bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidation of iso‐propanol and n‐butanol by catalase encapsulated within macroporous polyampholyte cryogel matrix
Authors: Smagulova Indira , Tatykhanova Gulnur , Shakhvorostov Alexey , Akbayeva Dina , Kudaibergenov Sarkyt
Published: May 2021

Iso‐propanol and n‐butanol were oxidized using catalase encapsulated within monolithic polyampholyte cryogel, p(APTAC‐co‐AMPS), derived from an anionic monomer, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid sodium salt (AMPS), and a cationic monomer, (3‐acrylamidopropyl) trimethylammonium chloride (APTAC). Macroporous polyampholyte cryogels containing various amounts of catalase were synthesized in situ under cryo‐polymerization conditions at a molar ratio of monomers [APTAC]:[AMPS] = 75:25 mol.% in the presence of 10 mol.% cross‐linking agent, N,N‐methylenebisacrylamide (MBAA). The oxidation of alcohols was carried out inside of a monolithic macroporous sample by passing the mixture of alcohol and hydrogen peroxide through at a fixed flow‐rate. Analysis using gas–liquid chromatography and gas chromatography–mass spectrometry showed that iso‐propanol is converted to acetone at a yield of 87.6%, whereas n‐butanol is converted to butyraldehyde at a yield of 80% at 20°C and atmospheric pressure. The influence of pH, temperature, and ratios of substrate to hydrogen peroxide on the degree of conversion of iso‐propanol was evaluated. SEM images of cryogel‐encapsulated catalase before and after several cycles of oxidation of iso‐propanol show collapsing, among other alterations, in the morphology of the cryogel matrix. The oxidation mechanism of iso‐propanol and n‐butanol using cryogel‐encapsulated catalase was suggested.
Functional motor improvement during inpatient rehabilitation among older adults with traumatic brain injury
Authors: Evans Emily , Krebill Cicely , Gutman Roee , Resnik Linda , Zonfrillo Mark R. , Lueckel Stephanie N. , Zhang Wenhan , Kumar Raj G. , Dams‐O'Connor Kristen , Thomas Kali S.
Published: May 2021

Background

Older adults comprise an increasingly large proportion of patients with traumatic brain injury (TBI) receiving care in inpatient rehabilitation facilities (IRF). However, high rates of comorbidities and evidence of declining preinjury health among older adults who sustain TBI raise questions about their ability to benefit from IRF care.

Objectives

To describe the proportion of older adults with TBI who exhibited minimal detectable change (MDC) and a minimally clinically important difference (MCID) in motor function from IRF admission to discharge; and to identify characteristics associated with clinically meaningful improvement in motor function and better discharge functional status.

Design

This retrospective cohort study used Medicare administrative data probabilistically linked to the National Trauma Data Bank to estimate the proportion of patients whose motor function improved during inpatient rehabilitation and identify factors associated with meaningful improvement in motor function and motor function at discharge.

Setting

Inpatient rehabilitation facilities in the United States.

Patients

Fee‐for‐service Medicare beneficiaries with TBI.

Main Outcome Measures

Minimal Detectable Change (MDC) and Minimally Clinically Important Difference (MCID) in the Functional Independence Measure motor (FIM‐M) score from admission to discharge, and FIM‐M score at IRF discharge.

Results

From IRF admission to discharge 84% of patients achieved the MDC threshold, and 68% of patients achieved the MCID threshold for FIM‐M scores. Factors associated with a higher probability of achieving the MCID for FIM‐M scores included better admission motor and cognitive function, lower comorbidity burden, and a length of stay longer than 10 days but only among individuals with lower admission motor function. Older age was associated with a lower FIM‐M discharge score, but not the probability of achieving the MCID in FIM‐M score.

