bluuebunny/crossref_metadata_2025 huggingface dataset:
The F-theorem in the melonic limit
Authors: Benedetti Dario , Gurau Razvan , Harribey Sabine , Lettera Davide
Published: February 2022

Abstract

The F-theorem states that in three dimensions the sphere free energy of a field theory must decrease between ultraviolet and infrared fixed points of the renormalization group flow, and it has been proven for unitary conformal field theories (CFTs).

We consider here the long-range bosonic O(N)3 model on a spherical background, at next-to-next-to-leading order of the 1/N expansion. The model displays four large-N fixed points and we test and confirm the F-theorem holds in this case. This is non-trivial as one of the couplings is imaginary, and therefore the model is non-unitary at finite N. Despite this, several tests indicating that the large-N CFTs are in fact unitary have been performed: for instance all the OPE coefficients computed so far in the large-N limit are real, and the spectrum of bilinear operators is real and above unitarity bounds. Our result, namely that the F theorem holds at large N, can be viewed as further indication that such theories are unitary.

As an added bonus, we show how conformal partial waves expansions in conformal field theory can be used to resum infinite classes of vacuum diagrams. Non-perturbatively, the jump in the value of the free energy has the interpretation of the inclusion at the ultraviolet fixed point of an extra non-normalizable contribution in the conformal partial wave expansion. This can be seen in perturbation theory as the reversal of the sign of an infinite class of diagrams due to the flow of a coupling constant.
Convexity, large charge and the large-N phase diagram of the φ4 theory
Authors: Moser Rafael , Orlando Domenico , Reffert Susanne
Published: February 2022

Abstract

In this note we discuss the phase space of the O(2N) vector model in the presence of a quadratic and a quartic interaction by writing the large-N effective potential using large charge methods in dimensions 2 < D < 4 and 4 < D < 6. Based on a simple discussion of the convexity properties of the grand potential, we find very different behavior in the two regimes: while in 2 < D < 4, the theory is well-behaved, the model in 4 < D < 6 leads to a complex CFT in the UV, consistently with earlier results. We also find a new metastable massive phase in the high-energy regime for the theory on the cylinder.
Vortex counting and the quantum Hall effect
Authors: Walton Edward
Published: February 2022

Abstract

We provide evidence for conjectural dualities between nonrelativistic Chern-Simons-matter theories and theories of (fractional, nonAbelian) quantum Hall fluids in 2 + 1 dimensions. At low temperatures, the dynamics of nonrelativistic Chern-Simons-matter theories can be described in terms of a nonrelativistic quantum mechanics of vortices. At critical coupling, this may be solved by geometric quantisation of the vortex moduli space. Using localisation techniques, we compute the Euler characteristicχ($$ \mathcal{L} $$Lλ) of an arbitrary powerλof a quantum line bundle$$ \mathcal{L} $$Lon the moduli space of vortices in U(Nc) gauge theory withNffundamental scalar flavours on an arbitrary closed Riemann surface. We conjecture that this is equal to the dimension of the Hilbert space of vortex states when the area of the metric on the spatial surface is sufficiently large. We find that the vortices in theories withNc=Nf=λbehave as fermions in the lowest nonAbelian Landau level, with strikingly simple quantum degeneracy. More generally, we find evidence that the quantum vortices may be regarded as composite objects, made of dual anyons. We comment on potential links between the dualities and three-dimensional mirror symmetry. We also compute the expected degeneracy of local Abelian vortices on the Ω-deformed sphere, finding it to be aq-analog of the undeformed case.
Multicolor strategies for investigating clonal expansion and tissue plasticity
Authors: Dumas L. , Clavreul S. , Michon F. , Loulier K.
Published: February 2022

Understanding the generation of complexity in living organisms requires the use of lineage tracing tools at a multicellular scale. In this review, we describe the different multicolor strategies focusing on mouse models expressing several fluorescent reporter proteins, generated by classical (MADM, Brainbow and its multiple derivatives) or acute (StarTrack, CLoNe, MAGIC Markers, iOn, viral vectors) transgenesis. After detailing the multi-reporter genetic strategies that serve as a basis for the establishment of these multicolor mouse models, we briefly mention other animal and cellular models (zebrafish, chicken, drosophila, iPSC) that also rely on these constructs. Then, we highlight practical applications of multicolor mouse models to better understand organogenesis at single progenitor scale (clonal analyses) in the brain and briefly in several other tissues (intestine, skin, vascular, hematopoietic and immune systems). In addition, we detail the critical contribution of multicolor fate mapping strategies in apprehending the fine cellular choreography underlying tissue morphogenesis in several models with a particular focus on brain cytoarchitecture in health and diseases. Finally, we present the latest technological advances in multichannel and in-depth imaging, and automated analyses that enable to better exploit the large amount of data generated from multicolored tissues.
Alteration of the translational readthrough isoform AQP4ex induces redistribution and downregulation of AQP4 in human glioblastoma
Authors: Valente Onofrio , Messina Raffaella , Ingravallo Giuseppe , Bellitti Emilio , Zimatore Domenico Sergio , de Gennaro Luigi , Abbrescia Pasqua , Pati Roberta , Palazzo Claudia , Nicchia Grazia Paola , Trojano Maria , Signorelli Francesco , Frigeri Antonio
Published: February 2022

