bluuebunny/crossref_metadata_2025 huggingface dataset:
FDA Approval Summary: Nivolumab Plus Ipilimumab for the Treatment of Patients with Hepatocellular Carcinoma Previously Treated with Sorafenib
Authors: Saung May Tun , Pelosof Lorraine , Casak Sandra , Donoghue Martha , Lemery Steven , Yuan Mengdie , Rodriguez Lisa , Schotland Peter , Chuk Meredith , Davis Gina , Goldberg Kirsten B. , Theoret Marc R. , Pazdur Richard , Fashoyin-Aje Lola
Published: May 2021

On March 10, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to nivolumab in combination with ipilimumab for the treatment of patients with hepatocellular carcinoma (HCC) previously treated with sorafenib. The recommended approved dosage was nivolumab 1 mg/kg i.v. plus ipilimumab 3 mg/kg i.v. every 3 weeks for four cycles, followed by nivolumab 240 mg i.v. every 2 weeks. The approval was based on data from cohort 4 of CheckMate 040, which randomized patients with advanced unresectable or metastatic HCC previously treated with or who were intolerant to sorafenib to receive one of three different dosing regimens of nivolumab in combination with ipilimumab. Investigator-assessed overall response rate (ORR) was the primary endpoint, and ORR assessed by blinded independent central review (BICR) was an exploratory endpoint. BICR-assessed ORR and duration of response (DoR) form the primary basis of the FDA's regulatory decision, and BICR-assessed ORR was comparable in all three arms at 31%–32% with 95% confidence interval [CI] 18%–47%. The DoR ranged from 17.5 to 22.2 months across the three arms, with overlapping 95% CIs. Adverse events (AEs) were generally consistent with the known AE profiles of nivolumab and ipilimumab, and no new safety events were identified. This article summarizes the FDA review of the data supporting the approval of nivolumab and ipilimumab for the treatment of HCC.

Implications for Practice

Nivolumab and ipilimumab combination therapy is another option for patients with advanced hepatocellular carcinoma who experience radiographic progression during or after sorafenib or sorafenib intolerance. No new toxicities were identified, but, as expected, increased toxicity was observed with the addition of ipilimumab to nivolumab as compared with nivolumab alone, which is also approved for the same indication. Whether to administer nivolumab as a single agent or in combination with ipilimumab is expected to be a joint decision between the oncologist and patient, taking into consideration the potential for a higher likelihood of response and the potentially higher rate of toxicity with the combination.
Effect of coir fiber and inorganic filler on physical and mechanical properties of epoxy based hybrid composites
Authors: H. M. Kavya , Bavan Saravana , B. Yogesha , M. R. Sanjay , Siengchin Suchart , Gorbatyuk Sergey
Published: May 2021

The present work's target is to study the impact of fly ash or TiC nanoparticles or both on the characteristics of coir fiber epoxy hybrid composites. Mechanical characteristics like tensile, flexural, inter‐laminar shear strength, impact strength, shore D hardness, and thermal stability or degradation characteristics were determined. The microstructure of the samples was observed from a scanning electron microscopy. It was observed that the addition of coir fiber, fly ash, and TiC nanoparticles in the epoxy polymer enhanced the mechanical and thermal characteristics of composites. It can be assigned to the better interaction and uniform distribution between the fillers and the epoxy polymer. Fillers acted a critical role in enhancing the characteristics of epoxy hybrid composites. Additionally, water absorption characteristics were also investigated for all specimens. A comparative examination was performed between various fabricated composite specimens. Results exhibited that, the water absorption of the composites improves considerably with the addition of reinforcements. Also, thermogravimetric analysis exhibited that the fabricated epoxy hybrid composites were stable thermally.
Self‐reported sensitivity to pain in early and moderately‐late preterm‐born adolescents: A community‐based cohort study
Authors: van Dokkum Nienke H. , de Kroon Marlou L. A. , Reijneveld Sijmen A. , Bos Arend F.
Published: May 2021

We aimed to compare ratings of self‐reported and parent‐reported pain sensitivity between early preterm (EP), moderately‐late preterm (MLP), and full‐term (FT) adolescents. For EP adolescents, we aimed to determine whether pain sensitivity was associated with early‐life events. EP (n = 68, response rate 47.4%), MLP (n = 128, response rate 33.0%), and FT (n = 78, response rate 31.1%) adolescents and their parents (n = 277) answered an author‐generated question on pain sensitivity at 14‐15 years of age within a community‐based cohort study. Differences between groups were determined using the chi‐square test for trends. For EP adolescents, we assessed associations of treatment modalities (inotrope treatment, mechanical ventilation, and C‐section) and neonatal morbidities (sepsis/necrotizing enterocolitis, small‐for‐gestational age status, asphyxia, and cerebral pathologies) with adolescent pain sensitivity using logistic regression analyses. Increased pain sensitivity was reported by 18% of EP adolescents, compared with 12% of MLP adolescents, and 7% of FT adolescents (P = 0.033). Parent‐reported pain sensitivity did not differ by gestational age group. For EP adolescents, inotrope treatment was associated with increased pain sensitivity (odds ratio, 5.00, 95% confidence interval, 1.23‐20.4, P = 0.025). No other neonatal treatment modalities or morbidities were associated with pain sensitivity in adolescence. In conclusion, we observed higher proportions of increased pain sensitivity for EP and MLP adolescents. Physicians treating preterm adolescents should be aware of altered pain sensitivity.
Novel antimicrobial anionic cecropins from the spruce budworm feature a poly‐L‐aspartic acid C‐terminus
Authors: Maaroufi Halim , Potvin Marianne , Cusson Michel , Levesque Roger C.
Published: May 2021

