bluuebunny/crossref_metadata_2025_split huggingface dataset:
A High-Resolution Liquid Chromatography-Mass Spectrometry Method for Identification of Toxic Natural Products in Clinical Cases
Authors: Luo Y R , Yun C , Lynch K L , Comstock K 
Published: October 2020

Abstract

Introduction/Objective
Many natural products have biological effects on humans and animals. Poisoning caused by natural products is often found in clinical toxicology cases. Liquid chromatography-high-resolution-mass spectrometry (LC-HRMS) has recently emerged as a powerful analytical tool for large-scale target screening, and the application of LC-HRMS can be expanded to solve the clinical cases of natural product poisoning.

Methods
The LC-HRMS method is based on a spectral library of 121 natural products. The spectral library was constructed by analyzing standards either in a Q-TOF mass spectrometer (only MS2 spectra acquired) or in an Orbitrap Tribrid mass spectrometer (MS2 and MS3 spectra acquired).

Results
The LC-HRMS method was verified for the limit of detection (LOD) and matrix effects in both serum and urine matrices. For each compound, the LOD was evaluated from 1.0 ng/ml to 1000 ng/ml for urine samples and from 0.50 ng/ml to 500 ng/ml for serum samples. The matrix effects were determined at three concentration levels andranged from 30.4% to 123.5% for urine samples and from 23.4% to 132.9% for serum samples. The LC-HRMS method was successfully applied to identify the culprits in three clinical cases. In addition, the combined use of MS2 and MS3 spectra enhanced the accuracy of compound identification, in library search reducing the importance of retention time that varies among instruments and consumable lots. In Case 1, the patient presented with paresthesias, arrhythmias, and stiffened arms and legs. The toxic alkaloid aconitine was identified in the serum sample and the extract of herbs that the patient ingested. In Case 2, the patients presented with weakness, dizziness, and vomiting.
The symptoms were caused by mistakenly taking Nicotiana glauca leaves and the alkaloid anabasine was identified as the culprit. In Case 3, the patients were suspected of intoxicated by taking too much extract of lupini beans. The culprit alkaloids from lupini beans lupanine and sparteine were found in the serum samples.

Conclusion
The involvement of a toxicology laboratory with the capability to perform the LC-HRMS method and with experience in the investigation of undifferentiated cases provides a unique diagnostic advantage in cases where exposure to toxic substances is possible.
A Rare Case of Babesia microti in San Francisco East Bay
Authors: Abdelmonem M , Yu T , Scot J , Bandak R , Davis V , Javaherchian V , Hatten G , Gines M 
Published: October 2020

Abstract

Introduction/Objective
Babesia microti, a zoonotic intraerythrocytic parasite, is the primary etiological agent of human Babesiosis in the United States. Human infections range from subclinical illness to severe disease resulting in death, with symptoms being related to host immune status. Despite advances in our understanding and management of B. microti, the incidence of infection in the United States has increased. Therefore, research focused on eradicating disease and optimizing clinical management is essential. Here we review this remarkable organism, with emphasis on the clinical, diagnostic, and therapeutic aspects of human disease.

Methods
A 71-year-old Asian man presented to the emergency department in our San Francisco East Bay community hospital in July 2019 with complaints of high fever and chills for the last five days. The patient is a resident of Taiwan. He was visiting his daughter in New Jersey where he worked in her garden. He came to California to visit his son when he noted feelings of excessive tiredness, muscle aches, and headache. He also described a decrease in appetite and nausea with vomiting and diarrhea.

