bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of LC-MS/MS and Enzymatic Methods for the Determination of Total Choline and Total Carnitine in Infant Formula and Milk Products
Authors: Gill Brendon D , Indyk Harvey E , Kobayashi Tadashi , McGrail Iain J , Woollard David C 
Published: April 2020

Abstract

Background
Choline and l-carnitine are classified as pseudo-vitamins because of their conditionally essential status. As they are involved in multiple physiological metabolic pathways in the human body, they are routinely fortified in infant and adult nutritional formulas.

Objective
The performance of an LC-MS/MS method for the analysis of choline and carnitine, compared with enzymatic methods in routine use for the analysis of total carnitine and total choline, is described.

Method
Powder samples were reconstituted, with release of carnitine and choline facilitated by both acid and alkaline hydrolysis and the extract analyzed by LC-MS/MS. Quantitation was by internal standard technique using deuterium-labeled carnitine and deuterium-labeled choline.

Results
Method range, specificity, sensitivity, precision, recovery, accuracy, and ruggedness were assessed for milk powders, infant formulas, and soy- and milk-based nutritional products. Spike recoveries of 94.0–108.4% were obtained for both total carnitine and choline, and no statistical bias (α = 0.05) between measured results and certified values (choline: P = 0.36; free carnitine: P = 0.67) was found for NIST 1849a certified reference material (NIST1849a). Precision, as repeatability relative standard deviation (RSD), was 2.0% RSDr for total carnitine and 1.7% RSDr for total choline. Equivalent results for total choline and total carnitine were obtained by LC-MS/MS and enzymatic methods (n = 30).

Conclusions
The described LC-MS/MS method is fit for purpose for routine product compliance release testing environments. This validation study has confirmed that alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.

Highlights
An LC-MS/MS method was evaluated and found to be fit-for-purpose for routine product compliance release testing of infant formula. The LC-MS/MS method was compared with enzymatic methods for the analysis of total carnitine and total choline. Alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.
Formaldehyde Reacts with Amino Acids and Peptides with a Potential Role in Acute Methanol Intoxication
Authors: Sýkora David , Jindřich Jindřich , Král Vladimír , Jakubek Milan , Tatar Ameneh , Kejík Zdeněk , Martásek Pavel , Zakharov Sergey 
Published: April 2020

Abstract
Methanol, an aliphatic alcohol widely used in the industry, causes acute and chronic intoxications associated with severe long-term health damage, including permanent visual impairment, brain damage, mainly necrosis of the basal ganglia and high mortality due to cancer. However, the role of formaldehyde, an intermediate metabolite of methanol oxidation, in methanol toxicity remains unclear. Thus, we studied the reactivity of several amino acids and peptides in the presence of formaldehyde by identifying products by direct infusion electrospray high-resolution mass spectrometry (MS) and matrix-assisted laser desorption-ionization MS. Cysteine, homocysteine and two peptides, CG and CGAG, provided cyclic products with a +12 amu mass shift with respect to the original compounds. The proposed structures of the products were confirmed by high-resolution tandem MS. Moreover, the formation of the products with +12 amu mass shift was also shown for two biologically relevant peptides, fragments of ipilimumab, which is a human IgG1 monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4. Overall, our experimental results indicate that formaldehyde reacts with some amino acids and peptides, yielding covalently modified structures. Such chemical modifications may induce undesirable changes in the properties and function of vital biomolecules (e.g., hormones, enzymes) and consequently pathogenesis.
The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study
Authors: Conley Barbara A , Staudt Lou , Takebe Naoko , Wheeler David A , Wang Linghua , Cardenas Maria F , Korchina Viktoriya , Zenklusen Jean Claude , McShane Lisa M , Tricoli James V , Williams Paul M , Lubensky Irina , O’Sullivan-Coyne Geraldine , Kohn Elise , Little Richard F , White Jeffrey , Malik Shakun , Harris Lyndsay N , Mann Bhupinder , Weil Carol , Tarnuzzer Roy , Karlovich Chris , Rodgers Brian , Shankar Lalitha , Jacobs Paula M , Nolan Tracy , Berryman Sean M , Gastier-Foster Julie , Bowen Jay , Leraas Kristen , Shen Hui , Laird Peter W , Esteller Manel , Miller Vincent , Johnson Adrienne , Edmondson Elijah F , Giordano Thomas J , Kim Benjamin , Ivy S Percy 
Published: April 2020

Abstract

Background
Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses.

