bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of leptospiral DNA in the follicular fluid of non‐pregnant cows
Authors: Di Azevedo Maria Isabel Nogueira , Pires Bruno Cabral , Barbosa Lucas Figueiredo Cardoso , Carvalho‐Costa Filipe Anibal , Lilenbaum Walter
Published: February 2021

Background

Bovine leptospirosis is mainly characterized by reproductive disorders. Contamination of the oocyte was previously demonstrated in vitro, resulting in some apparent damage. However, it is not clear whether it occurs under natural conditions. The present study aimed to characterize the presence of pathogenic Leptospira DNA in the ovarian follicles of non‐pregnant cows.

Methods

Follicular fluid samples were collected from 65 animals and subjected to lipL32 PCR and secY sequencing.

Results

In total, seven of 65 (10.8%) were positive, indicating a possible early infection of the oocyte. Moreover, secY sequencing identified L. interrogans and L. santarosai, both very closely related to bovine strains from the Sejroe serogroup (Hardjoprjitno and Guaricura). We demonstrated that ovarian follicles can also be infected.

Conclusions

It was hypothesised that ovarian infection can contribute to embryonic death, causing reproductive failure and estrus repetition. In the present study, we show that the organism identified in the follicle is closely related to one that is known to be associated with reproductive disorders.
A Comparative Analysis of Emulated and Real IEC-104 Spontaneous Traffic in Power System Networks
Authors: Lin C.-Y. , Nadjm-Tehrani Simin
Published: February 2021

Supervisory and Data Acquisition (SCADA) systems control and monitor modern power networks. As attacks targeting SCADA systems are increasing, significant research is conducted to defend SCADA networks including variations of anomaly detection. Due to the sensitivity of real data, many defence mechanisms have been tested only in small testbeds or emulated traffic that were designed with assumptions on how SCADA systems behave. This work provides a timing characterization of IEC-104 spontaneous traffic and compares the results from emulated traffic and real traffic to verify if the network characteristics appearing in testbeds and emulated traffic coincide with real traffic. Among three verified characteristics, two of them appear in the real dataset but in a less regular way, and one does not appear in the collected real data. The insights from these observations are discussed in terms of presumed differences between emulated and real traffic and how those differences are generated.
Correction to: Convolutional Gravitational Models for Economic Exchanges: Mathematical Extensions for Dynamic Processes and Knowledge Flows
Authors: Teodorescu Mike Horia
Published: February 2021

In the original version of the book, the following belated correction has been incorporated: Chapter 22 has been changed to Open Access.

The book and the chapter have been updated with the change.
The $$ \mathcal{N} $$ = 4 higher spin algebra for generic μ parameter
Authors: Ahn Changhyun , Kim Man Hea
Published: February 2021

Abstract

The $$ \mathcal{N} $$
N
= 4 higher spin generators for general superspin s in terms of oscillators in the matrix generalization of AdS3 Vasiliev higher spin theory at nonzero μ (which is equivalent to the ’t Hooft-like coupling constant λ) were found previously. In this paper, by computing the (anti)commutators between these $$ \mathcal{N} $$
N
= 4 higher spin generators for low spins s1 and s2 (s1 + s2 ≤ 11) explicitly, we determine the complete $$ \mathcal{N} $$
N
= 4 higher spin algebra for generic μ. The three kinds of structure constants contain the linear combination of two different generalized hypergeometric functions. These structure constants remain the same under the transformation μ ↔ (1 − μ) up to signs. We have checked that the above $$ \mathcal{N} $$
N
= 4 higher spin algebra contains the $$ \mathcal{N} $$
N
= 2 higher spin algebra, as a subalgebra, found by Fradkin and Linetsky some time ago.
Holographic renormalization group flow effect on quantum correlations
Authors: Park Chanyong , Lee Jung Hun
Published: February 2021

Abstract

We holographically study the finite-size scaling effects on macroscopic and microscopic quantum correlations deformed by excitation and condensation. The excitation (condensation) increases (decreases) the entanglement entropy of the system. We also investigate the two-point correlation function of local operators by calculating the geodesic length connecting two local operators. As opposed to the entanglement entropy case, the excitation (condensation) decreases (increases) the two-point function. This is because the screening effect becomes strong in the background with the large entanglement entropy. We further show that the holographic renormalization leads to the qualitatively same two-point function as the one obtained from the geodesic length.
$$ \mathcal{N} $$ = 2 AdS4 supergravity, holography and Ward identities
Authors: Andrianopoli L. , Cerchiai B. L. , Matrecano R. , Miskovic O. , Noris R. , Olea R. , Ravera L. , Trigiante M.
Published: February 2021