Results
His chest x-ray showed increased diffuse bilateral pulmonary infiltrate. He has a history of coronary artery disease post stent placement in 2011 and history of benign prostatic hypertrophy post transurethral resection of the prostate (TURP) On physical exam, He was febrile (103.1°F) and scleral icterus was identified. Laboratory workup revealed findings suggestive of hemolysis including increased LDH (401 U/L) and increased unconjugated bilirubin (1.7 mg/dL), critically low platelets and white blood cells of (32 and 2.9), while hemoglobin & hematocrit values in the normal range (13. g/dL & 36.8%, respectively). Elevated liver enzymes were also noted; AST 72 U/L and ALT 59 U/L. Upon examination of the blood smear, Malaria -like organisms were detected, and Maltese cross forms were also visible in the red blood cells. Those findings were also seen using Giemsa stain and were confirmed at the Alameda county lab. PCR was also positive for Babesia microti. Investigation for concurrent infection with Ehrlichia chaffeensis, Anaplasma phagocytophilum and Borrelia burgdorferi was negative.

Conclusion
This case highlights the importance of timely and effective collaboration between the laboratory staff and clinicians.
Transmission Of ESBL Producing Klebsiella Ozaenae Between Wildlife And Domesticated Animals
Authors: Leu-Burke G M , Hernandez B 
Published: October 2020

Abstract

Introduction/Objective
Animal and human interaction can result in zoonotic transmission, colonization and risk for infectious disease. However wildlife exposure to humans through domesticated animals is not fully understood.
Alaska’s largest urban city, Anchorage, is home to approximately one thousand moose migrating into city parks and suburban backyards with an environmental impact from fecal contamination. As domesticated canines inhabit the same environment there is a potential public health for microbial transfer from wildlife to humans.

Methods
In order to determine potential risk of zoonosis from wildlife to domesticated animals, we ground collected fecal samples from three related canines (Chico, Kali, Chubs), moose habituating the canine’s backyard and from an unrelated canine (Odin) who lived nearby, but did not inhabit the same backyard environment. Observation of canine outdoor activity, including rolling and digging in the soil, was also evaluated. Using standard microbial techniques, all fecal samples were cultured for enterobacteriaceae and further identified by biochemical testing, along with antimicrobial resistance using conventional minimum inhibition concentration antibiotic panels. Phenotypic evaluation for extended spectrum beta-lactamase enzyme was performed using antibiotic disc diffusion.

Results
Fecal samples from the moose contained identical biotype and antimicrobial resistance of ESBL producing Klebsiella ozaenae with related canines Chico and Chubs. Chico and Chubs consistently exposed themselves to moose fecal matter by digging in contaminated soil, indicating aerosol transmission. Although Kali and Odin interacted with Chico and Chubs, they were not colonized suggesting a lack of microbial transmission between domesticated animals.

Conclusion
Close proximity to moose in urban Anchorage draws our attention to their commensal microbiome and potential for infectious transfer. Domesticated animals inhabit shared environment and are at risk for colonization during exposure to wildlife fecal contaminated soil and water. In a limited study, we found transfer of ESBL Klebsiella ozaenae from moose to domesticated animals in a shared urban residence. Human contact with infected domesticated animals, along with aerosol soil exposure during gardening or landscaping activities, presents opportunity for zoonosis from urban wildlife and a risk for colonization of multi-drug resistant bacteria.
A Retrospective Analysis of Joint Cultures: Only Time Will Tell (Or Will It?)
Authors: Altenburger D , Strayer S , Carroll S 
Published: October 2020

Abstract

Introduction/Objective
Multiple textbooks and guidelines, including CLSI, recommend holding joint cultures for 14 days. This prevents false negative results from “slower growers” which include Actinomyces species and Propionibacterium acnes. Holding of these cultures can be a burden for small microbiology labs.

Methods
A retrospective analysis of three years of joint cultures held for 14 days was reviewed. The length of time for the culture to turn positive and the organism that grew was noted.

Results
A total of 67 positive joint cultures were evaluated, which covered a period of 3 years at our institution. Of these, only 1 culture turned positive following day 5 (Propionibacterium acnes grew on day 6). The average time to positive for Propionibacterium acnes was 4 days. In comparison, the average growth time for Staphylococcus aureus and Proteus was 1 day, Pseudomonas aeruginosa was 1.2 days, all Streptococcus species was 2.4 days and Staphylococcus epidermidis was 2.7 days. No cultures grew Actinomyces during our study.