Cecropins form a family of amphipathic α‐helical cationic peptides with broad‐spectrum antibacterial properties and potent anticancer activity. The emergence of bacteria and cancer cells showing resistance to cationic antimicrobial peptides (CAMPs) has fostered a search for new, more selective and more effective alternatives to CAMPs. With this goal in mind, we looked for cecropin homologs in the genome and transcriptome of the spruce budworm, Choristoneura fumiferana. Not only did we find paralogs of the conventional cationic cecropins (Cfcec+), our screening also led to the identification of previously uncharacterized anionic cecropins (Cfcec−), featuring a poly‐l‐aspartic acid C‐terminus. Comparative peptide analysis indicated that the C‐terminal helix of Cfcec− is amphipathic, unlike that of Cfcec+, which is hydrophobic. Interestingly, molecular dynamics simulations pointed to the lower conformational flexibility of Cfcec− peptides, relative to that of Cfcec+. Phylogenetic analysis suggests that the evolution of distinct Cfcec+ and Cfcec− peptides may have resulted from an ancient duplication event within the Lepidoptera. Finally, we found that both anionic and cationic cecropins contain a BH3‐like motif (G‐[KQR]‐[HKQNR]‐[IV]‐[KQR]) that could interact with Bcl‐2, a protein involved in apoptosis; this observation is congruent with previous reports indicating that cecropins induce apoptosis. Altogether, our observations suggest that cecropins may provide templates for the development of new anticancer drugs. We also estimated the antibacterial activity of Cfcec‐2 and a ∆Cfce‐2 peptide as AMPs by testing directly their ability in inhibiting bacterial growth in a disk diffusion assay and their potential for development of novel therapeutics.
Nuclear magnetic resonance studies on conformation and stability of mastoparan in methanol
Authors: Miura Yoshinori
Published: May 2021

Mastoparan is a small peptide composed of 14 amino acid residues found in wasp venom. It penetrates into cytoplasm through the cell membranes and then binds to a G protein to stimulate the release of histamine. Conformation and its thermal stability of mastoparan from Vespula lewisi (MP) in methanol are investigated by using proton nuclear magnetic resonance (NMR) spectroscopy. On the basis of data on NOESY cross peaks, spin–spin coupling constants between an amide proton (NH) and an α‐proton, NH chemical shift analyses, and temperature dependence of integrated intensity of NH resonance lines, we found that MP forms the helix between the 5th and 12th residues at low temperatures and the helix segment is maintained even at 54°C. This conformation is similar to that of MP bound to detergent micelles, and hence, methanol is considered to be appropriate as a membrane mimetic for MP. In connection with the function of the venom peptide, significance of high stability of the helical conformation is discussed.
High‐speed plasma treatment of polyethylene terephthalate films using ultrasound assisted dielectric barrier discharge
Authors: Fang Cheng , Kusano Yukihiro , Bardenshtein Alexander
Published: May 2021

Polyethylene‐terephthalate (PET) films were treated using an air‐to‐air type atmospheric pressure dielectric barrier discharge (DBD) plasma in helium with ultrasonic irradiation, particularly for aiming at improving wettability. Airborne ultrasound was irradiated to the plasma using a pneumo‐acoustic stem‐jet Hartmann's generator. The wettability was significantly improved even when the treatment speed was up to 300 mm/s, corresponding to an estimated exposure time of approximately 30 ms. It is at least a factor of 30 shorter than the time required to achieve the same level of plasma treatment effect without ultrasonic irradiation. This effect opens an opportunity for industrial implementation of high‐speed plasma treatment of PET flexible packaging films by a straightforward embedding of pneumatic generators of ultrasound into existing wide‐web roll‐to‐roll commercial machines based on DBD.
The critical probability for Voronoi percolation in the hyperbolic plane tends to 1/2
Authors: Hansen Benjamin T. , Müller Tobias
Published: May 2021

We consider percolation on the Voronoi tessellation generated by a homogeneous Poisson point process on the hyperbolic plane. We show that the critical probability for the existence of an infinite cluster tends to 1/2 as the intensity of the Poisson process tends to infinity. This confirms a conjecture of Benjamini and Schramm [5].
Monitoring COVID‐19 contagion growth
Authors: Agosto Arianna , Campmas Alexandra , Giudici Paolo , Renda Andrea
Published: May 2021

We present a statistical model that can be employed to monitor the time evolution of the COVID‐19 contagion curve and the associated reproduction rate. The model is a Poisson autoregression of the daily new observed cases and dynamically adapt its estimates to explain the evolution of contagion in terms of a short‐term and long‐term dependence of case counts, allowing for a comparative evaluation of health policy measures. We have applied the model to 2020 data from the countries most hit by the virus. Our empirical findings show that the proposed model describes the evolution of contagion dynamics and determines whether contagion growth can be affected by health policies. Based on our findings, we can draw two health policy conclusions that can be useful for all countries in the world. First, policy measures aimed at reducing contagion are very useful when contagion is at its peak to reduce the reproduction rate. Second, the contagion curve should be accurately monitored over time to apply policy measures that are cost‐effective.
Stressful life events and psychosis: Gender differences
Authors: Mansueto Giovanni , Faravelli Carlo
Published: May 2021

