bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal-spatial analysis of an age-space structured foot-and-mouth disease model with Dirichlet boundary condition
Authors: Wang Xiaoyan , Sun Hongquan , Yang Junyuan
Published: May 2021

Foot-and-mouth disease is a highly contagious and economically devastating disease of cloven-hoofed animals. The historic occurrences of foot-and-mouth diseases led to huge economic losses and seriously threatened the livestock food security. In this paper, a novel age-space diffusive foot-and-mouth disease model with a Dirichlet boundary condition, coupling the virus-to-animals and animals-to-animals transmission routes, has been proposed. The basic reproduction number R0 is defined as the spectral radius of a next generation operator K, which is calculated in an explicit form, and it serves as a vital value determining whether or not the disease persists. The existence of a unique trivial nonconstant steady state and at least one nonconstant endemic steady state of the system is established by a smart Lyapunov functional and the Kronoselskii fixed point theorem. An application to a foot-and-mouth outbreak in China is presented. The findings suggest that increasing the movements and disinfection of the environment for animals apparently reduce the risk of a foot-and-mouth infection.
Scaling up real networks by geometric branching growth
Authors: Zheng Muhua , García-Pérez Guillermo , Boguñá Marián , Serrano M. Ángeles
Published: May 2021

Significance

Branching processes underpin the complex evolution of many real systems. However, network models typically describe network growth in terms of a sequential addition of nodes. Here, we measured the evolution of real networks—journal citations and international trade—over a 100-y period and found that they grow in a self-similar way that preserves their structural features over time. This observation can be explained by a geometric branching growth model that generates a multiscale unfolding of the network by using a combination of branching growth and a hidden metric space approach. Our model enables multiple practical applications, including the detection of optimal network size for maximal response to an external influence and a finite-size scaling analysis of critical behavior.
On the Limits of Cultural Relativism as a Debiasing Method
Authors: Teira David
Published: May 2021

I analyze cultural relativism as a methodological strategy to correct for ethnocentric biases in anthropological fieldwork. I discuss the format debiasing norms may adopt (rules or standards) depending on whether a discipline has a causal or interpretative outlook. Franz Boas and his school advocated for an interpretative approach to ethnographic fieldwork, in which cultural relativism was implemented as a standard (only culturally unbiased reports are admissible) to be interpreted by expert third parties. Legitimate as it may be as a debiasing method, it does not allow anthropologists to adjudicate their debates on biases in their ethnographic record.
Simulation and Calibration: Mitigating Uncertainty
Authors: Haar Deborah
Published: May 2021

Calibrating a simulation is a crucial step for certain kinds of simulation modeling, and it results in a simulation that is epistemically different from its pre- or uncalibrated counterpart. This article discusses how simulation model builders mitigate uncertainty about model parameters that are necessary for modeling through calibration and argues that the simulation outcomes after calibration are physically meaningful and relevant. When evaluating the epistemic status of computer simulations, comparisons between computer simulations and traditional experiments need to consider this important methodological step.
Improving the strength-ductility trade-off of TiB2/Al-4.5%Cu composites via Mg–Ag microalloying and multi-step heat treatment
Authors: Xue Yanqing , Hao Qitang , Li Bo , Wang Xinliang , Yin Chengze , Zhang Han
Published: May 2021

To surmount the longstanding puzzle of strength-ductility trade-off, efforts had been made to apply Mg - Ag microalloying on 5%TiB2/Al-4.5%Cu composites by in situ molten salt reaction and subsequent heat treatment. The obtained composites achieve an eye-catching tensile elongation (δ) of 6.1 ± 0.4%, while maintaining elevated ultimate tensile strength (UTS) of 497 ± 4 MPa and yield strength (YS) of 401 ± 3MPa. Comprehensive characterization demonstrated that the uniformly distributed TiB2 particles together with semi-coherent grain boundaries between the α-Al matrix and reinforcement phase (TiB2 particles, Ω-Al2Cu, σ-Al5Cu6Mg2) facilitated the dislocation motion integrally, which eliminated the stress concentrations, may be the main reason for amelioration in the strength-ductility trade-off of the composites when subject to rigorous multi-step heat treatment.
Physical properties and compressibility of quail eggshell nanopowder with heat treatment temperature variations
Authors: Puspitasari Poppy , Chairil Muhammad , Sukarni Sukarni , Supriyanto Nicky Suwandhy Widhi
Published: May 2021

This research aimed to determine the effect of heat treatment temperature variations on the physical properties and the quail eggshell’s compressibility. The quail eggshells was obtained from the waste of restaurants and market traders and processed into powder form by ball milling method for 10 h and sintered at 900 °C, 1000 °C, and 1100 °C, a holding time of 1 h. The samples were characterized using x-ray Diffraction (XRD), Scanning Electron Microscope (SEM), and Pressure test for the compressibility result. The results showed that after the heat treatment process, the calcium carbonate phase (CaCO3) was transformed into calcium oxide (CaO). The crystal size on raw material was 52.18 nm and no more than 50 nm in all heat treatment samples. Morphology of eggshells showed variations in the size and shape of grains such as round, rod, and square. Whereas the compressibility test results showed that the addition of charging to the test conducted increased the compressibility value (density). The results also showed physical properties such as pore size and grain size affected quail eggshells’ compressibility value.
Carbon price dynamics in ambitious climate mitigation scenarios: an analysis based on the IAMC 1.5 °C scenario explorer
Authors: Meyer Mark , Löschel Andreas , Lutz Christian
Published: May 2021

