bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab
Authors: Gahrmann Renske , Smits Marion , Vernhout René Michel , Taal Walter , Kapsas Giorgios , de Groot Jan Cees , Hanse Monique , Vos Maaike , Beerepoot Laurens Victor , Buter Jan , Flach Zwenneke Hendrieke , van der Holt Bronno , van den Bent Martin 
Published: March 2022

Abstract

Background
The optimal volumetric threshold for determining progressive disease (PD) in recurrent glioblastoma is yet to be determined. We investigated a range of thresholds in association with overall survival (OS).

Methods
First recurrent glioblastoma patients treated with bevacizumab and/or lomustine were included from the phase II BELOB and phase III EORTC26101 trials. Enhancing and nonenhancing tumor volumes were measured at baseline, first (6 weeks), and second (12 weeks) follow-up. Hazard ratios (HRs) for the appearance of new lesions and several thresholds for tumor volume increase were calculated using cox regression analysis. Results were corrected in a multivariate analysis for well-established prognostic factors.

Results
At first and second follow-up, 138 and 94 patients respectively, were deemed eligible for analysis of enhancing volumes, while 89 patients were included in the analysis of nonenhancing volumes at first follow-up. New lesions were associated with a significantly worse OS (3.2 versus 11.2 months, HR = 7.03, P &lt; .001). At first follow-up a threshold of enhancing volume increase of ≥20% provided the highest HR (5.55, p = .001. At second follow-up, any increase in enhancing volume (≥0%) provided the highest HR (9.00, p &lt; .001). When measuring nonenhancing volume at first follow-up, only 6 additional patients were scored as PD with the highest HR of ≥25% increase in volume (HR=3.25, p = .008).

Conclusion
Early appearing new lesions were associated with poor OS. Lowering the volumetric threshold for PD at both first and second follow-up improved survival prediction. However, the additional number of patients categorized as PD by lowering the threshold was very low. The per-RANO added change in nonenhancing volumes to the analyses was of limited value.
Management of brain metastasis. Surgical resection versus stereotactic radiotherapy: a meta-analysis
Authors: Krist David T , Naik Anant , Thompson Charee M , Kwok Susanna S , Janbahan Mika , Olivero William C , Hassaneen Wael 
Published: March 2022

AbstractBackgroundTreatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter.MethodsAccording to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT).ResultsIn both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47–7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76–1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49–3.25, P &lt; .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68–5.13, P = .0002).ConclusionThe higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.
Flowering time runs hot and cold
Authors: Preston Jill C , Fjellheim Siri 
Published: March 2022

Abstract
Evidence suggests that anthropogenically-mediated global warming results in accelerated flowering for many plant populations. However, the fact that some plants are late flowering or unaffected by warming, underscores the complex relationship between phase change, temperature, and phylogeny. In this review, we present an emerging picture of how plants sense temperature changes, and then discuss the independent recruitment of ancient flowering pathway genes for the evolution of ambient, low, and high temperature-regulated reproductive development. As well as revealing areas of research required for a better understanding of how past thermal climates have shaped global patterns of plasticity in plant phase change, we consider the implications for these phenological thermal responses in light of climate change.
Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis
Authors: Gwinnutt James M , Norton Sam , Hyrich Kimme L , Lunt Mark , Combe Bernard , Rincheval Nathalie , Ruyssen-Witrand Adeline , Fautrel Bruno , McWilliams Daniel F , Walsh David A , Nikiphorou Elena , Kiely Patrick D W , Young Adam , Chipping Jacqueline R , MacGregor Alex , Verstappen Suzanne M M 
Published: March 2022

Abstract

Objectives
To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation.

Methods
Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, &lt;24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up.

Results
This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories.