Conclusion

Older adults with TBI have the potential to improve their motor function with IRF care. Baseline functional status and comorbidity burden, rather than acute injury severity, should be used to guide care planning.
The C5‐substituent effects on the formic acid‐assisted tautomerization of protonated cytosine: A lower isomerization barrier and potential biological importance
Authors: Jin Lingxia , Lv Mengdan , Shi Shengnan , Lu Jiufu , Wang Qin , Yu Xiaohu , Huang Wendeng
Published: May 2021

The continuous oxidative products of 5‐methylcytosine are called the “three new DNA bases.” When it comes to 5‐formylcytosine and 5‐carboxylcytosine, the electron densities at N3 sites of both bases tend to be decreased due to the presence of the electron withdrawing groups of CHO and COOH. The vital steps for mutations of DNA are tautomerism in nucleotide bases. Although there are great deal of studies on the protonated new DNA bases in photophysical and photochemical reactivity, the relationship of pKa at N3 position with the intermolecular tautomerization barrier is seldom reported. The C5 atom of cytosine is substituted by the CH3, HOCH2, CHO, and COOH, and their isomerization barriers in the presence of HCOOH have nearly linear relationship with the pKa at N3 positions of these bases. The solvent water affects the activation free energies of these paths, and yet their isomerization mechanisms are still more favorable in aqueous solution. Meantime, the rate constants could be calculated by the conventional transition state theory with Wigner's tunneling correction. The corrected rate constant for these paths is very consistent with uncorrected results. Finally, the product and reaction complexes are in a fast tautomerism equilibrium, which is a synchronous double proton transfer mechanism. The product complexes may further dissociated into the monomers. These researches may give a chemical basis for differentiating 5‐fCyt and 5‐caCyt from Cyt, 5‐MeCyt, and 5‐HCyt in the protein‐DNA interactions which might be used for selective recognition.
Family rules, routines, and caregiver distress during the first year of pediatric cancer treatment
Authors: Bates Carolyn R. , Pallotto Isabella K. , Moore Rachel M. , Fornander Mirae J. , Covitz Lynne M. , Dreyer Gillette Meredith L.
Published: May 2021

Objective

A new diagnosis of pediatric cancer may disrupt family functioning. The current study aimed to describe changes in family rules and routines during the first year of pediatric cancer treatment, and to explore associations with demographics, illness factors, and caregiver distress.

Methods

This exploratory mixed‐methods, cross‐sectional study examined 44 primary caregivers of youth in treatment for a new cancer diagnosis in 2019 and 2020, before the onset of the COVID‐19 pandemic. Caregivers completed validated questionnaires assessing demographic and child illness characteristics, psychosocial distress, and cancer‐related stressors, and participated in a semi‐structured interview about family rules and routines.

Results

Caregivers reported changes in bedtime, mealtime, and school routines, relaxed behavioral expectations and rules around screen time, and new rules and routines around treatment, medications, and infection control. Caregivers with elevated levels of psychosocial distress reported more changed routines than caregivers with low levels of psychosocial distress. Caregivers who endorsed more cancer‐related stressors reported more new rules and routines than those who reported fewer cancer‐related stressors. Demographic and illness factors were not significantly associated with the number of changed, new, or stable family rules and routines.

Conclusions

Families may relax rules and routines during the first several months of diagnosis, and this may be related to side effects of treatment and limited caregiver capacity. The long‐term impact of changes in family rules and routines during cancer treatment warrants further study given that accommodating parenting strategies have been associated with adverse short‐ and long‐term child health and behavior outcomes.
Thermally‐Driven Changes to Porosity in TATB‐Based High Explosives
Authors: Armstrong Christopher L. , Mang Joseph T.
Published: May 2021

Ultra‐small‐ and small‐angle neutron scattering techniques were employed to quantify thermally driven changes to the microstructure of the TATB‐based composite high explosive, PBX 9502. Samples of PBX 9502 were studied in‐situ at temperatures ranging from 25 to 220 °C and after re‐equilibration at ambient temperature. Significant changes to the void size and morphology within the PBX 9502 microstructure were observed upon heating and are consistent with the known increase in the shock sensitivity of thermally‐treated PBX 9502. More extensive microstructural changes were found after the thermally treated samples were re‐equilibrated at ambient temperature. Utilizing a model of ramified porosity, the size and the volume and surface dimensions of voids in the PBX 9502 microstructure were quantified as a function of temperature. The temperature dependence of the void radius of gyration is well correlated with the known increase in the shock sensitivity of PBX 9502 with increasing temperature, providing a microstructural origin for the increased shock sensitivity of PBX 9502 at elevated temperatures.
Stable Molybdenum Nitride Contact for Efficient Silicon Solar Cells
Authors: Li Yajuan , Li Yuxiong , Zhang Guohua , Li Jingye , Liang Dong , Wu Yanfei , Song Tao , Yang Xinbo , Li Dongdong , Jiang Chunping , Sun Baoquan
Published: May 2021