Methods
Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration &gt;3 times published median). Cases proposed by patients’ clinicians were reviewed by clinical and translational experts. Tumor and normal tissue (if possible) were profiled with whole exome sequencing and, if possible, targeted deep sequencing, RNA sequencing, methylation arrays, and immunohistochemistry. Potential germline mutations were tracked for relevance to disease.

Results
Cases reflected a variety of tumors and standard and investigational treatments. Of 520 cases, 476 (91.5%) were accepted for further review, and 222 of 476 (46.6%) proposed cases met requirements as exceptional responders. Clinical data were obtained from 168 of 222 cases (75.7%). Tumor was provided from 130 of 168 cases (77.4%). Of 117 of the 130 (90.0%) cases with sufficient nucleic acids, 109 (93.2%) were successfully analyzed; 6 patients had potentially actionable germline mutations.

Conclusion
Exceptional responses occur with standard and investigational treatment. Retrospective identification of exceptional responders, accessioning, and sequencing of pretreatment archived tissue is feasible. Data from molecular analyses of tumors, particularly when combining results from patients who received similar treatments, may elucidate molecular bases for exceptional responses.
Unexpected Cholera Bacteremia in a 91 Year Old Caucasian Male Patient
Authors: Thwe Phyu M , Schilling Matthew , Reynoso David , Ren Ping 
Published: April 2020

ABSTRACT
Cholera is an illness caused by Vibrio cholerae; its main symptom is acute watery diarrhea. Some infections are asymptomatic or result in patients presenting with mild diarrhea, but complications, such as bacteremia, can be fatal. Being endemic in Africa, Southeast Asia, and Haiti, V. cholerae infection cases in the United States are primarily considered travel-related. Herein, we report a case of a 91 year old Caucasian man, a Texas Gulf Coast resident, who developed bacteremia due to V. cholerae despite having no international travel history. Culture workup by mass spectrometry, automated biochemical system, and 16S ribosomal RNA (rRNA) gene sequencing confirmed V. cholerae. This case conveys an important reminder to clinicians and laboratory professionals regarding potentially serious cholera illnesses due to the domestic prevalence of V. cholerae in the coastal regions of the United States.
Case Report: Buprenorphine Induction Using Transdermal Buprenorphine in a Veteran With Opioid Use Disorder and Psychosis, Managing Precipitated Withdrawal
Authors: Kinasz Kathryn R , Herbst Ellen D , Kalapatapu Raj K 
Published: April 2020

Abstract
Buprenorphine induction can lead to precipitated opioid withdrawal, even when using novel techniques such as transdermal buprenorphine. Involuntary limb movements are a distressing symptom of precipitated withdrawal that can be difficult to treat. We report a case of a military veteran transitioning from methadone to buprenorphine for the treatment of opioid use disorder (OUD) using small doses of transdermal buprenorphine. Herein, we review the literature associated with opioid withdrawal-related restlessness. Despite the known risk of concurrent benzodiazepine and buprenorphine administration, including decreased respiratory rate and death, we present a clinical presentation in which this medication combination may be necessary while under medical supervision. We suggest a stepwise algorithm for pharmacotherapy in patients experiencing involuntary limb movements associated with precipitated withdrawal. To safeguard the success of medication-assisted treatment (MAT) for opioid addiction, clinicians should be aware of potential clinical challenges when managing precipitated opioid withdrawal in patients with complex psychiatric comorbidities.
The History of Swedish Military Healthcare System and Its Path Toward Civilian-Military Collaboration From a Total Defense Perspective
Authors: Khorram-Manesh Amir , Robinson Yohan , Boffard Ken , Örtenwall Per 
Published: April 2020

Abstract

Introduction
The interaction between military and civilian healthcare systems has contributed to the development of medical care. Swedish innovations such as the Seldinger technique for angiography, Leksell Gamma Knife for cranial surgery, and the introduction of pacemakers and ultrasound have contributed to the global development of medicine. Several authors have described the Swedish civilian healthcare system and its development. However, the development and history of its military healthcare system and its influence on the civilian healthcare system remain untold. This review aims to describe the historical development of the Swedish military healthcare system and its path toward civilian-military collaboration and a total defense healthcare system.