Conclusion
The consequences of missing a positive culture can be grave. In general, culture media has improved and provided increased growth rates. With resources becoming more limited, it may be time to revisit guidelines. This study is too small to be conclusive; a larger study may provide confirmation of the findings.
Use of the BioFire Film Array Blood Culture Identification(BCID) Panel(BioFire Diagnostics, Salt Lake City, Utah) on Pleural Fluid Samples in Pediatric Patients Hospitalized for Community Acquired Pneumonia(CAP)
Authors: Drehner D M , Nazario A , Franco G , Riggins S , Cadilla A , Alexander K 
Published: October 2020

Abstract

Introduction/Objective
CAP accounts for approximately 124,000 pediatric hospitalizations annually. Those patients often have received antibiotics prior to admission. Many have concurrent viral infections. Bacterial infections accompanying viral respiratory infections are known to increase morbidity and mortality. Traditional bacterial culture methods are often negative because of previous antibiotic therapy. The BCID, a multiplex polymerase chain reaction(PCR) assay, can identify 19 bacterial pathogens in approximately 90 minutes. It is FDA approved for blood culture isolates. We hypothesized it would detect bacterial pathogens in pleural effusions.

Methods
BCID panels were done on residual pleural fluid samples from 10 patients with severe community acquired pneumonia during the period 5/2018 – 12/2019. The patients had positive radiographic findings of pneumonia, were inpatients, had intact immune systems by clinical history and had received antibiotic therapy for more than 8 hours before specimen collection. Treatment required 133 inpatient days. 6 of 10 were diagnosed with viral respiratory pathogens. 1 of 9 had a positive blood culture. 1 of 10 had a positive pleural fluid culture.

Results
10 of 10 pleural fluid specimens were positive for a pathogen on the BCID panel – 8, Streptococcus pneumoniae, 1, Staphylococcus aureus and I, Streptococcus pyogens. Two of ten had confirmatory positive cultures. Also, one pleural fluid gram stain showed gram positive cocci in chains and clusters. The BCID detected Streptococcus pyogens. Anti Streptolysin O was strongly positive, 964(0 – 70) IU/mL.

Conclusion
The yield of bacterial culture plummets with previous antibiotic treatment. FDA approved multiplex PCR panels have narrowly defined specimen requirements. That increases the cost and decreases test applicability.
Despite a history of appropriate immunizations in the sample population Streptococcus pneumoniae may be prevalent in the complex pediatric pneumonia population. The BCID may be effective at pathogen detection in cases of complex pneumonia where patients have received prior antibiotic treatment.
Incidence of Androgen Receptor and DNA Repair Gene Mutations in Advanced Solid Malignancies: Clinical Impact of Liquid Biopsy at Veteran Affairs Medical Center
Authors: Dalal S , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
The advent of Liquid biopsy targeting genetic mutations in solid tumors is a major milestone in field of precision oncology. This minimally invasive, novel revolutionary technique analyses circulating tumor cells (CTC) in peripheral blood and detects signature genomic alterations. DNA repair gene (DDR) mutations have been reported in 25-40% of prostatic cancers and &gt;50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers. One of the DDR, especially Tp53 has been found to be associated with poor prognosis and increased germline mutations. We herein present a quality assurance study to determine feasibility of liquid biopsy for personalized management in veterans for advanced solid malignancies and its clinical impact.

Methods
Quality assurance documentation from Foundation One (Cambridge MA, NGS) on liquid biopsies performed for the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) from May 2019 to April 15, 2020 were reviewed. Statistical data for adequacy, cases with notable mutations, frequency and type of mutations of AR, DNA damage repair (DDR) gene and Tp53 were noted.