There is evidence that stressful events are associated with psychosis. This study aimed to explore sex differences in the association between stressful life events occurring during childhood and adulthood and psychosis. A total of 78 psychotic patients and 156 controls were enrolled. Childhood adversities were evaluated using a validated semi‐structured interview and the Childhood Experience of Care and Abuse Questionnaire. Recent life events were recorded using a semi‐structured interview with a normative and contextual approach. The diagnosis of psychosis was made according to Jablensky's criteria. χ2 and t‐test statistical analyses were run. Odds ratios were calculated in logistic regression. People with psychosis reported more exposure to both childhood adversities and recent events than the general population. An excess of childhood physical abuse was found among male psychotic patients, whereas both childhood sexual abuse and recent life events were overrepresented among female patients in comparison with the general population. There was a cumulative effect of stressful life events on psychosis, although it was stronger among females than in males. It is likely that there are gender differences in the association between stressful life events and psychosis.
Dimensionality reduction of complex reaction networks in heterogeneous catalysis: From linear‐scalingrelationships to statistical learning techniques
Authors: Pablo‐García Sergio , García‐Muelas Rodrigo , Sabadell‐Rendón Albert , López Núria
Published: May 2021

The mechanistic analysis in heterogeneous catalysis is based on listing all elementary steps and evaluating explicitly their energies. To this end, computational models based on Density Functional Theory have become a standard to estimate the information needed in mechanistic studies. Typically, either the minimum energy paths or those with the smaller span are summarized in reaction profiles. Such simplifications gather a lot of information, although further dimensionality reduction is required to obtain the most relevant descriptors of catalytic activity and generate the so‐called volcano plots. The selection of descriptors has been traditionally based on simple intermediates, such as central atoms in small molecules (as C in CH4), which have good thermodynamic correlations to other fragments containing them. Yet, in emerging processes (recent studies), the number of intermediates involved increase, configurational effects and lateral interactions become significant, and complex materials with low symmetry are employed, thus the simple rules encapsulated in linear scaling relationships lose their predictive power due to error accumulation. At the same time, large datasets generated for the intermediates call for statistical analysis and thus these techniques are being leveraged to chemical systems, particularly to reduce their dimensionality.

This article is categorized under:

Structure and Mechanism > Reaction Mechanisms and Catalysis

Structure and Mechanism > Computational Materials Science

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Analytic structure of all loop banana integrals
Authors: Bönisch Kilian , Fischbach Fabian , Klemm Albrecht , Nega Christoph , Safari Reza
Published: May 2021

Abstract

Using the Gelfand-Kapranov-Zelevinskĭ system for the primitive cohomology of an infinite series of complete intersection Calabi-Yau manifolds, whose dimension is the loop order minus one, we completely clarify the analytic structure of all banana integrals with arbitrary masses. In particular, we find that the leading logarithmic structure in the high energy regime, which corresponds to the point of maximal unipotent monodromy, is determined by a novel$$ \hat{\Gamma}\hbox{-} \mathrm{class} $$Γ̂‐classevaluation in the ambient spaces of the mirror, while the imaginary part of the integral in this regime is determined by the$$ \hat{\Gamma}\hbox{-} \mathrm{class} $$Γ̂‐classof the mirror Calabi-Yau manifold itself. We provide simple closed all loop formulas for the former as well as for the Frobeniusκ-constants, which determine the behaviour of the integrals when the momentum square equals the sum of the masses squared, in terms of zeta values. We extend our previous work from three to four loops by providing for the latter case a complete set of (inhomogeneous) Picard-Fuchs differential equations for arbitrary masses. This allows to evaluate the banana integral in very short time to very high numerical precision for all values of the physical parameters. Using modular properties of the periods we determine the value of the maximal cut equal mass four-loop integral at the attractor points in terms of periods of modular weight two and four Hecke eigenforms and the quasiperiods of their meromorphic cousins.
Zilch vortical effect for fermions
Authors: Alexandrov Artem , Mitkin Pavel
Published: May 2021

Abstract

We consider the notion of zilch current that was recently discussed in the literature as an alternative helicity measure for photons. Developing this idea, we suggest the generalization of the zilch for the systems of fermions. We start with the definition of the photonic zilch current in chiral kinetic theory framework and work out field-theoretical definition of the fermionic zilch using the Wigner function formalism. This object has similar properties to the photonic zilch and is conserved in the non-interacting theory. We also show that, in full analogy with a case of photons, the fermionic zilch acquires a non-trivial contribution due to the medium rotation - zilch vortical effect (ZVE) for fermions. Combined with a previously studied ZVE for photons, these results form a wider set of chiral effects parameterized by the spin of the particles and the spin of the current. We briefly discuss the origin of the ZVE, its possible relation to the anomalies in the underlying microscopic theory and possible application for studying the spin polarization in chiral media.
Anomaly inflow and holography
Authors: Hong Sungwoo , Rigo Gabriele
Published: May 2021

