bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in baseline risk estimated by physicians and patients with early breast cancer
Authors: Mori Makiko , Yoshimura Akiyo , Sawaki Masataka , Hattori Masaya , Kotani Haruru , Adachi Yayoi , Iwase Madoka , Kataoka Ayumi , Sugino Kayoko , Horisawa Nanae , Ozaki Yuri , Iwata Hiroji , Onishi Sakura , Gondo Naomi , Terada Mitsuo
Published: September 2021

Background

Physicians recommend adjuvant therapy to patients based on baseline risk. A common recognition for baseline risk between patients and physicians is critical for successful adjuvant therapy. We prospectively investigated the differences in estimated baseline risk between physicians and patients with early breast cancer.

Methods

This analysis was performed at a single institution in Japan. Early breast cancer patients over 18 years old were enrolled after surgery. After explaining the pathological results, physicians asked each patient about an estimated baseline risk. Differences in estimated baseline risk were defined as the baseline risk estimated by patients minus the baseline risk estimated by physicians. The primary endpoint was that the number of patients who estimate baseline risk higher than physicians was higher than those who estimate a lower baseline risk. The secondary endpoints were differences in estimated baseline risk by stage, subtype and the influence of patient factors to differences in estimated baseline risk.

Results

From July 2017 to December 2018, 262 patients were enrolled. Among the 262 patients, 190 estimated a higher baseline risk than physicians, 53 estimated a lower baseline risk and 19 estimated the same. Overall, patients estimated a significantly higher baseline risk than physicians (P < 0.001). Differences in estimated baseline risk was significantly smaller in patients who knew the term ‘baseline risk’ than patients who did not (P = 0.0037). Differences in estimated baseline risk were also significantly smaller in patients with stage II breast cancer than patients with stage I (P = 0.0239). However, there were no statistically significant differences of differences in estimated baseline risk according to other factors.

Conclusions

Patients with early breast cancer estimated a significantly higher baseline risk than physicians. Physicians should accurately explain baseline risk to patients for shared decision making.
Mule deer do more with less: comparing their nutritional requirements and tolerances with white-tailed deer
Authors: Staudenmaier Anna R , Shipley Lisa A , Camp Meghan J , Forbey Jennifer S , Hagerman Ann E , Brandt Abigail E , Thornton Daniel H
Published: September 2021

Congeneric species often share ecological niche space resulting in competitive interactions that either limit co-occurrence or lead to niche partitioning. Differences in fundamental nutritional niches mediated through character displacement or isolation during evolution are potential mechanisms that could explain overlapping distribution patterns of congenerics. We directly compared nutritional requirements and tolerances that influence the fundamental niche of mule (Odocoileus hemionus) and white-tailed deer (O. virginianus), which occur in allopatry and sympatry in similar realized ecological niches across their ranges in North America. Digestible energy and protein requirements and tolerances for plant fiber and plant secondary metabolites (PSMs) of both deer species were quantified using in vivo digestion and intake tolerance trials with six diets ranging in content of fiber, protein, and PSMs using tractable deer raised under identical conditions in captivity. We found that compared with white-tailed deer, mule deer required 54% less digestible protein and 21% less digestible energy intake per day to maintain body mass and nitrogen balance. In addition, they had higher fiber, energy, and dry matter digestibility and produced glucuronic acid (a byproduct of PSM detoxification) at a slower rate when consuming the monoterpene α-pinene. The mule deers’ enhanced physiological abilities to cope with low-quality, chemically defended forages relative to white-tailed deer might minimize potential competitive interactions in shared landscapes and provide a modest advantage to mule deer in habitats dominated by low-quality forages.
Population survey of small rodents on islands located inside a region of endemism for hantavirus pulmonary syndrome
Authors: Maroli Malena , Burgos Eliana Florencia , Piña Carlos Ignacio , Gómez Villafañe Isabel Elisa
Published: September 2021

Ecological studies of rodent species, especially as reservoirs of zoonoses, can identify spatiotemporal conditions associated with irruptions of abundances, as well as predict areas and times with higher risk of disease transmission. The aims of this research were to describe and identify (i) the rodent community composition; (ii) their population structure and breeding season; (iii) temporal and spatial variations in their population abundance; and (iv) the environmental factors associated with these variations on islands of upper Paraná River Delta, a zone of endemism for hantavirus pulmonary syndrome (HPS) in Argentina (Entre Ríos and Santa Fe provinces). We carried out seasonal surveys over 3 years (2014–2017) with live capture traps on seven islands (natural protected areas and under livestock grazing). Three hundred seventy-seven sigmodontine rodents of seven species were captured. While the maximum richness was seven, only four species coexisted at most on an island at the same time. Although changes in reproduction were detected throughout the year, seasonality, land use, and vegetation structure did not explain changes in abundance of rodents. Rodent abundances were affected mainly by flooding-related factors and meteorological conditions (rainfall and temperatures). The recovery of rodent populations after river flooding was species-specific and heterogeneous. The abundance of Oxymycterus rufus and Akodon azarae was affected by El Niño Southern Oscillation (ENSO); A. azarae did not recover after the flood at least during the study period. After the flood, populations of Oligoryzomys flavescens, the reservoir of HPS, also declined; however, this species’ populations were the first to recover its numbers, becoming dominant in the post-flood rodent community.
Dietary flexibility and high predator efficacy facilitate coexistence in a novel predator interaction
Authors: Moseby Katherine E , Jensen Melissa A , Tatler Jack
Published: September 2021