Conclusion
Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.
Assessing Bayesian Phylogenetic Information Content of Morphological Data Using Knowledge From Anatomy Ontologies
Authors: Porto Diego S , Dahdul Wasila M , Lapp Hilmar , Balhoff James P , Vision Todd J , Mabee Paula M , Uyeda Josef 
Published: March 2022

Abstract
Morphology remains a primary source of phylogenetic information for many groups of organisms, and the only one for most fossil taxa. Organismal anatomy is not a collection of randomly assembled and independent “parts”, but instead a set of dependent and hierarchically nested entities resulting from ontogeny and phylogeny. How do we make sense of these dependent and at times redundant characters? One promising approach is using ontologies—structured controlled vocabularies that summarize knowledge about different properties of anatomical entities, including developmental and structural dependencies. Here, we assess whether evolutionary patterns can explain the proximity of ontology-annotated characters within an ontology. To do so, we measure phylogenetic information across characters and evaluate if it matches the hierarchical structure given by ontological knowledge—in much the same way as across-species diversity structure is given by phylogeny. We implement an approach to evaluate the Bayesian phylogenetic information (BPI) content and phylogenetic dissonance among ontology-annotated anatomical data subsets. We applied this to data sets representing two disparate animal groups: bees (Hexapoda: Hymenoptera: Apoidea, 209 chars) and characiform fishes (Actinopterygii: Ostariophysi: Characiformes, 463 chars). For bees, we find that BPI is not substantially explained by anatomy since dissonance is often high among morphologically related anatomical entities. For fishes, we find substantial information for two clusters of anatomical entities instantiating concepts from the jaws and branchial arch bones, but among-subset information decreases and dissonance increases substantially moving to higher-level subsets in the ontology. We further applied our approach to address particular evolutionary hypotheses with an example of morphological evolution in miniature fishes. While we show that phylogenetic information does match ontology structure for some anatomical entities, additional relationships and processes, such as convergence, likely play a substantial role in explaining BPI and dissonance, and merit future investigation. Our work demonstrates how complex morphological data sets can be interrogated with ontologies by allowing one to access how information is spread hierarchically across anatomical concepts, how congruent this information is, and what sorts of processes may play a role in explaining it: phylogeny, development, or convergence. [Apidae; Bayesian phylogenetic information; Ostariophysi; Phenoscape; phylogenetic dissonance; semantic similarity.]
Cardiovascular Diseases Following Breast Cancer
Authors: Mery Benoite , Rowinski Elise , Rivier Charlène , Bouleftour Wafa , Sotton Sandrine , Tinquaut Fabien , Bertoletti Laurent , Tredan Olivier , Magne Nicolas 
Published: March 2022

Objectives:
To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score.

Materials and Methods:
The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities.

Results:
Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P<0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population.

Conclusion:
These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.
Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review
Authors: Bandeira Igor D. , Lins-Silva Daniel H. , Cavenaghi Vitor Breseghello , Dorea-Bandeira Ingrid , Faria-Guimarães Daniela , Barouh Judah L. , Jesus-Nunes Ana Paula , Beanes Graziele , Souza Lucca S. , Leal Gustavo C. , Sanacora Gerard , Miguel Euripedes C. , Sampaio Aline S. , Quarantini Lucas C. 
Published: March 2022

Abstract

Introduction
First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances, ketamine, as a potent N-methyl-D-aspartate receptor antagonist and glutamate modulator, offers alternative possibilities for OCD treatment.

Methods
This systematic review aims to investigate the effects of ketamine in OCD, following the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols (PRISMA-P). Searches were carried out using the PubMed/MEDLINE, Embase, and PsycINFO databases.

Results
Nine articles were included, of which three were randomized controlled trials, three case reports, two open-label trials, and one a retrospective chart review. Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single-session racemic ketamine treatments, administered intravenously, and the results have been erratic. In addition, none of the available evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy in controlling OCD symptoms, and only sparse evidence suggests that a combination of ketamine and psychotherapy could benefit patients with OCD.

Conclusion
In order to advance clinical practice regarding the use of ketamine in treating OCD, future randomized, double-blind, placebo-controlled trials are required. These trials need to use larger samples to explore ketamine and its enantiomers, with different methods of administration, multiple sessions, and appropriate washout periods.
Suicide Among American Indian and Alaska Native Veterans Who Use Veterans Health Administration Care
Authors: Mohatt Nathaniel V. , Hoffmire Claire A. , Schneider Alexandra L. , Goss Cynthia W. , Shore Jay H. , Spark Talia L. , Kaufman Carol E. 
Published: March 2022

Background:
American Indian and Alaska Natives (AI/ANs) veterans may be at elevated risk for suicide, but little is known about suicide among this population.

