bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boundary Heisenberg algebras and their deformations
Authors: Rojo Martín Enríquez , Safari H. R. 
Published: March 2022

Abstract
We investigate the deformations and rigidity of boundary Heisenberg-like algebras. In particular, we focus on the Heisenberg and Heisenberg ⊕ $$ \mathfrak{witt} $$
witt
algebras which arise as symmetry algebras in three-dimensional gravity theories. As a result of the deformation procedure we find a large class of algebras. While some of these algebras are new, some of them have already been obtained as asymptotic and boundary symmetry algebras, supporting the idea that symmetry algebras associated to diverse boundary conditions and spacetime loci are algebraically interconnected through deformation of algebras. The deformation/contraction relationships between the new algebras are investigated. In addition, it is also shown that the deformation procedure reaches new algebras inaccessible to the Sugawara construction. As a byproduct of our analysis, we obtain that Heisenberg ⊕ $$ \mathfrak{witt} $$
witt
and the asymptotic symmetry algebra Weyl-bms3 are not connected via single deformation but in a more subtle way.
Targeting the E1 ubiquitin-activating enzyme (UBA1) improves elexacaftor/tezacaftor/ivacaftor efficacy towards F508del and rare misfolded CFTR mutants
Authors: Borgo Christian , D’Amore Claudio , Capurro Valeria , Tomati Valeria , Sondo Elvira , Cresta Federico , Castellani Carlo , Pedemonte Nicoletta , Salvi Mauro 
Published: March 2022

AbstractThe advent of Trikafta (Kaftrio in Europe) (a triple-combination therapy based on two correctors—elexacaftor/tezacaftor—and the potentiator ivacaftor) has represented a revolution for the treatment of patients with cystic fibrosis (CF) carrying the most common misfolding mutation, F508del-CFTR. This therapy has proved to be of great efficacy in people homozygous for F508del-CFTR and is also useful in individuals with a single F508del allele. Nevertheless, the efficacy of this therapy needs to be improved, especially in light of the extent of its use in patients with rare class II CFTR mutations. Using CFBE41o- cells expressing F508del-CFTR, we provide mechanistic evidence that targeting the E1 ubiquitin-activating enzyme (UBA1) by TAK-243, a small molecule in clinical trials for other diseases, boosts the rescue of F508del-CFTR induced by CFTR correctors. Moreover, TAK-243 significantly increases the F508del-CFTR short-circuit current induced by elexacaftor/tezacaftor/ivacaftor in differentiated human primary airway epithelial cells, a gold standard for the pre-clinical evaluation of patients’ responsiveness to pharmacological treatments. This new combinatory approach also leads to an improvement in CFTR conductance on cells expressing other rare CF-causing mutations, including N1303K, for which Trikafta is not approved. These findings show that Trikafta therapy can be improved by the addition of a drug targeting the misfolding detection machinery at the beginning of the ubiquitination cascade and may pave the way for an extension of Trikafta to low/non-responding rare misfolded CFTR mutants.
Type I interferon-mediated tumor immunity and its role in immunotherapy
Authors: Yu Renren , Zhu Bo , Chen Degao 
Published: March 2022

AbstractImmune checkpoint blockade (ICB) therapies have achieved remarkable clinical responses in patients with many different types of cancer; however, most patients who receive ICB monotherapy fail to achieve long-term responses, and some tumors become immunotherapy-resistant and even hyperprogressive. Type I interferons (IFNs) have been demonstrated to inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, respectively. Furthermore, accumulating evidence indicates that endo- and exogenously enhancing type I IFNs have a synergistic effect on anti-tumor immunity. Therefore, clinical trials studying new treatment strategies that combine type I IFN inducers with ICB are currently in progress. Here, we review the cellular sources of type I IFNs and their roles in the immune regulation of the tumor microenvironment. In addition, we highlight immunotherapies based on type I IFNs and combination therapy between type I IFN inducers and ICBs.
Die Kohorte der 41.000 Langzeitüberlebenden des Deutschen Kinderkrebsregisters
Authors: Kaatsch Peter , Trübenbach Claudia , Kaiser Melanie , Erdmann Friederike , Spix Claudia , Grabow Desiree 
Published: March 2022