Predator diet can be influenced by competition and intraguild predation, leading to resource partitioning and/or avoidance. For sympatric, endemic predators, these processes form as predator species coevolve, facilitating coexistence. However, when novel predator interactions occur, significant dietary overlap could create acute levels of competition leading to intraguild predation and population extinction, or accelerated changes in diet and/or spatial and temporal avoidance. We measured diet, intraguild predation, and spatial and temporal overlap in two predator species in a novel predator interaction: the western quoll (Dasyurus geoffroii), a small, native carnivore reintroduced to semi-arid Australia, and the domestic cat (Felis catus), a larger introduced carnivore already resident at the release site. Both species exhibited high dietary overlap and fed on mammals, reptiles, birds, and invertebrates. Cats included quolls in their diet. Quoll diet was broader (including carrion, bats, and plant material) and flexible, changing significantly with age, sex, and season. Introduced rabbit was the most common prey item recorded for both species (frequency of occurrence = 40–50%). However, quolls consumed rabbits in relation to their availability while rabbit consumption in cats was unrelated to availability suggesting a stronger dependence on rabbit prey. Quoll diet did not change over time since release and they did not spatially or temporally avoid cats. However, cats were significantly spatially associated with rabbits while quolls were not, suggesting higher predation efficacy in quolls possibly due to their smaller body size enabling them to catch rabbits inside warrens. Despite high dietary overlap and intraguild predation, the quoll’s broad and flexible diet and high predation efficacy appeared to assist in facilitating coexistence and reducing competition in this novel predator interaction. This dietary flexibility may be harnessed to improve conservation outcomes: reducing introduced rabbits in our study area could naturally reduce feral cat populations while having less impact on native quolls.
Landscape dynamic network biomarker analysis reveals the tipping point of transcriptome reprogramming to prevent skin photodamage
Authors: Zhang Chengming , Zhang Hong , Ge Jing , Mi Tingyan , Cui Xiao , Tu Fengjuan , Gu Xuelan , Zeng Tao , Chen Luonan
Published: September 2021

Skin, as the outmost layer of human body, is frequently exposed to environmental stressors including pollutants and ultraviolet (UV), which could lead to skin disorders. Generally, skin response process to ultraviolet B (UVB) irradiation is a nonlinear dynamic process, with unknown underlying molecular mechanism of critical transition. Here, the landscape dynamic network biomarker (l-DNB) analysis of time series transcriptome data on 3D skin model was conducted to reveal the complicated process of skin response to UV irradiation at both molecular and network levels. The advanced l-DNB analysis approach showed that: (i) there was a tipping point before critical transition state during pigmentation process, validated by 3D skin model; (ii) 13 core DNB genes were identified to detect the tipping point as a network biomarker, supported by computational assessment; (iii) core DNB genes such as COL7A1 and CTNNB1 can effectively predict skin lightening, validated by independent human skin data. Overall, this study provides new insights for skin response to repetitive UVB irradiation, including dynamic pathway pattern, biphasic response, and DNBs for skin lightening change, and enables us to further understand the skin resilience process after external stress.
Mitotic inactivation of the cGAS‒MITA/STING pathways
Authors: Zhong Li , Shu Hong-Bing
Published: September 2021

The cyclic guanosine monophosphate‒adenosine monophosphate synthase (cGAS)‒mediator of interferon response factor 3 activation/stimulator of interferon genes (MITA/STING) axis has emerged as a major pathway, which senses microbial or mislocated cellular DNA in the cytosol to trigger innate immune responses. cGAS senses cytosolic DNA without a preference of self- or nonself-DNA. How the cGAS‒MITA/STING axis is inactivated upon nuclear envelope breakdown (NEBD) at mitotic entry in vertebrate cells to avoid self-DNA sensing remains unclear until very recently. In this review, we summarize the recent advances on how cGAS responds to chromosomes upon NEBD and the mechanisms involved in the inactivation of the cGAS‒MITA/STING pathways in mitosis.
Imaging neural circuit pathology of autism spectrum disorders: autism-associated genes, animal models and the application ofin vivotwo-photon imaging
Authors: Terashima Hiroshi , Minatohara Keiichiro , Maruoka Hisato , Okabe Shigeo
Published: September 2021