Abstract

We systematically study the perturbative anomaly inflow by the bulk Chern-Simons (CS) theory in a slice of five-dimensional anti-de Sitter spacetime (AdS5). The introduction of UV and IR 3-branes makes the anomaly story remarkably rich and many interesting aspects can be obtained, including weakly gauging and spontaneous symmetry breaking of the global symmetries of the dual 4D CFT. Our main contribution is to provide a unified and comprehensive discussion of the subject, together with a detailed description of the dual CFT picture for each case. To this end, we employ a gauge-fixed effective action suitable for a holographic study, which allows us to incorporate general UV and IR boundary conditions (BCs). As part of the process, we reproduce many known results in the literature, such as ’t Hooft anomaly matching for unbroken symmetry (Neumann IR-BC) and (gauged) Wess-Zumino-Witten (WZW) action for broken symmetry (IR-BC breaks the bulk group G → H). In addition, we show that anomaly matching occurs for ABJ anomalies as well as ’t Hooft anomalies, which suggests anomalies inflowed from the bulk CS theory are necessarily free of mixed anomalies with the confining gauge force of the 4D dual CFT. In the case of broken symmetry, we prove that the “would-be” Goldstone bosons associated with the weakly gauged symmetry are completely removed by a proper field redefinition, provided the anomaly from the bulk is exactly cancelled by the boundary contribution, hence confirming the standard expectation. Moreover, we present a holographic formulation of Witten’s argument for the quantization condition for the WZW action, and argue in favor of an alternative way to obtain the same condition using a “deformed” theory (different BCs). We work out several examples, including a product group with mixed anomaly, and identify the corresponding dual CFT picture. We consider a fully general case typically arising in the context of dynamical electroweak symmetry breaking.
From symmetric product CFTs to AdS3
Authors: Gaberdiel Matthias R. , Gopakumar Rajesh , Knighton Bob , Maity Pronobesh
Published: May 2021

Abstract

Correlators in symmetric orbifold CFTs are given by a finite sum of admissible branched covers of the 2d spacetime. We consider a Gross-Mende like limit where all operators have large twist, and show that the corresponding branched covers can be described via a Penner-like matrix model. The limiting branched covers are given in terms of the spectral curve for this matrix model, which remarkably turns out to be directly related to the Strebel quadratic differential on the covering space. Interpreting the covering space as the world-sheet of the dual string theory, the spacetime CFT correlator thus has the form of an integral over the entire world-sheet moduli space weighted with a Nambu-Goto-like action. Quite strikingly, at leading order this action can also be written as the absolute value of the Schwarzian of the covering map.

Given the equivalence of the symmetric product CFT to tensionless string theory on AdS3, this provides an explicit realisation of the underlying mechanism of gauge-string duality originally proposed in [1] and further refined in [2].
The 300 “correlators” suggests 4D, $$ \mathcal{N} $$ = 1 SUSY is a solution to a set of Sudoku puzzles
Authors: Cianciara Aleksander J. , James Gates S. , Hu Yangrui , Kirk Renée
Published: May 2021

Abstract

A conjecture is made that the weight space for 4D, $$ \mathcal{N} $$
N
-extended supersymmetrical representations is embedded within the permutahedra associated with permutation groups 𝕊d. Adinkras and Coxeter Groups associated with minimal representations of 4D, $$ \mathcal{N} $$
N
= 1 supersymmetry provide evidence supporting this conjecture. It is shown that the appearance of the mathematics of 4D, $$ \mathcal{N} $$
N
= 1 minimal off-shell supersymmetry representations is equivalent to solving a four color problem on the truncated octahedron. This observation suggest an entirely new way to approach the off-shell SUSY auxiliary field problem based on IT algorithms probing the properties of 𝕊d.
Analytic critical points of charged Rényi entropies from hyperbolic black holes
Authors: Ren Jie
Published: May 2021

Abstract

We analytically study phase transitions of holographic charged Rényi entropies in two gravitational systems dual to the $$ \mathcal{N} $$
N
= 4 super-Yang-Mills theory at finite density and zero temperature. The first system is the Reissner-Nordström-AdS5 black hole, which has finite entropy at zero temperature. The second system is a charged dilatonic black hole in AdS5, which has zero entropy at zero temperature. Hyperbolic black holes are employed to calculate the Rényi entropies with the entangling surface being a sphere. We perturb each system by a charged scalar field, and look for a zero mode signaling the instability of the extremal hyperbolic black hole. Zero modes as well as the leading order of the full retarded Green’s function are analytically solved for both systems, in contrast to previous studies in which only the IR (near horizon) instability was analytically treated.
Versorgung von rheumatologischen Patienten während des Lockdowns im Frühjahr 2020
Authors: Thiele Thea , Beider Sonja , Kühl Henrik , Mielke Gudrun , Holz Anna , Hirsch Stefanie , Witte Torsten , Hoeper Kirsten , Cossmann Anne , Happle Christine , Jablonka Alexandra , Ernst Diana
Published: May 2021

Hintergrund

In der ambulanten Versorgung wurde Telemedizin im Lockdown von März bis Mai 2020 eingesetzt. Ziel der Studie war es, Patienten aus einer Praxis und der Hochschulambulanz bezüglich Patientenzufriedenheit mit Telemedizin, COVID-19-Sorgen und Impfverhalten auszuwerten sowie die Gesprächsführung durch eine rheumatologische Fachassistenz (RFA) mit einem Arzt zu vergleichen.

Methoden

Patienten mit rheumatoider Arthritis, Psoriasisarthritis oder Spondyloarthritis ohne Therapieänderung seit der letzten Vorstellung wurde ein telemedizinischer Ersatztermin im Rahmen dieser Studie bei Terminabsage durch die versorgenden Zentren angeboten. Randomisiert wurden sie von einem Arzt oder einer RFA (RFA nur Universität) telemedizinisch versorgt. Die Anamnese erfolgte telefonisch standardisiert mittels Fragebogen. Die Krankheitsaktivität wurde mittels modifizierten Clinical Disease Activity Score (CDAI) und BASDAI festgestellt. Im Anschluss erhielten die Patienten einen pseudonymisierten Evaluationsbogen.