Zusammenfassung
Hintergrund und Ziel
Ein Drittel der Langzeitüberlebenden nach Krebs im Kindes- und Jugendalter leidet unter schweren Spätfolgen (z. B. Zweittumoren, kardiale Probleme). Am Deutschen Kinderkrebsregister (DKKR) sind ca. 70.000 inzidente Erkrankungsfälle dokumentiert, von denen sich über 41.000 in Langzeitbeobachtung befinden und für Spätfolgenstudien kontaktiert werden können. Diese Kohorte wird beschrieben, die bisher mit dem DKKR durchgeführten Spätfolgenstudien werden charakterisiert, die Teilnahmebereitschaft wird analysiert.

Methoden
Für die von 1980 bis 2019 mit Krebs diagnostizierten und am DKKR in der Langzeitbeobachtung befindlichen Patienten wurde die Verteilung nach Diagnose, aktuellem Alter, Beobachtungsdauer, Zahl an Zweittumoren zum Stichtag 16.07.2021 ermittelt. Berechnet wurden die Raten derer, die jeweils auf Verlaufsabfragen reagiert haben. Der Einfluss von Determinanten auf die Teilnahmebereitschaft wurde mithilfe von generalisierten Schätzgleichungen geschätzt.

Ergebnisse
In der Kohorte von 41.466 kontaktierbaren Langzeitüberlebenden sind über 10 % der Betroffenen über 40 Jahre alt, bei über 40 % liegt die Erkrankung über 20 Jahre zurück. Die Teilnahmebereitschaft bei den Befragungen liegt zwischen 30 % und 60 %. Sie ist abhängig vom Alter bei Diagnose, dem Befragungsumfang, der Zahl der zuvor schon durchgeführten Befragungen. Optimal erscheint ein Abstand zwischen Kontaktierungen von mindestens 4 Jahren.

Diskussion
Mit dieser einzigartigen Kohorte ist eine für Deutschland repräsentative Spätfolgenforschung möglich. Ein geeignetes Maß zu finden, wie häufig Überlebende kontaktiert werden dürfen, ist essenziell. Um nicht zu oft zu kontaktieren, sollte die Zahl der in eine Studie einzubeziehenden Betroffenen jeweils möglichst niedrig gehalten werden.
Opposing effects on regulated insulin secretion of acute vs chronic stimulation of AMP-activated protein kinase
Authors: Nguyen-Tu Marie-Sophie , Harris Joseph , Martinez-Sanchez Aida , Chabosseau Pauline , Hu Ming , Georgiadou Eleni , Pollard Alice , Otero Pablo , Lopez-Noriega Livia , Leclerc Isabelle , Sakamoto Kei , Schmoll Dieter , Smith David M. , Carling David , Rutter Guy A. 
Published: March 2022

Abstract
Aims/hypothesis
Although targeted in extrapancreatic tissues by several drugs used to treat type 2 diabetes, the role of AMP-activated protein kinase (AMPK) in the control of insulin secretion is still debatable. Previous studies have used pharmacological activators of limited selectivity and specificity, and none has examined in primary pancreatic beta cells the actions of the latest generation of highly potent and specific activators that act via the allosteric drug and metabolite (ADaM) site.

Methods
AMPK was activated acutely in islets isolated from C57BL6/J mice, and in an EndoC-βH3 cell line, using three structurally distinct ADaM site activators (991, PF-06409577 and RA089), with varying selectivity for β1- vs β2-containing complexes. Mouse lines expressing a gain-of-function mutation in the γ1 AMPK subunit (D316a) were generated to examine the effects of chronic AMPK stimulation in the whole body, or selectively in the beta cell.