We analyse global carbon price trajectories from integrated assessment studies of 2 °C and below-compatible emission pathways based on a new scenario ensemble that has been made publicly available together with other relevant data sets in the IAMC 1.5 °C Scenario Explorer. We complement and extent the findings of the initial study on carbon price variations in integrated assessment models of (Guivarch and Rogelji 2017 Carbon price variations in 2 °C scenarios explored, Carbon Pricing Leadership Coalition) by providing a broader and more robust empirical assessment based on a comprehensive statistical analysis. We discuss the prospects and challenges of in‐depth bivariate econometric analyses of key impact factors in data sets from integrated assessment models. We show that the amount of meta‐information reported for individual models differs significantly across all variables where a large part of all recorded scenario explorer variables can be attributed to only a small number of applied models. We analyse the trend patterns emerging from the analysed global carbon price trajectories based on a statistical trend identification procedure. About half of the analysed carbon price projections seem to be best characterised by long run exponential growth patterns in carbon prices. Moreover, we break down the explanatory contribution of individual components on global carbon prices by the Kaya identity, i.e. global GDP, primary energy intensity and emission intensity. We show that the price of carbon is lower in baseline scenarios with faster economic growth per capita, low‐energy consumption patterns and high potentials for low carbon technologies compared to fossil fuels. In contrast to previous findings, the observed carbon price developments are impacted much more strongly by scenario‐specific than by model‐specific influences. Next to the diagnostic indicators for models, further indicators for the categorization of scenarios describing key context and policy parameterisations applied in individual model runs should be developed and included in descriptions of integrated assessment studies.
Autologous Fat Grafting for Oncologic Patients: A Literature Review
Authors: Seitz Allison J , Asaad Malke , Hanson Summer E , Butler Charles E , Largo Rene D
Published: May 2021

Autologous fat grafting (AFG) serves as an effective method to address volume defects, contour irregularities, and asymmetry in both aesthetic and reconstructive procedures. In recent years, there has been growing concern about the potential of cancer recurrence and interference with cancer surveillance in oncologic patients receiving AFG. The adipose tissue contains adipose-derived stem cells (ASCs), a specific type of mesenchymal stem cells, that facilitate secretion of numerous growth factors which in turn stimulate tissue regeneration and angiogenesis. As such, it has been theorized that ASCs may also have the potential to stimulate cancer cell proliferation and growth when used in oncologic patients. Multiple research studies have demonstrated the ability of ACSs to facilitate tumor proliferation in animal models. However, clinical research in oncologic patients has yielded contradictory findings. Although the literature pertaining to oncologic safety in head and neck, as well as sarcoma, cancer patients remains limited, studies demonstrate no increased risk of tumor recurrence in these patient populations receiving AFG. Similarly, both the efficacy and safety of AFG have been well established in breast cancer patients through numerous clinical studies. More recently, preclinical research in animal models has shown that AFG has the potential to facilitate tissue regeneration and improve joint contracture following irradiation. Ultimately, further research is needed to elucidate the safety of AFG in a variety of oncologic patients, as well as explore its use in tissue regeneration, particularly in the setting of radiotherapy.

Level of Evidence: 4
UMI4Cats: an R package to analyze chromatin contact profiles obtained by UMI-4C
Authors: Ramos-Rodríguez Mireia , Subirana-Granés Marc , Pasquali Lorenzo
Published: May 2021

Motivation

UMI-4C, a technique that combines chromosome conformation capture (4C) and unique molecular identifiers (UMI), is widely used to profile and quantitatively compare targeted chromosomal contact profiles. The analysis of UMI-4C experiments presents several computational challenges, including the removal of the PCR duplication bias and the identification of differential chromatin contacts.

Results

We have developed UMI4Cats (UMI-4C Analysis Turned Simple), an R package that facilitates processing, analyzing and visualizing of data obtained by UMI-4C experiments.

Availability and implementation

UMI4Cats is implemented as an R package supported on Linux, MacOS and MS Windows. UMI4Cats is available from Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/UMI4Cats.html) and GitHub (https://github.com/Pasquali-lab/UMI4Cats).

Supplementary information

Supplementary data are available at Bioinformatics online.
Multiresponse Optimization of HPLC Method: Simultaneous Estimation of Protease Inhibitors and NNRTI in Human Plasma
Authors: Ganna Anitha , Vaithiyanathan Sree Janardhanan , V P Pandey , P Venkatesan
Published: May 2021

