bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gabapentin, a human therapeutic medication and an environmental substance transferring at trace levels to horses: a case report
Authors: Brewer Kimberly , Machin Jacob , Maylin George , Fenger Clara , Morales-Briceño Abelardo , Tobin Thomas 
Published: October 2022

AbstractGabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen involved were unable to pin down and therefore avoid the source of these identifications. Given that 44 ng/ml or less is an Irrelevant Plasma Concentration (IPC) of Gabapentin in horses, we proposed a 5 ng/ml plasma interim Screening Limit of Detection for Gabapentin identifications in Ohio racing, and an essentially similar 8 ng/ml plasma Screening Limit of Detection was suggested by a scientific advisor to the Ohio Horse Racing Commission. As such, an analytical Screening Limit of 8 ng /ml in plasma is an appropriate and pharmacologically conservative analytical “cut-off” or Screening Limit of Detection (SLOD) for Gabapentin in equine competitive events to avoid the calling of “positive” identifications on random unavoidable trace level identifications of this widely prescribed human therapeutic medication in equine forensic samples.
Pathologic complete response following low-dose radiation for advanced oral cavity cancer in a patient with human immunodeficiency virus
Authors: Leming Amy B. , Johnston Andrea L. , Krempl Greg A. , Fowle Evan J. , Morton Daniel J. , Henson Christina E. 
Published: October 2022

Background Advanced squamous cell carcinoma (SCCa) of the oral cavity is often not amenable to curative-intent therapy due to tumor location, tumor size, or comorbidities. Case presentation A 51-year-old male patient with human immunodeficiency virus and on highly active antiretroviral therapy (HAART) presented with a cT4aN2c SCCa of the tongue. He received a preoperative single course of Quad-Shot radiation therapy to 14 Gy in 4 fractions followed by surgical resection. Patient had no residual carcinoma on surgical pathology and no evidence of disease on subsequent clinical and radiological exams. Conclusions To our knowledge, this is the first case of pathologic complete response for a patient on HAART following a single cycle of the Quad-Shot regimen for advanced oral cavity SCCa. Protease inhibitors in HAART can induce spontaneous tumor regression via inhibition of proteasome function and activation of apoptosis, and thus act as a cancer therapeutic. Graphical abstract
Investigating the potential of the Nd:YAG and Er:YAG lasers for the cleaning of feathers: a pilot study
Authors: Bertasa Moira , Korenberg Capucine 
Published: October 2022

Abstract
A dual-wavelength Q-switched Nd:YAG laser emitting at 1064 nm and 532 nm and an Er:YAG laser were tested on a range of feathers containing melanin, carotenoids and psittacofulvins. Dyed, white and iridescent feathers, as well as down feathers, were also included in the study. First, the damage threshold fluence was determined for each type of feather and then, as appropriate, laser tests were conducted on feathers artificially soiled with dust or carbon black. The Nd:YAG laser was unsuccessful at cleaning feathers soiled with carbon black. Better outcomes were obtained on feathers soiled with dust: the Nd:YAG laser was effective at both wavelengths at removing dust from white feathers, dyed feathers and yellow feathers containing psittacofulvins. Feathers containing melanin, as their main colourant, were found to have a much lower damage threshold fluence than other feathers. Also, laser radiation at 532 nm at high fluences can cause discolouration on pink feathers containing carotenoids. Finally, it was not possible to remove dust from down feathers without causing thermal damage. This investigation showed that laser cleaning using a Q-switched Nd:YAG laser can remove dust from certain types of feathers. However, further research is needed to assess any potential chemical or long-term effects of laser cleaning on feathers. Finally, the Er:YAG laser was found to be unsuitable for laser cleaning resulting in thermal damage to all feathers at low fluences.
Exfoliation of stone cultural relics under the microclimate in the Yongling Mausoleum of the Former Shu Dynasty
Authors: Zhang Yao , Cui Deshan , Bao Xun , Liu Shiyi , Guo Hong , Li Bo 
Published: October 2022