Results
A total of 31 liquid biopsies were performed over this time period, of which 29/31 (93.50%) were adequate for evaluation. 23/29 (79.30%) showed notable mutations, in 4/23 (17.39%) guided treatment decisions based on androgen receptor (AR) amplification, and 7/29 (24.1%) of all cases showed DDR gene mutations indicating poor outcome and resistance to the current therapy. Greater than 50% (16/29 (55.7%)) of the veterans with advanced cancers harbored Tp53 mutation, which instills hope and future insight for patient tailored oncologic therapy.

Conclusion
The minimally invasive liquid biopsy shows a great promise as a diagnostic and prognostic tool in the personalized clinical management of advanced prostate and NSCLC in veteran patient population with unique demographic characteristics. Difference in frequency of the genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 in future for personalized targeted therapy.
Does the Two-Tier System Accurately Predict Progression of Endometrial Hyperplasia to Endometrial Carcinoma in High-Risk Populations? A Retrospective Study in a Safety-Net Hospital
Authors: Zhao X , Wang C , Taraif S 
Published: October 2020

Abstract

Introduction/Objective
In 2014, the WHO simplified the classification of endometrial hyperplasia (EH) into a two-tier system: endometrial hyperplasia without atypia/benign endometrial hyperplasia (BEH) and atypical endometrial hyperplasia (AEH)/endometrioid intraepithelial neoplasia (EIN), as opposed to the 1994 WHO 4-tier scheme. We conducted this study to assess the diagnostic validity of the two-tier scheme in predicting upgrade to endometrioid adenocarcinoma (EA) in our high-risk patient population.

Methods
Retrospective review from Aug 2009 to August 2019 revealed 144 cases of EH diagnosed on biopsy. The cases were reclassified using the 2014 two-tier scheme to 81 BEH and 63 AEH. The excisional diagnoses, if available, were compared with the initial biopsy results.

Results
At hysterectomy, 22 AEH (50%) were diagnosed as benign, with no residual AEH, 15 cases were upgraded to EA (34.1%), and 7 had residual AEH (15.9%). Endometrial polyp was identified in 29 cases out of 63 AEH, 24 of which had a follow-up excision. Among those, 6 were upgrade to EA (25%), significantly lower than the upgrade rate of AEH without polyp (45%) (p=0.0344).

Conclusion
In our high-risk patient population, the likelihood of upgrade to EA at excision of a biopsy-diagnosed AEH is significantly higher than BEH and is in line with what was reported in the literature for other populations. Patients with endometrial polyps were less likely to progress to EA. Our study demonstrated the diagnostic validity of the two- tiered classification in high-risk population and supports the emphasis on cytological atypia.
Host-dependent dispersal demonstrates both-sex host specificity in cuckoos
Authors: Lee Jin-Won , Moon Hye-Kyoung , Noh Hee-Jin , Kim Myun-Sik , Yoo Jeong-Chil 
Published: October 2020

AbstractIn a parasite species, the dispersal of individuals should be dependent on the host species to which they are specialized; thus, any sexual/individual difference in host specificity may influence their dispersal patterns and, hence, population genetic structures. However, such predictions remain poorly verified in generalist avian brood parasites that are composed of multiple lineages of host-specific races. Here, we show the dispersal consequences inferred from spatial genetic structures and their association with host specificity in brood parasitic common cuckoos Cuculus canorus in which female-specific host race formation has been widely accepted. Genetic sampling from adult cuckoos confirmed restricted dispersal in both sexes and resultant genetic structures between populations where different host species breed allopatrically, whereas it was not the case between distant areas inhabited by the same host species. Contrary to the female host race hypothesis, our results demonstrate that male cuckoos may also have host specificity and disperse accordingly, conclusively allowing us to hypothesize the formation of a host race including both sexes.
Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region
Authors: Li Hanshuang , Long Chunshen , Xiang Jinzhu , Liang Pengfei , Li Xueling , Zuo Yongchun 
Published: October 2020

