bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study
Authors:   for the CORONADO investigators, Wargny Matthieu , Potier Louis , Gourdy Pierre , Pichelin Matthieu , Amadou Coralie , Benhamou Pierre-Yves , Bonnet Jean-Baptiste , Bordier Lyse , Bourron Olivier , Chaumeil Claude , Chevalier Nicolas , Darmon Patrice , Delenne Blandine , Demarsy Delphine , Dumas Marie , Dupuy Olivier , Flaus-Furmaniuk Anna , Gautier Jean-François , Guedj Anne-Marie , Jeandidier Nathalie , Larger Etienne , Le Berre Jean-Philippe , Lungo Myriam , Montanier Nathanaëlle , Moulin Philippe , Plat Françoise , Rigalleau Vincent , Robert René , Seret-Bégué Dominique , Sérusclat Pierre , Smati Sarra , Thébaut Jean-François , Tramunt Blandine , Vatier Camille , Velayoudom Fritz-Line , Vergès Bruno , Winiszewski Patrice , Zabulon Audrey , Gourraud Pierre-Antoine , Roussel Ronan , Cariou Bertrand , Hadjadj Samy 
Published: February 2021

Abstract
Aims/hypothesis
This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).

Methods
The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days.

Results
We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors.

Conclusions/interpretation
In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period.

Trial registration
Clinicaltrials.gov identifier: NCT04324736

Graphical abstract
Pharmacogenetics of novel glucose-lowering drugs
Authors: Rathmann Wolfgang , Bongaerts Brenda 
Published: February 2021

AbstractThe aim of this work was to review studies in which genetic variants were assessed with respect to metabolic response to treatment with novel glucose-lowering drugs: dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i). In total, 22 studies were retrieved from the literature (MEDLINE). Variants of the GLP-1 receptor gene (GLP1R) were associated with a smaller reduction in HbA1c in response to DPP-4i. Variants of a number of other genes (KCNQ1, KCNJ11, CTRB1/2, PRKD1, CDKAL1, IL6 promoter region, TCF7L2, DPP4, PNPLA3) have also been related to DPP-4i response, although replication studies are lacking. The GLP1R gene was also reported to play a role in the response to GLP-1 RA, with larger weight reductions being reported in carriers of GLP1R variant alleles. There were variants of a few other genes (CNR1, TCF7L2, SORCS1) described to be related to GLP-1 RA. For SGLT2i, studies have focused on genes affecting renal glucose reabsorption (e.g. SLC5A2) but no relationship between SLC5A2 variants and response to empagliflozin has been found. The relevance of the included studies is limited due to small genetic effects, low sample sizes, limited statistical power, inadequate statistics (lack of gene–drug interactions), inadequate accounting for confounders and effects modifiers, and a lack of replication studies. Most studies have been based on candidate genes. Genome-wide association studies, in that respect, may be a more promising approach to providing novel insights. However, the identification of distinct subgroups of type 2 diabetes might also be necessary before pharmacogenetic studies can be successfully used for a stratified prescription of novel glucose-lowering drugs.
Graphical abstract
Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005–2017): the International Diabetes Management Practices Study (IDMPS)
Authors: Mbanya Jean Claude , Aschner Pablo , Gagliardino Juan J. , İlkova Hasan , Lavalle Fernando , Ramachandran Ambady , Chantelot Jean-Marc , Chan Juliana C. N. 
Published: February 2021

Abstract
Aims/hypothesis
Diabetes is the leading cause of kidney disease worldwide. There is limited information on screening, treatment and control of kidney disease in patients with diabetes in low-to-middle-income countries (LMICs).

Methods
The International Diabetes Management Practices Study is an ongoing, non-interventional study of clinical profiles and practices among patients receiving outpatient care mainly by internal medicine physicians and endocrinologists in LMICs. We examined screening, prevalence, treatment and control of kidney disease across seven waves (W) of data collection between 2005 and 2017.