Carrier‐selective passivating contacts play a crucial role in highly efficient silicon solar cells targeting the cost‐effective photovoltaic industry. Widely developed hole‐selective passivating‐contact molybdenum oxide (MoOx) exhibits inferior long‐term stability induced by chemical reactions between the MoOx and the adjacent metals. Herein, low‐temperature magnetron‐sputtering‐deposited molybdenum nitride (MoNx) films are developed as stable hole‐selective passivating contacts for crystal silicon solar cells. The work function of the MoNx films can be as deep as 5.62 eV featuring a low resistivity of 5.0 × 10−4 Ω cm by optimizing the deposition process. Quasi‐metallic MoNx integrated with a MoOx passivating layer is verified to act as effective hole‐selective passivating contacts for crystal silicon solar cells, yielding a power convertion efficiency (PCE) above 17%. Although the hole‐selective passivation of MoNx films is inferior to fresh MoOx ones, the device performance with MoNx film is kept stable with time in air exposure and surpasses MoOx films after 6 months. The stable performance is ascribed to the metal electrodes diffusion barrier and insusceptible work function of MoNx films compared to MoOx films. This work makes a preliminary exploration to develop efficient crystal silicon solar cells with stable and cost‐effective metal nitrides as hole‐selective passivating contacts.
The individual‐level surrogate threshold effect in a causal‐inference setting with normally distributed endpoints
Authors: Van der Elst Wim , Abad Ariel Alonso , Coppenolle Hans , Meyvisch Paul , Molenberghs Geert
Published: May 2021

In the meta‐analytic surrogate evaluation framework, the trial‐level coefficient of determination quantifies the strength of the association between the expected causal treatment effects on the surrogate (S) and the true (T) endpoints. Burzykowski and Buyse supplemented this metric of surrogacy with the surrogate threshold effect (STE), which is defined as the minimum value of the causal treatment effect on S for which the predicted causal treatment effect on T exceeds zero. The STE supplements with a more direct clinically interpretable metric of surrogacy. Alonso et al. proposed to evaluate surrogacy based on the strength of the association between the individual (rather than expected) causal treatment effects on S and T. In the current paper, the individual‐level surrogate threshold effect (ISTE) is introduced in the setting where S and T are normally distributed variables. ISTE is defined as the minimum value of the individual causal treatment effect on S for which the lower limit of the prediction interval around the individual causal treatment effect on T exceeds zero. The newly proposed methodology is applied in a case study, and it is illustrated that ISTE has an appealing clinical interpretation. The R package surrogate implements the methodology and a web appendix (supporting information) that details how the analyses can be conducted in practice is provided.
Are the body shape index, the body roundness index and waist‐to‐hip ratio better than BMI to predict recurrent pregnancy loss?
Authors: Kiremitli Tunay , Kiremitli Sevil , Ulug Pasa , Dinc Kemal , Uzel Kemine , Arslan Yusuf Kemal
Published: May 2021

Purpose

Etiology could not be determined in approximately 50% of recurrent pregnancy loss cases, and it was named unexpected recurrent pregnancy loss(URPL). A body shape index(ABSI), body roundness index(BRI), and waist‐to‐hip ratio(WtHR) are new indexes that are superior to BMI in showing body fat distribution. We aimed to investigate the potency of ABSI, BRI, and WtHR in URPL, their superiority to BMI, and their suitability for clinical use.

Methods

One hundred and thirty‐eight patients between the ages of 20‐40 who applied to our hospital for URPL between January 2016 and December 31, 2020 were included in our study. Weight, height, waist circumference, and hip circumference were measured, and indexes were calculated. Differences between the URPL and control groups were calculated using the IBM SPSS program.