Abstract

We develop in detail the holographic framework for an $$ \mathcal{N} $$
N
= 2 pure AdS supergravity model in four dimensions, including all the contributions from the fermionic fields and adopting the Fefferman-Graham parametrization. We work in the first order formalism, where the full superconformal structure can be kept manifest in principle, even if only a part of it is realized as a symmetry on the boundary, while the remainder has a non-linear realization. Our study generalizes the results presented in antecedent literature and includes a general discussion of the gauge-fixing conditions on the bulk fields which yield the asymptotic symmetries at the boundary. We construct the corresponding super- conformal currents and show that they satisfy the related Ward identities when the bulk equations of motion are imposed. Consistency of the holographic setup requires the super- AdS curvatures to vanish at the boundary. This determines, in particular, the expression of the super-Schouten tensor of the boundary theory, which generalizes the purely bosonic Schouten tensor of standard gravity by including gravitini bilinears. The same applies to the superpartner of the super-Schouten tensor, the conformino. Furthermore, the vanishing of the supertorsion poses general constraints on the sources of the three-dimensional boundary conformal field theory and requires that the super-Schouten tensor is endowed with an antisymmetric part proportional to a gravitino-squared term.
On the W&Y interpretation of high-energy Drell-Yan measurements
Authors: Torre Riccardo , Ricci Lorenzo , Wulzer Andrea
Published: February 2021

Abstract

High-energy neutral and charged Drell-Yan differential cross-section measurements are powerful probes of quark-lepton contact interactions that produce growing-with-energy effects. This paper provides theoretical predictions of the new physics effects at the Next-to-Leading order in QCD and including one-loop EW corrections at the single-logarithm accuracy. The predictions are obtained from SM Monte Carlo simulations through analytic reweighting. This eliminates the need of performing a scan on the new physics parameter space, enabling the global exploration of all the relevant interactions. Furthermore, our strategy produces consistently showered events to be employed for a direct comparison of the new physics predictions with the data, or to validate the unfolding procedure than underlies the cross-section measurements. Two particularly relevant interactions, associated with the W and Y parameters of EW precision tests, are selected for illustration. Projections are presented for the sensitivity of the LHC and of the HL-LHC measurements. The impact on the sensitivity of several sources of uncertainties is quantified.
Topological shadows and complexity of islands in multiboundary wormholes
Authors: Bhattacharya Aranya , Chanda Anindya , Maulik Sabyasachi , Northe Christian , Roy Shibaji
Published: February 2021

Abstract

Recently, remarkable progress in recovering the Page curve of an evaporating black hole (BH) in Jackiw-Teitelboim gravity has been achieved through use of Quantum Extremal surfaces (QES). Multi-boundary Wormhole (MbW) models have been crucial in parallel model building in three dimensions. Motivated by this we here use the latter models to compute the subregion complexity of the Hawking quanta of the evaporating BH in AdS3and obtain the Page curve associated with this information theoretic measure. We use three- andn-boundary wormhole constructions to elucidate our computations of volumes below the Hubeny-Rangamani-Takayanagi (HRT) surfaces at different times. Time is represented by the growing length of the throat horizons corresponding to smaller exits of the multi-boundary wormhole and the evaporating bigger exit shrinks with evolving time. We track the change in choice of HRT surfaces with time and plot the volume with time. The smooth transition of Page curve is realized by a discontinuous jump at Page time in volume subregion complexity plots and the usual Page transition is realized as a phase transition due to the inclusion of the island in this context. We discuss mathematical intricacies and physical insights regarding the inclusion of the extra volume at Page time. The analysis is backed by calculations and lessons from kinematic space and tensor networks.
Akzidentelle Atemkalkingestion im Rahmen eines Tauchganges
Authors: Michael Mark , Freise Noemi , Keitel Verena , Schaper Andreas , Plettenberg Christian , Dreyer Sven , Bernhard Michael
Published: February 2021