Glioblastoma multiforme (GBM) is characterized by a remarkable cellular and molecular heterogeneity that make the behavior of this tumor highly variable and resistant to therapy. In addition, the most serious clinical complication of GBM and other brain tumors is the development of vasogenic edema which dramatically increase the intracranial pressure. In the present study we evaluate the expression, supramolecular organization and spatial distribution of AQP4 and AQP4ex, the new readthrough isoform of AQP4, in relationship with the degree of vasogenic brain edema and tumor progression. To this purpose, tissue samples from regions of tumor core, peritumoral and non-infiltrated tissues of each GBM patient (n = 31) were analyzed. Immunofluorescence experiments revealed that the expression of AQP4ex was almost absent in tumoral regions while the canonical AQP4 isoforms appear mostly delocalized. In peritumoral tissues, AQP4 expression was found altered in those perivascular astrocyte processes where AQP4ex appeared reduced and partially delocalized. Protein expression levels measured by immunoblot showed that global AQP4 was reduced mainly in the tumor core. Notably, the relative amount of AQP4ex was more severely reduced starting from the peritumoral region. BN-PAGE experiments showed that the supramolecular organization of AQP4 is only partially affected in GBM. Edema assessment by magnetic resonance imaging revealed that the level of AQP4ex downregulation correlated with edema severity. Finally, the degree of BBB alteration, measured with sodium fluorescein content in GBM biopsies, correlated with the edema index and AQP4ex downregulation. Altogether these data suggest that the AQP4ex isoform is critical in the triggering event of progressive downregulation and mislocalization of AQP4 in GBM, which may affect the integrity of the BBB and contributes to accumulation of edema in the peritumoral tissue. Thus, AQP4ex could be considered as a potential early biomarker of GBM progression.
Impact of distant peptide substrate residues on enzymatic activity of SlyD
Authors: Pazicky Samuel , Werle Anna-Leoni A. , Lei Jian , Löw Christian , Weininger Ulrich
Published: February 2022

Peptidyl-prolyl isomerases (PPIases) catalyze intrinsically slow and often rate-limiting isomerization of prolyl-peptide bonds in unfolded or partially folded proteins, thereby speeding up the folding process and preventing misfolding. They often possess binding and chaperone domains in addition to the domain carrying the isomerization activity. Although generally, their substrates display no identity in their amino acid sequence upstream and downstream of the proline with 20 possibilities for each residue, PPIases are efficient enzymes. SlyD is a highly efficient PPIase consisting of an isomerase domain and an additional chaperone domain. The binding of peptide substrates to SlyD and its enzymatic activity depend to some extend on the proline-proximal residues, however, the impact of proline-distant residues has not been investigated so far. Here, we introduce a label-free NMR-based method to measure SlyD activity on different peptide substrates and analysed the data in the context of obtained binding affinities and several co-crystal structures. We show that especially charged and aromatic residues up to eight positions downstream and three positions upstream of the proline and outside the canonical region of similar conformations affect the activity and binding, although they rarely display distinct conformations in our crystal structures. We hypothesize that these positions primarily influence the association reaction. In the absence of the chaperone domain the isomerase activity strongly correlates with substrate affinity, whereas additional factors play a role in its presence. The mutual orientation of isomerase and chaperone domains depends on the presence of substrates in both binding sites, implying allosteric regulation of enzymatic activity.
A Note on Local Regularity of Axisymmetric Solutions to the Navier–Stokes Equations
Authors: Seregin G.
Published: February 2022

In the paper, a new slightly supercritical condition, providing local regularity of axially symmetric solutions to the non-stationary 3D Navier-Stokes equations, is discussed. It generalises almost all known results in the local regularity theory of weak axisymmetric solutions.
Auf Nummer sicher? Sicherheitskultur und Patientensicherheit an deutschen anästhesiologischen Kliniken – Eine deutschlandweite Umfrage zum Status quo
Authors: Marcus Hanke E. , Golbeck W. , Schieren M. , Defosse J. , Wappler F. , Böhmer A.
Published: February 2022

Hintergrund

Zur Erhöhung der Patientensicherheit sind verschiedene Instrumente wie etwa das „Critical Incident Reporting System“ (CIRS) oder die Verwendung des „Situation, Background, Assessment, Recommendation (SBAR) System“ entwickelt worden. Ziel war es zu ermitteln, wie Anästhesisten in Deutschland die Sicherheitskultur empfinden, und ob CIRS oder SBAR etabliert sind.

Methodik

Alle registrierten Mitglieder der anästhesiologischen Berufsverbände wurden zu einer Onlineumfrage zum Thema „Patientensicherheit“ eingeladen. Es wurden die Themengebiete Sicherheitskultur, CIRS und SBAR erfragt.

Ergebnisse

Die Bewertung der Sicherheitskultur der Anästhesieabteilung war in 76,6 % der Fälle positiv (gesamtes Krankenhaus 54,3 %). Fehlerhafte Verläufe wurden laut 76,5 % offen kommuniziert. 23 % haben den Eindruck, dass bei Fehlern die betreffende Person bloßgestellt würde. Bei einem Drittel finden keine Morbiditäts- und Mortalitäts(M&M)-Konferenzen statt.

CIRS ist 98,9 % der Befragten bekannt; bei 84,4 % existiert es. CIRS-Meldungen wurden bereits von 54,4 % abgegeben. Regelmäßiges Feedback zu Meldungen erhalten nur 29,4 %.

SBAR als Übergabehilfsmittel war 63,7 % unbekannt. 86,1 % halten die Verwendung eines Instruments zur Verbesserung der Übergabequalität für notwendig.

Schlussfolgerungen

Die Qualität der Sicherheitskultur von Anästhesieabteilungen wird positiver bewertet als die des übrigen Krankenhauses. M&M-Konferenzen sollten größere Verbreitung erfahren.