Results
Among 15,079 patients with type 1 and 66,088 patients with type 2 diabetes, screening for kidney disease increased between W2 and W3 followed by a plateau (type 1 diabetes: W2, 73.7%; W3, 84.1%; W7, 83.4%; type 2 diabetes: W2, 65.1%; W3, 82.6%; W7, 86.2%). There were also decreasing proportions of patients with microalbuminuria (type 1 diabetes: W1, 27.1%; W3, 14.7%; W7, 13.8%; type 2 diabetes: W1, 24.5%; W3, 12.6%; W7, 11.9%) and proteinuria (type 1 diabetes: W1, 14.2%; W3, 8.7%; W7, 8.2%; type 2 diabetes: W1, 15.6%; W3, 9.3%; W7, 7.6%). Fewer patients were reported as receiving dialysis for both type 1 diabetes (W2, 1.4%; W7, 0.3%) and type 2 diabetes (W2, 0.9%; W7, 0.2%) over time. While there was no change in mean HbA1c or prevalence of diagnosed hypertension (type 1 diabetes: W1, 22.7%; W7, 19.9%; type 2 diabetes: W1, 60.9%; W7, 66.2%), the use of statins had increased among patients diagnosed with dyslipidaemia (type 1 diabetes: W1, 77.7%; W7, 90.7%; type 2 diabetes: W1, 78.6%; W7, 94.7%). Angiotensin II receptor blockers (type 1 diabetes: W1, 18.0%; W7, 30.6%; type 2 diabetes: W1, 24.2%; W7, 43.6%) were increasingly used over ACE inhibitors after W1 (type 1 diabetes: W1, 65.0%; W7, 55.9%; type 2 diabetes: W1, 55.7%, W7, 41.1%) among patients diagnosed with hypertension.

Conclusions/interpretation
In LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.

Graphical abstract
Low percentage of surgeons meet the minimum recommended unicompartmental knee arthroplasty usage thresholds: Analysis of 3037 Surgeons from Three National Joint Registries
Authors: Klasan Antonio , Parker David A. , Lewis Peter L. , Young Simon W. 
Published: February 2021

Abstract
Purpose
The reported usage of UKA is around 10% in the UK, Australian and New Zealand joint registries. However, some authors recommend that a higher UKA usage of 20%, or a minimum 12 UKA cases per year, would reduce revision rates. The purpose of this study was to analyze the percentage of surgeons performing the recommended thresholds in these 3 registries.

Methods
Data from the UK, Australian and New Zealand registry databases was utilized from the time period since their respective introduction until 2017. All primary TKA and UKA performed for the diagnosis of osteoarthritis by surgeons with more than 100 recorded knee arthroplasties in their respective registry were included. The results between the registries were compared and a pooled analysis was performed. The number of surgeons meeting the recommended caseload of > 20% UKA yearly or 12 UKA cases yearly was calculated.

Results
We identified 3037 knee surgeons performing 1,556,440 knee arthroplasties, of which 131,575 were UKA (8.45%). Over 50% of knee surgeons in each registry had a proportion of less than 5% UKA of their knee replacement procedures. After pooling of data, median surgeon UKA usage was 2.0% (IQR 0–9.1%).
The percentage of surgeons meeting the proposed caseload criteria was highest in New Zealand, 16.3%, followed by the UK at 12.4% and Australia 11.3% (p = 0.28).

Conclusion
More than 50% of knee surgeons in UK, Australian and New Zealand joint registries perform less than 5% of UKA yearly. The majority of experienced knee surgeons are not meeting the recommended minimum thresholds, which might indicate that the recommended thresholds are not feasible for the vast majority of knee surgeons. The reasons behind this require further research.

Level of Evidence
Level III retrospective registry study.
Quadriceps tendon autograft is becoming increasingly popular in revision ACL reconstruction
Authors: Winkler Philipp W. , Vivacqua Thiago , Thomassen Stephan , Lovse Lisa , Lesniak Bryson P. , Getgood Alan M. J. , Musahl Volker 
Published: February 2021

Abstract
Purpose
To evaluate trends in revision anterior cruciate ligament reconstruction (ACL-R), with emphasis on intra-articular findings, grafts, and concurrent procedures. It was hypothesized that revision ACL-Rs over time show a trend toward increased complexity with increased use of autografts over allografts.