Results
Acute (1.5 h) treatment of wild-type mouse islets with 991, PF-06409577 or RA089 robustly stimulated insulin secretion at high glucose concentrations (p<0.01, p<0.05 and p<0.001, respectively), despite a lowering of glucose-induced intracellular free Ca2+ dynamics in response to 991 (AUC, p<0.05) and to RA089 at the highest dose (25 μmol/l) at 5.59 min (p<0.05). Although abolished in the absence of AMPK, the effects of 991 were observed in the absence of the upstream kinase, liver kinase B1, further implicating ‘amplifying’ pathways. In marked contrast, chronic activation of AMPK, either globally or selectively in the beta cell, achieved using a gain-of-function mutant, impaired insulin release in vivo (p<0.05 at 15 min following i.p. injection of 3 mmol/l glucose) and in vitro (p<0.01 following incubation of islets with 17 mmol/l glucose), and lowered glucose tolerance (p<0.001).

Conclusions/interpretation
AMPK activation exerts complex, time-dependent effects on insulin secretion. These observations should inform the design and future clinical use of AMPK modulators.

Graphical abstract
Medical Students from Socioeconomically Disadvantaged Backgrounds are Less Likely to Match into Surgery
Authors: Eguia Emanuel , Kolachina Shilpa , Miller Elizabeth , Eguia Mary A. 
Published: March 2022

AbstractBackgroundThis study aims to understand the demographic and academic characteristics that play a role in enrollment in surgical residency programs as well as any racial or socioeconomic disparities that may exist for medical students entering surgical specialties at the Loyola University Chicago Stritch School of Medicine (LUC‐SSOM).MethodsDemographic data for 993 medical students graduating between 2013 and 2019 from LUC‐SSOM were compared using a series of t tests, Chi‐square tests, and logistic regression models.ResultsStudents entering surgical residency programs had two times greater odds of coming from a family with a median family income greater than $75,000 than those entering non‐surgical residencies (OR 2.19, 95% CI [1.35, 3.53]). Students from disadvantaged backgrounds had 50% decreased odds of going into surgery when compared to those not entering surgery (OR 0.50, 95% CI [0.28, 0.90]).ConclusionsStudents from low socioeconomic status backgrounds face more barriers in pursuing surgical subspecialties.
Notifications and alerts in patient dose values for computed tomography and fluoroscopy-guided interventional procedures
Authors: Vano Eliseo , Loose Reinhard , Frija Guy , Paulo Graciano , Efstathopoulos Efstathios , Granata Claudio , Corridori Riccardo , Torresin Alberto , Andersson Jonas S. , Tsapaki Virginia , Ammon Josefin , Hoeschen Christoph ,   On behalf of the European Society of Radiology
Published: March 2022

Abstract
The terms “notifications” and “alerts” for medical exposures are used by several national and international organisations. Recommendations for CT scanners have been published by the American Association of Physicists in Medicine. Some interventional radiology societies as well as national authorities have also published dose notifications for fluoroscopy-guided interventional procedures. Notifications and alerts may also be useful for optimisation and to avoid unintended and accidental exposures. The main interest in using these values for high-dose procedures (CT and interventional) is to optimise imaging procedures, reducing the probability of stochastic effects and avoiding tissue reactions. Alerts in X-ray systems may be considered before procedures (as in CT), during procedures (in some interventional radiology systems), and after procedures, when the patient radiation dose results are known and processed. This review summarises the different uses of notifications and alerts to help in optimisation for CT and for fluoroscopy-guided interventional procedures as well as in the analysis of unintended and accidental medical exposures. The paper also includes cautions in setting the alert values and discusses the benefits of using patient dose management systems for the alerts, their registry and follow-up, and the differences between notifications, alerts, and trigger levels for individual procedures and the terms used for the collective approach, such as diagnostic reference levels.