Recent advances in human genetics identified genetic variants involved in causing autism spectrum disorders (ASDs). Mouse models that mimic mutations found in patients with ASD exhibit behavioral phenotypes consistent with ASD symptoms. These mouse models suggest critical biological factors of ASD etiology. Another important implication of ASD genetics is the enrichment of ASD risk genes in molecules involved in developing synapses and regulating neural circuit function. Sophisticated in vivo imaging technologies applied to ASD mouse models identify common synaptic impairments in the neocortex, with genetic-mutation-specific defects in local neural circuits. In this article, we review synapse- and circuit-level phenotypes identified by in vivo two-photon imaging in multiple mouse models of ASD and discuss the contributions of altered synapse properties and neural circuit activity to ASD pathogenesis.
Pazopanib or Sunitinib? cost-utility analysis of pazopanib versus sunitinib in the first-line treatment of metastatic renal cell carcinoma in Jordan
Authors: Al-Rabayah Abeer A , Sawalha Razan , Fawzi Al Froukh Rawan , Al-Bawab Rand , Jaddoua Saad M
Published: September 2021

Objectives

To evaluate the cost-effectiveness of pazopanib for the treatment of metastatic renal cell carcinoma (mRCC) in the first-line settings from a payer perspective.

Methods

A state-transition model with three health states was developed to estimate the incremental cost per quality-adjusted life years (QALY) gained for pazopanib compared to sunitinib. A lifelong time horizon was adopted in the base-case analysis. The transition probabilities were estimated based on the COMPRAZ trial, utility weights were taken from literature, and costs were based on estimating medical resource utilization data at King Hussein Cancer Centre (KHCC), deriving unit cost inputs from KHCC databases and the Jordan Food and Drug Administration website. Both costs and outcomes were discounted using 3% rate. The model’s uncertainty was tested using a probabilistic and deterministic sensitivity analyses.

Key findings

The base-case results showed that pazopanib was dominant when using the listed price for both medications. Pazopanib was associated with an incremental saving of −$10 721.55 and an incremental QALY of 0.08. The results were sensitive to utility values and the progression health state cost. The probabilistic sensitivity analysis showed that the probability of pazopanib being cost-effective compared to sunitinib is around 60–70% at KHCC cost-effectiveness threshold values. However, the result was reversed when the price of sunitinib was reduced by 40% making sunitinib the dominant strategy.

Conclusions

Pazopanib is a potential cost-effective option in the first-line settings for mRCC when the listed price of sunitinib is used. Therefore, price negotiations are recommended before final listing decisions to get the most cost-saving treatment.
Return to School and COVID-19 Vaccination for Pediatric Solid Organ Transplant Recipients in the United States: Expert Opinion for 2021-2022
Authors: Downes Kevin J , Statler Victoria A , Orscheln Rachel C , Cousino Melissa K , Green Michael , Michaels Marian G , Muller William J , Sharma Tanvi S , Danziger-Isakov Lara A , Ardura Monica I
Published: September 2021

The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021.
Feasibility of quantification of murine radiation-induced pulmonary fibrosis with microCT imaging
Authors: McIlrath Daniel R , Roach Elizabeth , Porro Gianna , Perez-Torres Carlos J
Published: September 2021

Mouse models of radiation-induced pulmonary fibrosis (RIPF) are commonly produced to find novel treatments for the condition. However, current models are not always assesed in a clinically-relevant manner. Clinics diagnose and track RIPF through CT scanning rather than observing time-to-death. An established timeline of RIPF lesion development in a murine model is therefore needed. Male C57Bl/6 mice (n=43) were irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an 320 kV X-Rad cabinet irradiator. CT was performed with respitory gating at two week time points and developed images to identify RIPF pathology in vivo. Confirmation of CT findings was performed via histology on the lungs using Mason’s trichrome staining. CT images were segmented to quantify fibrosis and lung which are then summed to give total volume. The fibrotic fraction was calculated upto 26 weeks. Significant increases in fibrotic fraction compared to the baseline microCT scans for each individual mouse acquired prior to the 20 Gy exposure are seen beginning at 10–12 weeks. Tidal lung volume was also calculated by subtracting expiration scan volumes from inspiration scan volumes. However the decrease in tidal lung volume over time was not statisitically significant. Computed tomography (CT) imaging was used to quantify the increase in fibrosis over time in our mouse model. However, the results were highly variable among individual mice after irradiation. CT imaging should be used in future studies looking at treatments for RIPF as it allows for measuring the extent of pathology non-invasively in a clinically-relevant manner.
Lost Things and the Making of Material Cultures in Eighteenth-Century London
Authors: Smith Kate
Published: September 2021