Atemkalk wird in Kreislauftauchgeräten beim technischen Tauchen („Rebreathern“) verwendet. Vergleichbar mit einem Narkosekreislaufgerät dient bei einem halb- bzw. geschlossenen Atemsystem der Kalk der Kohlendioxidabsorbtion. Der Atemkalk enthält meist Kalziumhydroxid, das unter Wassereinwirkung zu Natronlauge reagieren kann. Bei der Ingestion bzw. Aspiration von Bestandteilen des Atemkalks kann es zu Verätzungen mit der Bildung von Kolliquationsnekrosen kommen. Eine frühzeitige Endo- bzw. ggf. Bronchoskopie ist hier zur Abschätzung von Folgeschäden essenziell.
Evolving AAV-delivered therapeutics towards ultimate cures
Authors: He Xiangjun , Urip Brian Anugerah , Zhang Zhenjie , Ngan Chun Christopher , Feng Bo
Published: February 2021

Gene therapy has entered a new era after decades-long efforts, where the recombinant adeno-associated virus (AAV) has stood out as the most potent vector for in vivo gene transfer and demonstrated excellent efficacy and safety profiles in numerous preclinical and clinical studies. Since the first AAV-derived therapeutics Glybera was approved by the European Medicines Agency (EMA) in 2012, there is an increasing number of AAV-based gene augmentation therapies that have been developed and tested for treating incurable genetic diseases. In the subsequent years, the United States Food and Drug Administration (FDA) approved two additional AAV gene therapy products, Luxturna and Zolgensma, to be launched into the market. Recent breakthroughs in genome editing tools and the combined use with AAV vectors have introduced new therapeutic modalities using somatic gene editing strategies. The promising outcomes from preclinical studies have prompted the continuous evolution of AAV-delivered therapeutics and broadened the scope of treatment options for untreatable diseases. Here, we describe the clinical updates of AAV gene therapies and the latest development using AAV to deliver the CRISPR components as gene editing therapeutics. We also discuss the major challenges and safety concerns associated with AAV delivery and CRISPR therapeutics, and highlight the recent achievement and toxicity issues reported from clinical applications.
Clarithromycin impairs tissue-resident memory and Th17 responses to macrolide-resistant Streptococcus pneumoniae infections
Authors: Lindenberg Marc , Almeida Luis , Dhillon-LaBrooy Ayesha , Siegel Ekkehard , Henriques-Normark Birgitta , Sparwasser Tim
Published: February 2021

The increasing prevalence of antimicrobial resistance in pathogens is a growing public health concern, with the potential to compromise the success of infectious disease treatments in the future. Particularly, the number of infections by macrolide antibiotics-resistant Streptococcus pneumoniae is increasing. We show here that Clarithromycin impairs both the frequencies and number of interleukin (IL)-17 producing T helper (Th) 17 cells within the lungs of mice infected with a macrolide-resistant S. pneumoniae serotype 15A strain. Subsequently, the tissue-resident memory CD4+ T cell (Trm) response to a consecutive S. pneumoniae infection was impaired. The number of lung resident IL-17+ CD69+ Trm was diminished upon Clarithromycin treatment during reinfection. Mechanistically, Clarithromycin attenuated phosphorylation of the p90-S6-kinase as part of the ERK pathway in Th17 cells. Moreover, a strong increase in the mitochondrial-mediated maximal respiratory capacity was observed, while mitochondrial protein translation and mTOR sisgnaling were unimpaired. Therefore, treatment with macrolide antibiotics may favor the spread of antimicrobial-resistant pathogens not only by applying a selection pressure but also by decreasing the natural T cell immune response. Clinical administration of macrolide antibiotics as standard therapy procedure during initial hospitalization should be reconsidered accordingly and possibly be withheld until microbial resistance is determined.

Key messages

• Macrolide-resistant S. pneumoniae infection undergoes immunomodulation by Clarithromycin

• Clarithromycin treatment hinders Th17 and tissue-resident memory responses

• Macrolide antibiotics impair Th17 differentiation in vitro by ERK-pathway inhibition
ICD-11: Änderungen der diagnostischen Kriterien der Substanzabhängigkeit
Authors: Heinz Andreas , Gül Halil Melissa , Gutwinski Stefan , Beck Anne , Liu Shuyan
Published: February 2021

Hintergrund

In der ICD(International Classification of Diseases)-11 ändern sich die Kriterien für die Diagnose der Substanzabhängigkeit.

Ziel der Arbeit (Fragestellung)

Erörterung der Vor- und Nachteile der neu verfassten Diagnosekriterien.

Material und Methoden

Diskussion unter Berücksichtigung neurobiologischer, sozialer und klinischer Forschungsergebnisse.