CIRS ist nahezu allen befragten Anästhesisten bekannt – Feedback erfolgt selten. Es fehlt an Feedbackmechanismen für den Meldenden.

Zur Implementierung von Hilfsmitteln für strukturierte Patientenübergaben sollten in Zukunft mehr Anstrengungen unternommen werden.
Secular trends in childhood pain and comorbid psychiatric symptoms: a population-based study
Authors: Luntamo Terhi , Lempinen Lotta , Sourander Andre
Published: February 2022

Purpose

Pain symptoms are common in childhood. They often lead to functional impairment and co-occur with psychiatric difficulties. Although children’s lives have undergone enormous changes in recent decades, long-term data on changes in pain symptoms, and in comorbid psychiatric difficulties, is lacking. This knowledge is crucial, as co-occurring psychiatric symptoms are significant predictors of long-term outcome for children who suffer from pain. The main purpose of the present study was to explore secular changes in comorbid pain and psychiatric symptoms.

Methods

Four population-based, cross-sectional surveys of 8–9-year-old children were conducted in Southwest Finland in 1989, 1999, 2005, and 2013. Identical methodologies and questionnaire-based measures were used each study year. Participation ranged from 891 to 986 over the study period. The children were asked about the frequency of headache, abdominal pain, and other pains. Children, their parents, and teachers provided information on the child’s psychiatric difficulties, including internalizing and externalizing symptoms.

Results

The cumulative odds ratios and 95% confidence intervals for the overall prevalence of pain symptoms increased among both genders from 1989 to 2013 and ranged from 1.4 (1.03–1.8) for other pains to 2.4 (1.7–3.3) for abdominal pain. Comorbid internalizing symptoms increased among girls with odd ratios and 95% CIs of 1.8 (1.03–3.1) for children with any kind of pain, and 3.0 (1.4–6.2) for children with headache. No changes were found among boys.

Conclusion

Overall pain symptoms doubled in both genders, but the most novel finding was that comorbid emotional difficulties tripled among girls who reported headaches. Further research is needed to confirm, and explain, these findings.
The effect of alkyl substitution on the oxidative metabolism and mutagenicity of phenanthrene
Authors: Wang Danlei , Schramm Viktoria , Pool Jeroen , Pardali Eleni , Brandenburg Annemarijn , Rietjens Ivonne M. C. M. , Boogaard Peter J.
Published: February 2022

Alkyl-substituted PAHs may be present in certain petroleum-derived products and in the environment and may eventually end up in consumer products, such as foodstuffs, cosmetics and pharmaceuticals. Safety concerns over possible exposure to alkylated PAHs have emerged. Bioactivation is a prerequisite for the mutagenicity and carcinogenicity of PAHs and has been extensively studied for non-substituted PAHs, while data on the bioactivation of alkyl-substituted PAHs are scarce. The present study investigated the effect of alkyl substitution on the CYP 450-mediated metabolism of phenanthrene and eight of its alkylated congeners by quantifying metabolite formation in rat and human liver microsomal incubations. Furthermore, the mutagenicity of four selected methylated phenanthrenes was compared to that of phenanthrene using the Ames test. The obtained results support the hypothesis that alkyl substitution shifts the oxidative metabolism from the aromatic ring to the alkyl side chain. Increasing the length of the alkyl chain reduced overall metabolism with metabolic conversion for 1-n-dodecyl-phenanthrene (C12) being negligible. 1- and 9-methyl-phenanthrene, in which the methyl group generates an additional bay region-like structural motif, showed mutagenicity toward Salmonella typhimurium TA98 and TA 100, whereas phenanthrene and also 2- and 3-methyl-phenanthrene, without such an additional bay region-like structural motif, tested negative. It is concluded that the position of the alkylation affects the metabolism and resulting mutagenicity of phenanthrene with the mutagenicity increasing in cases where the alkyl substituent creates an additional bay region-like structural motif, in spite of the extra possibilities for side chain oxidation.
On the maximal operator of a general Ornstein–Uhlenbeck semigroup
Authors: Casarino Valentina , Ciatti Paolo , Sjögren Peter
Published: February 2022

If Q is a real, symmetric and positive definite $$n\times n$$

n
×
n

matrix, and B a real $$n\times n$$

n
×
n

matrix whose eigenvalues have negative real parts, we consider the Ornstein–Uhlenbeck semigroup on $$\mathbb {R}^n$$

R

n

with covariance Q and drift matrix B. Our main result says that the associated maximal operator is of weak type (1, 1) with respect to the invariant measure. The proof has a geometric gist and hinges on the “forbidden zones method” previously introduced by the third author.
The influences of target size and recent experience on the vigour of adjustments to ongoing movements
Authors: Brenner Eli , Hardon Hidde , Moesman Ryan , Crowe Emily M. , Smeets Jeroen B. J.
Published: February 2022

People adjust their on-going movements to changes in the environment. It takes about 100 ms to respond to an abrupt change in a target’s position. Does the vigour of such responses depend on the extent to which responding is beneficial? We asked participants to tap on targets that jumped laterally once their finger started to move. In separate blocks of trials the target either remained at the new position so that it was beneficial to respond to the jump, or jumped back almost immediately so that it was disadvantageous to do so. We also varied the target’s size, because a smaller, less vigorous adjustment is enough to place the finger within a larger target. There was a systematic relationship between the vigour of the response and the remaining time until the tap: the shorter the remaining time the more vigorous the response. This relationship did not depend on the target’s size or whether or not the target jumped back. It was already known that the vigour of responses to target jumps depends on the magnitude of the jump and on the time available for adjusting the movement to that jump. We show that the vigour of the response is precisely tuned to the time available for making the required adjustment irrespective of whether responding in this manner is beneficial.
Orientation-preserving and orientation-reversing mappings: a new description
Authors: Higgins Peter M. , Vernitski Alexei
Published: February 2022