This article focuses on everyday occurrences of loss and losing in urban spaces to examine the role that absence played in shaping material cultures in the past. It returns to a site that has remained central to material histories, eighteenth-century London, and shows how possessions regularly went missing due to theft and forgetfulness. Examining daily newspapers, alongside court cases, diary entries, and handbills, demonstrates how experiences of loss prompted urban denizens to devise systems of reclamation. “Lost” notices placed in London’s new daily newspapers became crucial to ensuring the return of lost possessions. While these systems were largely managed by thief-takers such as Jonathan Wild in the early decades of the eighteenth century, after Wild’s death in 1725, it fell to Londoners themselves to remember the salient features of their possessions and write the notices. These writings and the material practices that underpinned them shaped how people understood the material world around them and how they operated in urban spaces. As such, the article demonstrates the significance of absence in shaping urban material cultures.
How do machine translators measure up to human literary translators in stylometric tests?
Authors: Lee Changsoo
Published: September 2021

This study aims to test the classification of literary translations by human and machine translators in a bid to explore stylistic distinctions between the two groups and among machine translators and their evolution over 1 year between 2019 and 2020. For this, the study takes a stylometric approach by employing two statistical methods popularly used in authorship attribution—support vector machine (SVM) and principal component analysis (PCA), which are applied to analyzing three types of features—1-grams, 2-grams, and 3 grams. The results show that over the researched period, the three machine translators investigated (Google, Bing, and Papago) moved in the direction of converging in style while advancing toward human translators. The distance gained by them on human translators, however, was not significant enough to challenge the clear-cut divide between the two groups. The PCA tests additionally revealed some characteristics of the machine translator that might be responsible for the stylistic distinction between them and their human counterparts including their tendency of overusing basic standard language.
Neurobehavioral Symptoms in U.S. Special Operations Forces in Rehabilitation After Traumatic Brain Injury: A TBI Model Systems Study
Authors: Garcia Amanda , Miles Shannon R , Reljic Tea , Silva Marc A , Dams-O’Connor Kristen , Belanger Heather G , Bajor Laura , Richardson Risa
Published: September 2021

Introduction

Special Operations Forces (SOF) personnel are at increased risk for traumatic brain injury (TBI), when compared with conventional forces (CF). Prior studies of TBI in military samples have not typically investigated SOF vs. CF as specific subgroups, despite documented differences in premorbid resilience and post-injury comorbidity burden. The aim of the current study was to compare SOF vs. CF on the presence of neurobehavioral symptoms after TBI, as well as factors influencing perception of symptom intensity.

Materials and Methods

This study conducted an analysis of the prospective veterans affairs (VA) TBI Model Systems Cohort, which includes service members and veterans (SM/V) who received inpatient rehabilitation for TBI at one of the five VA Polytrauma Rehabilitation Centers. Of those with known SOF status (N = 342), 129 participants identified as SOF (average age = 43 years, 98% male) and 213 identified as CF (average age = 38.7 years, 91% male). SOF vs. CF were compared on demographics, injury characteristics, and psychological and behavioral health symptoms. These variables were then used to predict neurobehavioral symptom severity in univariable and multivariable analyses.

Results

SOF personnel reported significantly greater posttraumatic stress disorder (PTSD) symptoms but less alcohol and drug use than the CF. SOF also reported greater neurobehavioral symptoms. When examining those with TBIs of all severities, SOF status was not associated with neurobehavioral symptom severity, while race, mechanism of TBI, and PTSD symptoms were. When examining only those with mTBI, SOF status was associated with lower neurobehavioral symptoms, while PTSD severity, white race, and certain mechanisms of injury were associated with greater neurobehavioral symptoms.

Conclusions

Among those receiving inpatient treatment for TBI, SOF SM/V reported higher neurobehavioral and symptom severity. PTSD was the strongest predictor of neurobehavioral symptoms and should be considered an important treatment target in both SOF and CF with co-morbid PTSD/TBI. A proactive human performance approach towards identification and treatment of psychological and neurobehavioral symptoms is recommended for SOF.
Disc fragmentation and oligarchic growth of protostellar systems in low-metallicity gas clouds
Authors: Chiaki Gen , Yoshida Naoki
Published: September 2021

