bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, in vitro 2D/3D human lung cell cultures, and in vivo efficacy
Authors: Acosta Maria F. , Muralidharan Priya , Grijalva Carissa L. , Abrahamson Michael D. , Hayes Don , Fineman Jeffrey R. , Black Stephen M. , Mansour Heidi M. 
Published: March 2021

Inhalable nanostructured microparticles of simvastatin, a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor, were rationally designed for targeted pulmonary delivery as dry powder inhalers (DPIs) for the treatment of pulmonary hypertension (PH). Advanced particle engineering design technology was employed to develop inhalable dry powders using different dilute feed concentrations and spray drying pump rates. Several analytical techniques were used comprehensively to characterize the physicochemical properties of the resulting powders. Scanning electron microscopy (SEM) was used to visualize particle morphology (shape), surface structure, size, and size distribution. Karl Fischer titration (KFT) was employed to quantify the residual water content in the powders. X-ray powder diffraction (XRPD) was used to determine crystallinity. Hot-stage microscopy (HSM) under cross-polarizing lens was used to observe the presence or absence of birefringence characteristic of crystallinity. Differential scanning calorimetry (DSC) was employed to quantify thermotropic phase behavior. Attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy were used to determine the molecular fingerprint of simvastatin powders before and after particle engineering design. In vitro aerosol dispersion performance was performed with three different Food and Drug Administration (FDA)-approved human DPI devices. Cell viability and transepithelial electrical resistance (TEER) were demonstrated using different in vitro human pulmonary cell two and three-dimensional models at the air–liquid interface, and in vivo safety in healthy rats by inhalation. Efficacy was demonstrated in the in vivo lamb model of PH. Four different inhalable powders of simvastatin were successfully produced. They possessed nanostructured surfaces and were in the inhalable size range. Simvastatin retained its crystallinity following particle engineering design. The more dilute feed concentration spray dried at the lower pump rate produced the smallest particles. All powders successfully aerosolized with all three DPI human devices. Inhaled simvastatin as an aerosol restored the endothelial function in the shunt lamb model of PH, as demonstrated by the reduction of pulmonary vascular resistance (PVR) in response to the endothelium-dependent vasodilator acetylcholine. The reviews of this paper are available via the supplemental material section.
Pulmonary hypertension due to interstitial lung disease or chronic obstructive pulmonary disease: a patient experience study of symptoms and their impact on quality of life
Authors: DuBrock Hilary M. , Nathan Steven D. , Reeve Bryce B. , Kolaitis Nicholas A. , Mathai Stephen C. , Classi Peter M. , Nelsen Andrew C. , Olayinka‐Amao Bimpe , Norcross Lindsey N. , Martin Susan A. 
Published: March 2021

Pulmonary hypertension resulting from chronic lung disease such as chronic obstructive pulmonary disease and interstitial lung disease is categorized by the World Health Organization as Group 3 pulmonary hypertension. To identify the symptoms and impacts of World Health Organization Group 3 pulmonary hypertension and to capture data related to the patient experience of this disease, qualitative research interviews were undertaken with 3 clinical experts and 14 individuals with pulmonary hypertension secondary to chronic obstructive pulmonary disease or interstitial lung disease. Shortness of breath, fatigue, cough, and swelling were the most frequently reported symptoms of pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease, and shortness of breath was further identified as the single most bothersome symptom for most patients (71.4%). Interview participants also described experiencing a number of impacts related to pulmonary hypertension and pulmonary hypertension symptoms, including limitations in the ability to perform activities of daily living and impacts on physical functioning, family life, and social life as well as emotional impacts, which included frustration, depression, anxiety, isolation, and sadness. Results of these qualitative interviews offer an understanding of the patient experience of pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease, including insight into the symptoms and impacts that are most important to patients in this population. As such, these results may help guide priorities in clinical treatment and assist researchers in their selection of patient‐reported outcome measures for clinical trials in patients with pulmonary hypertension due to chronic obstructive pulmonary disease or interstitial lung disease.
Temporomandibular Joint Osteoarthrosis: A Review of Clinical Aspects and Management
Authors: Al-Ani Ziad 
Published: March 2021