Material and Methods
A search for all published scientific papers in Swedish and English, along with available legal documents and directives, was made. We used CINAHL, PubMed, Scopus, and Gothenburg University’s databases and search engines. The following keywords, Swedish, military, civilian, healthcare, collaboration, and development, were searched for, alone or in combination, using a PRISMA flow chart. Duplicates, abstracts, and nonscientific publications were excluded.

Results
Each of the four distinct periods of historical development in the Swedish military healthcare system can be characterized by the changes necessary for transforming Sweden from an aggressive to a defensive and collaborative nation, with national and international engagement. Collaboration not only encompasses readiness and willingness to share resources and information, and to adjust routines and guidelines, but also needs a culture of consensus and respect for each other’s limitations and capabilities. The definition of military medicine and the military physician’s role in Sweden is imperative for further civilian-military collaboration.

Conclusions
Recent global sociopolitical changes necessitate civilian-military healthcare collaboration. Although civilian-military healthcare partnerships in various medical fields have been reported earlier, the Swedish concept of total defense’s healthcare system integration and collaboration may be a more fruitful approach. The collaboration within the total defense healthcare system will result in technical achievements, innovations, and medical advancements for the benefit of the whole nation.
Colour–colour and colour–magnitude diagrams for hot Jupiters
Authors: Melville G , Kedziora-Chudczer L , Bailey J 
Published: April 2020

ABSTRACT
We use ground-based and space-based eclipse measurements for the near-infrared (IR) bands (JHKs) and Spitzer 3.6- and 4.5-μm bands to construct colour–colour and colour–magnitude diagrams for hot Jupiters. We compare the results with previous observations of substellar objects and find that hot Jupiters, when corrected for their inflated radii, lie near the blackbody line and in the same region of the colour–magnitude diagrams as brown dwarfs, including low-gravity dwarfs that have been previously suggested as exoplanet analogues. We use theoretical emission spectra to investigate the effects of different metallicity, C/O ratios, and temperatures on the IR colours. In general, we find that while differences in C/O ratio and metallicity do correspond to different locations on these diagrams, the measurement errors are too large to use this method to put strong constraints on the composition of individual objects. However, as a class, hot Jupiters cluster around the location expected for solar metallicity and C/O ratio.
The flatness problem and the age of the Universe
Authors: Helbig Phillip 
Published: April 2020

ABSTRACT
Several authors have made claims, none of which has been rebutted, that the flatness problem, as formulated by Dicke and Peebles, is not really a problem but rather a misunderstanding. Nevertheless, the flatness problem is still widely perceived to be real. Most of the arguments against the idea of a flatness problem are based on the change with time of the density parameter Ω and normalized cosmological constant λ and, since the Hubble constant H is not considered, are independent of time-scale. An independent claim is that fine-tuning is required in order to produce a Universe which neither collapsed after a short time nor expanded so quickly that no structure formation could take place. I show that this claim does not imply that fine-tuning of the basic cosmological parameters is necessary, in part for similar reasons as in the more restricted flatness problem and in part due to an incorrect application of the idea of perturbing the early Universe in a gedankenexperiment; I discuss some typical pitfalls of the latter.
The CO-dark molecular gas mass in 30 Doradus
Authors: Chevance Mélanie , Madden Suzanne C , Fischer Christian , Vacca William D , Lebouteiller Vianney , Fadda Dario , Galliano Frédéric , Indebetouw Remy , Kruijssen J M Diederik , Lee Min-Young , Poglitsch Albrecht , Polles Fiorella L , Cormier Diane , Hony Sacha , Iserlohe Christof , Krabbe Alfred , Meixner Margaret , Sabbi Elena , Zinnecker Hans 
Published: April 2020