Key Points
• Notifications and alerts on patient dose values for computed tomography (CT) and fluoroscopy-guided interventional procedures (FGIP) allow to improve radiation safety and contribute to the avoidance of radiation injuries and unintended and accidental exposures.
• Alerts may be established before the imaging procedures (as in CT) or during and after the procedures as for FGIP.
• Dose management systems should include notifications and alerts and their registry for the hospital quality programmes.
Diagnostics and prognostic evaluation in renal cell tumors: the German S3 guidelines recommendations
Authors: Junker Kerstin , Hallscheidt Peter , Wunderlich Heiko , Hartmann Arndt 
Published: March 2022

AbstractThe German guidelines on renal cell carcinoma (RCC) have been developed at highest level of evidence based on systematic literature review. In this paper, we are presenting the current recommendations on diagnostics including preoperative imaging and imaging for stage evaluation as well as histopathological classification. The role of tumor biopsy is further discussed. In addition, different prognostic scores and the status of biomarkers in RCC are critically evaluated.
Family therapy for persons with schizophrenia: neglected yet important
Authors: Hahlweg Kurt , Baucom Donald H. 
Published: March 2022

AbstractSince the 1950s, the observed disturbances in family relationships in which a member has been diagnosed as having schizophrenia has led many systemic family therapists to the hypothesis that these family interactions may have preceded the onset of illness and contributed to it. However, attempts at using traditional family therapy with families of patients with schizophrenia were not successful or widely adopted. With the introduction of neuroleptic medication, the treatment of schizophrenia changed dramatically, and patients often returned to their family in varying stages of partial remission, increasing the burden on relatives. Furthermore, research based on the expressed emotion concept demonstrated that the chance of relapse increases by a factor of 2.5 when a patient returns to a high-EE-family in contrast to a low-EE-family environment; consequently, the vulnerability–stress model started to guide treatment development. Based on these developments, since 1980, several psychoeducational family management programs have been evaluated showing a significant reduction in relapse when compared to standard psychiatric care from 49 to 13%. To date, at least 50 RCT studies have been published showing the effectiveness of family interventions in various culturally diverse countries. Therefore, according to the NICE and other guidelines, family intervention should be offered to all families of people with psychosis who live with or are in close contact with the patient, in conjunction with neuroleptic treatment. Despite this strong recommendation, family involvement is under-implemented in mental health care, despite its strong scientific, economic, legal and moral basis. To improve the psychosocial health of patients with psychotic disorders and their relatives, more research is necessary, as well as more training for professionals in effective family interventions.
Description of the first Spanish case of Gerstmann–Sträussler–Scheinker disease with A117V variant: clinical, histopathological and biochemical characterization
Authors: Eraña Hasier , San Millán Beatriz , Díaz-Domínguez Carlos M. , Charco Jorge M. , Rodríguez Rosa , Viéitez Irene , Pereda Arrate , Yañez Rosa , Geijo Mariví , Navarro Carmen , Perez de Nanclares Guiomar , Teijeira Susana , Castilla Joaquín 
Published: March 2022

AbstractGerstmann–Sträussler–Scheinker disease (GSS) is a rare neurodegenerative illness that belongs to the group of hereditary or familial Transmissible Spongiform Encephalopathies (TSE). Due to the presence of different pathogenic alterations in the prion protein (PrP) coding gene, it shows an enhanced proneness to misfolding into its pathogenic isoform, leading to prion formation and propagation. This aberrantly folded protein is able to induce its conformation to the native counterparts forming amyloid fibrils and plaques partially resistant to protease degradation and showing neurotoxic properties. PrP with A117V pathogenic variant is the second most common genetic alteration leading to GSS and despite common phenotypic and neuropathological traits can be defined for each specific variant, strikingly heterogeneous manifestations have been reported for inter-familial cases bearing the same pathogenic variant or even within the same family. Given the scarcity of cases and their clinical, neuropathological, and biochemical variability, it is important to characterize thoroughly each reported case to establish potential correlations between clinical, neuropathological and biochemical hallmarks that could help to define disease subtypes. With that purpose in mind, this manuscript aims to provide a detailed report of the first Spanish GSS case associated with A117V variant including clinical, genetic, neuropathological and biochemical data, which could help define in the future potential disease subtypes and thus, explain the high heterogeneity observed in patients suffering from these maladies.
Temporal contrast adaptation in the analysis of visual function in primary open-angle glaucoma
Authors: Wu Qianru , Xie Minyue , Chen Xuhao , Zhang Di , Chen Xiaoyong , Xu Ke , Hong Ying , Zhang Chun 
Published: March 2022

