bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification
Authors: Hollis Robert L. , Stanley Barbara , Thomson John P. , Churchman Michael , Croy Ian , Rye Tzyvia , Bartos Clare , Nussey Fiona , Mackean Melanie , Meynert Alison M. , Semple Colin A. , Gourley Charlie , Herrington C. Simon 
Published: June 2021

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.
Comparison of bias and resolvability in single-cell and single-transcript methods
Authors: Rammohan Jayan , Lund Steven P. , Alperovich Nina , Paralanov Vanya , Strychalski Elizabeth A. , Ross David 
Published: June 2021

AbstractSingle-cell and single-transcript measurement methods have elevated our ability to understand and engineer biological systems. However, defining and comparing performance between methods remains a challenge, in part due to the confounding effects of experimental variability. Here, we propose a generalizable framework for performing multiple methods in parallel using split samples, so that experimental variability is shared between methods. We demonstrate the utility of this framework by performing 12 different methods in parallel to measure the same underlying reference system for cellular response. We compare method performance using quantitative evaluations of bias and resolvability. We attribute differences in method performance to steps along the measurement process such as sample preparation, signal detection, and choice of measurand. Finally, we demonstrate how this framework can be used to benchmark different methods for single-transcript detection. The framework we present here provides a practical way to compare performance of any methods.
Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor
Authors: Dowsett Joseph , Ferkingstad Egil , Rasmussen Line Jee Hartmann , Thørner Lise Wegner , Magnússon Magnús K. , Sugden Karen , Thorleifsson Gudmar , Frigge Mike , Burgdorf Kristoffer Sølvsten , Ostrowski Sisse Rye , Sørensen Erik , Erikstrup Christian , Pedersen Ole Birger , Hansen Thomas Folkmann , Banasik Karina , Brunak Søren ,   DBDS Genomic Consortium,   Denmark, Andersen Steffen , Jemec Gregor , Jennum Poul , Nielsen Rene Kasper , Nyegaard Mette , Paarup Helene Martina , Petersen Mikkel , Werge Thomas ,   Iceland, Gudbjartsson Daniel , Stefansson Kari , Þorsteinsdóttir Unnur , Tragante Vinicius , Lund Sigrun Helga , Stefansdottir Lilja , Gunnarson Bjarni , Poulton Richie , Arseneault Louise , Caspi Avshalom , Moffitt Terrie E. , Gudbjartsson Daníel , Eugen-Olsen Jesper , Stefánsson Hreinn , Stefánsson Kári , Ullum Henrik 
Published: June 2021

AbstractSoluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.
Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis
Authors: Saeki Kohei , Chang Gregory , Kanaya Noriko , Wu Xiwei , Wang Jinhui , Bernal Lauren , Ha Desiree , Neuhausen Susan L. , Chen Shiuan 
Published: June 2021

AbstractThe female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas (https://mouse-mammary-epithelium-integrated.cells.ucsc.edu) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner
Authors: Li Zhongqi , Chen Xinyi , Vong Joaquim S. L. , Zhao Lei , Huang Junzhe , Yan Leo Y. C. , Ip Bonaventure , Wing Yun Kwok , Lai Hei-Ming , Mok Vincent C. T. , Ko Ho 
Published: June 2021

AbstractPharmacological reversal of brain aging is a long-sought yet challenging strategy for the prevention and treatment of age-related neurodegeneration, due to the diverse cell types and complex cellular pathways impacted by the aging process. Here, we report the genome-wide reversal of transcriptomic aging signatures in multiple major brain cell types, including glial and mural cells, by systemic glucagon-like peptide-1 receptor (GLP-1R) agonist (GLP-1RA) treatment. The age-related expression changes reversed by GLP-1RA encompass both shared and cell type-specific functional pathways that are implicated in aging and neurodegeneration. Concomitantly, Alzheimer’s disease (AD)-associated transcriptomic signature in microglia that arises from aging is reduced. These results show the feasibility of reversing brain aging by pharmacological means, provide mechanistic insights into the neurological benefits of GLP-1RAs, and imply that GLP-1R agonism may be a generally applicable pharmacological intervention for patients at risk of age-related neurodegeneration.
Simulating molecules on a cloud-based 5-qubit IBM-Q universal quantum computer
Authors: Leontica S. , Tennie F. , Farrow T. 
Published: June 2021

