medna-metadata: an open-source data management system for tracking environmental DNA samples and metadata.

MOTIVATION: Environmental DNA (eDNA), as a rapidly expanding research field, stands to benefit from shared resources including sampling protocols, study designs, discovered sequences, and taxonomic assignments to sequences. High-quality community shareable eDNA resources rely heavily on comprehensive metadata documentation that captures the complex workflows covering field sampling, molecular biology lab work, and bioinformatic analyses. There are limited sources that provide documentation of database development on comprehensive metadata for eDNA and these workflows and no open-source software. RESULTS: We present medna-metadata, an open-source, modular system that aligns with Findable, Accessible, Interoperable, and Reusable guiding principles that support scholarly data reuse and the database and application development of a standardized metadata collection structure that encapsulates critical aspects of field data collection, wet lab processing, and bioinformatic analysis. Medna-metadata is showcased with metabarcoding data from the Gulf of Maine (Polinski et al., 2019). AVAILABILITY AND IMPLEMENTATION: The source code of the medna-metadata web application is hosted on GitHub (https://github.com/Maine-eDNA/medna-metadata). Medna-metadata is a docker-compose installable package. Documentation can be found at https://medna-metadata.readthedocs.io/en/latest/?badge=latest. The application is implemented in Python, PostgreSQL and PostGIS, RabbitMQ, and NGINX, with all major browsers supported. A demo can be found at https://demo.metadata.maine-edna.org/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Phase I study of the antineovascularization drug CM101.

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.

Traumatic brain injury imaging research roadmap.

The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent "Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic" on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

Rhizobium meliloti exopolysaccharides: synthesis and symbiotic function.

Bacterial exopolysaccharide (EPS) is required for establishment of the nitrogen-fixing symbiosis between Rhizobium meliloti and its host plant, Medicago sativa (alfalfa), but the precise role of EPS in this interaction is not well defined. Bacterial mutants which fail to produce EPS induce nodules on the roots of the host plant, but fail to invade these root nodules. Research conducted in our lab and others suggests that EPS plays a specific role in the R. meliloti-M. sativa symbiosis. A common theme emerging from these studies is that small quantities of low-molecular-weight (LMW) EPS are sufficient to mediate successful invasion by R. meliloti mutants which fail to produce EPS, implying that LMW EPS may act as a signaling molecule during this process.

The sacred disease of Cambyses II.

Herodotus' account of the mad acts of the Persian king Cambyses II contains one of the two extant pre-Hippocratic Greek references to epilepsy. This reference helps to illuminate Greek thinking about epilepsy, and disease more generally, in the time immediately preceding the publication of the Hippocratic treatise on epilepsy, On the Sacred Disease. Herodotus attributed Cambyses' erratic behavior as ruler of Egypt to either the retribution of an aggrieved god or to the fact that he had the sacred disease. Herodotus considered the possibility that the sacred disease was a somatic illness, agreeing with later Hippocratic authors that epilepsy has a natural rather than a divine cause. Archaeological evidence suggests Herodotus slanders Cambyses, and there is no corroboration that the Persian king had epilepsy or any other disease. However, the view of epilepsy as a somatic disease and uncertainty about the cause of madness shows Herodotus as a transitional figure between supernatural and naturalistic medical theories.

Hughlings Jackson's theory of recovery.

John Hughlings Jackson proposed a mechanism of neurologic compensation based on his theory of cerebral localization. According to Hughlings Jackson, there are three levels of evolution of the nervous system. Each element of each level contains a complete representation of the next lower level. Each element of the middle and highest levels contain a representation of the entire body, weighted for a particular part of the body. If the nervous system is damaged so that an area heavily weighted for a particular part of the body is destroyed, less heavily weighted areas are immediately activated according to their weighting. This activation partially compensates for the function of the destroyed tissue. As time passes, the weighting of representation in the unaffected areas changes, amplifying the degree of recovery. Recent clinical studies and PET cerebral blood flow studies show that various ipsilateral and contralateral areas are activated in recovery. The activated areas reside in what Hughlings Jackson would call the middle and highest evolutionary levels. Modern clinical and neurophysiologic observations are therefore consistent with Hughlings Jackson's theory of compensation.

Paroxysmal genital pain: an unusual manifestation of epilepsy.

A male patient who is now 15 years old has experienced a seizure disorder since age 9 years. The seizures were expressed as episodes of excruciating pain localized to the genital region. Appropriate anticonvulsant medication has controlled both pain and seizures.

Thymic carcinoma. A clinicopathologic study of 13 cases.

Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas or thymic cysts, we conclude that TCA is derived from thymic epithelium.

Effects of group B Streptococcus toxin on long-term survival of mice bearing transplanted Madison lung tumors.

GBS toxin is a polysaccharide exotoxin produced by group B Streptococcus. This organism causes sepsis and respiratory distress in human neonates (so-called early onset disease). This disease is marked by a strong inflammatory response only in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage, and occurs only during the first few days after birth. We have found that a similar inflammatory response can be induced by i.v. infusion of picomole quantities of GBS toxin in the developing vasculature of transplanted tumors in mice and can significantly retard the tumor growth. When optimum treatment with GBS toxin was started shortly after tumor implantation, a majority of tumors in the mice regressed and the mice remained tumor-free for over 5 months. Some tumors regressed in mice receiving short-term treatment with GBS toxin, but recurred after the treatment was stopped. Median survival times were extended by all regimens and all doses of GBS toxin tested. No evidence of toxicity to the vasculature of other tissues was observed. GBS toxin is being tested for cancer therapy in humans.

The ESEM used to image crystalline structures of polymers and to image ink on paper.

This article describes two cases in which the advantages of the ESEM have been exploited in unanticipated ways. First, we have found that etching occurs as the electron beam scans the surface of uncoated polymers in the ESEM. The surface topography caused by this etching, as seen in ESEM images, reflects the morphology of crystalline structures in the polymers. This technique has been valuable in the study of such textures in polymers. The second application is related to our use of the ESEM in support of research on the deinking of paper. In this effort we have learned that an unconventional contrast mechanism can be used during ESEM imaging to distinguish between inked and non-inked areas of newsprint. Under usual operating conditions, ESEM imaging does not distinguish between inked and non-inked areas. However, at relatively low sample chamber pressures the non-inked areas appear brighter than inked areas in ESEM images.

Baby Doe regulations and medical judgment.

The potential for conflict between social policy and medical judgment can be examined in relation to the 'Baby Doe' regulations issued by the U.S. Federal Government in 1984. These regulations identify the circumstances in which medical treatment may be withheld from handicapped infants. This article reports on a national survey of perinatal social workers which compared their responses to the answers of physicians to similar questions published earlier. These social workers failed to express a conflict between sound medical judgment and the federal regulations when confronted with three hypothetical cases. The same was true in the published study of physicians but that data was erroneously interpreted as providing evidence of a conflict between medical judgment and federal regulations. On some general opinion statements, the social workers were similar to physicians in their criticism of these regulations but on others they were equivocal. While the majority of responses of social workers to other questions about these regulations was rather similar to the responses of physicians, the social workers were found to be more inclined than physicians to express the view that these regulations were needed to protect the rights of handicapped infants and the view that the physician's practice had been changed as a result of these regulations.

The Baby Doe regulations: views from perinatal social workers.

In 1984 the federal government issued the "Baby Doe" regulations, designed to protect the rights of handicapped infants. Members of the National Association of Perinatal Social Workers were asked to evaluate these regulations and were given the opportunity to comment on their impact. The authors present and discuss these comments with respect to the helpfulness of the regulations, physician discretion, parental rights, and the social work role.

Effect of o-acyl substituents on the functional behaviour of Rhizobium meliloti succinoglycan.

The effects of selective removal of acetyl or succinyl substituents on the functionality of succinoglycan polysaccharide have been studied by comparing the behaviour of the polysaccharides isolated from native Rhizobium meliloti strain Rm1021, and genetically modified R. meliloti species. Removal of the succinyl groups was found to dramatically improve pseudoplasticity of the aqueous succinoglycan samples and also increase the cooperativity of the order-disorder transition exhibited by the polysaccharide. Removal of the acetyl substituent led to a decrease in the order-disorder transition temperature, whereas the removal of the succinyl groups led to an increase.

NMR studies of succinoglycan repeating-unit octasaccharides from Rhizobium meliloti and Agrobacterium radiobacter.

Complete 1H and 13C-nuclear magnetic resonance assignments have been obtained for the octasaccharide repeating units of the bacterial polysaccharide succinoglycan from Rhizobium meliloti Rm1021 and Agrobacterium radiobacter NCIB 11883. The assignments were used to determine the locations of the O-succinyl and O-acetyl substituents. The O-acetyl substituent in Rm1021 was attached to the 3rd residue from the reducing end, and the O-succinyl group was attached to the 7th residue in both octasaccharides. The structure of the Rm1021 octasaccharide is as shown below: [formula: see text] A small amount of succinate was also attached to C6 of the 6th residue in both octasaccharides.

