bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parathyroid carcinoma in the Yorkshire and Humber region of the UK – a multi-centre study of presentation, management and outcomes
Authors: Davies Matthew , Balasubramanian Saba , Fraser Sheila , England James , Jackson Richard 
Published: March 2022

Abstract

Purpose
Our objective is to report on the management strategies and outcomes of patients with parathyroid cancer (PC) in the Yorkshire and Humber region of the UK.
Pathology databases were interrogated for patients diagnosed with PC at three major centres in the region. Data was collected by two observers and all pathology reports were reviewed by a single consultant pathologist. The analyses were primarily descriptive and outcomes were compared with recently published literature.

Methods
All cases of PC diagnosed between 2006 and June 2019 were included.
Data on presentation, treatment, histology and outcomes were recorded for each case.

Results
The series includes 27 patients, with a median age of 56 (range 46.5–72.5) years. No gender predisposition (M: F 13:14) was present. Twenty-two had the ipsilateral thyroid lobe (+/- lymph nodes) excised as part of definitive treatment. Nine of these had definitive surgery in two stages. Capsular, vascular and thyroid/soft tissue invasion were seen in 89%, 70% and 70% of patients respectively. One patient received adjuvant radiotherapy treatment. Recurrence was confirmed in one patient, causing mortality 70 months post diagnosis. Three other patients died of other causes during the study period, one of whom was suspected to have recurrent disease.

Conclusions
Rates of recurrence and mortality were low following surgical treatment for PC; however, diagnostic strategies and surgical practices were variable. The development of guidelines on the management of PC may reduce variability in treatment and improve patient outcomes.
Impact of pre-operative Metyrapone therapy on post-operative Steroid dependence in patients undergoing Adrenalectomy for Cushing’s Syndrome
Authors: Clayton Bethan , Doran Helen , Kearney Tara 
Published: March 2022

Abstract

Introduction
Prolonged elevated cortisol in Cushing’s Syndrome can lead to adrenal insufficiency post-adrenalectomy. Metyrapone is licensed to suppress endogenous cortisol production pre-operatively for symptom relief. The aim of this study was to investigate whether pre-treatment of patients with metyrapone led to reduced adrenal insufficiency, hence reduced steroid dependence post-op.

Methods
Cases were identified from UKRETS submissions between 2008–2020, with Electronic Patient Records used for data collection. Patients with adrenocortical carcinoma (ACC) and/or lost to follow-up were excluded. The remaining cases were divided into those treated with metyrapone pre-operatively and those not. Results were analysed via IBM SPSS Statistics software.

Results
Of 59 patients, those lost to follow up (n=6) and those with ACC (n=4) were excluded leaving 49 cases. Metyrapone patients (n=29) had a median of 3 symptoms of cortisol excess (0–9) compared to 2 symptoms (0–5) in non-metyrapone (n=20) (p=0.061). 82.8% (n=24) of metyrapone patients and 65% (n=13) of non-metyrapone patients were successfully weaned off steroids post-op, with the remaining patients still steroid dependent. Cox proportional hazards regression showed metyrapone did not impact steroid dependence (p=0.230). Metyrapone treatment increased the likelihood of adrenal recovery whereas increasing symptom burden reduced the likelihood (hazard ratio 0.271 and -0.143 respectively), however these findings were not significant (p=0.445 and p=0.117 respectively).

Conclusion
We found metyrapone had no significant impact on rate of adrenal failure. A larger series may more accurately determine whether metyrapone pre-operatively confers a higher likelihood of adrenal recovery and determine whether high symptom burden pre-operatively increases risk of steroid dependence post-operatively.
Microglial large extracellular vesicles propagate early synaptic dysfunction in Alzheimer’s disease
Authors: Gabrielli Martina , Prada Ilaria , Joshi Pooja , Falcicchia Chiara , D’Arrigo Giulia , Rutigliano Grazia , Battocchio Elisabetta , Zenatelli Rossella , Tozzi Francesca , Radeghieri Annalisa , Arancio Ottavio , Origlia Nicola , Verderio Claudia 
Published: March 2022