AbstractSimulating the behaviour of complex quantum systems is impossible on classical supercomputers due to the exponential scaling of the number of quantum states with the number of particles in the simulated system. Quantum computers aim to break through this limit by using one quantum system to simulate another quantum system. Although in their infancy, they are a promising tool for applied fields seeking to simulate quantum interactions in complex atomic and molecular structures. Here, we show an efficient technique for transpiling the unitary evolution of quantum systems into the language of universal quantum computation using the IBM quantum computer and show that it is a viable tool for compiling near-term quantum simulation algorithms. We develop code that decomposes arbitrary 3-qubit gates and implement it in a quantum simulation first for a linear ordered chain to highlight the generality of the approach, and second, for a complex molecule. We choose the Fenna-Matthews-Olsen (FMO) photosynthetic protein because it has a well characterised Hamiltonian and presents a complex dissipative system coupled to a noisy environment that helps to improve the efficiency of energy transport. The method can be implemented in a broad range of molecular and other simulation settings.
Effect of chemically induced permittivity changes on the plasmonic properties of metal nanoparticles
Authors: Saito Noboru , Ryuzaki Sou , Tsuji Yuta , Noguchi Yutaka , Matsuda Rintaro , Wang Pangpang , Tanaka Daisuke , Arima Yusuke , Okamoto Koichi , Yoshizawa Kazunari , Tamada Kaoru 
Published: June 2021

AbstractUnderstanding chemical effects on the plasmonic properties of a metal nanomaterial due to the surface molecules on that metal is of great importance in the field of plasmonics and these effects have yet to be completely elucidated. Here, we report mechanisms of the chemically induced change in the electronic state at the metal-ligand interface of silver nanoparticles due to the ligand molecules, and the effect of this change on the plasmonic properties of those nanoparticles. It was found that changes in the electron density of states at the metal-ligand interface cause alterations in the induced and permanent dipole moments, and eventually to the permittivity at the interface, when the wave function near the Fermi level is localized at the interface. These alterations play a key role in determining the plasmonic properties of silver nanoparticles. The present findings provide a more precise understanding of the interconnection between the electronic states at the metal-organic interface and the plasmonic properties of the metal.
Referral Criteria for Preschool Hearing Screening in Resource-Constrained Settings: A Comparison of Protocols
Authors: Eksteen Susan , Eikelboom Robert H. , Launer Stefan , Kuper Hannah , Swanepoel De Wet 
Published: June 2021

Purpose
This study aimed to describe and compare the performance of two screening protocols used for preschool hearing screening in resource-constrained settings.

Method
Secondary data analysis was done to determine the performance of two protocols implemented during a preschool hearing screening program using mobile health technology in South Africa. Pure-tone audiometry screening at 25 dB HL for 1000, 2000, and 4000 Hz in each ear was used by both protocols. The fail criterion for the first protocol (2,147 children screened) constituted a no-response on one or more frequencies in either ear. The second protocol required two or more no-responses (5,782 children). Multivariate logistic regression models were used to investigate associations between outcomes and protocol, age, gender, and duration.

Results

Fail rates for the one-frequency fail protocol was 8.7% (
n
= 186) and 4.3% (
n
= 250) for the two-frequency fail protocol. Children screened with the two-frequency fail protocol were 52.9% less likely to fail (
p
< .001;
OR
= 0.471; 95% confidence interval [0.385, 0.575]). Gender (
p
= .251) and age (
p
= .570) had no significant effect on screening outcome. A percentage of cases screened (44.7%) exceeded permissible noise levels in at least one ear at 1000 Hz across both protocols. True- and false-positive cases did not differ significantly between protocols. Protocol type (
p
= .204), gender (
p
= .314), and age (
p
= .982) did not affect the odds of being a true-positive result. Average screening time was 72.8 s (78.66
SD
) and 64.9 s (55.78
SD
) for the one-frequency and two-frequency fail protocols, respectively.

Conclusions
A two-frequency fail criterion and immediate rescreen of failed frequencies significantly reduced referral rate for follow-up services that are often overburdened in resourced-constrained settings. Future protocol adaptations can also consider increasing the screening levels at 1000 Hz to minimize the influence of environmental noise.
Diagnostik und Therapie der HIV-assoziierten Lymphome: Update 2021
Authors: Hentrich Marcus 
Published: June 2021