Methods
This was a two-center retrospective study including patients undergoing revision ACL-R between 2010 and 2020. Demographic and surgical data including intra-articular findings and concurrent procedures were collected and compared for the time periods 2010–2014 and 2015–2020. All collected variables were compared between three pre-defined age groups (< 20 years, 20–30 years, > 30 years), right and left knees, and males and females. A time series analysis was performed to assess trends in revision ACL-R.

Results
This study included 260 patients with a mean age of 26.2 ± 9.4 years at the time of the most recent revision ACL-R, representing the first, second, third, and fourth revision ACL-R for 214 (82%), 35 (14%), 10 (4%), and 1 (< 1%) patients, respectively. Patients age > 30 years showed a significantly longer mean time from primary ACL-R to most recent revision ACL-R (11.1 years), compared to patients age < 20 years (2.2 years, p < 0.001) and age 20–30 years (5.5 years, p < 0.05). Quadriceps tendon autograft was used significantly more often in 2015–2020 compared to 2010–2014 (49% vs. 18%, p < 0.001). A high rate of concurrently performed procedures including meniscal repairs (45%), lateral extra-articular tenodesis (LET; 31%), osteotomies (13%), and meniscal allograft transplantations (11%) was shown. Concurrent LET was associated with intact cartilage and severely abnormal preoperative knee laxity and showed a statistically significant and linear increase over time (p < 0.05). Intact cartilage (41%, p < 0.05), concurrent medial meniscal repairs (39%, p < 0.05), and LET (35%, non-significant) were most frequently observed in patients aged < 20 years.

Conclusion
Quadriceps tendon autograft and concurrent LET are becoming increasingly popular in revision ACL-R. Intact cartilage and severely abnormal preoperative knee laxity represent indications for LET in revision ACL-R. The high rate of concurrent procedures observed demonstrates the high surgical demands of revision ACL-R.

Level of evidence
Level III.
Support of a laboratory-hosted Athlete Biological Passport Management Unit (APMU) to the anti-doping organisations
Authors: Schobinger C. , Emery C. , Schweizer-Gründisch C. , Kuuranne T. 
Published: February 2021

AbstractThe athlete biological passport (ABP) is an established means for longitudinal monitoring of selected individual biomarkers of an athlete to obtain indirect but potentially long-term indications of the use of substances or methods prohibited in sport. Along the change from population-based reference values to individual profiling, the ABP aims at triggering follow-up investigations concerning the potential use of endogenous substances with doping potential, which might be difficult either to identify with the existing analytical methods or to interpret based only on the results of a single biological sample. The ABP program has been on-going within the World Anti-Doping Agency (WADA) management since 2009, when the hematological module was officially established to discover blood doping practices, such as administration of erythropoietin (EPO) or application of blood transfusion. Since 2014, the ABP has been complemented by the steroid module, with the aim of targeting the prohibited use of testosterone and other endogenous anabolic androgenic steroids with performance enhancing or masking capability. Although the main objective is to guide and assist the anti-doping organizations in their test distribution plans, the ABP may also be used to proceed with a case to an anti-doping rule violation. Evaluation of biological markers, especially in distinguishing between doping from other confounding factors, requires high level and diversity of expertise, which is coordinated by the athlete biological passport management unit (APMU). Since 2019, the WADA accredited anti-doping laboratories are defined as the host organizations for the APMUs. The benefit of such a structure is to obtain a fully anonymous evaluation process for the passports and an additional level of expertise for the interpretation of analytical results as well as to have a fluent communication line with the analyzing laboratories when further details are needed for the analytical testing and documentation.
Forensisch-biomechanische Aspekte von gebrauchten, leeren 0,5-l-Bierflaschen aus Glas als Schlagwaffe gegen den Schädel
Authors: Nentwig C. , Schütz A. , Steinhoff S. , Adamec J. , Kunz S. N. 
Published: February 2021

Zusammenfassung
Hintergrund
Die rechtsmedizinische Begutachtung von Verletzungen im Kopfbereich durch Schläge mit Bierflaschen aus Glas ist oftmals die Folge einer körperlichen Auseinandersetzung in Schankgaststätten. Im Rahmen der juristischen Aufarbeitung eines entsprechenden Sachverhalts stellen sich die Fragen nach der tatsächlich erfolgten Tathandlung und der akuten sowie potenziellen Lebensgefahr einer getroffenen Person.