We study low-metallicity star formation with a set of high-resolution hydrodynamics simulations for various gas metallicities over a wide range 0–$10^{-3} \ {\rm Z_{\bigodot }}$. Our simulations follow non-equilibrium chemistry and radiative cooling by adopting realistic elemental abundance and dust size distribution. We examine the condition for the fragmentation of collapsing clouds (cloud fragmentation; CF) and of accretion discs (disc fragmentation; DF). We find that CF is suppressed due to rapid gas heating accompanied with molecular hydrogen formation even with efficient dust cooling for metallicities ${\gtrsim}10^{-5} \ {\rm Z_{\bigodot }}$. Instead, DF occurs in almost all runs regardless of metallicity. We also find that, in the accretion discs, the growth of the protostellar systems is overall oligarchic. The primary protostar grows through the accretion of gas, and secondary protostars form through the interaction of spiral arms or the break-up of a rapidly rotating protostar. Despite vigorous fragmentation, a large fraction of secondary protostars are destroyed through mergers or tidal disruption events. For a few hundred years after the first adiabatic core formation, only several protostars survive in the disc, and the total mass of protostars is 0.52–$3.8 \ {\rm M_{\bigodot }}$.
Behavioural responses of Anodonta anatina and Unio pictorum to temperature and algal concentration
Authors: Zapitis Charitos , Huck Maren , Mehra Aradhana , Bulling Mark T , Ramsey Andrew
Published: September 2021

Using time-lapse photography in a laboratory setting, we exposed Anodonta anatina and Unio pictorum for 4 h to algal (Chlorella vulgaris) concentrations ranging from 0.5 to 20.0 mg ash-free dry mass l−1 and to three different temperatures (11 ± 1, 15 ± 1 and 19 ± 1 °C). We analysed the proportion of mussels in locomotion, duration of locomotory activities, posterior tip movement and valve opening behaviour. The proportion of mussels in locomotion was significantly higher for A. anatina and for A. anatina was significantly lower at 11 °C. For both species, the proportion of mussels in locomotion, the duration of locomotion and movement of the posterior tip decreased with increasing algal concentration. The locomotory duration was significantly shorter in U. pictorum. In both species, valve opening peaked at intermediate algal concentrations, with the deviation from the peak being more prominent in A. anatina. Finally, we recorded a contrasting locomotory strategy for the two species (A. anatina crawled on the sediment surface, whereas U. pictorum moved through the sediment) and identified potential density dependence in behavioural adaptation.
Treatment and outcome of intracranial ependymoma after first relapse in the 2nd AIEOP protocol
Authors: Massimino Maura , Barretta Francesco , Modena Piergiorgio , Johann Pascal , Ferroli Paolo , Antonelli Manila , Gandola Lorenza , Garrè Maria Luisa , Bertin Daniele , Mastronuzzi Angela , Mascarin Maurizio , Quaglietta Lucia , Viscardi Elisabetta , Sardi Iacopo , Ruggiero Antonio , Boschetti Luna , Giagnacovo Marzia , Biassoni Veronica , Schiavello Elisabetta , Chiapparini Luisa , Erbetta Alessandra , Mussano Anna , Giussani Carlo , Mura Rosa Maria , Barra Salvina , Scarzello Giovanni , Scimone Giuseppe , Carai Andrea , Giangaspero Felice , Buttarelli Francesca Romana
Published: September 2021

Background

More than 40% of patients with intracranial ependymoma need a salvage treatment within 5 years after diagnosis, and no standard treatment is available as yet. We report the outcome after first relapse of 64 patients treated within the 2nd AIEOP protocol.

Methods

We considered relapse sites and treatments, that is, various combinations of complete/incomplete surgery, if followed by standard or hypofractionated radiotherapy (RT) ± chemotherapy (CT). Molecular analyses were available for 38/64 samples obtained at first diagnosis. Of the 64 cases, 55 were suitable for subsequent analyses.

Results

The median follow-up was 147 months after diagnosis, 84 months after first relapse, 5-year EFS/OS were 26.2%/30.8% (median EFS/OS 13/32 months) after relapse. For patients with a local relapse (LR), the 5-year cumulative incidence of second LRs was 51.6%, with a 5-year event-specific probability of being LR-free of 40.0%. Tumor site/grade, need for shunting, age above/below 3 years, molecular subgroup at diagnosis, had no influence on outcomes. Due to variation in the RT dose/fractionation used and the subgroup sizes, it was not possible to assess the impact of the different RT modalities. Multivariable analyses identified completion of surgery, the absence of symptoms at relapse, and female sex as prognostically favorable. Tumors with a 1q gain carried a higher cumulative incidence of dissemination after first relapse.

Conclusions

Survival after recurrence was significantly influenced by symptoms and completeness of surgery. Only a homogeneous protocol with well-posed, randomized questions could clarify the numerous issues, orient salvage treatment, and ameliorate prognosis for this group of patients.
Body CT and PET/CT detection of extracranial lymphoma in patients with newly diagnosed central nervous system lymphoma
Authors: Hyun Suh Chong , Kim Ho Sung , Ahn Sung Soo , Seong Minjung , Han Kichang , Park Ji Eun , Chai Jung Seung , Gon Choi Choong , Joon Kim Sang , Min Lee Sang , Hoon Kim Jeong , Lee Seung-Koo , Hong Choi Seung , Tae Kim Sung , Nayak Lakshmi , Batchelor Tracy T , Huang Raymond Y , Guenette Jeffrey P
Published: September 2021

Background

We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease.