The symptoms of TMJ Osteoarthrosis/Osteoarthritis(TMJ OA) are characteristic and in most cases specific to the disorder. There is, however, an overlap of symptoms with other TMDs. Treatment of TMJ OA is generally directed towards management of the symptoms as the temporomandibular joint does retain the capacity throughout life to repair and remodel. Non-conservative and invasive treatment is only rarely necessary. It should be remembered that the mandibular condyle retains the capacity to repair and remodel throughout life and patients should be encouraged to bear this in mind. Conservative measures are usually sufficient to treat symptoms and a period of time should be allowed to elapse before undertaking a more aggressive treatment plan, which, in the overwhelming majority of patients, will not be necessary. This disorder should be approached on the terms of ‘a quality of life issue’ and treatment should be directed towards patient needs.
Medical Device Regulation: Requirements for Dental Professionals Who Prescribe and Manufacture Custom-Made Devices
Authors: Green James I. J. 
Published: March 2021

A custom-made device (CMD) is a medical device intended for the sole use of a particular patient. In a dental setting, CMDs include prosthodontic devices, orthodontic appliances, bruxism splints, speech prostheses and devices for the treatment of obstructive sleep apnoea, trauma prevention and orthognathic surgery facilitation (arch bars and interocclusal wafers). Since 1993, the production and provision of CMDs have been subject to European Union (EU) Directive 93/42/EEC (Medical Device Directive, MDD) given effect in the UK by The Medical Devices Regulations 2002 (Statutory Instrument 2002/618), and its subsequent amendments. Regulation (EU) 2017/745 (Medical Device Regulation, EU MDR) replaces the MDD and the other EU Directive pertaining to Medical Devices, Council Directive 90/385/EEC (Active Implantable Medical Device Directive, AIMDD). The EU MDR was published on 5 April 2017, came into force on 25 May 2017 and, following a three-year transition period was due to be fully implemented and repeal the MDD on 26 May 2020, but was deferred until 26 May 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. In the UK, in preparation for the country’s planned departure from the EU, the EU MDR, with necessary amendments, was transposed into UK law (Medical Devices (Amendment etc.) (EU Exit) Regulations 2019, UK MDR). The UK left the Union on 31 January 2020 and entered a transition period that ended on 31 December 2020, meaning that, from 1 January 2021, dental professionals in Great Britain who prescribe and manufacture CMDs are mandated to do so in accordance with the new legislation while Northern Ireland remains in line with the EU legislation and implementation date. This paper sets out the requirements that relate to the production and provision of CMDs in a UK dental setting.
An evaluation of antipseudomonal dosing on the incidence of treatment failure
Authors: Hawkins Brandon K , Wingler Mary Joyce B , Cretella David A , Barber Katie E , Stover Kayla R , Wagner Jamie L 
Published: March 2021

Introduction: Significant mortality is associated with delays in appropriate antibiotic therapy in Pseudomonas aeruginosa infections. The impact of empiric dosing on clinical outcomes has been largely unreported. Methods: This retrospective cohort compared treatment failure in patients receiving guideline-concordant or guideline-discordant empiric therapy with cefepime, meropenem, or piperacillin/tazobactam. Patients with culture-positive P. aeruginosa between 1 July 2013 and 31 July 2019 were eligible for inclusion. Patients with cystic fibrosis, polymicrobial infection, and urinary or pulmonary colonization were excluded. The composite primary outcome was treatment failure, defined as (1) therapy modification due to resistance/perceived treatment failure, (2) increased/unchanged qSOFA, or (3) persistent fever 48 h after initiating appropriate therapy. Secondary outcomes included rate of infectious diseases consultation, all-cause inpatient mortality, mechanical ventilation requirement, and infection-related intensive care unit and hospital lengths of stay. Results: In total, 198 patients were included: 90 guideline-concordant and 108 guideline-discordant. Baseline characteristics were balanced. Treatment failure was more common in the guideline-discordant than the guideline-concordant group (62% versus 48%; p = 0.04). This remained significant when adjusting for supratherapeutic dosing ( p = 0.02). Infectious diseases consultation was higher in the guideline-discordant group (46% versus 29%, p = 0.01), while intensive care unit length of stay was longer in the guideline-concordant group (4.5 versus 3 days, p = 0.03). Additional secondary outcomes were similar. Conclusion: Treatment failure was significantly higher in patients receiving guideline-discordant empiric antipseudomonal dosing. Guideline-directed dosing, disease states, and patient-specific factors should be assessed when considering empiric antipseudomonal dosing.
The Effect of Health Literacy on a Brief Intervention to Improve Advance Directive Completion: A Randomized Controlled Study
Authors: Barker Paige C. , Holland Neal P. , Shore Oliver , Cook Robert L. , Zhang Yang , Warring Carrie D. , Hagen Melanie G. 
Published: March 2021