Material und Methoden
Hinsichtlich ihres Bruchverhaltens und ihres Verletzungspotentials bei Schlägen auf den Schädel wurden 30 gebrauchte, leere Bierflaschen der Augustiner Brauerei München untersucht. Manuell wurden die Glasflaschen auf einen Dummy-Kopf aus Aluminium geschlagen, welcher mit einem Acryl-Kopfhautsurrogat und alternativ mit Schweineschwarte überzogen und auf einer Kistler-Kraftmessplatte fixiert war. Im Fokus der Untersuchungen standen die maximal übertragbare Kraft auf den Schädel sowie die Bruchschwelle und das Bruchverhalten der Glasflaschen.

Ergebnisse
Die auf den Schädel übertragene Kraft steht in Wechselwirkung mit dem Bruchverhalten des Schlagwerkzeugs und den hierdurch entstehenden Verletzungen. Die Intensität stumpfer Verletzungen steigt mit zunehmender Kontaktkraft bis zum Niveau der Frakturtoleranz der Bierflaschen. Kommt es zu einem Bruch der Flasche, so steigt das Risiko für scharfe Verletzungen bei gleichzeitiger Intensitätsreduktion der Verletzungen durch stumpfe Gewalt. Schläge mit einer gebrauchten 0,5-l-Bierflasche gegen den Kopf einer Person sind grundsätzlich in der Lage, Frakturen des Gesichtsschädels hervorzurufen. Das Risiko der Entstehung von Frakturen des Hirnschädels ist demgegenüber, zumindest bei Schlägen mit der Seite der Flasche, als äußerst unwahrscheinlich einzuschätzen. Eine abschließende Beurteilung des Gefährdungspotenzials einer konkreten Behandlung kann in jedem Fall erst nach Kenntnis sämtlicher den Einzelfall betreffender Informationen und Variablen erfolgen.
On the existence of the Green function for elliptic systems in divergence form
Authors: Giunti Arianna , Otto Felix 
Published: February 2021

AbstractWe study the existence of the Green function for an elliptic system in divergence form$$-\nabla \cdot a\nabla $$-∇·a∇in$${\mathbb {R}}^d$$Rd, with$$d>2$$d>2. The tensor field$$a=a(x)$$a=a(x)is only assumed to be bounded and$$\lambda $$λ-coercive. For almost every point$$y \in {\mathbb {R}}^d$$y∈Rd, the existence of a Green’s function$$G(\cdot , y)$$G(·,y)centered inyhas been proven in Conlon et al. (Calc Var PDEs 56(6), (2017))[2]. In this paper we show that the set of points$$y \in {\mathbb {R}}^d$$y∈Rdfor which$$G( \cdot , y)$$G(·,y)does not exist has zerop-capacity, for an exponent$$p >2$$p>2depending only on the dimensiondand the ellipticity ratio ofa.
A Machine Learning Approach for Postoperative Outcome Prediction: Surgical Data Science Application in a Thoracic Surgery Setting
Authors: Salati Michele , Migliorelli Lucia , Moccia Sara , Andolfi Marco , Roncon Alberto , Guiducci Gian Marco , Xiumè Francesco , Tiberi Michela , Frontoni Emanuele , Refai Majed 
Published: February 2021