Ergebnisse

Von 112/116 (96 %) eingeschlossenen Patienten schickten 88/112 (79 %) den Fragebogen zurück. RFAs führten 19/112 (17 %) Telefonate. Die Therapie wurde in 19/112 (17 %) geändert. Die meisten Sorgen bezüglich COVID-19 hatten Patienten mit der höchsten Krankheitsaktivität (p = 0,031), den meisten schmerzhaften Gelenken (p = 0,001) sowie den meisten Schmerzen (VAS Score ≥7) (p = 0,009). Diese Patienten hätten auch selbst ihren Termin abgesagt (p = 0,015). Die Patientenzufriedenheit mit der Gesprächsführung war gut (Mittelwert 4,3/5,0 modifizierter FAPI), unabhängig von der Institution, der Gesprächsdauer oder dem Gesprächspartner. Patienten mit hoher Schmerzintensität waren am unzufriedensten (p = 0,036); 42/100 (38,2 %) Patienten waren gegen Pneumokokken und 59/100 (53,6 %) gegen Influenza geimpft.

Für ausgewählte Patienten ist die telemedizinische Versorgung im Rahmen eines Telefongespräches gut geeignet. Hinsichtlich der Patientenzufriedenheit ist die Delegation einer telefonischen Visite an eine RFA möglich. Bezüglich des Impfverhaltens besteht Verbesserungsbedarf.
Flexor tenodesis procedure in the treatment of lesser toe deformities
Authors: de Cesar Netto Cesar , Schmidt Eli L , Lalevee Matthieu , Mansur Nacime Salomao Barbachan
Published: May 2021

In this technical report study, we describe the use of a flexor tenodesis procedure in the treatment of lesser toe deformities (LTD). Using a specific implant, both the flexor digitorum longus and brevis tendons are attached to the plantar aspect of the proximal phalanx, allowing dynamic correction of flexible deformities of metatarsophalangeal and interphalangeal joints. Good clinical results and absence of complications were observed in a series of 3 patients, with considerable correction of the LTD, and absence of substantial residual floating toe or metatarsophalangeal joint stiffness.

Level of evidence

V – Technical Report/Case Report/Expert Opinion.
Cell wall characteristics during sexual reproduction of Mougeotia sp. (Zygnematophyceae) revealed by electron microscopy, glycan microarrays and RAMAN spectroscopy
Authors: Permann Charlotte , Herburger Klaus , Niedermeier Martin , Felhofer Martin , Gierlinger Notburga , Holzinger Andreas
Published: May 2021

Mougeotia spp. collected from field samples were investigated for their conjugation morphology by light-, fluorescence-, scanning- and transmission electron microscopy. During a scalarifom conjugation, the extragametangial zygospores were initially surrounded by a thin cell wall that developed into a multi-layered zygospore wall. Maturing zygospores turned dark brown and were filled with storage compounds such as lipids and starch. While M. parvula had a smooth surface, M. disjuncta had a punctated surface structure and a prominent suture. The zygospore wall consisted of a polysaccharide rich endospore, followed by a thin layer with a lipid-like appaerance, a massive electron dense mesospore and a very thin exospore composed of polysaccharides. Glycan microarray analysis of zygospores of different developmental stages revealed the occurrence of pectins and hemicelluloses, mostly composed of homogalacturonan (HG), xyloglucans, xylans, arabino-galactan proteins and extensins. In situ localization by the probe OG7-13AF 488 labelled HG in young zygospore walls, vegetative filaments and most prominently in conjugation tubes and cross walls. Raman imaging showed the distribution of proteins, lipids, carbohydrates and aromatic components of the mature zygospore with a spatial resolution of ~ 250 nm. The carbohydrate nature of the endo- and exospore was confirmed and in-between an enrichment of lipids and aromatic components, probably algaenan or a sporopollenin-like material. Taken together, these results indicate that during zygospore formation, reorganizations of the cell walls occured, leading to a resistant and protective structure.
Application of Dried Blood Spots and Serum Samples for the Determination of Vitamin D Metabolites in the Group of Healthy Women and with Hashimoto’s Thyroiditis
Authors: Rola R. , Trusewicz E. , Bieńkowski T. , Studzińska S.
Published: May 2021

Purpose

The relationship between Hashimoto's thyroiditis and vitamin D concentration was already presented in many studies. The aim of this study was to analyze the differences in the concentration of vitamin D metabolites between healthy women and women with Hashimoto's thyroiditis (HT).

Methods

The quantitative analysis of five vitamin D metabolites was carried out using liquid chromatography coupled with tandem mass spectrometry. The analyzed materials were serum and dried blood spots (DBS). The results obtained for the two materials were also compared.

Results

No statistically significant differences were found in the mean concentration of the 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 1,25(OH)2D3 metabolites between the test and the control groups. However, a strong correlation was found between the 25(OH)D3 and 24,25(OH)2D3 metabolites.