Was ist neu?
Epidemiologie und Risikofaktoren Bei Personen mit HIV ist das Risiko für ein Non-Hodgkin-Lymphom (HIV-NHL) bzw. Hodgkin-Lymphom (HIV-HL) auch unter kombinierter antiretroviraler Therapie um das 10–20- bzw. 5–15-Fache erhöht. Wichtige Risikofaktoren sind der CD4-Zell-Nadir und die kumulative HIV-Viruslast.
Prognose Die Prognose wird durch den pathologischen Subtyp und den Internationalen Prognose-Index sowie durch die Zahl der CD4-Zellen bei Lymphom-Diagnose und durch molekulare Marker wie die Expression von MYC oder BCL2 bestimmt.
Therapie Standardtherapie des diffus großzelligen B-Zell-Lymphoms sind 6 Zyklen R-CHOP. Patienten mit Burkitt-Lymphom erhalten eine Therapie nach dem B-ALL/NHL-Protokoll der GMALL. Für das plasmoblastische Lymphom ist keine Standardtherapie etabliert, Therapie der Wahl sind CHOP oder EPOCH plus Bortezomib. Die Prognose von Patienten mit primärem Erguss-Lymphom ist weiterhin ungünstig. In kleinen Fallserien wurden relativ gute Ergebnisse mit DA-EPOCH ± Bortezomib erzielt. Die Ganzhirnbestrahlung ist bei Patienten mit HIV und primärem ZNS-Lymphom obsolet. Protokolle mit HD-MTX sind gut machbar und effektiv. Hodgkin-Lymphom: Stadien-adaptierte Therapie mit ABVD und/oder BEACOPP basis. Bei Patienten mit rezidivierter oder refraktärer Erkrankung kommt eine Hochdosischemotherapie mit autologer Stammzelltransplantation zum Einsatz. Zudem gibt es zahlreiche Fallberichte zur erfolgreichen Therapie mit Nivolumab oder Pembrolizumab.
Rezidivtherapie Die Rezidivrate nach kompletter Remission beträgt bei Patienten mit NHL ca. 11 %. Standardtherapie ist die autologe Stammzelltransplantation, sofern Patienten dafür geeignet sind. Eine Therapie mit CAR-T-Zellen sollte HIV-Patienten nicht vorenthalten werden.
Lyme-Borreliose und Neuroborreliose – Was ist neu?
Authors: Dersch Rick , Fingerle Volker 
Published: June 2021

Was ist neu?
Diagnostik Zellbasierte Verfahren (z. B. LTT, ELISPOT) sollten nicht für die Diagnosestellung einer Borreliose verwendet werden.
Therapie Eine aktuelle randomisiert-kontrollierte Studie hat bestätigt, dass Doxycyclin- und Betalaktam-Antibiotika gleichwertig eingesetzt werden können. Es gibt keine statistisch signifikanten Unterschiede hinsichtlich neurologischer Symptome nach Therapie und Nebenwirkungen. Dementsprechend wird in der S3-Leitlinie Neuroborreliose kein Präparat bevorzugt empfohlen.
Prognose Mehreren Studien mit Patienten mit antibiotisch behandelter Neuroborreliose zeigen im Langzeitverlauf keine erhöhte Rate an Fatigue im Vergleich zu gesunden Kontrollpersonen. Ebenso findet sich für Lebensqualität, Depression und Kognition kein Unterschied zwischen Patienten mit Neuroborreliose nach Antibiotikatherapie und gesunden Kontrollpersonen im Langzeitverlauf.

Prophylaxe Eine prophylaktische Antibiotikagabe nach Zeckenstich wird derzeit in Deutschland nicht empfohlen.
Bruxismus – vom Kieferpressen und Zähneknirschen
Authors: Christoph Türp Jens 
Published: June 2021

SummaryDie unter dem Begriff „Bruxismus“ zusammengefassten Parafunktionen Zähneknirschen und Kieferpressen sind so alt wie die Menschheit. In der Bevölkerung sind sie weit verbreitet. Einerseits dienen diese Unterkieferaktivitäten dem Stressabbau, andererseits können sie die Zahnhartsubstanzen schädigen und zu Verspannungen und Schmerzen im Bereich der Kaumuskeln und Kiefergelenke führen.Mittels Anamnese, klinischer Untersuchung und radiologischer Befunde erfolgt eine relativ sichere Diagnosestellung. Therapeutisch empfehlenswert sind Selbstbeobachtung, Muskelentspannung und Tragen einer oralen Schiene während des Schlafs, je nach Fall angereichert durch Eigenmassage und professionelle Physiotherapie.
Detección de tornillos prominentes en la articulación radiocarpiana mediante la proyección tangencial del escafoides dorsal
Authors: Breyer Juan Manuel , Pérez Alfonso , Vergara Pamela , Ruiz Pedro 
Published: June 2021