Abstract
Many degradation processes of cultural heritage objects are associated with unsuitable microclimatic conditions. One of the most ubiquitous deteriorations is the crystallization of salts in pores, which can accelerate the erosion rate of masonry historical relics. In this study, the microclimate of the burial tomb and exfoliation of sandstone in the Yongling Mausoleum of the Former Shu Dynasty in Chengdu were monitored for 1 year to determine the development of the degradation. We established a connection between the monitoring data and exfoliation variations of the stone with time. To predict the deterioration of the stone, a three-dimensional computational finite element model was used to simulate the detailed process of the thermo-hygrometric performance that led to salt crystallization and artwork deterioration. Two results were obtained. In the simulation of the microclimate, the temperature ranged from 15 to 22.6 °C, and the relative humidity was heterogeneous and varied between 60 and 100%. The other was the relationship between the microclimate and exfoliation. It was found that the exfoliation was more severe in the higher relative humidity areas where the water vapor frequently interacted with the relics. The crystallization and hydration of sulfate produced stress, which damaged the stone relics. These results provide a rationale analysis and a reference for better management of the environmental interactions and reduction of the environmental impacts in the subsequent scientific conservation of ancient Chinese cultural relics in tombs.
The effectiveness of value-based messages to engage gun owners on firearm policies: a three-stage nested study
Authors: Boine Claire , Siegel Michael , Maiga Abdine 
Published: October 2022

Abstract
Background
Although gun owners overwhelmingly support violence prevention policies, they are hesitant to speak up publicly to advocate for these policies. We tested a series of communication messages on gun owners’ level of support for various firearm violence prevention policies and on their willingness to engage in gun violence prevention advocacy.

Methods
We conducted three consecutive experiments, testing a total of thirteen messages on a sample of gun owners over 18 years old who live in the U.S. The first was a random experiment, the second a quasi-experiment, and the third a randomized control trial. The goal of having these varied methods was to develop messages applicable to different contexts with different levels of information about the audience.

Results
The most effective message was a script showing respect for gun owners’ decisions to purchase a firearm and proposing a balanced policy roadmap to end gun violence, which led to an increase in gun owner’s willingness to engage in eight different advocacy activities. We also found a value-based message conveying loyalty to increase support for domestic violence related prohibitions and willingness to engage in advocacy for gun violence prevention policies.

Conclusions
Public health professionals need to develop communication strategies that are aligned with gun owners’ values and that affirm respect for gun culture and for gun owners’ decisions to own a gun.
Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges
Authors: Wu Chongyun , Yang Luoman , Feng Shu , Zhu Ling , Yang Luodan , Liu Timon Cheng-Yi , Duan Rui 
Published: October 2022

AbstractAlzheimer’s disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients’ and families’ quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.
A Low-Frequency APOB p.(Pro955Ser) Variant Contributes to the Severity of/Variability in Familial Hypercholesterolemia
Authors: Hori Mika , Takahashi Atsushi , Hosoda Kiminori , Ogura Masatsune , Harada-Shiba Mariko 
Published: October 2022

Abstract

Context
Heterozygous familial hypercholesterolemia (HeFH) is caused by a rare pathogenic variant in the LDLR, APOB, and PCSK9 genes. However, the causative variants in these genes have not been identified in approximately 40% of HeFH patients.

Objective
Our aim was to identify novel (or additional) genes/variants that contribute to HeFH.

Methods
Whole-exome sequencing was performed for 215 family members from 122 families with HeFH without pathogenic variants in the LDLR or PCSK9 genes.

Results
We could not find novel causative familial hypercholesterolemia (FH) genes/variants by family analysis. Next, we examined all APOB variants. Twenty-four nonsynonymous APOB variants were identified. The allele frequencies of the c.2863C &gt; T:p.(Pro955Ser) variant in the HeFH probands and the general Japanese population were 0.15 and 0.034, respectively [odds ratio 4.9 (95% CI 3.4-7.1); P = 6.9 × 10−13]. The patients harboring the c.2863C &gt; T:p.(Pro955Ser) variant accounted for 9.8% (n = 63) of unrelated patients with HeFH (n = 645). The penetrance of the c.2863C &gt; T:p.(Pro955Ser) variant was low in the pedigree-based genetic analysis. In an in vitro assay, low-density lipoprotein (LDL) uptake from patients with the homozygous c.2863C &gt; T:p.(Pro955Ser) variant was 44% of the LDL uptake from control subjects, and it was similar to that of the LDL uptake from patients with the known pathogenic heterozygous p.(Arg3527Gln) variant.