Multiresponse optimization approach to develop a simple isocratic, highly sensitive and accurate HPLC method for the simultaneous determination of Efavirenz, Atazanavir, Lopinavir and Ritonavir in human blood plasma along with carvedilol as an internal standard. Optimized the factors (ACN, buffer concentration and flow rate) effecting and interacting with the responses (k1, Rs2,1, Rs3,2 and tR5) applying Central Composite Design a chemometric tool. All the mathematical models as well as response surfaces were defined and derived for the separation using this strategy. Chromatography was performed on Thermo Hypersil C18 column using mobile phase comprising of ACN: 10 mM KH2PO4 (51.2:48.8) with 1 mL min−1 flow rate and detection wavelength was fixed at 210 nm. The analysis time was within 9 min. The method developed was validated by following “Bioanalytical method validation” [USFDA-CDER, 2001]. The developed method can be applied for bioavailability and pharmacokinetic studies.
2D high resolution vs. 3D whole heart myocardial perfusion cardiovascular magnetic resonance
Authors: Nazir Muhummad Sohaib , Shome Joy , Villa Adriana D M , Ryan Matthew , Kassam Ziyan , Razavi Reza , Kozerke Sebastian , Ismail Tevfik F , Perera Divaka , Chiribiri Amedeo , Plein Sven
Published: May 2021

Aims

Developments in myocardial perfusion cardiovascular magnetic resonance (CMR) allow improvements in spatial resolution and/or myocardial coverage. Whole heart coverage may provide the most accurate assessment of myocardial ischaemic burden, while high spatial resolution is expected to improve detection of subendocardial ischaemia. The objective of this study was to compare myocardial ischaemic burden as depicted by 2D high resolution and 3D whole heart stress myocardial perfusion in patients with coronary artery disease.

Methods and results

Thirty-eight patients [age 61 ± 8 (21% female)] underwent 2D high resolution (spatial resolution 1.2 mm2) and 3D whole heart (in-plane spatial resolution 2.3 mm2) stress CMR at 3-T in randomized order. Myocardial ischaemic burden (%) was visually quantified as perfusion defect at peak stress perfusion subtracted from subendocardial myocardial scar and expressed as a percentage of the myocardium. Median myocardial ischaemic burden was significantly higher with 2D high resolution compared with 3D whole heart [16.1 (2.0–30.6) vs. 13.4 (5.2–23.2), P = 0.004]. There was excellent agreement between myocardial ischaemic burden (intraclass correlation coefficient 0.81; P < 0.0001), with mean ratio difference between 2D high resolution vs. 3D whole heart 1.28 ± 0.67 (95% limits of agreement −0.03 to 2.59). When using a 10% threshold for a dichotomous result for presence or absence of significant ischaemia, there was moderate agreement between the methods (κ = 0.58, P < 0.0001).

Conclusion

2D high resolution and 3D whole heart myocardial perfusion stress CMR are comparable for detection of ischaemia. 2D high resolution gives higher values for myocardial ischaemic burden compared with 3D whole heart, suggesting that 2D high resolution is more sensitive for detection of ischaemia.
Resistant hyponatraemia in a patient with follicular lymphoma and heart failure with reduced ejection fraction: a case report
Authors: Butler Jennifer , Miro Firas , Al-Mohammad Abdallah
Published: May 2021

Background

Hyponatraemia is a common problem in patients with heart failure. It can be difficult to treat, especially in the presence of the patient’s needs for diuresis and manipulation of the renin–angiotensin–aldosterone system (RAAS).

Case summary

This concerns a 74-year-old woman with follicular lymphoma and severe global left ventricular systolic dysfunction secondary to treatment with R-CHOP chemotherapy. She presented a difficult challenge in the management of her decompensated heart failure alongside hyponatraemia as low as 113 mmol/L. This was resistant to standard treatment. The resistance to usual measures necessitated treatment with Tolvaptan, a selective arginine vasopressin V2 inhibitor used to treat hyponatraemia in syndrome of inappropriate anti-diuretic hormone. This, along with a strict fluid restriction of 500 mL/day, resolved the patient’s hyponatraemia and enabled her discharge home on tolerated heart failure treatment. She has now remained stable for almost 12 months.

Discussion

The potential causes of hyponatraemia are discussed along with the role of Tolvaptan in its management.
The neural G protein Gαo tagged with GFP at an internal loop is functional in Caenorhabditis elegans
Authors: Kumar Santosh , Olson Andrew C , Koelle Michael R
Published: May 2021

Gαo is the alpha subunit of the major heterotrimeric G protein in neurons and mediates signaling by every known neurotransmitter, yet the signaling mechanisms activated by Gαo remain to be fully elucidated. Genetic analysis in Caenorhabditis elegans has shown that Gαo signaling inhibits neuronal activity and neurotransmitter release, but studies of the molecular mechanisms underlying these effects have been limited by lack of tools to complement genetic studies with other experimental approaches. Here, we demonstrate that inserting the green fluorescent protein (GFP) into an internal loop of the Gαo protein results in a tagged protein that is functional in vivo and that facilitates cell biological and biochemical studies of Gαo. Transgenic expression of Gαo-GFP rescues the defects caused by loss of endogenous Gαo in assays of egg laying and locomotion behaviors. Defects in body morphology caused by loss of Gαo are also rescued by Gαo-GFP. The Gαo-GFP protein is localized to the plasma membrane of neurons, mimicking localization of endogenous Gαo. Using GFP as an epitope tag, Gαo-GFP can be immunoprecipitated from C. elegans lysates to purify Gαo protein complexes. The Gαo-GFP transgene reported in this study enables studies involving in vivo localization and biochemical purification of Gαo to compliment the already well-developed genetic analysis of Gαo signaling.
‘I was trying to get there, but I couldn’t’: social norms, vulnerability and lived experiences of home delivery in Mashonaland Central Province, Zimbabwe
Authors: Webb Karen A , Mavhu W , Langhaug L , Chitiyo V , Matyanga P , Charashika P , Patel D , Prost A , Ferrand Rashida A , Bernays S , Cislaghi B , Neuman M
Published: May 2021