Ergebnisse

Im ICD-11 werden wie bisher Abhängigkeitserkrankungen und schädlicher Gebrauch unterschieden. Zur Diagnose der Abhängigkeit werden die ehemals 6 Diagnosekriterien in 3 Paaren gebündelt, von denen künftig 2 erfüllt sein müssen. Innerhalb der Paare genügt ein erfülltes Kriterium, damit das Paar als bejaht gilt. Unter Bezugnahme wissenschaftlicher Erkenntnisse im Suchtbereich zeigen sich Vor- und Nachteile. Hierbei könnte sich die Spezifität der Diagnosestellung gegenüber dem ICD-10 verschlechtern, da pro Paar nur ein Kriterium erfüllt sein muss und somit die Möglichkeit besteht, dass nicht problematisches Konsumverhalten inkorrekt pathologisiert und falsch diagnostiziert wird. Das erscheint als problematisch, da die Definition des ICD-10 „Anhaltender Konsum trotz eindeutiger schädlicher Folgen“, im ICD-11 weiter gefasst wird als „Oft fortgeführter Konsum trotz Auftreten von Problemen“. Dies könnte dazu führen, dass das Kriterium einfach deshalb erfüllt wird, weil der Konsum einer Substanz in einem bestimmten Land illegal ist. In der bisher größten multinationalen Studie in 10 Ländern zur Konkordanz der Diagnosesysteme wurde unter Verwendung der ICD-11 die Alkoholabhängigkeit ca. 10 % häufiger gestellt als mittels ICD-10.

Schlussfolgerung

In der ICD-11 werden die Diagnosen der Substanzabhängig und des Missbrauchs als klinisch sinnvolle Syndrome aufrechterhalten. Ob die diagnostischen Neuerungen in der Praxis hilfreich sind oder beispielsweise negative soziale Auswirkungen für die Betroffenen im Sinne unangemessener Pathologisierung mit sich bringen, ist systematisch zu prüfen.
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

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

The 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

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

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

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

The 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

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

We 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

Background

The 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.

Methods

We 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.

Results

We 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.

Conclusions

Using 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.
Correction to: Factors Associated with Unexpected Readmission Following Lung Resection
Authors: Uchida Shinsuke , Yoshida Yukihiro , Yotsukura Masaya , Nakagawa Kazuo , Watanabe Shun‐ichi
Published: February 2021

In the original version of the online article some of the entries appeared in the wrong column. Following is the corrected table. The original article has also been corrected.
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

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

Machine 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.
Reporting quality of surgical randomised controlled trials in head and neck cancer: a systematic review
Authors: Canagarajah Netanya Aarabi , Porter George James , Mitra Kurchi , Chu Timothy Shun Man
Published: February 2021

Purpose

Randomised controlled trials (RCTs) are considered the gold standard for evaluating the efficacy of an intervention. However, previous research has shown that RCTs in several surgical specialities are poorly reported, making it difficult to ascertain if various biases have been appropriately minimised. This systematic review assesses the reporting quality of surgical head and neck cancer RCTs.

Methods

A literature search of PubMed and Embase was performed. Papers were included if they reported RCTs which assessed a surgical technique used to treat or diagnose head and neck cancer published during or after 2011. The CONSORT 2010 checklist was used to evaluate the reporting quality of these trials.

Results

41 papers were included. The mean CONSORT score was 16.5/25 (66% adherence) and the scores ranged from 7.5 (30%) to 25. The most common omissions were full trial protocol (found in 14.6%), participant recruitment method (22%) and effect size with a precision estimate for all outcome measures (29.3%). The full design and implementation of the randomisation methods were reported in 6 (14.6%). Papers published in journals which endorsed CONSORT had significantly higher scores (p = 0.02) and the journal impact factor was significantly correlated with CONSORT score (p = 0.01).

Conclusion

We have identified several pieces of information that are underreported in surgical head and neck cancer RCTs. These omissions make understanding and comparing the methodologies and conclusions of RCTs more difficult. The endorsement of CONSORT by journals improved adherence, suggesting that wider adoption of the checklist may improve reporting.
Organ doses of the fetus from external environmental exposures
Authors: Petoussi-Henss Nina , Satoh Daiki , Schlattl Helmut , Zankl Maria , Spielmann Vladimir
Published: February 2021