Conclusion

The study showed that healthy women and women with Hashimoto's disease had similar concentration of vitamin D metabolites. Research also proved that DBS is a good alternative to serum. The differences in 25(OH)D concentration were not statistically significant (17.0 and 15.5 ng mL−1 for serum and DBS, respectively). DBS can be successfully used in research on a large group of people, since the process of material collection, as well as sample preparation, is fast and simple. It is also easy to transport and store, and requires small volume of blood.
Structure-preserving interpolation of bilinear control systems
Authors: Benner Peter , Gugercin Serkan , Werner Steffen W. R.
Published: May 2021

In this paper, we extendthe structure-preserving interpolatory model reduction framework, originally developed for linear systems, to structured bilinear control systems. Specifically, we give explicit construction formulae for the model reduction bases to satisfy different types of interpolation conditions. First, we establish the analysis for transfer function interpolation for single-input single-output structured bilinear systems. Then, we extend these results to the case of multi-input multi-output structured bilinear systems by matrix interpolation. The effectiveness of our structure-preserving approach is illustrated by means of various numerical examples.
Fractionation of pulp and precipitated CaCO3–pulp composites: effects on sheet properties of selective CaCO3 precipitation onto fiber size fractions
Authors: Laukala Teija , Backfolk Kaj , Heiskanen Isto
Published: May 2021

CaCO3-pulp composite was prepared via precipitation of calcium hydroxide in the presence of pulp. In order to investigate the precipitation selectivity and mechanism, the substrate pulps and the obtained composites were fractionated (R30, R100, R200, R400 and a sedimented fraction that passed the 400 mesh wire) using a Bauer-McNett unit. The main fractionation criterion was therefore fiber length. The pulp used was CTMP (chemithermomechanical pulp), yielding a precipitated calcium carbonate-chemithermomechanical pulp (PCC-CTMP) composite with a targeted PCC-to-CTMP ratio of 1:1. The PCC consisted primarily of nano-sized primary particles which formed aggregates and clusters on the fibers. When the fiber morphology, zeta potential and surface charge density of the fractions were determined, a correlation was found between the surface charge density of the CTMP and the ash content of the corresponding PCC-CTMP fractions. This supports the hypothesis that the precipitation on the CTMP fiber is driven by the charge interparticle interaction. The use of refined CTMP furnishes and fractionation of the PCC-CTMP furnishes demonstrates that PCC is preferably fixed on fines and fibrils since it appears at a higher content in the fines fractions. Fiber activation via fiber split, removal of primary wall and surface defibrillation enhanced the affinity of the PCC for the fibrils. The laboratory handsheets prepared from the material demonstrated the importance of controlling the substrate fiber properties for the mineral-fiber composite, e.g. via refining, as differences between the refining levels and fractions were found to lead to differences in both optical properties and bonding.

Graphic abstract
Correction to: Student Loans at the Dinner Table: Family Communication Patterns About Student Loans Before Accrual and During Repayment
Authors: Miller Julie , Brady Samantha , Balmuth Alexa , D’Ambrosio Lisa , Coughlin Joseph
Published: May 2021

A correction to this paper has been published: https://doi.org/10.1007/s10834-021-09772-6
Monitoring drought response and chlorophyll content in Quercus by consumer-grade, near-infrared (NIR) camera: a comparison with reflectance spectroscopy
Authors: Raddi Sabrina , Giannetti Francesca , Martini Sofia , Farinella Fabio , Chirici Gherardo , Tani Andrea , Maltoni Alberto , Mariotti Barbara
Published: May 2021

A user-friendly and affordable broad-band digital Near Infrared (NIR) camera (Canon PowerShot S110 NIR) was compared with a narrow-band reflectance spectrometer (USB2000, Ocean Optics) at leaf scale for monitoring changes in response to drought of three ecologically contrasting Quercus species (Q. robur, Q. pubescens, and Q. ilex). We aimed to (a) compare vegetation indices (VIs; that is: NDVI, Normalized Difference Vegetation Index; GNDVI, Green NDVI and NIRv, near-infrared reflectance of vegetation) retrieved by NIR-camera and spectrometer in order to test the reliability of a simple, low-cost, and rapid setup for widespread field applications; (b) to assess if NIR-camera VIs might be used to quantify water stress in oak seedlings; and (c) to track changes in leaf chlorophyll content. The study was carried out during a water stress test on 1-year-old seedlings in a greenhouse. The camera detected plant status in response to drought with results highly comparable to the visible/NIR (VIS/NIR) spectrometer (by calibration and standard geometry). Consistency between VIs and morpho-physiological traits was higher in Q. robur, the most drought-sensitive among the three species. Chlorophyll content was estimated with a high goodness-of-fit by VIs or reflectance bands in the visible range. Overall, NDVI performed better than GNDVI and NIRv, and VIs performed better than single bands. Looking forward, NIR-camera VIs are adequate for the early monitoring of drought stress in oak seedlings (or small trees) in the post-planting phase or in nursery settings, thus offering a new, reliable alternative for when costs are crucial, such as in the context of restoration programs.
Buildings’ Energy Efficiency and the Probability of Mortgage Default: The Dutch Case
Authors: Billio Monica , Costola Michele , Pelizzon Loriana , Riedel Max
Published: May 2021