Increasing facility-based delivery rates is pivotal to reach Sustainable Development Goals to improve skilled attendance at birth and reduce maternal and neonatal mortality in low- and middle-income countries (LMICs). The translation of global health initiatives into national policy and programmes has increased facility-based deliveries in LMICs, but little is known about the impact of such policies on social norms from the perspective of women who continue to deliver at home. This qualitative study explores the reasons for and experiences of home delivery among women living in rural Zimbabwe. We analysed qualitative data from 30 semi-structured interviews and 5 focus group discussions with women who had delivered at home in the previous 6 months in Mashonaland Central Province. We found evidence of strong community-level social norms in favour of facility-based delivery. However, despite their expressed intention to deliver at a facility, women described how multiple, interacting vulnerabilities resulted in delivery outside of a health facility. While identified as having delivered ‘at home’, narratives of birth experiences revealed the majority of women in our study delivered ‘on the road’, en route to the health facility. Strong norms for facility-based delivery created punishments and stigmatization for home delivery, which introduced additional risk to women at the time of delivery and in the postnatal period. These consequences for breaking social norms promoting facility-based delivery for all further increased the vulnerability of women who delivered at home or on the road. Our findings highlight that equitable public health policy and programme designs should include efforts to actively identify, mitigate and evaluate unintended consequences of social change created as a by-product of promoting positive health behaviours among those most vulnerable who are unable to comply.
Future Tail Tales: A Forward-Looking, Integrative Perspective on Tail Research
Authors: Schwaner M J , Hsieh S T , Braasch I , Bradley S , Campos C B , Collins C E , Donatelli C M , Fish F E , Fitch O E , Flammang B E , Jackson B E , Jusufi A , Mekdara P J , Patel A , Swalla B J , Vickaryous M , McGowan C P
Published: May 2021

Synopsis Tails are a defining characteristic of chordates and show enormous diversity in function and shape. Although chordate tails share a common evolutionary and genetic-developmental origin, tails are extremely versatile in morphology and function. For example, tails can be short or long, thin or thick, and feathered or spiked, and they can be used for propulsion, communication, or balancing, and they mediate in predator–prey outcomes. Depending on the species of animal the tail is attached to, it can have extraordinarily multi-functional purposes. Despite its morphological diversity and broad functional roles, tails have not received similar scientific attention as, for example, the paired appendages such as legs or fins. This forward-looking review article is a first step toward interdisciplinary scientific synthesis in tail research. We discuss the importance of tail research in relation to five topics: (1) evolution and development, (2) regeneration, (3) functional morphology, (4) sensorimotor control, and (5) computational and physical models. Within each of these areas, we highlight areas of research and combinations of long-standing and new experimental approaches to move the field of tail research forward. To best advance a holistic understanding of tail evolution and function, it is imperative to embrace an interdisciplinary approach, re-integrating traditionally siloed fields around discussions on tail-related research.
Plasma concentrations of persistent organic pollutants and pancreatic cancer risk
Authors: Porta Miquel , Gasull Magda , Pumarega José , Kiviranta Hannu , Rantakokko Panu , Raaschou-Nielsen Ole , Bergdahl Ingvar A , Sandanger Torkjel Manning , Agudo Antoni , Rylander Charlotta , Nøst Therese Haugdahl , Donat-Vargas Carolina , Aune Dagfinn , Heath Alicia K , Cirera Lluís , Goñi-Irigoyen Fernando , Alguacil Juan , Giménez-Robert Àlex , Tjønneland Anne , Sund Malin , Overvad Kim , Mancini Francesca Romana , Rebours Vinciane , Boutron-Ruault Marie-Christine , Kaaks Rudolf , Schulze Matthias B , Trichopoulou Antonia , Palli Domenico , Grioni Sara , Tumino Rosario , Naccarati Alessio , Panico Salvatore , Vermeulen Roel , Quirós J Ramón , Rodríguez-Barranco Miguel , Colorado-Yohar Sandra M , Chirlaque María-Dolores , Ardanaz Eva , Wareham Nick , Key Tim , Johansson Mattias , Murphy Neil , Ferrari Pietro , Huybrechts Inge , Chajes Veronique , Gonzalez Carlos Alberto , Bueno-de-Mesquita Bas , Gunter Marc , Weiderpass Elisabete , Riboli Elio , Duell Eric J , Katzke Verena , Vineis Paolo
Published: May 2021

Background

Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.

Methods

We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.

Results

Some associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.