Conclusions
The low-frequency APOB c.2863C &gt; T:p.(Pro955Ser) variant is not an FH-causative variant, but it has a moderate effect size in HeFH. These findings suggest that the combination of the APOB c.2863C &gt; T:p.(Pro955Ser) variant and age, environmental factors, or other genetic factors contributes to the severity of or variability in the HeFH phenotype.
Sequential and additive expression of miR-9 precursors control timing of neurogenesis
Authors: Soto Ximena , Burton Joshua , Manning Cerys S. , Minchington Thomas , Lea Robert , Lee Jessica , Kursawe Jochen , Rattray Magnus , Papalopulu Nancy 
Published: October 2022

ABSTRACT
MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.
Formation and function of a highly specialised type of organelle in cardiac valve cells
Authors: Meyer Christian , Breitsprecher Leonhard , Bataille Laetitia , Vincent Alain J. M. , Drechsler Maik , Meyer Heiko , Paululat Achim 
Published: October 2022

ABSTRACT
Within a cell, vesicles play a crucial role in the transport of membrane material and proteins to a given target membrane, and thus regulate a variety of cellular functions. Vesicular transport occurs by means of, among others, endocytosis, where cargoes are taken up by the cell and are processed further upon vesicular trafficking, i.e. transported back to the plasma membrane via recycling endosomes or the degraded by fusion of the vesicles with lysosomes. During evolution, a variety of vesicles with individual functions arose, with some of them building up highly specialised subcellular compartments. In this study, we have analysed the biosynthesis of a new vesicular compartment present in the valve cells of Drosophila melanogaster. We show that the compartment is formed by invaginations of the plasma membrane and grows via re-routing of the recycling endosomal pathway. This is achieved by inactivation of other membrane-consuming pathways and a plasma membrane-like molecular signature of the compartment in these highly specialised heart cells.
Highly sensitive refractive index sensor based on the lossy mode resonance enhanced photonic spin Hall effect
Authors: Wang Huixin , He Ying , Zhang Jing , Xu Yi 
Published: October 2022

Different from surface plasmon resonance (SPR) that only can be excited by

p

-polarized light, lossy mode resonance (LMR) can be achieved with both

p

- and

s

-polarized light, thus providing a pathway for enhanced transverse spin-dependent shift (SDS) of the photonic spin Hall effect (PSHE) for the horizontal and vertical polarization states. The maximum transverse SDSs of 13.28 µm and 7.64 µm for the horizontal and vertical polarization states are achieved, respectively, which are about 12 and 7 times the wavelength of incident light. A refractive index sensor based on the LMR enhanced PSHE is proposed, and the maximum refractive index sensitivity of 13500 µm/RIU (RIU, refractive index unit) can be obtained. Our investigation provides an alternative method for the enhancement of PSHE, thus opening up opportunities for the design of various photonic devices based on PSHE.
Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy
Authors: Koike Akito , Becker Frank , Sennhenn Peter , Kim Jason , Zhang Jenny , Hannus Stefan , Brehm Klaus 
Published: October 2022

Background
The potentially lethal zoonosis alveolar echinococcosis (AE) is caused by the metacestode larval stage of the tapeworm Echinococcus multilocularis. Current AE treatment options are limited and rely on surgery as well as on chemotherapy involving benzimidazoles (BZ). BZ treatment, however, is mostly parasitostatic only, must be given for prolonged time periods, and is associated with adverse side effects. Novel treatment options are thus urgently needed.

Methodology/principal findings
By applying a broad range of kinase inhibitors to E. multilocularis stem cell cultures we identified the proto-oncogene PIM kinase as a promising target for anti-AE chemotherapy. The gene encoding the respective E. multilocularis ortholog, EmPim, was characterized and in situ hybridization assays indicated its expression in parasite stem cells. By yeast two-hybrid assays we demonstrate interaction of EmPim with E. multilocularis CDC25, indicating an involvement of EmPim in parasite cell cycle regulation. Small molecule compounds SGI-1776 and CX-6258, originally found to effectively inhibit human PIM kinases, exhibited detrimental effects on in vitro cultured parasite metacestode vesicles and prevented the formation of mature vesicles from parasite stem cell cultures. To improve compound specificity for EmPim, we applied a high throughput in silico modelling approach, leading to the identification of compound Z196138710. When applied to in vitro cultured metacestode vesicles and parasite cell cultures, Z196138710 proved equally detrimental as SGI-1776 and CX-6258 but displayed significantly reduced toxicity towards human HEK293T and HepG2 cells.