AbstractSynaptic dysfunction is an early mechanism in Alzheimer’s disease that involves progressively larger areas of the brain over time. However, how it starts and propagates is unknown.Here we show that amyloid-β released by microglia in association with large extracellular vesicles (Aβ-EVs) alters dendritic spine morphology in vitro, at the site of neuron interaction, and impairs synaptic plasticity both in vitro and in vivo in the entorhinal cortex–dentate gyrus circuitry. One hour after Aβ-EV injection into the mouse entorhinal cortex, long-term potentiation was impaired in the entorhinal cortex but not in the dentate gyrus, its main target region, while 24 h later it was also impaired in the dentate gyrus, revealing a spreading of long-term potentiation deficit between the two regions. Similar results were obtained upon injection of extracellular vesicles carrying Aβ naturally secreted by CHO7PA2 cells, while neither Aβ42 alone nor inflammatory extracellular vesicles devoid of Aβ were able to propagate long-term potentiation impairment. Using optical tweezers combined to time-lapse imaging to study Aβ-EV–neuron interaction, we show that Aβ-EVs move anterogradely at the axon surface and that their motion can be blocked through annexin-V coating. Importantly, when Aβ-EV motility was inhibited, no propagation of long-term potentiation deficit occurred along the entorhinal–hippocampal circuit, implicating large extracellular vesicle motion at the neuron surface in the spreading of long-term potentiation impairment.Our data indicate the involvement of large microglial extracellular vesicles in the rise and propagation of early synaptic dysfunction in Alzheimer’s disease and suggest a new mechanism controlling the diffusion of large extracellular vesicles and their pathogenic signals in the brain parenchyma, paving the way for novel therapeutic strategies to delay the disease.
Factors Associated With Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People With Human Immunodeficiency Virus on Antiretroviral Therapy
Authors: Looby Sara E , Kantor Amy , Burdo Tricia H , Currier Judith S , Fichtenbaum Carl J , Overton Edgar T , Aberg Judith A , Malvestutto Carlos D , Bloomfield Gerald S , Erlandson Kristine M , Cespedes Michelle , Kallas Esper G , Masiá Mar , Thornton Alice C , Smith Mandy D , Flynn Jacqueline M , Kileel Emma M , Fulda Evelynne , Fitch Kathleen V , Lu Michael T , Douglas Pamela S , Grinspoon Steven K , Ribaudo Heather J , Zanni Markella V 
Published: March 2022

Abstract

Background
Among antiretroviral therapy (ART)–treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH.

Methods
Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL).

Results
The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels.

Conclusions
Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects.

Clinical Trials Registration
NCT0234429.
Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs
Authors: Huerga Helena , Khan Uzma , Bastard Mathieu , Mitnick Carole D , Lachenal Nathalie , Khan Palwasha Y , Seung Kwonjune J , Melikyan Nara , Ahmed Saman , Rich Michael L , Varaine Francis , Osso Elna , Rashitov Makhmujan , Salahuddin Naseem , Salia Gocha , Sánchez Epifanio , Serobyan Armine , Rafi Siddiqui Muhammad , Grium Tefera Dri , Vetushko Dmitry , Yeghiazaryan Lusine , Holtzman David , Islam Shirajul , Kumsa Andargachew , Jacques Leblanc Gamarly , Leonovich Olga , Mamsa Shahid , Manzur-ul-Alam Mohammad , Myint Zaw , Padayachee Shrivani , Franke Molly F , Hewison Catherine 
Published: March 2022

Abstract

Background
Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.

Methods
We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented.

Results
Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure.

Conclusions
Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.
The mysterious role of fibrillin in plastid metabolism: current advances in understanding
Authors: Kim Inyoung , Kim Hyun Uk 
Published: March 2022

AbstractFibrillins (FBNs) are a family of genes in cyanobacteria, algae, and plants. The proteins they encode possess a lipid-binding motif, exist in various types of plastids, and are associated with lipid bodies called plastoglobules, implicating them in lipid metabolism. FBNs present in the thylakoid and stroma are involved in the storage, transport, and synthesis of lipid molecules for photoprotective functions against high-light stress. In this review, the diversity of subplastid locations in the evolution of FBNs, regulation of FBNs expression by various stresses, and the role of FBNs in plastid lipid metabolism are comprehensively summarized and directions for future research are discussed.
Investigating the nature of the ultraluminous X-ray sources in the galaxy NGC 925
Authors: Salvaggio Chiara , Wolter A , Pintore F , Pinto C , Ambrosi E , Israel G L , Marino A , Salvaterra R , Zampieri L , Belfiore A 
Published: March 2022