AbstractBackgroundThe use of innovative methodologies, such as Surgical Data Science (SDS), based on artificial intelligence (AI) could prove to be useful for extracting knowledge from clinical data overcoming limitations inherent in medical registries analysis. The aim of the study is to verify if the application of an AI analysis to our database could develop a model able to predict cardiopulmonary complications in patients submitted to lung resection.MethodsWe retrospectively analyzed data of patients submitted to lobectomy, bilobectomy, segmentectomy and pneumonectomy (January 2006–December 2018). Fifty preoperative characteristics were used for predicting the occurrence of cardiopulmonary complications. The prediction model was developed by training and testing a machine learning (ML) algorithm (XGBOOST) able to deal with registries characterized by missing data. We calculated the receiver operating characteristic curve, true positive rate (TPR), positive predictive value (PPV) and accuracy of the model.ResultsWe analyzed 1360 patients (lobectomy: 80.7%, segmentectomy: 11.9%, bilobectomy 3.7%, pneumonectomy: 3.7%) and 23.3% of them experienced cardiopulmonary complications. XGBOOST algorithm generated a model able to predict complications with an area under the curve of 0.75, a TPR of 0.76, a PPV of 0.68. The model's accuracy was 0.70. The algorithm included all the variables in the model regardless of their completeness.ConclusionsUsing SDS principles in thoracic surgery for the first time, we developed an ML model able to predict cardiopulmonary complications after lung resection based on 50 patient characteristics. The prediction was also possible even in the case of those patients for whom we had incomplete data. This model could improve the process of counseling and the perioperative management of lung resection candidates.
Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer
Authors: Li Chao , Hart Lowell , Owonikoko Taofeek K. , Aljumaily Raid , Rocha Lima Caio Max , Conkling Paul R. , Webb Roy Timothy , Jotte Robert M. , Schuster Steven , Edenfield William J. , Smith Deborah A. , Sale Mark , Roberts Patrick J. , Malik Rajesh K. , Sorrentino Jessica A. 
Published: February 2021

Abstract
Purpose
Trilaciclib is a first-in-class CDK4/6 inhibitor that transiently arrests hematopoietic stem and progenitor cells (HSPCs) in the G1 phase of the cell cycle to preserve them from chemotherapy-induced damage (myelopreservation). We report integrated analyses of preclinical and clinical data that informed selection of the recommended Phase II dose (RP2D) used in trilaciclib trials in extensive-stage small cell lung cancer (ES-SCLC).

Methods
A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model developed from preclinical data guided selection of an optimal dose for G1 bone marrow arrest in a first-in-human Phase I study (G1T28-1-01). PK, PD, safety, and efficacy data from G1T28-1-01 and two Phase Ib/IIa studies (G1T28-02/-03) in ES-SCLC were analyzed to support RP2D selection.

Results
Model simulation of bone marrow arrest based on preclinical data predicted that a ≥ 192 mg/m2 dose would induce a 40–50% decrease in total bone marrow proliferation in humans and almost 100% cell cycle arrest of cycling HSPCs. Consistent with this model, analysis of bone marrow aspirates in healthy volunteers after trilaciclib 192 mg/m2 administration demonstrated almost 100% G1 arrest in HSPCs and 40% decrease in total bone marrow proliferation, with minimal toxicity. G1T28-02/-03 reported similar PK parameters with trilaciclib 200 mg/m2 but slightly lower exposures than expected compared with healthy volunteers; consequently, 240 and 280 mg/m2 doses were also tested to match healthy volunteer exposures. Based on PK and relevant safety data, 240 mg/m2 was selected as the RP2D, which was also favored by myelopreservation endpoints in G1T28-02/-03.

Conclusion
Integrated PK/PD, safety, and efficacy data support 240 mg/m2 as the RP2D for trilaciclib.

ClinicalTrials.gov Identifiers
NCT02243150; NCT02499770; NCT02514447.
Machine intelligence today: applications, methodology, and technology
Authors: Humm Bernhard G. , Bense Hermann , Fuchs Michael , Gernhardt Benjamin , Hemmje Matthias , Hoppe Thomas , Kaupp Lukas , Lothary Sebastian , Schäfer Kai-Uwe , Thull Bernhard , Vogel Tobias , Wenning Rigo 
Published: February 2021

AbstractMachine intelligence, a.k.a. artificial intelligence (AI) is one of the most prominent and relevant technologies today. It is in everyday use in the form of AI applications and has a strong impact on society. This article presents selected results of the 2020 Dagstuhl workshop on applied machine intelligence. Selected AI applications in various domains, namely culture, education, and industrial manufacturing are presented. Current trends, best practices, and recommendations regarding AI methodology and technology are explained. The focus is on ontologies (knowledge-based AI) and machine learning.