Methods:
We conducted a retrospective cohort analysis of AI/AN veterans who received health care services provided or paid for by the Veterans Health Administration (VHA) between October 1, 2002, and September 30, 2014, and who were alive as of September 30, 2003. Age-specific and age-adjusted suicide rates through 2018, per 100,000 person-years (PY) at risk and 95% confidence intervals were computed.

Results:
Age-adjusted suicide rates among AI/AN veterans in this cohort more than doubled (19.1–47.0/100,000 PY) over the 15-year observation period. In the most recent observation period (2014–2018), the age-adjusted suicide rate was 47.0 per 100,000 PY, with the youngest age group (18–39) exhibiting the highest suicide rate (66.0/100,000 PY). The most frequently used lethal means was firearms (58.8%), followed by suffocation (19.3%), poisoning (17.2%), and other (4.7%).

Conclusions:
Results suggest that: (1) suicide is an increasing problem among AI/AN VHA veterans; and (2) younger AI/AN VHA veterans are at particularly high risk and warrant focused prevention efforts. Findings are similar to those observed in general AI/AN population. There is a compelling need to review and strengthen VHA suicide prevention efforts directed towards AI/AN veterans.
Lipofilling in Osteoarthritis of the Finger Joints: Initial Prospective Long-Term Results
Authors: Meyer-Marcotty Max , Batsilas Ioannis , Sanders Agnes , Dahmann Sonja , Happe Caroline , Herold Christian 
Published: March 2022

Background:
There is considerable interest in the possibility of offering an alternative and less invasive method of treatment for osteoarthritis that will preserve the joint. This article presents for the first time the long-term results of a prospective study following autologous fat transfer to arthritic finger joints.

Methods:
The authors report on 28 finger joints with osteoarthritis that they treated by injecting fatty tissue into the joints. The degree of pain, force of pinch grip, and fist closure were assessed and hand function was determined using the German version of the Disabilities of the Arm, Shoulder and Hand questionnaire.

Results:
The average follow-up period during the study was 44 months. The median force of pinch grip rose highly significantly from 2.00 kg (range, 0.00 to 11.00 kg) to 4.30 kg (range, 2.00 to 12.00 kg) (p < 0.001). The median force of fist closure rose from 15.00 kg (range, 2.00 to 44.00 kg) to 18.00 kg (range, 3.78 to 42.00 kg) (p = 0.082). The median Disabilities of the Arm, Shoulder and Hand value improved nonsignificantly from 50 (range, 3 to 72) to 25 (range, 0 to 85) (p = 0.129). The median level of pain experienced showed a highly significant improvement from 6.0 (range, 1.0 to 10.0) to 0.5 (range, 0.0 to 6.5) (p < 0.001).

Conclusions:
Even over a long-term study period, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe and promising alternative treatment to conventional surgical procedures that offers significant improvements in terms of osteoarthritis symptoms. Because this method preserves the joint, conventional resection surgery still remains a later option.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Brain vasculature disturbance in schizophrenia
Authors: Puvogel Sofía , Palma Verónica , Sommer Iris E.C. 
Published: March 2022

Purpose of review
The vascular hypothesis of schizophrenia (SZ) postulates that brain endothelial dysfunction contributes to brain pathophysiology. This review discusses recent evidence for and against this hypothesis, including data related to blood–brain barrier (BBB), brain endothelium, and brain blood supply, to provide a critical weighed update.

Recent findings
Different studies report a consistent proportion of SZ patients showing increased BBB permeability, reflected by higher levels of albumin in the cerebral spinal fluid. Of note, this was not a result of antipsychotic medication. The high inflammatory profile observed in some SZ patients is strongly associated with increased BBB permeability to circulating immune cells, and with more severe cognitive deficiencies. Also, sex was found to interact with BBB integrity and permeability in SZ. The strongest independent genetic association with SZ has been identified in FZD1, a hypoxia-response gene that is 600-fold higher expressed in early development endothelium as compared to adult brain endothelium. Regarding brain blood supply, there is evidence to suggest alterations in proper brain perfusion in SZ. Nonetheless, ex-vivo experiments suggested that widely used antipsychotics favor vasoconstriction; thus, alterations in cerebral perfusion might be related to the patients′ medication.