We characterise the respective semigroups of mappings that preserve, or that preserve or reverse orientation of a finite cycle, in terms of their actions on oriented triples and oriented quadruples. This leads to a proof that the latter semigroup coincides with the semigroup of all mappings that preserve intersections of chords on the corresponding circle.
Cellular and soluble immune checkpoint signaling forms PD-L1 and PD-1 in renal tumor tissue and in blood
Authors: Keber Corinna U. , Derigs Marcus , Schultz Carolin , Wegner Moritz , Lingelbach Susanne , Wischmann Viktoria , Hofmann Rainer , Denkert Carsten , Hegele Axel , Hänze Jörg
Published: February 2022

Immune checkpoint blockade therapy is a treatment option of various metastatic cancer diseases including renal cell carcinoma (RCC). Approved antibody drugs target the co-inhibitory signaling of Programmed Cell Death Ligand-1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1). The combined evaluation of PD-L1 and PD-1 at the mRNA and protein levels in tumor tissue with differentiation of tumor and immune cells as well as of soluble forms (sPD-L1) and (sPD-1) in blood is of basic interest in assessing biomarker surrogates. Here, we demonstrate that PD-L1 determined as fraction of stained tumor cells (TPS-score) correlates with PD-L1-mRNA in tumor tissue, reflecting the predominant expression of PD-L1 in tumor cells. Conversely, PD-1 in immune cells of tumor tissue (IC-score) correlated with PD-1-mRNA tissue levels reflecting the typical PD-1 expression in immune cells. Of note, sPD-L1 in blood did not correlate with either the TPS-score of PD-L1 or with PD-L1-mRNA in tumor tissue. sPD-L1 released into the supernatant of cultured RCC cells closely followed the cellular PD-L1 expression as tested by interferon γ (IFNG) induction and siRNA knockdown of PD-L1. Further analysis in patients revealed that sPD-L1 significantly increased in blood following renal tumor resection. In addition, sPD-L1 correlated significantly with inflammation marker C-reactive protein (CRP) and with PD-L1 mRNA level in whole blood. These results indicate that the major source of sPD-L1 in blood may be peripheral blood cells and not primarily tumor tissue PD-L1.
Approaches to Surgical Debridement in Necrotizing Soft Tissue Infections: Outcomes of an Animated, Interactive Survey
Authors: Suijker Jaco , Hofmans Fabienne A. C. , van Zuijlen Paul P. M. , Cense Huib A. , Bonjer H. Jaap , Vries Annebeth Meij‐de
Published: February 2022

Background

Necrotizing soft tissue infections (NSTI) affect long‐term quality of life in survivors. Different approaches to debridement may influence quality of life. The aim of this study was to assess the current practice of the debridement of NSTI in the Netherlands.

Methods

An animated, interactive online survey was distributed among general surgeons and plastic surgeons in the Netherlands. Two NSTI‐cases were presented, followed by questions regarding the preferred surgical approach. Case one described a woman with a swollen, red leg, with signs of sepsis and without visible necrosis. Case two described an immunocompromised man with septic shock syndrome and extensive necrosis.

Results

In total 232 responses were included (143 general surgeons, 89 plastic surgeons). In case one, 32% chose to preserve all skin, while 17% chose to resect all skin above the affected fascia, including normal‐looking skin. In case two, all participants resected necrotic skin, and most (88%) also blue discolored skin. While 32% did not resect more than blue discolored and necrotic skin, 35% also resected red‐colored skin, and 21% all skin overlying the affected fascia, including normal colored skin. Respondents working in a hospital with a burn center tended to preserve more skin, whereas plastic surgeons chose more often for skin resection compared to general surgeons.

Conclusions

By using a novel approach to a survey, the authors demonstrate the existence of extensive practice variety regarding the approach to debridement of NSTI among Dutch general and plastic surgeons. Consensus is needed, followed by targeted education of surgeons.
Exact prediction intervals for future exponential and Pareto lifetimes based on ordered ranked set sampling of non-random and random size
Authors: Barakat H. M. , Newer Haidy A.
Published: February 2022

In the present paper, two pivotal statistics are suggested to construct prediction intervals of future observations from the exponential and Pareto distributions in the context of ordered ranked set sample. Our study encompasses two cases. The first case, when the sample size is assumed to be fixed and the second case when the sample size is assumed to be a positive integer-valued random variable. In addition to deriving explicit forms for the distribution functions of the two pivotal statistics, we consider some special cases for the random size of the sample. Moreover, a simulation study is carried out to assess the efficiency of the suggested methods. Finally, an example representing lifetime data is analyzed.
Effect of orographic gravity wave drag on Northern Hemisphere climate in transient simulations of the last deglaciation
Authors: Snoll Brooke , Ivanovic Ruza F. , Valdes Paul J. , Maycock Amanda C. , Gregoire Lauren J.
Published: February 2022