Resumen
Introducción Una de las complicaciones de la osteosíntesis retrógrada del escafoides es la protrusión del tornillo en la articulación radiocarpiana, dada la limitada visualización intraoperatoria del polo proximal del escafoides con las proyecciones tradicionales.
Objetivo Evaluar la capacidad de una nueva proyección radiológica, la proyección “tangencial del escafoides dorsal”, o TED, para identificar tornillos prominentes radiocarpianos durante la osteosíntesis retrógrada del escafoides con tornillos canulados.
Materiales y Métodos Estudio cadavérico en muñecas frescas congeladas. Se introdujo en el escafoides un tornillo canulado con técnica retrógrada estándar.La proyección TED fue evaluada en 5 muñecas, con angulaciones del antebrazo de 15°, 30° y 45° para definir la mejor visualización del polo proximal del escafoides y del tornillo.Se comparó la capacidad para identificar la prominencia del tornillo en el polo proximal de la proyección TED de 30° con 5 proyecciones tradicionales de escafoides en 9 muñecas. El tornillo se posicionó a nivel de la superficie del escafoides, y luego se avanzó a intervalos de 0,5 mm bajo visualización directa por artrotomía dorsal. Tras cada intervalo, se repitieron todas las proyecciones para determinar su capacidad de detectar tornillos prominentes en el escafoides.
Resultados La mejor visualización del polo proximal del escafoides se logró con la proyección TED de 30°. Al comparar la proyección TED de 30° y las tradicionales, con la TED se logró identificar tornillos prominentes a 0,8 mm promedio, seguida por la proyección posteroanterior con cubitalización y extensión a 1.3 mm (p = 0.014), con una alta precisión y correlación interobservador de estas proyecciones.
Conclusión La proyección TED demostró ser la más sensible para detectar tornillos prominentes en la articulación radiocarpiana. Su uso rutinario podría evitar complicaciones durante la osteosíntesis.
Covid-19 y cirugía ortopédica: Revisión de la literatura y evidencias
Authors: Weissmann Karen A. , Huaiquilaf Carlos , Costa Marcelo , Correa Cristian , Bey Alan , Bahamonde M Luis 
Published: June 2021

ResumenSe ha declarado una pandemia ante la propagación de un nuevo virus con alta contagiosidad, llamado síndrome respiratorio agudo severo coronavirus 2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV2). El mundo ha quedado detenido ante la rápida expansión del virus, con una letalidad que en algunos países llega a 15%. En Chile, el gobierno ha tomado medidas rápidas y agresivas que han permitido mantener la curva de contagios a un nivel que permita atender de manera adecuada a la población. Dentro de estas medidas, se contempla la suspensión de cirugías y consultas ambulatorias. Como cirujanos ortopédicos, nos hemos visto afectados por estas medidas, y existe confusión respecto a cuál es la conducta más adecuada. Quisimos hacer esta guía para resumir parte de las evidencias disponibles y orientar a los cirujanos ortopédicos respecto a esta patología. El comportamiento de esta guía es dinámico, dadas las múltiples opiniones, experiencias y evidencias, que surgen diariamente, por lo que recomendamos mantenerlo como referencia, no como certeza.
A De Novo Mosaic PHEX Variant Causing Sporadic X-Linked Hypophosphatemic Rickets in a 2-Year-Old Girl
Authors: Poon Kok-Siong , Tan Karen Mei-Ling , Zacharin Margaret , Ho Cindy Wei-Li 
Published: June 2021

AbstractPathogenic variants in the PHEX gene are causative of X-linked hypophosphatemic rickets (XLH). We present a case of a 2-year-old girl with hypophosphatemic rickets with genu varum and short stature without any family history of XLH. Next generation sequencing of the PHEX gene identified a splice donor variant, NM_000444.6:c.1173 + 5G > A in intron 10. This variant had a mosaic pattern with only 22% of the sequence reads showing the variant allele and was not present in the girl's parents, both of whom had a normal phenotype. This is a sporadic case of a de novo mosaic splice-site variant in the PHEX gene.
Morphological Changes in Faces Depending on Posture
Authors: Nishioka Hiroshi , Hishikawa Miki , Nagai Fumio , Yuzuriha Shunsuke 
Published: June 2021

AbstractFacial surgeries are usually performed with the patient in the supine position; however, it is crucial to predict postoperative results in the upright position. This study aimed to clarify the posture-related morphological changes in the facial soft tissue regarding age and sex, using physical measurements to obtain results in specific linear metric measurements of standard facial features. One hundred healthy volunteers were divided into four groups based on age and sex (25 young men, 25 young women, 25 old men, 25 old women). For all participants, 18 measuring points were marked on the skin along with 18 paired linear measurements, and the angle was measured using a digital sliding caliper and angle meter in both upright and supine positions. In all four groups, the intercanthal width (en-en), binocular width (ex-ex), length of the eye fissure (en-ex), length of the nasal bridge (n-prn), width of the nose (al-al), height of the lower face (sn-gn), vermilion height of the lower lip (sto-li), height of the lower lip (sto-sl), width of the philtrum (cphi-cphi), width of the mouth (ch-ch), and nasolabial angle (NLA) were significantly larger in the supine position than in the upright position. The increase was larger in the older age groups than in the younger age groups. Moreover, the increase was larger in old men than in old women. During facial surgery involving these areas, surgeons should consider the patient's age and sex and understand what facial figuration change would occur depending on posture and change their preoperative design or make minor adjustments during operation in the supine position to increase patient satisfaction.