Methods

An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared.

Results

One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001).

Conclusion

Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.
DNA methylation-based prognostic subtypes of chordoma tumors in tissue and plasma
Authors: Zuccato Jeffrey A , Patil Vikas , Mansouri Sheila , Liu Jeffrey C , Nassiri Farshad , Mamatjan Yasin , Chakravarthy Ankur , Karimi Shirin , Almeida Joao Paulo , Bernat Anne-Laure , Hasen Mohammed , Singh Olivia , Khan Shahbaz , Kislinger Thomas , Sinha Namita , Froelich Sébastien , Adle-Biassette Homa , Aldape Kenneth D , De Carvalho Daniel D , Zadeh Gelareh
Published: September 2021

Background

Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes.

Methods

Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available.

Results

Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1–94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing “Immune-infiltrated” subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing “Cellular” subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52–1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data.

Conclusions

Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.
Charmonium and charmoniumlike states at the BESIII experiment
Authors: Yuan Chang-Zheng
Published: September 2021

Charmonium is a bound state of a charmed quark and a charmed antiquark, and a charmoniumlike state is a resonant structure that contains a charmed quark and antiquark pair but has properties that are incompatible with a conventional charmonium state. While operating at center-of-mass energies from 2 to 5 GeV, the BESIII experiment can access a wide mass range of charmonium and charmoniumlike states, and has contributed significantly in this field. We review BESIII results involving conventional charmonium states, including the first observation of the M1 transition ψ(2S) → γηc(2S) and the discovery of the ψ2(3823) state; and report on studies of charmoniumlike states, including the discoveries of the Zc(3900) and Zc(4020) tetraquark candidates, the resolution of the fine structure of the Y(4260) state, the discovery of the new production process e+e− → γX(3872) and the uncovering of strong evidence for the commonality among the X(3872), Y(4260) and Zc(3900) states. The prospects for further research at BESIII and proposed future facilities are also presented.
The dynamics of disability and benefit receipt in Britain
Authors: Jones Melanie K , McVicar Duncan
Published: September 2021

This article provides a comprehensive analysis of the dynamic relationship between disability and welfare benefit receipt in Britain. Exploiting rarely used longitudinal data, it examines the impact of disability onset and disability exit on receipt of a range of beneficial outcomes, utilizing differences in the timing of onset/exit for identification. Disability onset increases receipt of disability insurance (DI), sickness benefits, and non-sickness benefits by 6, 8, and 9 percentage points in the onset year, although almost 70% of those experiencing onset remain independent of the welfare system in the short-run. DI reforms that toughened screening, reduced generosity, and increased conditionality appear to have substantially reduced DI inflows following onset, but without affecting the overall probability of welfare receipt. Disability exit, although neglected in the literature, is common during working-age and leads to a decrease in DI (and total welfare receipt), suggesting DI is not an absorbing state.
Hepatitis C Resistance-Associated Substitutions Among People Who Inject Drugs Treated With Direct-Acting Antiviral-Containing Regimens
Authors: Akiyama Matthew J , Riback Lindsey , Reeves Jacqueline D , Lie Yolanda S , Agyemang Linda , Norton Brianna L , Arnsten Julia H , Litwin Alain H
Published: September 2021

Background

Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and after virologic failure in DAA-naive and protease inhibitor-experienced PWID.

Methods

We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b.

Results

Among the 139 (92.7%) DAA-naive PWID, 85 of 139 (61.2%) had baseline RASs—67 of 139 (48.2%) in NS3 (predominantly Q80K/L); 25 of 139 (18.0%) in NS5A; and 8 of 139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N = 1, Q80K N = 9) and 4 had baseline NS5A RASs (M28V N = 2, H58P N = 1, A92T N = 1). Among the 11 participants who had posttreatment samples with detectable virus (7 treatment failures, 1 late relapse, 3 reinfections), 1 sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected.

Conclusions

Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2 of 150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.
Political Purposes, Anti-entrenchment and Judicial Protection of the Democratic Process
Authors: Rowbottom Jacob
Published: September 2021

The legality of decisions made for political purposes is a recurring issue in administrative law. In this article, it will be argued that generalisations should not be made about ‘political’ decisions as a single category. Instead, there are different types of political consideration, which raise different issues when assessing the legality of a decision. This article singles out a particular type of political decision for condemnation: decisions made to gain a political advantage by deliberately changing the systems of democratic accountability. Examples include the engineering of the electoral system to produce favourable results, the use of public power to punish critics and the use of public resources to publish partisan propaganda. The article will argue that the legality of such political decisions should not be assessed solely within the ordinary administrative law framework, but under a constitutional principle of anti-entrenchment and process protection.
Reddening and darkening trends of on/off swirls and the relationship with magnetic field strength
Authors: Cho Eunjin , Sim Chae Kyung , Baek Seul-Min , Jeong Minsup , Choi Young-Jun
Published: September 2021