Abstract
Developmental pluripotency-associated 2 (Dppa2) and developmental pluripotency-associated 4 (Dppa4) as positive drivers were helpful for transcriptional regulation of zygotic genome activation (ZGA). Here, we systematically assessed the cooperative interplay of Dppa2 and Dppa4 in regulating cell pluripotency and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells (ESCs). Compared with other pluripotency transcription factors, Dppa2/4 can regulate majorities of signaling pathways by binding on CG-rich region of proximal promoter (0–500 bp), of which 85% and 77% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found alkaline phosphatase, placental-like 2 (Alppl2) was completely silenced when Dppa2 and 4 single- or double-knockout in ESC, which is consistent with Dux. Moreover, Alppl2 was significantly activated in mouse 2-cell embryos and 4–8 cells stage of human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a ZGA candidate driver to facilitate pre-embryonic development.
Chapter Four Didymus and comedy
Authors: Benuzzi Federica 
Published: October 2020

Abstract
Didymus’ commentaries on the comic playwrights and his Comic Vocabulary responded to the interests of the readership of Attic comedy primarily in two ways: by summarizing the opinions of previous scholars and by offering a wide range of explanations, useful also to less specialized readers. Although his exegesis of comedy is now preserved only through quotations (mainly in the scholia to Aristophanes), it is still possible to identify the main features and interests of Didymus’ interpretative work and highlight its relevance for both ancient and contemporary readers of Greek comedy.
Chapter SixThe compiler compiled: Didymus in Imperial scholarly and miscellanistic literature
Authors: DiGiulio Scott J 
Published: October 2020

Abstract
Few ancient scholars were as prolific as Didymus of Alexandria, who was hailed by some in antiquity as the greatest of the grammarians. Yet, despite his polymathic output and seemingly positive ancient reputation, Didymus was much maligned for his carelessness and the compilatory nature of his work, attitudes which have continued in modern scholarship. This chapter aims to reassess the earliest period of Didymus’ reception by looking closely at the scholarly and miscellaneous texts of the Roman Empire that cite and discuss the Alexandrian. By examining four particular points of reception—Roman educationalists, Harpocration, Athenaeus, and Macrobius—this chapter illustrates that while Roman authors were particularly interested in using a caricature of Didymus as a straw man for their own arguments, Greek figures more readily engaged with Didymus and his work per se. These two traditions evolve in parallel and use Didymus to represent both the positive and negative facets of polymathy; each freely cites, and transforms, him to suit their literary purposes. As a result, Didymus’ reception throughout antiquity is considerably more complex than has been previously acknowledged: he is a figure of both authority and consternation, even among the authors most similar to himself.
Indigenous Systems of Management for Culturally and Ecologically Resilient Pacific Salmon (Oncorhynchusspp.) Fisheries
Authors: Atlas William I , Ban Natalie C , Moore Jonathan W , Tuohy Adrian M , Greening Spencer , Reid Andrea J , Morven Nicole , White Elroy , Housty William G , Housty Jess A , Service Christina N , Greba Larry , Harrison Sam , Sharpe Ciara , Butts Katherine I R , Shepert William M , Sweeney-Bergen Elissa , Macintyre Donna , Sloat Matthew R , Connors Katrina 
Published: October 2020

AbstractPacific salmon (Oncorhynchus spp.) are at the center of social–ecological systems that have supported Indigenous peoples around the North Pacific Rim since time immemorial. Through generations of interdependence with salmon, Indigenous Peoples developed sophisticated systems of management involving cultural and spiritual beliefs, and stewardship practices. Colonization radically altered these social–ecological systems, disrupting Indigenous management, consolidating authority within colonial governments, and moving most harvest into mixed-stock fisheries. We review Indigenous management of salmon, including selective fishing technologies, harvest practices, and governance grounded in multigenerational place-based knowledge. These systems and practices showcase pathways for sustained productivity and resilience in contemporary salmon fisheries. Contrasting Indigenous systems with contemporary management, we document vulnerabilities of colonial governance and harvest management that have contributed to declining salmon fisheries in many locations. We suggest that revitalizing traditional systems of salmon management can improve prospects for sustainable fisheries and healthy fishing communities and identify opportunities for their resurgence.