Conclusions

Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
The Effect of Locomotion Mode on Body Shape Evolution in Teleost Fishes
Authors: Friedman Sarah T , Price Samantha A , Wainwright Peter C
Published: May 2021

Teleost fishes vary in their reliance on median and paired fins (MPF) or undulation of the body (BCF) to generate thrust during straight-line, steady swimming. Previous work indicates that swimming mode is associated with different body shapes, though this has never been empirically demonstrated across the diversity of fishes. As the body does not play as active a mechanical role in steady swimming by MPF swimmers, this may relax constraints and spur higher rates of body shape diversification. We test these predictions by measuring the impact of the dominant steady swimming mode on the evolution of body shape across 2295 marine teleost fishes. Aligning with historical expectations, BCF swimmers exhibit a more elongate, slender body shape, while MPF propulsion is associated with deeper and wider body shapes. However, in contrast to expectations, we find that BCF propulsion is associated with higher morphological diversity and greater variance around trait optima. This surprising result is consistent with the interpretation that stronger functional trade-offs stimulate phenotypic evolution, rather than constrain it.
Estimation of Multiple Fixed-Dose Combination Products of Ramipril and Aspirin by GERV-Chromatography Using DoE and Risk-Based Enhanced Analytical Quality by Design Approach
Authors: Prajapati Pintu B , Jayswal Kajal V , Shah Shailesh A
Published: May 2021

Background

Numerous chromatographic methods have been published for estimation of fixed-dose combinations (FDCs) of aspirin and ramipril with other drugs. But no published report has been found which promotes simultaneous estimation of FDCs of aspirin and ramipril with other drugs using a single chromatography condition.

Objective

Hence, the HPTLC method was developed for simultaneous estimation of FDCs of aspirin and ramipril with the drugs under study to save solvent, cost, and time for analysis using a risk- and DoE-based AQbD approach.

Method

The risk-based AQbD approach was implemented using the risk priority number (RPN) ranking and filtering method as per the ICH Q9 guideline. The DoE-based AQbD approach was applied through a screening study using Placket-Burman design, followed by response surface analysis by Box-Behnken design as per the ICH Q8 guideline.

Results

The risks from critical method risk parameters were mitigated by navigating method operable design ranges and framing the control strategy for the target method. The method was validated as per ICH Q2 (R1) guidelines. The developed method was applied for simultaneous assay of six different FDCs of aspirin and ramipril and results agreed with the label claims.

Conclusions

The developed method is the best alternative to published chromatographic methods for estimation of the FDC products under study and saves solvent, time, and cost of analysis. Hence, the developed “GERV”-chromatography method is found to be green (G), economical (E), robust (R), and versatile (V), for estimation of the said FDC products.

Highlights

Development of GERV-chromatography for simultaneous estimation of multiple FDCs of ramipril and aspirin using a risk-based AQbD approach. Application of the developed method for simultaneous estimation of six different FDC products.
In a Case of Death Involving Steroids, Hair Testing is More Informative than Blood or Urine Testing
Authors: Kintz Pascal , Gheddar Laurie , Blanchot Adeline , Ameline Alice , Raul Jean-Sébastien
Published: May 2021

A 59-year-old male was found dead at home, with two empty vials of an oily preparation obtained from a manufacturer from East Europe. There was no label on the vial. The subject was a former weightlifter, also known as an anabolic steroids abuser. The local prosecutor ordered a body examination, which was unremarkable, and allowed collecting femoral blood, urine and scalp hair (6 cm, brown). He was treated for cardiac insufficiency with quinidine. Biological specimens were submitted not only to standard toxicological analyses including a screening with liquid chromatography (LC)–quadrupole time of flight, but also to a specific LC–tandem mass spectrometry method for anabolic steroids testing. Ethanol was not found in both blood and urine. Quinidine blood concentration (791 ng/mL) was therapeutic. No drug of abuse was identified. In blood, testosterone was less that 1 ng/mL and no other steroid was identified. In urine, testosterone/epitestosterone was 1.56 and boldenone was present at a concentration of 9 ng/mL. The hair test results, performed on the whole length, demonstrated repetitive steroids abuse, including not only testosterone (140 pg/mg), testosterone propionate (605 pg/mg) and testosterone decanoate (249 pg/mg), but also boldenone (160 pg/mg), trenbolone (143 pg/mg) and metandienone (60 pg/mg). Since forensic laboratories have limited access to steroid urinary metabolite reference material due to specific regulations (to avoid testing athletes before anti-doping verifications), hair analyses seem to be the best approach to document anabolic agents abuse. Indeed, in hair, the target drug is the parent compound; in addition, when compared to blood or urine, this matrix has a much larger window of detection. The pathologist concluded cardiac insufficiency in a context involving repetitive abuse of anabolic drugs. This case indicates that more attention should be paid to anabolic steroids, in a context of sudden cardiac death.
11-Year Study of Fentanyl in Driving Under the Influence of Drugs Casework
Authors: Chan-Hosokawa Ayako , Bierly Jolene J
Published: May 2021