Objective Completion of an advance directive (AD) document is one component of advanced care planning. We evaluated a brief intervention to enhance AD completion and assess whether the intervention effect varied according to health literacy. Methods A randomized controlled study was conducted in 2 internal medicine clinics. Participants were over 50, without documented AD, no diagnosis of dementia, and spoke English. Participants were screened for health literacy utilizing REALM-SF. Participants were randomized in a 1:1 ratio to the intervention, a 15-minute scripted introduction (grade 7 reading level) to our institution’s AD forms (grade 11 reading level) or to the control, in which subjects were handed blank AD forms without explanation. Both groups received reminder calls at 1, 3, and 5 months. The primary outcome was AD completion at 6 months. Results Five hundred twenty-nine subjects were enrolled; half were of limited and half were of adequate health literacy. The AD completion rate was 21.7% and was similar in the intervention vs. the control group (22.4% vs 22.2%, P = .94).More participants with adequate health literacy completed an AD than those with limited health literacy (28.4% vs 16.2%, P = .0008), although the effect of the intervention was no different within adequate or limited literacy groups. Conclusion A brief intervention had no impact on AD completion for subjects of adequate or limited health literacy. Practice Implications Our intervention was designed for easy implementation and to be accessible to patients of adequate or limited health literacy. This intervention was not more likely than the control (handing patients an AD form) to improve AD completion for patients of either limited or adequate health literacy. Future efforts and research to improve AD completion rates should focus on interventions that include: multiple inperson contacts with patients, contact with a trusted physician, documents at 5th grade reading level, and graphic/video decision aids. Trial Registration Number NCT02702284, Protocol ID IRB201500776
Influence of Handgrip Strength and Paraspinal Muscles’ Volume on Clinical Outcomes in the Patients With Each Sagittal Imbalance and Lumbar Spinal Stenosis
Authors: Shen Feng , Kim Ho-Joong , Jeon Seung Won , Chang Bong-Soon , Lee Choon-Ki , Yeom Jin S. 
Published: March 2021

Study Design: Cross-sectional study. Objective: To compare handgrip strength (HGS), paraspinal muscles’ (PSM) volume, and their effects on clinical symptom severity between the patients with sagittal imbalance (SI) and symptomatic lumbar spinal stenosis (LSS). Methods: A total of 54 paired consecutive patients with SI and LSS were enrolled after propensity score matching. Preoperative HGS, cross-sectional area (CSA) of psoas (PS) and multifidus (MF) muscles, and patient-reported measures, including visual analog scale (VAS) for back/ leg pain, Oswestry Disability Index (ODI), and EuroQOL (EQ-5D) were compared between both groups. Within each SI and LSS group, patient-reported measures were compared between high and low HGS subgroups. The correlation of HGS and CSA of PSMs to patient-reported measures was evaluated. Results: There was no difference in HGS between 2 groups, however, the CSA of PS and MF muscles in SI group was significantly lower than those in LSS group. Patients with low HGS showed inferior results for ODI and EQ-5D, compared to those with high HGS subgroup in both SI and LSS groups. HGS and CSA of MF muscle were correlated with ODI in both groups. Conclusions: There was no significant difference between the SI and LSS groups in HGS, however, PSMs’ volume in SI group were significantly lower than those in LSS group. Therefore SI would be associated with loss of localized muscle mass in back area, rather than global skeletal muscle weakness. HGS and PSMs’ volume were adversely associated with functional status in SI and LSS patients.
Combined Anterior Cruciate Ligament Reconstruction Revision and Double-Bundle Medial Collateral Ligament and Posterior Oblique Ligament Reconstruction
Authors: Valette Arnault , Mouarbes Dany , Marot Vincent , Cavaignac Etienne 
Published: March 2021