Abstract
Variability is a powerful tool to investigate properties of X-ray binaries (XRB), in particular for Ultraluminous X-ray sources (ULXs) that are mainly detected in the X-ray band. For most ULXs the nature of the accretor is unknown, although a few ULXs have been confirmed to be accreting at super-Eddington rates on to a neutron star (NS). Monitoring these sources is particularly useful both to detect transients and to derive periodicities, linked to orbital and super-orbital modulations. Here, we present the results of our monitoring campaign of the galaxy NGC 925, performed with the Neil Gehrels Swift Observatory. We also include archival and literature data obtained with Chandra, XMM–Newton, and NuSTAR. We have studied spectra, light curves, and variability properties on days to months time-scales. All the three ULXs detected in this galaxy show flux variability. ULX-1 is one of the most luminous ULXs known, since only 10 per cent of the ULXs exceed a luminosity of ∼5 × 1040 erg s−1, but despite its high flux variability we found only weak spectral variability. We classify it as in a hard ultraluminous regime of super-Eddington accretion. ULX-2 and ULX-3 are less luminous but also variable in flux and possibly also in spectral shape. We classify them as in between the hard and the soft ultraluminous regimes. ULX-3 is a transient source: by applying a Lomb–Scargle algorithm, we derive a periodicity of ∼126 d, which could be associated with an orbital or superorbital origin.
Angular systematics-free cosmological analysis of galaxy clustering in configuration space
Authors: Paviot Romain , de la Torre Sylvain , de Mattia Arnaud , Zhao Cheng , Bautista Julian , Burtin Etienne , Dawson Kyle , Escoffier Stéphanie , Jullo Eric , Raichoor Anand , Ross Ashley J , Rossi Graziano 
Published: March 2022

ABSTRACTGalaxy redshift surveys are subject to incompleteness and inhomogeneous sampling due to the various constraints inherent to spectroscopic observations. This can introduce systematic errors on the summary statistics of interest, which need to be mitigated in cosmological analysis to achieve high accuracy. Standard practices involve applying weighting schemes based on completeness estimates across the survey footprint, possibly supplemented with additional weighting schemes accounting for density-dependent effects. In this work, we concentrate on pure angular systematics and describe an alternative approach consisting in analysing the galaxy two-point correlation function where angular modes are nulled. By construction, this procedure removes all possible known and unknown sources of angular observational systematics, but also part of the cosmological signal. We use a modified Landy–Szalay estimator for the two-point correlation function that relies on an additional random catalogue where angular positions are randomly drawn from the galaxy catalogue, and provide an analytical model to describe this modified statistic. We test the model by performing an analysis of the full anisotropic clustering in mock catalogues of luminous red and emission-line galaxies at 0.43 &lt; z &lt; 1.1. We find that the model fully accounts for the modified correlation function in redshift space, without introducing new nuisance parameters. The derived cosmological parameters from the analysis of baryon acoustic oscillations and redshift-space distortions display slightly larger statistical uncertainties, mostly for the growth rate of structure parameter fσ8 that exhibits a $50{{\ \rm per\ cent}}$ statistical error increase, but free from angular systematic error.
Characteristics of chromospheric oscillation periods in magnetic bright points
Authors: Sadeghi Rayhane , Tavabi Ehsan 
Published: March 2022

ABSTRACTIn this investigation, oscillation periods in Mg ii k-line intensity, brightness temperature, and Doppler velocity obtained above magnetic bright points (MBPs) are investigated. For this purpose, data from the Interface Region Imaging Spectrometer (IRIS) observing the higher chromosphere and transition region (TR) were analysed, together with imaging and magnetogram data obtained by the Solar Dynamics Observatory(SDO). The MBPs were identified by combining Si iv 1403-Å slit-jaw images with magnetogram information from the Heliospheric and Magnetic Imager (HMI). A time-slice analysis followed by a wavelet inspection were carried out on the Mg ii k (2796-Å and 10 000 K) resonance lines for the detection of the oscillation period. Finally, a power spectrum analysis was performed to characterize the oscillations. It was found that the network points feature a typical intensity, temperature, and velocity oscillation period of about 300 s. The internetwork points have a mean intensity oscillation period of about 180 s, a mean temperature oscillation period of about 202 s, and a mean velocity oscillation period of about 202 s. In addition, one BP that was analysed in detail demonstrates intensity oscillation periods with a value of 500 s, which are obviously not related to the common 3- or 5-min oscillations typically found elsewhere in chromospheric/photospheric structures.
The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase
Authors: Wei Yong , Redel Cornelia , Ahlner Alexandra , Lemak Alexander , Johansson-Åkhe Isak , Houliston Scott , Kenney Tristan M G , Tamachi Aaliya , Morad Vivian , Duan Shili , Andrews David W , Wallner Björn , Sunnerhagen Maria , Arrowsmith Cheryl H , Penn Linda Z 
Published: March 2022