Prior to 2017, heroin and other prescription opioids were the most prevalent opioids implicated in driving under the influence of drugs (DUID) investigation cases, and fentanyl was rarely included in the scope of toxicological analysis. Fentanyl has become the most frequently identified opioid in DUID cases, with many suspected heroin cases turning out to be only fentanyl. A review of fentanyl-positive DUID cases at NMS Labs was performed to provide prevalence information, change in concentration, patterns of combined drug use, indicators of impairment and driving behavior in order to assist with the toxicological interpretation of DUID scenarios involving fentanyl. Fentanyl-positive DUID cases received between January 2010 and December 2020 were examined. Blood results were confirmed and quantitated for fentanyl, norfentanyl and acetylfentanyl using a liquid chromatography--tandem mass spectrometry analysis with a limit of quantitation of 0.10, 0.20 and 0.10 ng/mL, respectively. Of 153,234 blood cases examined for DUID over 11 years, fentanyl was confirmed positive in 6,779 (4.4%) cases. However, there were significant changes in positivity over time. Fentanyl percentage positivity increased from 0.60% in 2010 to 12% in 2020. Of 5,976 confirmed fentanyl-positive cases in 2018–2020, blood concentrations >4.0 ng/mL were observed in 44% (2018), 55% (2019) and 59% (2020) of cases. Polypharmacy was common with 87% of blood samples confirmed positive for fentanyl and at least one other compound. Stimulant was the most commonly identified drug class in cases where at least one additional drug class was present. This study illustrates the importance of including fentanyl in a routine blood DUID panel.
Implementing video visits into an orthopedic hip arthroscopy practice: a case study
Authors: Wickman John , Ferlotti Colleen , Ferrell Justin , Hutyra Carolyn , Phinney Donna , Wahl Megan , Mather Richard C
Published: May 2021

Telehealth videoconferencing has been shown to be feasible, cost-effective and safe in numerous fields of medicine. In an effort to increase access and improve the quality of care offered to patients we implemented a telehealth initiative allowing for remote orthopedic clinic visits at a major academic medical center. Here we report on our experience and early outcomes. A telehealth platform was launched for a single fellowship trained orthopedic surgeon at a major academic hospital in August 2018. New patients residing outside the metro area, all return patients and patients with an uncomplicated post-operative course were offered the option to complete patient encounters remotely via a telehealth platform. Each patient was offered a Patient Satisfaction Survey following video visit. Patient zip codes were used to estimate patient commutes. Ninety-six percent of patients agreed/strongly agreed with the statement ‘I was satisfied with my Telehealth experience’ while 51% agreed/strongly agreed with the statement ‘This visit was just as good as a face to face visit’. In all, 94% of patients agreed/strongly agreed with the statement ‘Having a telehealth visit made receiving care more accessible for me’. The median miles saved on commutes were 123.3 miles. The no show rate for telehealth visits was 8.2% versus 3.2% for in-person (P < 0.001). Telehealth video visits provided patients with a modality for completing orthopedic clinic visits while maintaining a high-quality care and patient satisfaction. Patient convenience was optimized with video visits with elimination of long commutes. Level of evidence: IV.
Surgical upstaging rates in patients meeting the eligibility for active surveillance trials
Authors: Iwamoto Naoko , Nara Miyako , Horiguchi Shin-ichiro , Aruga Tomoyuki
Published: May 2021

Purpose

Four clinical active surveillance trials including LORIS, COMET, LORD and LORETTA, are being conducted to assess whether women with low-risk ductal carcinoma in situ can safely avoid surgery. The present study aimed to determine the rate of upstaging to invasive cancer among patients with a preoperative diagnosis of ductal carcinoma in situ and to evaluate the incidence of upstaging in patients meeting the eligibility criteria for four active surveillance clinical trials.

Methods

The present study initially enrolled 180 patients with 183 calcifications who received the diagnosis of ductal carcinoma in situ by biopsy. Patients were classified as eligible for four clinical trials according to the respective inclusion criteria.

Results

In total, 152 patients with 155 calcifications were analyzed. Of these, 32 (21%) were upstaged to invasive disease based on the final pathological analysis of surgical specimens. Of the 152 patients, 53 (35%), 90 (59%), 24 (16%) and 34 (22%) met the eligibility criteria for the LORIS, COMET, LORD and LORETTA trial, respectively. Among patients with low-risk ductal carcinoma in situ, 10 (19%), 14 (16%), 6 (25%) and 4 (12%) patients were upstaged to invasive disease in LORIS, COMET, LORD and LORETTA, respectively. The upstaging to pT1b or higher rates were 2% (1/53), 3% (3/90), 0% (0/24) and 3% (1/34) in LORIS, COMET, LORD and LORETTA, respectively.

Conclusions

The upstaging rate in patients eligible for the clinical active surveillance trials was 12–25%. Although the rate of upstaging to pT1b or higher was low, further studies are required to determine the rates of upstaging to invasive cancer and the risk factors among patients with low-risk ductal carcinoma in situ.
Expression and Prognostic Value of the Immune Checkpoints Galectin-9 and PD-L1 in Glioblastomas
Authors: Knudsen Arnon Møldrup , Rudkjøbing Sisse Josephine , Sørensen Mia Dahl , Dahlrot Rikke Hedegaard , Kristensen Bjarne Winther
Published: May 2021