We investigate the relationship between building energy efficiency and the probability of mortgage default. To this end, we construct a novel panel data set by combining Dutch loan-level mortgage information with provisional building energy ratings provided by the Netherlands Enterprise Agency. Using the logit regression and the extended Cox model, we find that building energy efficiency is associated with a lower probability of mortgage default. There are three possible channels that might drive the results: (i) personal borrower characteristics captured by the choice of an energy-efficient building, (ii) improvements in building performance that could help to free-up the borrower’s disposable income, and (iii) improvements in dwelling value that lower the loan-to-value ratio. We address all three channels. In particular, we find that the default rate is lower for borrowers with less disposable income. The results hold for a battery of robustness checks. This suggests that the energy efficiency ratings complement borrowers’ credit information and that a lender using information from both sources can make superior lending decisions than a lender using only traditional credit information. These aspects are not only crucial for shaping future energy policy, but also have implications for the risk management of European financial institutions.
Does Financial Development Reduce the Poverty Gap?
Authors: de Haan Jakob , Pleninger Regina , Sturm Jan-Egbert
Published: May 2021

Financial development may affect poverty directly and indirectly through its impact on income inequality, economic growth, and financial instability. Previous studies do not consider all these channels simultaneously. To proxy financial development, we use the ratio of private credit to GDP or an IMF composite measure. Our preferred measure for poverty is the poverty gap, i.e. the shortfall from the poverty line. Our fixed effects estimation results for an unbalanced panel of 84 countries over the 1975–2014 period suggest that financial development does not have a direct effect on the poverty gap. However, as financial development leads to greater inequality, which, in turn, results in more poverty, financial development has an indirect effect on poverty through this transmission channel. Only if we use poverty lines of $3.20 or $5.50 (instead of $1.90 a day as in our baseline model) to define the poverty gap, we find that economic growth reduces poverty. This implies that in those cases the overall effect of financial development on poverty may be positive or negative, depending on which indirect effect, i.e. that of income inequality or growth, is stronger. Financial instability does not seem to affect the poverty gap. These results are consistent across various robustness checks.
Characterizing antibiotics in LCA—a review of current practices and proposed novel approaches for including resistance
Authors: Nyberg O. , Rico A. , Guinée J. B. , Henriksson P. J. G.
Published: May 2021

Purpose

With antibiotic resistance (ABR) portrayed as an increasing burden to human health, this study reviews how and to what extent toxicological impacts from antibiotic use are included in LCAs and supplement this with two novel approaches to include ABR, a consequence of antibiotic use, into the LCA framework.

Methods

We review available LCA studies that deal with toxicological aspects of antibiotics to evaluate how these impacts from antibiotics have been characterized. Then, we present two novel approaches for including ABR-related impacts in life cycle impact assessments (LCIAs). The first approach characterizes the potential for ABR enrichment in the environmental compartment as a mid-point indicator, based on minimum selective concentrations for pathogenic bacteria. The second approach attributes human health impacts as an endpoint indictor, using quantitative relationships between the use of antibiotics and human well-being.

Results and discussion

Our findings show that no LCA study to date have accounted for impacts related to ABR. In response, we show that our novel mid-point indicator approach could address this by allowing ABR impacts to be characterized for environmental compartments. We also establish cause-effect pathways between antibiotic use, ABR, and human well-being that generate results which are comparable with USEtox and most endpoint impact assessment approaches for human toxicology.

Conclusions

Our proposed methods show that currently overlooked impacts from ABR enrichment in the environment could be captured within the LCA framework as a robust characterization methodology built around the established impact model USEtox. Substantial amounts of currently unavailable data are, however, needed to calculate emissions of antibiotics into the environment, to develop minimum selective concentrations for non-pathogenic bacteria, and to quantify potential human health impacts from AB use.
Software-based planning of ultrasound and CT-guided percutaneous radiofrequency ablation in hepatic tumors
Authors: van Amerongen M. J. , Mariappan P. , Voglreiter P. , Flanagan R. , Jenniskens S. F. M. , Pollari M. , Kolesnik M. , Moche M. , Fütterer J. J.
Published: May 2021

Objectives

Radiofrequency ablation (RFA) can be associated with local recurrences in the treatment of liver tumors. Data obtained at our center for an earlier multinational multicenter trial regarding an in-house developed simulation software were re-evaluated in order to analyze whether the software was able to predict local recurrences.

Methods

Twenty-seven RFA ablations for either primary or secondary hepatic tumors were included. Colorectal liver metastases were shown in 14 patients and hepatocellular carcinoma in 13 patients. Overlap of the simulated volume and the tumor volume was automatically generated and defined as positive predictive value (PPV) and additionally visually assessed. Local recurrence during follow-up was defined as gold standard. Sensitivity and specificity were calculated using the visual assessment and gold standard.

Results

Mean tumor size was 18 mm (95% CI 15–21 mm). Local recurrence occurred in 5 patients. The PPV of the simulation showed a mean of 0.89 (0.84–0.93 95% CI). After visual assessment, 9 incomplete ablations were observed, of which 4 true positives and 5 false positives for the detection of an incomplete ablation. The sensitivity and specificity were, respectively, 80% and 77% with a correct prediction in 78% of cases. No significant correlation was found between size of the tumor and PPV (Pearson Correlation 0.10; p = 0.62) or between PPV and recurrence rates (Pearson Correlation 0.28; p = 0.16).