Lunar swirls are albedo features associated with magnetic anomalies, and their formation mechanism has long been debated. Because spectral properties of lunar swirls provide information on space weathering environments and surface compositions, differences in the spectra between swirls and background regions can give a clue to their formation. We analyze space weathering for swirls in the lunar highlands and maria using the VIS-NIR spectral slope, 1550 nm reflectance, and 950 nm band depth. We find that highland swirls show lower reddening-to-darkening ratios than off-swirl regions, implying more decreases of nanophase iron relative to microphase iron on swirls. We also use magnetic field data to investigate the influence of the crustal magnetic field on the space weathering of a few selected swirls. The Reiner Gamma swirl becomes more immature as the magnetic field strength increases, although the entire swirl has a high albedo. Especially, the Reiner Gamma tail shows that the stronger magnetic field makes the surface undergo less spectral reddening. Our results support the solar wind stand-off hypothesis, which is that the solar wind deflected by the crustal field determines the optical property of the surface.
Multi-frequency radio observations of the radio-loud magnetar XTE J1810−197
Authors: Eie Sujin , Terasawa Toshio , Akahori Takuya , Oyama Tomoaki , Hirota Tomoya , Yonekura Yoshinori , Enoto Teruaki , Sekido Mamoru , Takefuji Kazuhiro , Misawa Hiroaki , Tsuchiya Fuminori , Kisaka Shota , Aoki Takahiro , Honma Mareki
Published: September 2021

We report on the multi-frequency multi-epoch radio observations of the magnetar XTE J1810−197, which exhibited a radio outburst from 2018 December after its 10-year quiescent period. We performed quasi-simultaneous observations with VERA (22 GHz), Hitachi (6.9 GHz and 8.4 GHz), Kashima (2.3 GHz), and Iitate (0.3 GHz) radio telescopes located in Japan to trace the variability of the magnetar radio pulsations during the observing period from 2018 December 13 to 2019 June 12. The pulse width becomes narrower as the observing frequency goes higher, analogous to the general profile narrowing behavior of ordinary pulsars. When assuming a simple power law in the range of 2.3 GHz and 8.7 GHz, the radio spectrum of the magnetar goes steeper with the average spectral index 〈α〉 ≈ −0.85 for the first four months. The wide-band radio spectra gathered from our observations and the literature suggest that XTE J1810−197 would have a double-peaked spectrum with a valley point in 22–150 GHz, where the first spectral peak implies a gigahertz-peaked spectrum (GPS) feature with a peak at a few GHz. The GPS and the high-frequency peak have been identified in the spectra of other radio-loud magnetars, thus they may be intrinsic features that can give a new insight to the understanding of various emission mechanisms and the surrounding environments of radio magnetars. Our study emphasizes the importance of simultaneous long-term broad-band observations toward radio-loud magnetars to capture the puzzling spectral features and establish a link to other types of neutron stars.
Democracy in Spanish America: The Early Adoption of Universal Male Suffrage, 1810–1853
Authors: Aguilar Rivera José Antonio , Posada-Carbó Eduardo , Zimmermann Eduardo
Published: September 2021

Universal manhood suffrage — the right to an equal vote for all adult males, regardless of racial, economic or literacy conditions, as adopted by some Spanish American countries in the 1850s, at a time when very few countries in the Western world had done so — is the subject of this article. It considers in more detail the experience of New Granada (Colombia), with some comparative references, especially to Argentina and Mexico, in the wider context of the 1848 European revolutions. It offers a novel contribution to the wider historiography of suffrage while also contributing to a growing literature that seeks to decentre the history of democracy. Additionally, in as much as issues related to suffrage were central to the process of constitution-making, what we detail here has some bearing on the renewed interest in constitutional history. While this is above all an engagement with history, it is hoped that its findings will have relevance to theoretical discussions among social scientists on the expansion of suffrage.
The calcium-dependent protein kinase CPK28 is targeted by the ubiquitin ligases ATL31 and ATL6 for proteasome-mediated degradation to fine-tune immune signaling in Arabidopsis
Authors: Liu Xiaotong , Zhou Yuanyuan , Du Mingshuo , Liang Xuelian , Fan Fenggui , Huang Guozhong , Zou Yanmin , Bai Jiaojiao , Lu Dongping
Published: September 2021