Immunotherapeutic targeting of the PD-1/PD-L1 axis has been widely implemented for treatment of several cancer types but shown disappointing results in glioblastomas (GBMs), potentially due to compensatory mechanisms of other expressed immune checkpoints. Galectin-9 is an immune-checkpoint protein that facilitates T-cell exhaustion and apoptosis and could be a potential target for immune-checkpoint inhibition. A total of 163 GBMs IDH wildtype were immunostained with anti-Galectin-9 and PD-L1 antibodies. Software-based quantitation of immunostainings was performed and co-expression was investigated using double immunofluorescence. Both Galectin-9 and PD-L1 protein expression were found in all 163 tumors and showed a significant positive correlation (p = 0.0017). Galectin-9 expression varied from 0.01% to 32% (mean = 6.61%), while PD-L1 membrane expression ranged from 0.003% to 0.14% (mean = 0.048%) of total tumor area. Expression of Galectin-9 and PD-L1 was found on both microglia/macrophages and tumor cells, and colocalization of both markers was found in 88.3% of tumors. In multivariate analysis, neither Galectin-9 (HR = 0.99), PD-L1 (HR = 1.05), nor their combinations showed prognostic value. Galectin-9 and PD-L1 were expressed in all investigated GBMs and the majority of patients had co-expression, which may provide rationale for multi-targeted immune checkpoint inhibition.
Application of Genome-Wide DNA Methylation Analysis to Differentiate a Case of Radiation-Induced Glioblastoma From Late-Relapsed Medulloblastoma
Authors: Hiraki Takamasa , Fukuoka Kohei , Mori Makiko , Arakawa Yuki , Matsushita Yuko , Hibiya Yuko , Honda Satoko , Kobayashi Masao , Tanami Yutaka , Ichimura Koichi , Hirato Junko , Kurihara Jun , Nakazawa Atsuko , Koh Katsuyoshi
Published: May 2021

Recurrent medulloblastoma can be difficult to diagnose with conventional diagnostic methods because other lesions mimic tumor relapse, particularly at later stages. We report 2 cases of medulloblastoma, both of which seemed to develop late recurrences. Case 1 was a 6-year-old girl who had a medulloblastoma with focal desmoplasia. She was in complete remission for 9 years after treatment but developed an intradural lesion in her thoracic spine, which was pathologically confirmed as tumor recurrence by biopsy. Case 2 was a 10-year-old girl who had a nonmetastatic medulloblastoma. She developed a left cerebellar mass 5 years after the initial diagnosis; the pathological diagnosis was tumor relapse. We performed t-distributed stochastic neighbor embedding of the methylation data from these cases and reference data. In contrast to the consistency of methylation profiling and copy number abnormalities between primary and recurrent tumors of Case 1, the analysis of the recurrent tumor in Case 2 was distinct from medulloblastomas and clustered with “IDH-wild type glioblastomas,” suggesting that the recurrent tumor was a radiation-induced glioblastoma. This report highlights the clinical utility of molecular genetic/epigenetic analysis combined with a standard diagnostic approach to confirm the diagnosis of brain tumor recurrence.
Collision between molecular clouds – III: the effects of cloud initial density profile on head-on collisions
Authors: Tanvir Tabassum S , Dale James E
Published: May 2021

In this third paper of our cloud collision series, we present the results from simulations of head-on collisions with a strongly centrally condensed initial density profile of ρ ∝ R−2. We investigate the impact of these density profiles on the overall evolution of the simulations: the structures formed, their dynamical evolution, and their star formation activity. We consider clouds that are globally bound and globally unbound, leading to three different scenarios – the collision of a bound cloud with a bound cloud, the collision of two unbound clouds, or the collision of one cloud of each type.

In all the simulations, dense star clusters form before the collisions occur, and we find that star formation remains confined to these systems and is little affected by the collisions. If the clouds are both initially bound, the collision forms a filamentary structure, but otherwise this does not occur. We observe that rotating structures form around the clusters, but they also form in our non-colliding control simulations, so are not a consequence of the collisions. The dissipation of kinetic energy in these simulations is inefficient because of the substructure created in the clouds by turbulence before the collisions. As a result, although some gas is left bound in the COM frame, the star clusters formed in the simulations do not become bound to each other.
A kinematic analysis of the CO clouds toward a reflection nebula NGC 2023 observed using the Nobeyama 45 m telescope: Further evidence for a cloud–cloud collision in the Orion region
Authors: Yamada Rin I , Enokiya Rei , Sano Hidetoshi , Fujita Shinji , Kohno Mikito , Tsutsumi Daichi , Nishimura Atsushi , Tachihara Kengo , Fukui Yasuo
Published: May 2021

We performed fully sampled J = 1–0 line observations of 12CO and 13CO toward the reflection nebula NGC 2023 using the Nobeyama 45 m telescope. It covered the entire NGC 2023 region with angular and velocity resolutions of 19″ corresponding to 0.04 pc and 0.33 km s−1, respectively. We analyzed the data focusing on gas dynamics and revealed two velocity components, each with a mass of $\sim\! 3000 \mbox{$\, {M}_\odot $}$, at radial velocities of 10 and 12 km s−1. These components show spatially complementary distributions and are connected in velocity, both of which are the typical signatures of cloud–cloud collision (CCC). Although previous studies favored a scheme of triggering by the H ii region of IC 434, our results show that the effect of the H ii region is limited only to the surface of the molecular cloud, and does not contribute to the entire gas compression and the overall star formation. Comparing the present results with those for neighboring NGC 2024, we find that their active star formation can be explained by a single CCC event. We suggest that the 10 and 12 km s−1 clouds collided ∼0.4 Myr ago, which is common to the regions, but triggered the B1.5V-type star HD 37903 as well as ∼20 low-mass stars in NGC 2023, and ∼20 OB stars in NGC 2024. The column density in NGC 2023 is two to three times lower than that of NGC 2024, which may result in the different star formation activity suggested by the trend of ∼50 other CCC-triggered star-forming regions in the literature.
Genome-wide association study reveals the genetic architecture of 27 agronomic traits in tomato
Authors: Ye Jie , Wang Xin , Wang Wenqian , Yu Huiyang , Ai Guo , Li Changxing , Sun Pengya , Wang Xianyu , Li Hanxia , Ouyang Bo , Zhang Junhong , Zhang Yuyang , Han Heyou , Giovannoni James J , Fei Zhangjun , Ye Zhibiao
Published: May 2021