ABSTRACT
Determining the efficiency with which gas is converted into stars in galaxies requires an accurate determination of the total reservoir of molecular gas mass. However, despite being the most abundant molecule in the Universe, H2 is challenging to detect through direct observations and indirect methods have to be used to estimate the total molecular gas reservoir. These are often based on scaling relations from tracers such as CO or dust, and are generally calibrated in the Milky Way. Yet, evidence that these scaling relations are environmentally dependent is growing. In particular, the commonly used CO-to-H2 conversion factor (XCO) is expected to be higher in metal-poor and/or strongly UV-irradiated environments. We use new SOFIA/FIFI-LS observations of far-infrared fine-structure lines from the ionized and neutral gas and the Meudon photodissociation region model to constrain the physical properties and the structure of the gas in the massive star-forming region of 30 Doradus in the Large Magellanic Cloud, and determine the spatially resolved distribution of the total reservoir of molecular gas in the proximity of the young massive cluster R136. We compare this value with the molecular gas mass inferred from ground-based CO observations and dust-based estimates to quantify the impact of this extreme environment on commonly used tracers of the molecular gas. We find that the strong radiation field combined with the half-solar metallicity of the surrounding gas is responsible for a large reservoir of ‘CO-dark’ molecular gas, leaving a large fraction of the total H2 gas (≳75 per cent) undetected when adopting a standard XCO factor in this massive star-forming region.
The closest extremely low-mass white dwarf to the Sun
Authors: Kawka Adela , Simpson Jeffrey D , Vennes Stéphane , Bessell Michael S , Da Costa Gary S , Marino Anna F , Murphy Simon J 
Published: April 2020

ABSTRACT
We present the orbit and properties of 2MASS J050051.85−093054.9, establishing it as the closest (d ≈ 71 pc) extremely low-mass white dwarf to the Sun. We find that this star is hydrogen rich with $T_\textrm {eff}\approx 10\, 500$ K, log g ≈ 5.9, and, following evolutionary models, has a mass of ≈0.17 M⊙. Independent analysis of radial velocity and Transiting Exoplanet Survey Satellite(TESS) photometric time series reveals an orbital period of ≈9.5 h. Its high velocity amplitude ($K\approx 144~\textrm {km}\, \textrm {s}^{-1}$) produces a measurable Doppler beaming effect in the TESSlight curve with an amplitude of 1 mmag. The unseen companion is most likely a faint white dwarf. J0500−0930 belongs to a class of post-common envelope systems that will most likely merge through unstable mass transfer and in specific circumstances lead to Type Ia supernova explosions.
H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes
Authors: Kwon Minjung , Park Kihyun , Hyun Kwangbeom , Lee Jeong-Heon , Zhou Linjiao , Cho Young-Wook , Ge Kai , Skalnik David G , Muir Tom W , Kim Jaehoon 
Published: April 2020

Abstract
In mammalian cells, distinct H3K4 methylation states are created by deposition of methyl groups by multiple complexes of histone lysine methyltransferase 2 (KMT2) family proteins. For comprehensive analyses that directly compare the catalytic properties of all six human KMT2 complexes, we employed a biochemically defined system reconstituted with recombinant KMT2 core complexes (KMT2CoreCs) containing minimal components required for nucleosomal H3K4 methylation activity. We found that each KMT2CoreC generates distinct states and different levels of H3K4 methylation, and except for MLL3 all are stimulated by H2Bub. Notably, SET1BCoreC exhibited the strongest H3K4 methylation activity and, to our surprise, did not require H2B ubiquitylation (H2Bub); in contrast, H2Bub was required for the H3K4me2/3 activity of the paralog SET1ACoreC. We also found that WDR5, RbBP5, ASH2L and DPY30 are required for efficient H3K4 methyltransferase activities of all KMT2CoreCs except MLL3, which could produce H3K4me1 in the absence of WDR5. Importantly, deletion of the PHD2 domain of CFP1 led to complete loss of the H3K4me2/3 activities of SET1A/BCoreCs in the presence of H2Bub, indicating a critical role for this domain in the H2Bub-stimulated H3K4 methylation. Collectively, our results suggest that each KMT2 complex methylates H3K4 through distinct mechanisms in which individual subunits differentially participate.
Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu
Authors: Karambelkar Shweta , Udupa Shubha , Gowthami Vykuntham Naga , Ramachandra Sharmila Giliyaru , Swapna Ganduri , Nagaraja Valakunja 
Published: April 2020