Background: Nonsurgical treatment of concomitant medial collateral ligament (MCL) in the setting of anterior cruciate ligament reconstruction (ACLR) increases the risk of graft failure. Few published cases of medial complex reconstruction combined with ACLR with no clear consensus on the optimal technique to treat these complex injuries. Indications: A female patient aged 41 years, with failure of ACLR in 2009 and 2 revisions in 2013 and 2014, associated with concomitant nontreated MCL and posterior oblique ligament (POL) injury. Physical examination showed valgus test laxity grade III at 30° of knee flexion and at full extension, with Lachman and pivot-shift test grade III. Imaging showed normal long-leg standing axis with 10° posterior tibial slope on radiograph, and associated MCL and POL injury on magnetic resonance imaging. Technique Description: ACLR and anterolateral tenodesis using the fascia lata leaving its distal insertion on the Gerdy tubercle, with double-stranded contralateral gracilis, was completed. A new femoral tunnel was made from outside to inside, with preservation of the previous tibial tunnel. The transplant was fixed with 2 interference screws. Second, the contralateral semitendinous autograft was used for MCL and POL reconstruction. A single strand of the graft was used for femoral fixation created on femoral epicondyle to cover MCL and POL origins, and double strands were used for distal fixation of MCL at the level of hamstring insertion and POL at the posteromedial corner of medial tibial plateau. The graft was secured with 3 interference screws at 30 knee flexion for MCL and full extension for POL. Results: The results include favorable functional and clinical outcome with improvement in the anteroposterior and rotatory knee stability at mid-term follow-up. Lateral extra-articular tenodesis in supplementing ACLR controls internal tibial rotatory knee stability. Double-bundle reconstruction of MCL and POL improved both valgus and anteromedial rotatory instability by restraining external rotation. Discussion/Conclusion: Surgeons should consider the need for surgical treatment of concomitant MCL injury to prevent chronic valgus laxity and increased strain on the anterior cruciate ligament (ACL) graft, potentially increasing the risk of ACLR revision. Our described technique offers a safe method for ACLR and lateral tenodesis with an advantage to avoid tunnel convergence, and medial stabilization to restore native valgus and rotatory stability and prevent increased stress on ACL graft.
Thebaite-(NH4), (NH4,K)3Al(C2O4)(PO3OH)2(H2O), a new phosphate–oxalate mineral from the Rowley mine, Arizona, USA
Authors: Kampf Anthony R. , Cooper Mark A. , Celestian Aaron J. , Nash Barbara P. , Marty Joe 
Published: March 2021

AbstractThebaite-(NH4), (NH4,K)3Al(C2O4)(PO3OH)2(H2O), is a new mineral species (IMA2020-072) from the Rowley mine, Maricopa County, Arizona, USA. It occurs in an unusual bat-guano-related, post-mining assemblage of phases that include a variety of vanadates, phosphates, oxalates and chlorides, some containing NH4+. Other secondary minerals found in association with thebaite-(NH4) are antipinite, vanadinite and at least one other new mineral. Crystals of thebaite-(NH4) are colourless blades up to ~0.1 mm in length. The streak is white, lustre is vitreous, Mohs hardness is 1½–2, tenacity is brittle and fracture is splintery. There are two good cleavages in the [010] zone, probably {100} and {10$\bar{2}$}. The calculated density is 2.093 g⋅cm–3. Thebaite-(NH4) is optically biaxial (–) with α = 1.490(2), β = 1.534(2), γ = 1.570(2) (white light); 2V = 82.7(5)°; slight r > v dispersion; and orientation X = b, Y ^ c = 13° in obtuse β. Electron microprobe analysis gave the empirical formula [(NH4)2.12K0.69Na0.20]Σ3.01(Al0.84Fe3+0.11V3+0.04)Σ0.99(C2O4)[(P0.98Si0.02)O3OH]2(H2O), with the C, N and H contents constrained by the crystal structure. Raman spectroscopy confirmed the presence of NH4 and C2O4. Thebaite-(NH4) is monoclinic, P21/c, with a = 11.156(9), b = 6.234(6), c = 18.651(16) Å, β = 102.928(15)°, V = 1264.2(19) Å3 and Z = 4. The structural unit in the crystal structure of thebaite-(NH4) (R1 = 0.0612 for 863 Io > 2σI reflections) is a double-strand chain of corner-sharing AlO6 octahedra and PO3OH tetrahedra decorated by additional PO3OH tetrahedra and C2O4 groups. The decorated chains connect to one another through bonds to NH4+ and K+ and through hydrogen bonds.
Exploring short k-mer profiles in cells and mobile elements from Archaea highlights the major influence of both the ecological niche and evolutionary history
Authors: Bize Ariane , Midoux Cédric , Mariadassou Mahendra , Schbath Sophie , Forterre Patrick , Da Cunha Violette 
Published: March 2021