Conclusions

The simulation software shows promise in estimating the completeness of liver RFA treatment and predicting local recurrence rates, but could not be performed real-time. Future improvements in the field of registration could improve results and provide a possibility for real-time implementation.
The first robotic transanal minimally invasive surgery in Ireland: a case-based review
Authors: Hannan Enda , Feeney Gerard , Ullah Mohammad Fahad , Amin Kamran , Coffey John Calvin , Peirce Colin
Published: May 2021

Transanal minimally invasive surgery (TAMIS) has gained worldwide acceptance as a means of local excision of early rectal cancers and benign rectal lesions. However, it is technically challenging due to the limitations of rigid laparoscopic instruments in the narrow rectal lumen. Robotic platforms offer improved ergonomics that are valuable in operative fields with limited space. Robotic TAMIS represents an exciting new development that may be more versatile than traditional TAMIS. In this review, we describe the first case of robotic TAMIS performed in our country and a review of current literature on the technique.
A review and perspective on the assessment, management and prevention of fragility fractures in patients with osteoporosis and chronic kidney disease
Authors: Hampson Geeta , Elder Grahame J. , Cohen-Solal Martine , Abrahamsen Bo
Published: May 2021

This article aims to review the methods used for the assessment of fracture risk and the use of osteoporosis medications for fracture prevention in the population with CKD, and highlights the difficulties faced by clinicians in the management of these patients and the latest recommendations and guidelines. Chronic kidney disease (CKD) and osteoporosis often co-exist in older adults, and they present a major healthcare challenge. CKD mineral and bone disorder (CKD-MBD) occurs as renal function declines and this syndrome affects most patients in CKD stages 4 and 5. The biochemical abnormalities of CKD-MBD, renal bone disease and risk factors associated with age-related bone loss and osteoporosis lead to a cumulative effect on fracture risk and mortality. There is a need for routine evaluation of fracture risk and fracture prevention in this population. Measurement of bone mineral density (BMD) and the use of the FRAX tool have predictive value for incident fractures in the general population and in CKD. This enables physicians to identify CKD patients most at risk of sustaining a fragility fracture and allows a more targeted approach to fracture prevention. Data analysis from the pivotal trials of therapeutic agents used in osteoporosis show that these drugs can be considered in mild and moderate CKD (stages 1–3 CKD). Off-label drug use in patients with CKD-MBD and more severe renal impairment (CKD stages 4 and 5) could offer significant benefits to sub-groups of patients when carefully tailored to each individual’s bone turnover and calcium and phosphate balance. However, this requires a selective approach and treatment decisions based on inference from pathophysiology while we await further trials. Guidelines advocate the correction and/or reduction of the biochemical abnormalities of CKD-MBD before initiation of treatment with osteoporosis drugs and close monitoring during treatment.
Long-Term Results of Hybrid Left Ventricular Reconstruction in the Treatment of Ischemic Cardiomyopathy
Authors: Naar Jan , Skalský Ivo , Krűger Andreas , Málek Filip , Van Bladel Kevin , Annest Lon S. , Moučka Petr , Mráz Tomáš , Reddy Vivek Y. , Neužil Petr
Published: May 2021

The evidence supporting surgical aneurysmectomy in ischemic heart failure is inconsistent. The aim of the study was to describe long-term effect of minimally invasive hybrid transcatheter and minithoracotomy left ventricular (LV) reconstruction in patients with ischemic cardiomyopathy. Twenty-three subjects with transmural anterior wall scarring, LV ejection fraction 15–45%, and New York Heart Association class ≥ II were intervened using Revivent TC anchoring system. LV end-systolic volume index was reduced from 73.2 ± 27 ml at baseline to 51.5 ± 22 ml after 6 months (p < 0.001), 49.9 ± 20 ml after 2 years (p < 0.001), and 56.1 ± 16 ml after 5 years (p = 0.047). NYHA class improved significantly at 5 years compared to baseline. Six-min walk test distance increased at 2 years compared to the 6-month visit. Hybrid LV reconstruction using the anchoring system provides significant and durable LV volume reduction during 5-year follow-up in preselected patients with ischemic heart failure.

Graphical abstract
Zyklisches di-AMP — ein essenzielles Signalmolekül mit vielen Facetten
Authors: Stülke Jörg
Published: May 2021

Many bacteria form the second messenger nucleotide cyclic di-AMP (c-di-AMP). This molecule is essential for many of the bacteria that produce it due to its central role in the control of potassium and osmolyte homeostasis. Moreover, under conditions of potassium starvation, a c-di-AMP target protein can trigger (p)ppGpp accumulation and thus a global reprogramming of cellular activities. Moreover, c-di-AMP formed by pathogens binds the human STING protein and triggers thus an immune response.
RNA-basierte Regulation der Genexpression: künstliche Genschalter
Authors: Finke Monika , Spöring Maike , Hartig Jörg S.
Published: May 2021

RNA-based gene control mechanisms pose an elegant and straightforward way to switch on, off, or fine-tune transgene expression without the need for expressing regulatory proteins. A small molecule effector binds directly to a ligand-binding aptamer RNA structure and thereby modulates expression of an associated target gene. We established genetic switches based on regulation of self-cleaving ribozymes and polyadenylation that allow for control of transgene expression in bacteria, yeast, human cell lines and Caenorhabditis elegans in a robust and dose-dependent manner.
SARS-CoV-PLpro-Inhibitoren als mögliche Breitspektrum-Virostatika
Authors: Hammerschmidt Stefan Josef , Müller Patrick , Schirmeister Tanja
Published: May 2021

The SARS-CoV-encoded papain-like cysteine protease (PLpro) plays crucial roles in viral replication and maturation processes. It is required to cleave the precursor polyproteins into functional proteins. Thus, it is considered to be a promising target for developing specific drugs. For rational optimization of hit compounds, information about the structure-activity relationship (SAR) is fundamental. Herein, we characterize isoindolines as a new class of PLpro inhibitors.