Long transient simulations of the last deglaciation are increasingly being performed to identify the drivers of multiple rapid Earth system changes that occurred in this period. Such simulations frequently prescribe temporal variations in ice sheet properties, which can play an important role in controlling atmospheric and surface climate. To preserve a model’s standard performance in simulating climate, it is common to apply time dependent orographic variations, including parameterised sub-grid scale orographic variances, as anomalies from the pre-industrial state. This study investigates the causes of two abrupt climate change events in the Northern Hemisphere extratropics occurring between 16 and 14 thousand years ago in transient simulations of the last deglaciation from the Hadley Centre coupled general circulation model (HadCM3). One event is characterized by regional Northern Hemisphere changes comprising a centennial scale cooling of ~ 10 °C across Fennoscandia followed by rapid warming in less than 50 years as well as synchronous shifts in the Northern Annular Mode. The second event has comparable but temporally reversed characteristics. Sensitivity experiments reveal the climate anomalies are exclusively caused by artificially large values of orographic gravity wave drag, resulting from the combined use of the orographic anomaly method along with a unique inclusion of transient orography that linearly interpolates between timesteps in the ice sheet reconstruction. Palaeoclimate modelling groups should therefore carefully check the effects of their sub-grid scale orographic terms in transient palaeoclimate simulations with prescribed topographic evolution.
The role of serum D-Dimer for the diagnosis of periprosthetic shoulder infection
Authors: Akgün Doruk , Al-Muhtaresh Faisal , Paksoy Alp , Lacheta Lucca , Minkus Marvin , Karczewski Daniel , Moroder Philipp
Published: February 2022

Introduction

D-Dimer was recently identified as an additional biomarker in the diagnosis of hip and knee periprosthetic joint infection (PJI). Currently, there is only one study in literature dealing with the role of D-Dimer in the diagnosis of shoulder PJI. The purpose of this study was, therefore, to validate the sensitivity and specificity of D-Dimer in detecting shoulder PJI.

Materials and methods

All patients, who underwent septic or aseptic revision shoulder arthroplasty in our institution between November 2018 und March 2021, were analyzed. Our cohort consisted of 30 patients, of that 14 (47%) had a shoulder PJI according the last proposed criteria of the International Consensus Meeting. The diagnostic validity of serum D-Dimer regarding the detection of PJI was analyzed.

Results

The mean D-Dimer level was significantly higher for the patients with shoulder PJI compared to patients with aseptic failure (1.44 ± 1 mg/l vs. 0.76 ± 0.6 mg/l, p = 0.025). Coagulase-negative staphylococci were the most commonly isolated pathogens, in 9/14 patients (64%), followed by Cutibacterium acnes in 5/14 patients (36%). According to the ROC analysis, a serum D-Dimer threshold of 0.75 mg/l had a sensitivity of 86% and a specificity of 56% for detection of a shoulder PJI. The area under curve was 0.74. A serum C-reactive protein (CRP) cutoff of 10 mg/l showed a sensitivity of 69% and a specificity of 88%. When both serum D-Dimer and CRP above the thresholds of 0.75 mg/l and 10 mg/l, respectively, were used to identify a PJI the sensitivity and specificity were 57% and 100%, respectively.

Conclusions

Serum D-Dimer showed a good sensitivity but a poor specificity for the diagnosis of shoulder PJI. Combination D-Dimer and CRP led to improvement of the specificity, however, at the cost of sensitivity. Thus, combination of both methods may be used as a confirmatory test in the diagnosis of shoulder PJI but not to rule out infection.

Level of evidence

Diagnostic level II.
Evaluation of the Bonebridge BCI 602 active bone conductive implant in adults: efficacy and stability of audiological, surgical, and functional outcomes
Authors: Cywka Katarzyna B. , Skarzynski Piotr H. , Krol Bartlomiej , Hatzopoulos Stavros , Skarzynski Henryk
Published: February 2022

Purpose

(1) To assess the effectiveness and safety of a bone-conduction implant, the Bonebridge BCI 602, in adults with conductive or mixed hearing loss. (2) To investigate whether the Bonebridge BCI 602 is at least as effective as the Bonebridge BCI 601 in such patients.

Methods

The study group included 42 adults who had either conductive or mixed hearing loss. All patients underwent Bonebridge BCI 602 implant surgery. Before and after implantation, pure-tone audiometry, speech recognition tests (in quiet and noise), and free-field audiometry were performed. Word recognition scores were evaluated using the Polish Monosyllabic Word Test. Speech reception thresholds in noise were assessed using the Polish Sentence Matrix Test. Subjective assessment of benefits was done using the APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire.

Results

The APHAB questionnaire showed that difficulties in hearing decreased after BCI 602 implantation. Both word recognition in quiet and speech reception threshold in noise were significantly better after BCI 602 implantation and remained stable for at least 12 months. A significant advantage of the device is a reduced time for surgery while maintaining safety. In this study, the mean time for BCI 602 implantation was 28.3 min ± 9.4.

Conclusions

The second-generation Bonebridge BCI 602 implant is an effective hearing rehabilitation device for patients with conductive or mixed hearing loss. Patient satisfaction and audiological results confirm its efficacy and safety. Its new shape and dimensions allow it to be used in patients previously excluded due to insufficient or difficult anatomical conditions. The new BCI 602 implant is as effective as its predecessor, the BCI 601.
Body-kun/body-chan style model figures for artists in forensic visualization applications
Authors: Potente Stefan , Heinbuch Sara , Ramsthaler Frank , Schmidt Peter
Published: February 2022