This article presents nuclide-specific organ dose rate coefficients for environmental external exposures due to soil contamination assumed as a planar source at a depth of 0.5 g cm−2in the soil and submersion to contaminated air, for a pregnant female and its fetus at the 24th week of gestation. Furthermore, air kerma free-in-air coefficient rates are listed. The coefficients relate the organ equivalent dose rates (Sv s−1) to the activity concentration of environmental sources, in Bq m−2or Bq m−3, allowing to time-integrate over a particular exposure period. The environmental radiation fields were simulated with the Monte Carlo radiation transport codes PHITS and YURI. Monoenergetic organ dose rate coefficients were calculated employing the Monte Carlo code EGSnrc simulating the photon transport in the voxel phantom of a pregnant female and fetus. Photons of initial energies of 0.015–10 MeV were considered including bremsstrahlung. By folding the monoenergetic dose coefficients with the nuclide decay data, nuclide-specific organ doses were obtained. The results of this work can be employed for estimating the doses from external exposures to pregnant women and their fetus, until more precise data are available which include coefficients obtained for phantoms at different stages of pregnancy.
Ten years of molecular ballistics—a review and a field guide
Authors: Euteneuer Jan , Courts Cornelius
Published: February 2021

Molecular ballistics combines molecular biological, forensic ballistic, and wound ballistic insights and approaches in the description, collection, objective investigation, and contextualization of the complex patterns of biological evidence that are generated by gunshots at biological targets. Setting out in 2010 with two seminal publications proving the principle that DNA from backspatter collected from inside surfaces of firearms can be retreived and successfully be analyzed, molecular ballistics covered a lot of ground until today. In this review, 10 years later, we begin with a comprehensive description and brief history of the field and lay out its intersections with other forensic disciplines like wound ballistics, forensic molecular biology, blood pattern analysis, and crime scene investigation. In an application guide section, we aim to raise consciousness to backspatter traces and the inside surfaces of firearms as sources of forensic evidence. Covering crime scene practical as well as forensic genetic aspects, we introduce operational requirements and lay out possible procedures, including forensic RNA analysis, when searching for, collecting, analyzing, and contextualizing such trace material. We discuss the intricacies and rationales of ballistic model building, employing different tissue, skin, and bone simulants and the advantages of the “triple-contrast” method in molecular ballistics and give advice on how to stage experimental shootings in molecular ballistic research. Finally, we take a look at future applications and prospects of molecular ballistics.
Porcine Aorto-Renal Artery (PARA) model for laparoscopic transcystic common bile duct exploration: the evolution of a training model to meet new clinical needs
Authors: Brewer James O. , Navaratne Lalin , Marchington Stephen W. , Martínez Cecilia David , Quiñones Sampedro Jose , Muñoz Bellvis Luis , Isla Alberto Martínez
Published: February 2021

Background

The transcystic approach to laparoscopic common bile duct exploration has gained popularity for the single-stage management of choledocholithiasis with concomitant gallstones. Our team previously described the use of a porcine aorta segment to simulate the common bile duct during laparoscopic skill training.

Methods

With the advent of the transcystic approach as a contender for the first-line technique of accessing the common bile duct, we present an evolution of the laparoscopic training model using a Porcine Aorta-Renal Artery (PARA) specimen to simulate the structural integrity, dimensions and spatial distribution of both the human cystic and common bile ducts.

Results

This training model allows the use of a choledochoscope for transcystic exploration of the biliary tree. It combines fidelity and reproducibility required for a simulated training model to offer experience in laparoscopic transcystic common bile duct exploration. Validation of the model was demonstrated by 21 surgeons who completed a questionnaire after performing the simulated procedure. In all sections assessing reliability, face validity and content validity of the model, mean rating scores were between 4 and 5 out of five (good or excellent).

Conclusions

We present the evolution of an established training model for laparoscopic common bile duct exploration which focusses the attention on the transcystic approach to the common bile duct and the use of lithotripsy techniques. The need for such a model reflects the shift in the current practice of the laparoendoscopic management of choledocholithiasis with concomitant gallstones from transductal to transcystic approach.
How to improve eyewitness testimony research: theoretical and methodological concerns about experiments on the impact of emotions on memory performance
Authors: Głomb Kaja
Published: February 2021

The purpose of this paper is to present crucial shortcomings of research into eyewitness testimony. It presents the state-of-the-art of research on the relationship between emotions and memory performance. In addition, it addresses contradictions and concerns about previous studies. Despite the declarations of consensus on the role of emotions in memory coding and retrieving, there are as many studies suggesting that emotional events are better remembered than neutral ones, as there are reports that show the opposite. Therefore, by indicating the theoretical and methodological limitations of previous studies, this paper advocates a more rigorous approach to the investigation of emotions and their impact on the quality and quantity of testimony. It also provides a framework for inquiry that allows better comparisons between studies and results, and may help to build a more comprehensive theory of the effects of emotion on memory