Abstract

Purpose
To explore the utility of the recovery time (RT) after temporal contrast adaptation in primary open-angle glaucoma (POAG) visual function analysis, especially in severe and end-stage glaucoma, by the Erlanger Flicker Test (EFT).

Methods
This study included 80 POAG eyes (45 subjects) and 20 normal eyes (20 subjects). POAG eyes were divided into 5 groups. The diagnostic efficacy of the EFT was assessed, and the RT of POAG eyes at different stages was compared. The EFT results were compared with glaucomatous structure and function test results. A nomogram was developed to predict disease progression by the RT and structural indicators.

Results
In the normal eyes, as the test contrast increased, the RT gradually decreased. The EFT test–retest reproducibility was good, with intraclass correlation coefficient values of 0.6 (P < 0.05) for each test contrast. At 12%, 25%, and 35% contrast, the RT in the severe and end-stage glaucoma eyes was significantly prolonged compared with the control group (P < 0.05). The RT at different contrasts was significantly correlated with visual acuity, mean defect, mean sensitivity, and general and individual quadrant optic nerve fiber layer thickness (P ≤ 0.001). The receiver operating curve indicated that RT12% showed the best overall area under the curve (0.863). We included RT25% and average optic nerve fiber layer thickness in constructing the nomogram. POAG eyes were further divided into 8 stages. According to the probability distribution, this model showed good performance for visual function analysis in advanced glaucoma.

Conclusions
Combined with traditional glaucomatous structural and functional parameters, the EFT can be used in the diagnosis and visual function analysis of POAG, especially for severe and end-stage glaucoma. It could be a potential test for disease staging in severe and end-stage glaucoma.
The effect of exercise on left ventricular global longitudinal strain
Authors: Murray James , Bennett Hunter , Bezak Eva , Perry Rebecca , Boyle Terry 
Published: March 2022

AbstractExercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre–post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59; 95% CI 0.16–1.02; p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.
Sleep disorders predict the 1-year onset, persistence, but not remission of psychotic experiences in preadolescence: a longitudinal analysis of the ABCD cohort data
Authors: Reeve Sarah , Bell Vaughan 
Published: March 2022

AbstractThe relationship between sleep disorder and psychotic experiences in preadolescence has not been extensively studied despite the potential for intervention. The current study addressed this relationship using the Adolescent Brain and Cognitive Development (ABCD) cohort, which provided baseline data from 11,830 10- to 11-year-old; for 4910 of these, 1-year follow-up data were also available. A set of pre-registered multi-level regression models were applied to test whether (a) sleep disorder is associated with psychotic experiences at baseline; (b) baseline sleep disorder predicts psychotic experiences at follow-up; (c) the persistence of sleep disorder predicts persistence of psychotic experiences at follow-up; d) the remission of sleep disorder predicts the remission of psychotic experiences at follow-up. After controlling for potential confounders, sleep disorder was associated with psychotic experiences cross-sectionally (OR = 1.40, 95% CI 1.20–1.63), at 1-year follow-up (OR = 1.32, 95% CI 1.11–1.57), and the persistence of sleep disorder predicted the persistence of psychotic experiences (OR = 1.72, 95% CI 1.44–2.04). However, remission of sleep problems did not predict remission of psychotic experiences (OR = 1.041, 95% CI 0.80–1.35). The results indicate that sleep disorders in preadolescence are common and associated with psychotic experiences, although the lack of co-remission raises questions about the mechanism of association. However, given these findings, and existing evidence in later adolescence and adults, further investigation of sleep as a preventative mental health intervention target in this age group is warranted.