Posture and body position are often in the focus of forensic medicine. Visualization for the purposes of documentation, teaching, scientific presentation or expert opinion in court is often desired. Plenty of possible tools to support visualization are available. However, there is a significant gap between quick drawings and more complex techniques. Body-chan (female) and body-kun (male) artist’s model figurines (genericized trademark) may provide a useful means to fill this gap. These models, about 12–15 cm in height, are multi-articulated humanoids of realistic proportions, intended to serve as models for manga (japanese comic) drawing. Plenty of different models are available in different quality which usually are equipped with interchangeable hand and feet attachments, a frame for ‘levitating’ positions as well as assorted objects to scale. These inexpensive models may be positioned quickly and intuitively. Photodocumentation from various angles can be performed using a mobile phone camera. Images may be further improved applying digital image manipulation software. Taken together, the process is quick and intuitive and the level of achievable complexity is sufficient for many forensic applications.
Coronary angiography in acute ischemic stroke patients: frequency and determinants of pathological findings in a multicenter cohort study
Authors: Litmeier Simon , Meinel Thomas R. , von Rennenberg Regina , Kniepert Joachim U. , Audebert Heinrich J. , Endres Matthias , Jung Simon , Scheitz Jan F. , Nolte Christian H.
Published: February 2022

Background

Myocardial injury as indicated by cardiac troponin elevation is associated with poor prognosis in acute stroke patients. Coronary angiography (CAG) is the diagnostic gold-standard to rule-out underlying obstructive coronary artery disease (CAD) in these patients. However, weighing risks and benefits of coronary angiography (CAG) against each other is particularly challenging, because stroke patients undergoing CAG may have a higher risk for secondary intracranial bleeding. Current guidelines remain vague. Thus, the aim of this study was to analyze frequency of pathological findings of CAG and associated clinical factors.

Methods

We analyzed indications and frequency of CAG performed in acute ischemic stroke patients in clinical routine in two European tertiary care hospitals from 2011 to 2018. All data were obtained retrospectively. Multiple logistic regression analyses were performed to identify variables associated with absence of obstructive coronary artery disease defined as presence of at least one coronary vessel stenosis ≥ 50%.

Results

A total of 139 AIS patients underwent CAG. Frequent indications for CAG were suspected acute coronary syndrome (N = 114) or scheduled cardiac surgery (N = 25). Acute coronary stenting was applied in 51/139 patients. Among patients with suspected acute coronary syndrome, no obstructive CAD was found in 27/114 patients. Absence of obstructive CAD was associated with insular cortex lesions, no clinical symptoms for ACS, less than three cardiovascular risk factors, younger age and normal wall motion.

Conclusion

Several variables suggest absence of CAD in AIS patients and may help in clinical decision making in stroke patients with myocardial injury.
The time course of different neuromuscular adaptations to short-term downhill running training and their specific relationships with strength gains
Authors: Bontemps Bastien , Gruet Mathieu , Louis Julien , Owens Daniel J. , Miríc Stella , Erskine Robert M. , Vercruyssen Fabrice
Published: February 2022

Purpose

Due to its eccentric nature, downhill running (DR) training has been suggested to promote strength gains through neuromuscular adaptations. However, it is unknown whether short-term chronic DR can elicit such adaptations.

Methods

Twelve untrained, young, healthy adults (5 women, 7 men) took part in 4 weeks’ DR, comprising 10 sessions, with running speed equivalent to 60–65% maximal oxygen uptake ($$\dot{V}$$

V
˙

O2max, assessed at weeks 0 and 4). Isometric and isokinetic knee-extensor maximal voluntary torque (MVT), vastus lateralis (VL) muscle morphology/architecture (anatomical cross-sectional area, ACSA; physiological CSA, PCSA; volume; fascicle length, Lf; pennation angle, PA) and neuromuscular activation (VL EMG) were assessed at weeks 0, 2 and 4.

Results

MVT increased by 9.7–15.2% after 4 weeks (p < 0.01). VL EMG during isometric MVT increased by 35.6 ± 46.1% after 4 weeks (p < 0.05) and correlated with changes in isometric MVT after 2 weeks (r = 0.86, p = 0.001). VL ACSA (+2.9 ± 2.7% and +7.1 ± 3.5%) and volume (+2.5 ± 2.5% and +6.6 ± 3.2%) increased after 2 and 4 weeks, respectively (p < 0.05). PCSA (+3.8 ± 3.3%), PA (+5.8 ± 3.8%) and Lf (+2.7 ± 2.2%) increased after 4 weeks (p < 0.01). Changes in VL volume (r = 0.67, p = 0.03) and PCSA (r = 0.71, p = 0.01) correlated with changes in concentric MVT from 2 to 4 weeks. $$\dot{V}$$

V
˙

O2max (49.4 ± 6.2 vs. 49.7 ± 6.3 mL·kg−1·min−1) did not change after 4 weeks (p = 0.73).

Conclusion

Just 4 weeks’ moderate-intensity DR promoted neuromuscular adaptations in young, healthy adults, typically observed after high-intensity eccentric resistance training. Neural adaptations appeared to contribute to most of the strength gains at 2 and 4 weeks, while muscle hypertrophy seemed to contribute to MVT changes from 2 to 4 weeks only.
Surgical and endovascular revascularization of chronic mesenteric ischemia
Authors: Wolk Steffen , Kapalla Marvin , Ludwig Stefan , Radosa Christoph , Hoffmann Ralf-Thorsten , Weitz Jürgen , Reeps Christian
Published: February 2022

Purpose

Chronic mesenteric ischemia (CMI) is a rare but life-threatening disease. This study reviewed outcomes in patients treated surgically for CMI by open treatment (OT) and endovascular treatment (ET), analyzing risk factors for endovascular failure.

Methods

Clinical data for 36 patients treated for CMI from 2007 to 2017 were retrospectively analyzed. The study’s primary endpoint was symptom-free survival. The secondary endpoint was the primary technical success for endovascular and open surgical treatments. Risk factors for endovascular failure were identified by using univariate analysis.