AbstractBackgroundK-mer-based methods have greatly advanced in recent years, largely driven by the realization of their biological significance and by the advent of next-generation sequencing. Their speed and their independence from the annotation process are major advantages. Their utility in the study of the mobilome has recently emerged and they seem a priori adapted to the patchy gene distribution and the lack of universal marker genes of viruses and plasmids.To provide a framework for the interpretation of results from k-mer based methods applied to archaea or their mobilome, we analyzed the 5-mer DNA profiles of close to 600 archaeal cells, viruses and plasmids.Archaeais one of the three domains of life. Archaea seem enriched in extremophiles and are associated with a high diversity of viral and plasmid families, many of which are specific to this domain. We explored the dataset structure by multivariate and statistical analyses, seeking to identify the underlying factors.ResultsFor cells, the 5-mer profiles were inconsistent with the phylogeny of archaea. At a finer taxonomic level, the influence of the taxonomy and the environmental constraints on 5-mer profiles was very strong. These two factors were interdependent to a significant extent, and the respective weights of their contributions varied according to the clade. A convergent adaptation was observed for the classHalobacteria, for which a strong 5-mer signature was identified. For mobile elements, coevolution with the host had a clear influence on their 5-mer profile. This enabled us to identify one previously known and one new case of recent host transfer based on the atypical composition of the mobile elements involved. Beyond the effect of coevolution, extrachromosomal elements strikingly retain the specific imprint of their own viral or plasmid taxonomic family in their 5-mer profile.ConclusionThis specific imprint confirms that the evolution of extrachromosomal elements is driven by multiple parameters and is not restricted to host adaptation. In addition, we detected only recent host transfer events, suggesting the fast evolution of short k-mer profiles. This calls for caution when using k-mers for host prediction, metagenomic binning or phylogenetic reconstruction.
Chromosome-length genome assembly and structural variations of the primal Basenji dog (Canis lupus familiaris) genome
Authors: Edwards Richard J. , Field Matt A. , Ferguson James M. , Dudchenko Olga , Keilwagen Jens , Rosen Benjamin D. , Johnson Gary S. , Rice Edward S. , Hillier La Deanna , Hammond Jillian M. , Towarnicki Samuel G. , Omer Arina , Khan Ruqayya , Skvortsova Ksenia , Bogdanovic Ozren , Zammit Robert A. , Aiden Erez Lieberman , Warren Wesley C. , Ballard J. William O. 
Published: March 2021

AbstractBackgroundBasenjis are considered an ancient dog breed of central African origins that still live and hunt with tribesmen in the African Congo. Nicknamed the barkless dog, Basenjis possess unique phylogeny, geographical origins and traits, making their genome structure of great interest. The increasing number of available canid reference genomes allows us to examine the impact the choice of reference genome makes with regard to reference genome quality and breed relatedness.ResultsHere, we report two high quality de novo Basenji genome assemblies: a female, China (CanFam_Bas), and a male, Wags. We conduct pairwise comparisons and report structural variations between assembled genomes of three dog breeds: Basenji (CanFam_Bas), Boxer (CanFam3.1) and German Shepherd Dog (GSD) (CanFam_GSD). CanFam_Bas is superior to CanFam3.1 in terms of genome contiguity and comparable overall to the high quality CanFam_GSD assembly. By aligning short read data from 58 representative dog breeds to three reference genomes, we demonstrate how the choice of reference genome significantly impacts both read mapping and variant detection.ConclusionsThe growing number of high-quality canid reference genomes means the choice of reference genome is an increasingly critical decision in subsequent canid variant analyses. The basal position of the Basenji makes it suitable for variant analysis for targeted applications of specific dog breeds. However, we believe more comprehensive analyses across the entire family of canids is more suited to a pangenome approach. Collectively this work highlights the importance the choice of reference genome makes in all variation studies.