Abstract
Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control MYC phosphorylation, chromatin occupancy, and stability, however the molecular basis remains unclear. Here we demonstrate that MYC interacts directly with PNUTS through the MYC homology Box 0 (MB0), a highly conserved region recently shown to be important for MYC oncogenic activity. By NMR we identified a distinct peptide motif within MB0 that interacts with PNUTS residues 1–148, a functional unit, here termed PNUTS amino-terminal domain (PAD). Using NMR spectroscopy we determined the solution structure of PAD, and characterised its MYC-binding patch. Point mutations of residues at the MYC-PNUTS interface significantly weaken their interaction both in vitro and in vivo, leading to elevated MYC phosphorylation. These data demonstrate that the MB0 region of MYC directly interacts with the PAD of PNUTS, which provides new insight into the control mechanisms of MYC as a regulator of gene transcription and a pervasive cancer driver.
Correlation Between Temperature Rise After Sympathetic Block and Pain Relief in Patients with Complex Regional Pain Syndrome
Authors: Samen Christelle D K , Sutton Olivia M , Rice Ambrose E , Zaidi Munfarid A , Siddarthan Ingharan J , Crimmel Stephanie D , Cohen Steven P 
Published: March 2022

AbstractObjectiveDetermine the correlation between post–sympathetic block temperature change and immediate- and intermediate-term pain relief.DesignRetrospective analysis.SettingAcademic setting.SubjectsSeventy-nine patients with complex regional pain syndrome who underwent sympathetic block.MethodsPre- and post-block temperatures in the affected extremity and pain scores immediately (based on 6-hour pain diary) after the block and at the intermediate-term 4- to 8-week follow-up were recorded. Post-block pain reductions of 30–49% and ≥50% were designated as partially sympathetically maintained pain and sympathetically maintained pain, respectively. A decrease in pain score ≥2 points lasting ≥4 weeks was considered a positive intermediate-term outcome for sympathetic block.ResultsA weak correlation was found between immediate-term pain relief and the extent of temperature rise for the cohort (R = 0.192, P = 0.043). Greater immediate-term pain reduction was reported among patients who experienced a temperature increase ≥7.5°C (mean 4.1; 95% confidence interval [CI]: 3.33 to 4.76) than among those who experienced a temperature increase &lt;2°C (2.3; 95% CI: 1.36 to 3.31) or ≥2°C to &lt;7.5°C (2.9; 95% CI: 1.8 to 3.9; P = 0.036). The correlations between temperature increase and intermediate-term pain score reduction at 4–8 weeks (R = 0.052, P = 0.329) and between immediate- and intermediate-term pain relief (R = 0.139, P = 0.119) were not statistically significant.ConclusionsA weak correlation was found for those who experienced greater temperature increases after the block to also experience greater immediate pain relief. Higher temperature increase cutoffs than are typically used might be necessary to determine whether a patient with complex regional pain syndrome has sympathetically maintained pain.
Origin and Diversification of the Saguaro Cactus (Carnegiea gigantea): A Within-Species Phylogenomic Analysis
Authors: Sanderson Michael J , Búrquez Alberto , Copetti Dario , McMahon Michelle M , Zeng Yichao , Wojciechowski Martin F 
Published: March 2022

AbstractReconstructing accurate historical relationships within a species poses numerous challenges, not least in many plant groups in which gene flow is high enough to extend well beyond species boundaries. Nonetheless, the extent of tree-like history within a species is an empirical question on which it is now possible to bring large amounts of genome sequence to bear. We assess phylogenetic structure across the geographic range of the saguaro cactus, an emblematic member of Cactaceae, a clade known for extensive hybridization and porous species boundaries. Using 200 Gb of whole genome resequencing data from 20 individuals sampled from 10 localities, we assembled two data sets comprising 150,000 biallelic single nucleotide polymorphisms (SNPs) from protein coding sequences. From these, we inferred within-species trees and evaluated their significance and robustness using five qualitatively different inference methods. Despite the low sequence diversity, large census population sizes, and presence of wide-ranging pollen and seed dispersal agents, phylogenetic trees were well resolved and highly consistent across both data sets and all methods. We inferred that the most likely root, based on marginal likelihood comparisons, is to the east and south of the region of highest genetic diversity, which lies along the coast of the Gulf of California in Sonora, Mexico. Together with striking decreases in marginal likelihood found to the north, this supports hypotheses that saguaro’s current range reflects postglacial expansion from the refugia in the south of its range. We conclude with observations about practical and theoretical issues raised by phylogenomic data sets within species, in which SNP-based methods must be used rather than gene tree methods that are widely used when sequence divergence is higher. These include computational scalability, inference of gene flow, and proper assessment of statistical support in the presence of linkage effects. [Phylogenomics; phylogeography; rooting; Sonoran Desert.]