Results

Patients were analyzed as treated: 21 patients (58.3%) in the ET and 15 (41.6%) in the OT group. Overall, 20 patients (56%) presented with abdominal angina, 9 (25%) with rest pain, and 7 (19%) without symptoms. An ET was initially attempted in 31 patients (86.1%). The conversion rate from ET to OT was 32.3%, which resulted in a primary technical success of 67.6% in ET and 100% in OT. Six patients from the ET group (19.3%) required surgical revision due to restenosis. One-year (OT 91.6% vs. ET 96.8%; n.s.) and three-year primary patency (OT 91.6% vs. ET 80.6%; n.s.) as well as 3-year symptom-free survival did not differ between the groups (OT 62.5% vs. ET 69.4%; n.s). Overall, in-hospital mortality was 2.8% (n = 1), which was not statistically different between the groups (OT 6% vs. ET 0%; n.s.). High-grade stenosis of the superior mesenteric artery tended to be associated with higher technical failure (P = 0.06).

Conclusions

ET showed a comparable perioperative outcome with higher technical failure. OT was distinguished by excellent early and late technical success.
Impaired detection of omicron by SARS-CoV-2 rapid antigen tests
Authors: Osterman Andreas , Badell Irina , Basara Elif , Stern Marcel , Kriesel Fabian , Eletreby Marwa , Öztan Gamze Naz , Huber Melanie , Autenrieth Hanna , Knabe Ricarda , Späth Patricia M. , Muenchhoff Maximilian , Graf Alexander , Krebs Stefan , Blum Helmut , Durner Jürgen , Czibere Ludwig , Dächert Christopher , Kaderali Lars , Baldauf Hanna-Mari , Keppler Oliver T.
Published: February 2022

Since autumn 2020, rapid antigen tests (RATs) have been implemented in several countries as an important pillar of the national testing strategy to rapidly screen for infections on site during the SARS-CoV-2 pandemic. The current surge in infection rates around the globe is driven by the variant of concern (VoC) omicron (B.1.1.529). Here, we evaluated the performance of nine SARS-CoV-2 RATs in a single-centre laboratory study. We examined a total of 115 SARS-CoV-2 PCR-negative and 166 SARS-CoV-2 PCR-positive respiratory swab samples (101 omicron, 65 delta (B.1.617.2)) collected from October 2021 until January 2022 as well as cell culture-expanded clinical isolates of both VoCs. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 1.77 × 106 to 7.03 × 107 RNA copies subjected to the RAT for omicron compared to 1.32 × 105 to 2.05 × 106 for delta. To score positive in these point-of-care tests, up to 10-fold (LoD50) or 101-fold (LoD95) higher virus loads were required for omicron- compared to delta-containing samples. The rates of true positive test results for omicron samples in the highest virus load category (Ct values < 25) ranged between 31.4 and 77.8%, while they dropped to 0–8.3% for samples with intermediate Ct values (25–30). Of note, testing of expanded virus stocks suggested a comparable RAT sensitivity of both VoCs, questioning the predictive value of this type of in vitro-studies for clinical performance. Given their importance for national test strategies in the current omicron wave, awareness must be increased for the reduced detection rate of omicron infections by RATs and a short list of suitable RATs that fulfill the minimal requirements of performance should be rapidly disclosed.
Auriculotemporal Frey syndrome not associated with surgery or diabetes: systematic review
Authors: Betti Céline , Milani Gregorio P. , Lava Sebastiano A. G. , Bianchetti Mario G. , Bronz Gabriel , Ramelli Gian P. , Goeggel Simonetti Barbara , Bergmann Marcel M.
Published: February 2022

Patients who undergo salivary gland, neck, or facelift surgery or suffer from diabetes mellitus often develop Frey syndrome (also known as auriculotemporal syndrome or gustatory sweating). Frey syndrome has been occasionally reported to occur in subjects without history of surgery or diabetes but this variant of Frey syndrome has not been systematically investigated. We searched for original articles of Frey syndrome unrelated to surgery or diabetes without date and language restriction. Article selection and data extraction were performed in duplicate. Our systematic review included 76 reports describing 121 individual cases (67 males and 54 females) of Frey syndrome not associated with surgery or diabetes. The age at onset of symptoms was ≤ 18 years in 113 (93%) cases. The time to diagnosis was 12 months or more in 55 (45%) cases. On the other hand, an allergy evaluation was performed in half of the cases. A possible cause for Frey syndrome was detected in 85 (70%) cases, most frequently history of forceps birth (N = 63; 52%). The majority of the remaining 22 cases occurred after a blunt face trauma, following an auriculotemporal nerve neuritis or in association with a neurocutaneous syndrome. The cause underlying Frey syndrome was unknown in 36 cases.

   Conclusion: Frey syndrome not associated with surgery or diabetes almost exclusively affects subjects in pediatric age and is uncommon and underrecognized. Most cases occur after forceps birth. There is a need to expand awareness of this pseudo-allergic reaction among pediatricians and allergists.What is Known:• Pre-auricular reddening, sweating, and warmth in response to mastication or a salivary stimulus characterize Frey syndrome.• It usually occurs after salivary gland surgery and in diabetes.What is New:• In children, Frey syndrome is rare, and most cases occur after a forceps-assisted birth.• In childhood, this condition is often erroneously attributed to food allergy.
Anti-CD20–atezolizumab–polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma
Authors: Topp Max S. , Eradat Herbert , Florschütz Axel , Hochhaus Andreas , Wrobel Tomasz , Walewski Jan , Knopinska-Posluszny Wanda , Kanate Abraham S. , Lech-Maranda Ewa , Brunnberg Uta , Chitra Surya , Nielsen Tina G. , Sellam Gila , Shivhare Mahesh , Lossos Izidore S.
Published: February 2022

Purpose

New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations.