Conclusions/significance
Repurposing of kinase inhibitors initially designed to affect mammalian kinases for helminth disease treatment is often hampered by adverse side effects of respective compounds on human cells. Here we demonstrate the utility of high throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. We propose EmPim as a promising target for respective approaches towards AE treatment.
Co-creating safe spaces: Study protocol for translational research on innovative alternatives to the emergency department for people experiencing emotional distress and/or suicidal crisis
Authors: Banfield Michelle , Fitzpatrick Scott J. , Lamb Heather , Giugni Melanie , Calear Alison L. , Stewart Erin , Pavloudis Maree , Ellen Lucy , Sargent Ginny , Skeat Helen , Edwards Bronwen , Miller Benn , Gulliver Amelia , Ellis Louise A. , Bliokas Vida , Goj Purity , Lee Melissa , Stewart Kelly , Webb Glenda , Main Merkitta , Lumby Carrie , Wells Kelly , McKay Carolyn , Batterham Philip J. , Morse Alyssa R. , Shand Fiona ,   Stride Safe Space Team
Published: October 2022

IntroductionSafe spaces are an alternative to emergency departments, which are often unable to provide optimum care for people experiencing emotional distress and/or suicidal crisis. At present, there are several different safe space models being trialled in Australia. However, research examining the effectiveness of safe space models, especially in community settings, is rare. In this paper, we present a protocol for a study in which we will investigate the implementation, effectiveness, and sustainability of safe space models as genuine alternatives for people who might usually present to the emergency department or choose not to access help due to past negative experiences.Material and methodsWe will use a mixed methods, co-designed study design, conducted according to the principles of community-based participatory research to obtain deep insights into the benefits of different safe space models, potential challenges, and facilitators of effective practice. We developed the study plan and evaluation framework using the RE-AIM framework, and this will be used to assess key outcomes related toreach,effectiveness,adoption,implementation, andmaintenance. Data collection will comprise quantitative measures on access, use, satisfaction, (cost) effectiveness, distress, and suicidal ideation; and qualitative assessments of service implementation, experience, feasibility, acceptability, community awareness, and the fidelity of the models to service co-design. Data will be collected and analysed concurrently throughout the trial period of the initiatives.DiscussionThis study will enable an extensive investigation of safe spaces that will inform local delivery and provide a broader understanding of the key features of safe spaces as acceptable and effective alternatives to hospital-based care for people experiencing emotional distress and/or suicidal crisis. This study will also contribute to a growing body of research on the role and benefits of peer support and provide critical new knowledge on the successes and challenges of service co-design to inform future practice.
Low-dose versus high-dose dexamethasone for hospitalized patients with COVID-19 pneumonia: A randomized clinical trial
Authors: Wu Huimin , Daouk Salim , Kebbe Jad , Chaudry Fawad , Harper Jarrod , Brown Brent 
Published: October 2022

Background
Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit of high-dose dexamethasone is limited. The goal of this study was to assess the effects of 6 mg daily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia.

Methods
We conducted a single-center, randomized, clinical trial involving hospitalized patients with COVID-19 pneumonia. Participants were randomized 1:1 to dexamethasone 6 mg daily or dexamethasone 20 mg daily, and were stratified by the WHO-Ordinal Scale for Clinical Improvement (OSCI). The primary outcome was clinical improvement equal to or greater than 2 points by OSCI on day 28. Secondary outcomes were 28-day mortality, intensive care unit-free days, and ventilator-free days on day 28.

Results
Of the 107 patients who enrolled and completed the follow up, 55 patients enrolled in the low-dose group and 52 patients enrolled in the high-dose group. Treatment with dexamethasone 20 mg daily compared with dexamethasone 6 mg daily did not result in better clinical improvement based on OSCI on day 28 (71.2% vs. 78.2%; odds ratio, 1.45 [0.55–3.86]; p = 0.403). For participants who required high-flow oxygen or noninvasive ventilation at randomization, the 6-mg group had better survival than the 20-mg group on day 28 (100% vs. 57.1%; p = 0.025). Although more participants in the 6-mg group received immune modulators (40% vs. 21.2%; p = 0.035), 50% of death cases in the 20-mg group who required high-flow oxygen or noninvasive ventilation at randomization received immune modulators.

Conclusions
Dexamethasone 20 mg daily did not result in better clinical outcome improvement, and was probably associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation, compared with dexamethasone 6 mg daily.

Trial registration
Clinialtrials.gov number, NCT04707534, registered January 13, 2021