Sweat sodium and chloride analysis using BM/Hitachi 911 ion-selective electrodes.

The suitability of Hitachi 911 ion-selective electrodes to analyse neat sweat samples for sodium and chloride was investigated. Sweat samples obtained using the Gibson and Cooke method were analysed by flame photometry for sodium and coulometry for chloride. Specimens obtained by the Wescor Macroduct collection procedure were analysed by ion-specific electrodes. No significant differences between sodium and chloride results were found between the two different collection methods and analysis procedures. Analysis of neat sweat can reduce errors in sweat analysis by eliminating extraction and dilution stages. Errors could occur with use of a serum compensator in the calibration of ion-selective electrodes.

Stimulation by cigarette smoke of glutathione peroxidase system enzyme activities in rat lung.

This study was undertaken to evaluate the effect of in vivo cigarette smoke exposure on glutathione peroxidase--related enzyme systems of the rat lung. These enzymes, acting in concert, are thought to be responsible for disposing of toxic lipid peroxides in pulmonary tissue. Thirty-day-old rats were exposed to thirteen cigarettes per day for 21 days with a Walton reverse-smoking exposure apparatus. After 21 days of smoke exposure, the activities of glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were increased 34%, 24%, and 38%, respectively, over control values. This level of cigarette smoke exposure did not cause detectable histological lesions. We present the hypothesis that short-term, low-level cigarette smoke exposure is capable of initiating metabolic alterations in lung cells at exposures at which histological changes are not detectable by light microscopy.

Biochemical effect of ozone exposure in rats exposed to cigarette smoke.

Rats were exposed to three cigarettes per day for 35 days, under realistic conditions. Pulmonary glucose-6-phosphate dehydrogenase (G-6-PD) activity in the exposed animals increased 27% over control values (P less than .05). Subsequent exposure to acute, high-dose ozone (3 ppm for 4 hr) decreased the augmented G-6-PD activities to near normal levels, whereas ozone exposures in animals not exposed to cigarette smoke caused mild decreases in pulmonary G-6-PD activities. The importance of these findings with respect to the susceptibility of the smoker to oxidant exposures is unknown.

Brown-Séquard's theory of recovery.

Charles Edouard Brown-Séquard used observation of recovered patients and experimental animals to support his theory of cerebral localization. Recovery theories assume that the nervous system is composed of one organ or many, and that each organ has one function or many. From his own studies as well as others, Brown-Séquard concluded that the brain contained at least nine separate organs, each with a single distinct function, and that each organ is organized, not as a geographically isolated cluster of neurons, but as a widely disseminated network. According to his view, function is not uniformly distributed in an organ. Focal necrosis of part of an organ temporarily inhibits the action of distant, undamaged parts; resolution of this inhibition results in recovery. Using this theory of cerebral localization and recovery, Brown-Séquard practiced an early form of scientific neurology.

Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings.

Though cortical abnormalities have been demonstrated in moderate and severe traumatic brain injured (TBI) patients, there have been no studies examining cortical changes following blast related mild TBI (mTBI). The purpose of this study was to determine the effects and functional relevance of blast mTBI on cortical thickness in a small cohort of carefully screened blast injured US Service Members (SM). Twelve SM with mTBI acquired through blast injury were compared to 11 demographically matched control SM without TBI. Both mTBI and control participants were active duty and had completed a combat deployment. Subjects underwent MRI examination and the T1 weighted anatomic images were processed using the FreeSurfer suite of tools. Cortical thickness maps were compared between groups and examined for relationships with time since injury (TSI). Utilizing a large database of functional imaging results (BrainMap), significant regions of interest (ROI) were used to determine the behavioral profiles most consistently associated with the specific ROI. In addition, clinical variables were examined as part of post-hoc analysis of functional relevance. Group comparisons controlling for age demonstrated several significant clusters of cortical thinning for the blast injured SM. After multiple comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters remained significant (left superior temporal (STG) and frontal (SFG) gyri). No clusters were significantly correlated with TSI after FDR correction. Behavioral analysis for the STG and SFG clusters demonstrated three significant behavioral/cognitive sub-domains, each associated with audition and language. Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and SFG. These areas have been previously shown to be associated with audition and language. Post-hoc analyses of clinical records demonstrated significant abnormal audiology reports for the blast injured SM suggesting that the thinning in these ROIs might be related to injury to the external auditory system rather than direct injury to the brain from the blast. It is clear that additional replication is needed in much larger cohorts. Importantly, the combination of imaging tools and methods in this study successfully demonstrated the potential to define unique ROIs and functional correlates that can be used to design future studies.