Methods

Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola; 1.4 mg/kg/1.8 mg/kg) and patients with R/R diffuse large B-cell lymphoma (DLBCL; n = 23) received rituximab (R)-atezo-pola. The primary efficacy endpoint was complete response (CR) at end of induction (EOI) by PET-CT (investigator assessed; modified Lugano 2014 criteria). Safety endpoints were also assessed.

Results

13 FL patients were treated and evaluable for safety; 2/23 DLBCL patients did not receive treatment and were not included in the safety population. Median observation time was 23.3 and 5.7 months in the FL and DLBCL cohorts, respectively. At EOI, CR rates in FL patients treated with G-atezo-pola at pola doses of 1.4 mg/kg (N = 3) and 1.8 mg/kg (N = 7) were 33% and 14%, respectively. In DLBCL patients receiving R-atezo-pola, the CR rate at EOI was 13%. In the FL cohort, 62% of patients experienced a grade 3–5 adverse event (AE; including two deaths) and 31% developed a serious AE (SAE). In DLBCL patients, R-atezo-pola was associated with a lower incidence of grade 3–5 AEs (24%; one death) and SAEs (10%). In both cohorts, the most common grade 3–5 AEs were hematologic toxicities.

Conclusion

Based on these safety issues, considered as related specifically to G-atezo-pola, and limited efficacy, no further development of either combination is planned.

Trial registration

NCT02729896; Date of registration: April 6, 2016.
D,L-Methadone enhances the cytotoxic activity of standard chemotherapeutic agents on pediatric rhabdomyosarcoma
Authors: Urla Cristian , Corteletti Irene , Raible Ann-Sophie , Handgretinger Rupert , Fuchs Jörg , Warmann Steven W. , Schmid Evi
Published: February 2022

Purpose

In advanced tumor stages, pediatric rhabdomyosarcoma (RMS) shows an intrinsic resistance to standard chemotherapy, which is associated with a dismal prognosis. Alternative therapeutic approaches and optimization of already existent treatment protocols are urgently needed in these conditions. The µ-opioid receptor (OPRM1) agonist, D,L-methadone is frequently used for analgesia in oncological patients. Recent evidence has shown that D,L-methadone in combination with chemotherapeutic agents may enhance their cytotoxic effect against cancer cells. There are no related data in pediatric rhabdomyosarcoma (RMS).

Methods

Antitumor effects of combined D,L-methadone and doxorubicin, carboplatin, and vincristine on RMS cell lines RD and RH30 were analyzed using following outcome data: expression of the OPRM1 receptor (Western blot), cell growth inhibition (MTT assay), cell migration (wound-healing assay), apoptosis induction (caspase-3/7 assay), and reactive oxygen species (ROS) production (flow cytometry).

Results

In both cell lines, OPRM1 expression was significantly increased after combined treatment of D,L-methadone with all three cytotoxic drugs tested, which resulted in suppression of tumor cell growth and increase of apoptosis rates. These effects were mediated by increased ROS production and up-regulation of caspase-3/7 activity. Doxorubicin combined with D,L-methadone significantly reduced cell migration in both cell lines. Carboplatin or vincristine in combination with D,L-methadone had only an impact on cell migration in RH30 cells.

Conclusions

This new therapeutic approach in RMS provides strong antitumor effects in vitro. The combination of standard chemotherapy and D,L-methadone requires further investigation. Especially advanced tumors with a limited effectiveness of conventional treatment regimens seem a potential target of this approach.
Integrative analysis of the pharmaceutical active ingredient and transcriptome of the aerial parts of Glycyrrhiza uralensis under salt stress reveals liquiritin accumulation via ABA-mediated signaling
Authors: Bi Quan , Yao Hua , Wang Fei , He Dajun , Xu Wenbin , Xie Shuangquan , Chen Xifeng , Li Yuxia , Liu Hailiang , Shen Haitao , Li Hongbin
Published: February 2022

The aerial parts of Glycyrrhiza uralensis supply substantial raw material for the extraction of active pharmaceutical ingredients comprehensively utilized in many industries. Our previous study indicated that salt stress increased the content of active ingredients. However, the regulatory mechanism remains unclear. In this study, RNA-sequencing (RNA-seq) of the aerial parts of G. uralensis treated with 150 mM NaCl for 0, 2, 6, and 12 h was performed to identify the key genes and metabolic pathways regulating pharmacological active component accumulation. The main active component detection showed that liquiritin was the major ingredient and exhibited more than a ten-fold significant increase in the 6 h NaCl treatment. Temporal expression analysis of the obtained 4245 differentially expressed genes (DEGs) obtained by RNA-seq revealed two screened profiles that included the significant up-regulated DEGs (UDEGs) at different treatment points. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these UDEGs identified phenylpropanoid metabolism and flavonoid biosynthesis as the most significantly enriched pathways in 2 h treated materials. Interestingly, the carotenoid biosynthesis pathway that is related to ABA synthesis was also discovered, and the ABA content was significantly promoted after 6 h NaCl treatment. Following ABA stimulation, the content of liquiritin demonstrated a significant and immediate increase after 2 h treatment, with the corresponding consistent expression of genes involved in the pathways of ABA signal transduction and flavonoid biosynthesis, but not in the pathway of glycyrrhizic acid biosynthesis. Our study concludes that salt stress might promote liquiritin accumulation through the ABA-mediated signaling pathway, and provides effective reference for genetic improvement and comprehensive utilization of G. uralensis.