Immune responses are triggered when pattern recognition receptors recognize microbial molecular patterns. The Arabidopsis (Arabidopsis thaliana) receptor-like cytoplasmic kinase BOTRYTIS-INDUCED KINASE1 (BIK1) acts as a signaling hub of plant immunity. BIK1 homeostasis is maintained by a regulatory module in which CALCIUM-DEPENDENT PROTEIN KINASE28 (CPK28) regulates BIK1 turnover via the activities of two E3 ligases. Immune-induced alternative splicing of CPK28 attenuates CPK28 function. However, it remained unknown whether CPK28 is under proteasomal control. Here, we demonstrate that CPK28 undergoes ubiquitination and 26S proteasome-mediated degradation, which is enhanced by flagellin treatment. Two closely related ubiquitin ligases, ARABIDOPSIS TÓXICOS EN LEVADURA31 (ATL31) and ATL6, specifically interact with CPK28 at the plasma membrane; this association is enhanced by flagellin elicitation. ATL31/6 directly ubiquitinate CPK28, resulting in its proteasomal degradation. Furthermore, ATL31/6 promotes the stability of BIK1 by mediating CPK28 degradation. Consequently, ATL31/6 positively regulate BIK1-mediated immunity. Our findings reveal another mechanism for attenuating CPK28 function to maintain BIK1 homeostasis and enhance immune responses.
Evaluating Completeness of Discrete Data on Physical Functioning for Children With Cerebral Palsy in a Pediatric Rehabilitation Learning Health System
Authors: Koscielniak Nikolas J , Tucker Carole A , Grogan-Kaylor Andrew , Friedman Charles P , Richesson Rachel , Tucker Josh S , Piatt Gretchen A
Published: September 2021

Objective

The purpose of this study was to determine the extent that physical function discrete data elements (DDE) documented in electronic health records (EHR) are complete within pediatric rehabilitation settings.

Methods

A descriptive analysis on completeness of EHR-based DDEs detailing physical functioning for children with cerebral palsy was conducted. Data from an existing pediatric rehabilitation research learning health system data network, consisting of EHR data from 20 care sites in a pediatric specialty health care system, were leveraged. Completeness was calculated for unique data elements, unique outpatient visits, and unique outpatient records.

Results

Completeness of physical function DDEs was low across 5766 outpatient records (10.5%, approximately 2 DDEs documented). The DDE for Gross Motor Function Classification System level was available for 21% (n = 3746) outpatient visits and 38% of patient records. Ambulation level was the most frequently documented DDE. Intercept only mixed effects models demonstrated that 21.4% and 45% of the variance in completeness for DDEs and the Gross Motor Function Classification System, respectively, across unique patient records could be attributed to factors at the individual care site level.

Conclusion

Values of physical function DDEs are missing in designated fields of the EHR infrastructure for pediatric rehabilitation providers. Although completeness appears limited for these DDEs, our observations indicate that data are not missing at random and may be influenced by system-level standards in clinical documentation practices between providers and factors specific to individual care sites. The extent of missing data has significant implications for pediatric rehabilitation quality measurement. More research is needed to understand why discrete data are missing in EHRs and to further elucidate the professional and system-level factors that influence completeness and missingness.

Impact

Completeness of DDEs reported in this study is limited and presents a significant opportunity to improve documentation and standards to optimize EHR data for learning health system research and quality measurement in pediatric rehabilitation settings.
Brahmin Left Versus Merchant Right: Changing Political Cleavages in 21 Western Democracies, 1948–2020
Authors: Gethin Amory , Martínez-Toledano Clara , Piketty Thomas
Published: September 2021

This article sheds new light on the long-run evolution of political cleavages in 21 Western democracies. We exploit a new database on the socioeconomic determinants of the vote, covering more than 300 elections held between 1948 and 2020. In the 1950s and 1960s, the vote for social democratic, socialist, and affiliated parties was associated with lower-educated and low-income voters. It has gradually become associated with higher-educated voters, giving rise in the 2010s to a disconnection between the effects of income and education on the vote: higher-educated voters now vote for the “left,” while high-income voters continue to vote for the “right.” This transition has been accelerated by the rise of green and anti-immigration movements, whose distinctive feature is to concentrate the votes of the higher-educated and lower-educated electorates. Combining our database with historical data on political parties’ programs, we provide evidence that the reversal of the education cleavage is strongly linked to the emergence of a new “sociocultural” axis of political conflict.
Public Firm Borrowers of the U.S. Paycheck Protection Program
Authors: Cororaton Anna , Rosen Samuel
Published: September 2021

We document that nearly half of U.S. public firms were eligible for the Paycheck Protection Program (PPP) in 2020, with 41.8% of those eligible choosing to borrow. Consistent with the program’s objectives, borrowers tended to be smaller with less cash, higher leverage, and fewer investment opportunities. In addition, firm values declined upon PPP loan announcement and borrowers grew slower in 2020 relative to nonborrowers. We document that 13.5% of PPP borrowers, in particular those facing more public scrutiny, returned their loans after public backlash. Overall, concerns of reputational harm appeared to dissuade eligible public firms from availing emergency government funding. (JEL E61, E65, G38, H81)