Tomato (Solanum lycopersicum) is a highly valuable fruit crop, and yield is one of the most important agronomic traits. However, the genetic architecture underlying tomato yield-related traits has not been fully addressed. Based on ∼4.4 million single nucleotide polymorphisms obtained from 605 diverse accessions, we performed a comprehensive genome-wide association study for 27 agronomic traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many previously reported and additional genes related to vegetative and reproductive development, were identified, and these loci explained an average of ∼8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection during tomato domestication and improvement. Furthermore, a candidate gene, Sl-ACTIVATED MALATE TRANSPORTER15, that encodes an aluminum-activated malate transporter was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation, thereby affecting photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.
Physical Work Exposures of Older Workers: Does Measurement Make a Difference?
Authors: Andrasfay Theresa , Pebley Anne R , Goldman Noreen
Published: May 2021

Physically demanding work at later ages, which is especially prevalent among disadvantaged groups, is associated with long-term health outcomes and may contribute to health inequality over the life course. Past studies of these issues have relied on occupational characteristics from the Occupational Information Network (O*NET), but few have assessed how O*NET compares to survey reports when measuring occupational exposures in analyses of socioeconomic status, work conditions, and health. We compare Health and Retirement Study (HRS, N = 16,683 working respondents) and O*NET measurements of general physical activity, frequency of lifting/handling objects, and frequency of stooping-related postures required at work. Pearson correlations between the HRS items and corresponding O*NET items vary from weak to moderate for lifting/handling and stooping-related postures to relatively large for general physical activity. Though they are measured on different scales, both the HRS and O*NET measures of physical demands reveal similar sex, racial/ethnic, and educational differentials in exposure to physically strenuous work. We fit random effects Poisson models to assess how these measures predict accumulation of functional limitations, a potential long-term consequence of strenuous working conditions. Comparable HRS and O*NET measures have similar associations with functional limitations. We also consider an average of physical demand items available in O*NET, finding that this measure has similar associations with functional limitations as the O*NET measure of general physical activity. These results suggest that O*NET characteristics and HRS respondent reports produce comparable disparities in physical work exposures (PWEs) and associations between physically demanding work and declines in physical functioning.
Synthesis and Characterization of a Copper‐Based Macrocyclic Chelate for Quantitation and Sequestration of Oxalate: the Major Component of Kidney Stones
Authors: VanWert Adam L , Hensley Jayden L , Hontz David S , Torsiello Maria L , Venditto Michael L , Luchetta Jared L , Lucent Del L , Terzaghi William L
Published: May 2021

Background

Roughly eighty percent of kidney stones are calcium oxalate‐based. Oxalate is found both in diet and synthesized in the liver. Furthermore, blood‐borne oxalate likely undergoes enteroenteric recirculation via transporters in the small intestine (SLC26A6, secretory) and colon (SLC26A3, absorptive). There is a great need for pharmacotherapeutic options to prevent and treat calcium‐oxalate kidney stones. Furthermore, methods for quantifying oxalate in biological matrices are costly and time consuming.

Objective

We aimed to synthesize and further characterize a small‐molecule oxalate binder, with two ultimate goals in mind: (1st) to be employed in a quantitative fluorescence‐based oxalate assay, and (2nd) to prevent colonic oxalate absorption.

Methods & Results

We optimized the synthesis of a copper‐based chelate (~70% yield) and expanded characterization beyond literature reports: (1) for the first time we crystallized the chelate and determined its lattice unit cell as triclinic via X‐ray crystallography; (2) for the first time we obtained NMR spectra of the chelate; (3) we obtained mass spectra of the two intermediates, showing excellent purity; (4) we confirmed the ability of the chelate to quench eosin Y fluorescence, and to release eosin Y upon oxalate binding; and (5) we have, for the first time, determined that citrate can also give a positive fluorescence response, unlike other acids.

Conclusions

The macrocyclic chelate can be produced readily with high yield and purity. Its crystal structure helps to predict the binding orientation of oxalate, which may lead to more specific oxalate binders. We have found, for the first time, that although the compound is selective for oxalate, contrary to previous reports, it is not specific. These findings indicate that the chelate may serve as a useful tool for quantifying oxalate provided that a strategy for mitigating citrate binding is developed. Furthermore, armed with more thorough knowledge on its specificity for oxalate and other biological chemicals, developing the chelate as prophylaxis for oxalate kidney stones is becoming a promising goal.

Support or Funding Information

All work was funded by Wilkes University

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.