AbstractThe broad host range bacteriophage Mu employs a novel ‘methylcarbamoyl’ modification to protect its DNA from diverse restriction systems of its hosts. The DNA modification is catalyzed by a phage-encoded protein Mom, whose mechanism of action is a mystery. Here, we characterized the co-factor and metal-binding properties of Mom and provide a molecular mechanism to explain ‘methylcarbamoyl’ation of DNA by Mom. Computational analyses revealed a conserved GNAT (GCN5-related N-acetyltransferase) fold in Mom. We demonstrate that Mom binds to acetyl CoA and identify the active site. We discovered that Mom is an iron-binding protein, with loss of Fe2+/3+-binding associated with loss of DNA modification activity. The importance of Fe2+/3+ is highlighted by the colocalization of Fe2+/3+ with acetyl CoA within the Mom active site. Puzzlingly, acid-base mechanisms employed by &gt;309,000 GNAT members identified so far, fail to support methylcarbamoylation of adenine using acetyl CoA. In contrast, free-radical chemistry catalyzed by transition metals like Fe2+/3+ can explain the seemingly challenging reaction, accomplished by collaboration between acetyl CoA and Fe2+/3+. Thus, binding to Fe2+/3+, a small but unprecedented step in the evolution of Mom, allows a giant chemical leap from ordinary acetylation to a novel methylcarbamoylation function, while conserving the overall protein architecture.
Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic
Authors: Anders Hans-Joachim , Bruchfeld Annette , Fernandez Juarez Gema Maria , Floege Jürgen , Goumenos Dimitrios , Turkmen Kultigin , van Kooten Cees , Tesar Vladimir , Segelmark Mårten 
Published: April 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.
Sleep disturbances among medical workers during the outbreak of COVID-2019
Authors: Wang S , Xie L , Xu Y , Yu S , Yao B , Xiang D 
Published: April 2020

Abstract

Background
The outbreak of Corona Virus Disease-2019 (COVID-19) has posed unprecedented pressure and threats to healthcare workers in Wuhan and the entire country.

Aims
To assess the effect of the COVID-19 outbreak on the sleep quality of healthcare workers in a children’s healthcare centre in Wuhan.

Methods
A cross-sectional, anonymized, self-reported questionnaire survey was conducted at the Children’s Healthcare Centre of Renmin Hospital, Wuhan University, Wuhan, China. The questionnaire consisted of three parts, including socio-demographic characteristics and COVID-19 epidemic-related factors, the Pittsburgh sleep quality index (PSQI), and Zung’s self-rating anxiety scale (SAS) and self-rating depression scale (SDS).

Results
In total, 47 out of 123 (38%) participants with PSQI scores &gt; 7 were identified as having sleep disturbance. A logistic regression analysis showed that sleep disturbance was independently associated with being an only child (adjusted odds ratio (OR) and 95% confidence interval (CI) 3.40 (1.21–9.57), P &lt; 0.05), exposure to COVID-19 patients (adjusted OR and 95% CI 2.97 (1.08–8.18), P &lt; 0.05) and depression (adjusted OR and 95% CI 2.83 (1.10–7.27), P &lt; 0.05).

Conclusions
We observed that, during the outbreak of COVID-19, sleep disturbance was highly prevalent among paediatric healthcare workers, and sleep disturbance was independently associated with being an only child, exposure to COVID-19 patients and depression. Therefore, more mental health services are required for front-line paediatric healthcare workers in Wuhan.