complex microbial communities with up to 700 different bacterial taxa. We report here the use of metatranscriptomic analysis to study patterns of community gene expression in a multispecies biofilm model composed of species found in healthy oral biofilms (Actinomyces naeslundii, Lactobacillus casei, Streptococcus mitis, Veillonella parvula, and Fusobacterium nucleatum) and the same biofilm plus the periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The presence of the periodontopathogens altered patterns in gene expression, and data indicate that transcription of protein-encoding genes and small noncoding RNAs is stimulated. In the healthy biofilm hypothetical proteins, transporters and transcriptional regulators were upregulated while chaperones and cell division proteins were downregulated. However, when the pathogens were present, chaperones were highly upregulated, probably due to increased levels of stress. We also observed a significant upregulation of ABC transport systems and putative transposases. Changes in Clusters of Orthologous Groups functional categories as well as gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that in the absence of pathogens, only sets of proteins related to transport and secondary metabolism were upregulated, while in the presence of pathogens, proteins related to growth and division as well as a large portion of transcription factors were upregulated. Finally, we identified several small noncoding RNAs whose predicted targets were genes differentially expressed in the open reading frame libraries. These results show the importance of pathogens controlling gene expression of a healthy oral community and the usefulness of metatranscriptomic techniques to study gene expression profiles in complex microbial community models.
A Single-Domain FlgJ Contributes to Flagellar Hook and Filament Formation in the Lyme Disease Spirochete Borrelia burgdorferi

ABSTRACT FlgJ plays a very important role in flagellar assembly. In the enteric bacteria, flgJ null mutants fail to produce the flagellar rods, hooks, and filaments but still assemble the integral membrane-supramembrane (MS) rings. These mutants are nonmotile. The FlgJ proteins consist of two functional domains. The N-terminal rod-capping domain acts as a scaffold for rod assembly, and the C-terminal domain acts as a peptidoglycan (PG) hydrolase (PGase), which allows the elongating flagellar rod to penetrate through the PG layer. However, the FlgJ homologs in several bacterial phyla (including spirochetes) often lack the PGase domain. The function of these single-domain FlgJ proteins remains elusive. Herein, a single-domain FlgJ homolog (FlgJBb) was studied in the Lyme disease spirochete Borrelia burgdorferi. Cryo-electron tomography analysis revealed that the flgJBb mutant still assembled intact flagellar basal bodies but had fewer and disoriented flagellar hooks and filaments. Consistently, Western blots showed that the levels of flagellar hook (FlgE) and filament (FlaB) proteins were substantially decreased in the flgJBb mutant. Further studies disclosed that the decreases of FlgE and FlaB in the mutant occurred at the posttranscriptional level. Microscopic observation and swarm plate assay showed that the motility of the flgJBb mutant was partially deficient. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these results indicate that FlgJBb is involved in the assembly of the flagellar hook and filament but not the flagellar rod in B. burgdorferi. The observed phenotype is different from that of flgJ mutants in the enteric bacteria.
Bacterial Degradation of tert-Amyl Alcohol Proceeds via Hemiterpene 2-Methyl-3-Buten-2-ol by Employing the Tertiary Alcohol Desaturase Function of the Rieske Nonheme Mononuclear Iron Oxygenase MdpJ

ABSTRACT Tertiary alcohols, such as tert-butyl alcohol (TBA) and tert-amyl alcohol (TAA) and higher homologues, are only slowly degraded microbially. The conversion of TBA seems to proceed via hydroxylation to 2-methylpropan-1,2-diol, which is further oxidized to 2-hydroxyisobutyric acid. By analogy, a branched pathway is expected for the degradation of TAA, as this molecule possesses several potential hydroxylation sites. In Aquincola tertiaricarbonis L108 and Methylibium petroleiphilum PM1, a likely candidate catalyst for hydroxylations is the putative tertiary alcohol monooxygenase MdpJ. However, by comparing metabolite accumulations in wild-type strains of L108 and PM1 and in two mdpJ knockout mutants of strain L108, we could clearly show that MdpJ is not hydroxylating TAA to diols but functions as a desaturase, resulting in the formation of the hemiterpene 2-methyl-3-buten-2-ol. The latter is further processed via the hemiterpenes prenol, prenal, and 3-methylcrotonic acid. Likewise, 3-methyl-3-pentanol is degraded via 3-methyl-1-penten-3-ol. Wild-type strain L108 and mdpJ knockout mutants formed isoamylene and isoprene from TAA and 2-methyl-3-buten-2-ol, respectively. It is likely that this dehydratase activity is catalyzed by a not-yet-characterized enzyme postulated for the isomerization of 2-methyl-3-buten-2-ol and prenol. The vitamin requirements of strain L108 growing on TAA and the occurrence of 3-methylcrotonic acid as a metabolite indicate that TAA and hemiterpene degradation are linked with the catabolic route of the amino acid leucine, including an involvement of the biotin-dependent 3-methylcrotonyl coenzyme A (3-methylcrotonyl-CoA) carboxylase LiuBD. Evolutionary aspects of favored desaturase versus hydroxylation pathways for TAA conversion and the possible role of MdpJ in the degradation of higher tertiary alcohols are discussed.