Summary
In some patients with SZ, a vulnerable brain endothelium may be interacting with environmental stressors, such as inflammation or hypoxia, converging into a more severe SZ symptomatology. Gene expression and performance of human brain endothelium could vary along with development and the establishment of the BBB; therefore, we encourage to investigate its possible contribution to SZ considering this dynamic context.
The association between major trauma centre care and outcomes of adult patients injured by low falls in England and Wales
Authors: Tonkins Michael , Bouamra Omar , Lecky Fiona 
Published: March 2022

ABSTRACTBackgroundDisability and death due to low falls is increasing worldwide and disproportionately affects older adults. Current trauma systems were not designed to suit the needs of these patients. This study assessed the effectiveness of major trauma centre care in adult patients injured by low falls.MethodsData were obtained from the Trauma Audit and Research Network on adult patients injured by falls from <2 metres between 2017-2019 in England and Wales. 30-day survival, length of hospital stay and discharge destination were compared between major trauma centres (MTCs) and trauma units or local emergency hospitals (TU/LEHs).Results127,334 patients were included of whom 27.6% attended an MTC. The median age was 79.4 years (IQR 64.5-87.2 years), and 74.2% of patients were aged >65 years. MTC care was not associated with improved 30-day survival (adjusted odds ratio [AOR] 0.91, 95% CI 0.87-0.96). Transferred patients had a significant impact upon the results. After excluding transferred patients, the AOR for survival in MTCs was 1.056 (95% CI 1.001-1.113).ConclusionTU/LEH care is at least as effective as MTC care due to the facility for secondary transfer from TU/LEHs to MTCs. In patients who are not transferred, MTCs are associated with greater odds of 30-day survival in the whole cohort and in the most severely injured patients. Future research must determine the optimum means of identifying patients in need of higher-level care; the components of care which improve patient outcomes; and develop patient-focused outcomes which reflect the characteristics and priorities of contemporary trauma patients.KEY MESSAGESWhat is already known on this topicCurrent trauma systems were not designed to manage rising numbers of elderly patients injured by low falls.Previous evidence for the role of major trauma centre (MTC) care in such patients yielded conflicting results.What this study addsThis study demonstrates that non-trauma centre care is no worse than MTC care, as long as the possibility of transfer exists.Therefore MTCs do have a role in the management of elderly adults injured by low falls, particularly the severely injured.How this study might affect research, policy or practiceResearch must identify those patients who need transfer, the most effective components of care, and patient-centric outcomes.
QUALITY CONTROL OF STAPHYLOCOCCUS AUREUS IN RIO GRANDE AND MENONITA CRIOLLO CHEESES FROM THE ALEJO CALATAYUD MARKET
Authors: Litze Abigayl Choque Rojas , Rosy Fuentes Condori , Janethe Vania López Vargas , Carlos Pardo Aranibar , Magali Dian Rojas Nogales 
Published: March 2022

SUMMARYIntroductionThe Staphylococcus aureus count is one of the indicators of the microbiological quality of cheeses according to the parameters of the Bolivian Standard 32004, since this bacterium can cause food poisoning.ObjectiveTo determine the presence and quantity of Staphylococcus aureus in Rio Grande and Menonita Creole cheeses in the Alejo Calatayud Market in the city of Cochabamba during the month of July 2019 according to parameters established by Bolivian Standard 32004.MethodsEight samples taken from different cheeses randomly selected from the market were analyzed and subjected to quantitative analysis of CFU/g of Staphylococcus aureus in three different dilutions for each sample, giving a total of 24, 13 were discarded due to impossibility of counting and the remaining samples were subjected to confirmatory tests. The parameters established in the NB32004 were used for the qualification of the results of analysis and tests.ResultsIn 100% of the samples (8 of 8), the presence of S. aureus bacteria was found in quantities higher than the acceptable CFU/g, determining as deficient the hygienic-sanitary quality of the ripened Creole cheeses sold in the Alejo Calatayud Market.ConclusionCreole cheeses marketed in the Alejo Calatayud Market have a high degree of contamination by S. aureus and therefore do not comply with the parameters of NB32004 and the population is exposed to food poisoning.