Results

There was a significant difference between the two groups for BRI, ABSI, and WtHR values, while there was no significant difference in BMI. BRI(4.4 ± 1.7vs3.9 ± 1.5), ABSI(0.08 ± 0.005 vs 0.078 ± 0.004), and WtHR(0.84 ± 0.06vs0.82 ± 0.05) values were higher in the URPL group. ROC analysis showed us that BRI, ABSI, and WtHR have a diagnostic value for URPL(P < .05). When indexes were above the cutoff values, RPL risk increased 3.59 times in ABSI, 2.26 times in BRI, and 2.9 times in WtHR(P < .05).

Conclusions

The relationship between obesity and URPL can be explained more clearly by using effective indexes that show body fat distribution rather than BMI. Ethics committee approval was obtained from Erzincan Binali Yildirim University in 14.01.2021. Clinical Research Ethics Committee no: 01/01.
Emergence of Ni‐Based Chalcogenides (S and Se) for Clean Energy Conversion and Storage
Authors: Maurya Oshnik , Khaladkar Somnath , Horn Michael R. , Sinha Bhavesh , Deshmukh Rajendra , Wang Hongxia , Kim TaeYoung , Dubal Deepak P. , Kalekar Archana
Published: May 2021

Nickel chalcogenide (S and Se) based nanostructures intrigued scientists for some time as materials for energy conversion and storage systems. Interest in these materials is due to their good electrochemical stability, eco‐friendly nature, and low cost. The present review compiles recent progress in the area of nickel‐(S and Se)‐based materials by providing a comprehensive summary of their structural and chemical features and performance. Improving properties of the materials, such as electrical conductivity and surface characteristics (surface area and morphology), through strategies like nano‐structuring and hybridization, are systematically discussed. The interaction of the materials with electrolytes, other electro‐active materials, and inactive components are analyzed to understand their effects on the performance of energy conversion and storage devices. Finally, outstanding challenges and possible solutions are briefly presented with some perspectives toward the future development of these materials for energy‐oriented devices with high performance.
Two‐Dimensional Metal Halide Perovskite Nanosheets for Efficient Photocatalytic CO2 Reduction
Authors: Wu Li-Yuan , Zhang Meng-Ran , Feng You-Xiang , Zhang Wen , Zhang Min , Lu Tong-Bu
Published: May 2021

Metal halide perovskite (MHP) nanocrystals (NCs) have attained ever‐increasing attention in the field of artificial photosynthesis, due to their desirable strong light‐harvesting capacity and long lifetime of photogenerated carriers. However, the well‐known inherent instability and inferior activity of MHP NCs limit their application foreground in photocatalysis. Herein, a series of 2D MHP nanosheets have been synthesized based on a facile approach at room temperature. These 2D materials are used as photocatalysts for the photocatalysis of CO2 reduction without any organic sacrificial agents, which display significantly improved stability compared to traditional MHP NCs in water‐contained reaction system. More importantly, benefitting from the large proportion of low‐coordinated metal atoms and short carrier diffusion distance, these MHP nanosheets exhibit a remarkably increased performance for photocatalytic CO2 reduction. The judicious modulation of halide component endows the MHP nanosheets with a highest electron consumption rate of 87.8 μmol g−1 h−1 among the reported pure MHP catalysts for photocatalytic CO2 conversion, which is over seven times higher than that of traditional MHP NCs.
Methodological aspects of the acromiohumeral distance measurement with ultrasonography—Reliability and effects of extrinsic and intrinsic factors in overhead and non‐overhead athletes
Authors: Rentz Carolin , Legerlotz Kirsten
Published: May 2021

Introduction

To improve comparability and interpretation of acromiohumeral distance (AHD) measurements, consequences of varying methodological approaches and population specific effects have to be known. This study aimed to investigate the intra‐ and inter‐rater reliability of different AHD ultrasound image analysis approaches in asymptomatic overhead‐ and non‐overhead athletes. Furthermore, the impact of shoulder muscle activity as well as relationships between AHD and individual factors were examined in different measurement positions.

Methods

Isometric shoulder strength, shoulder range of motion (ROM) and AHD were measured in 27 male and female participants (14 overhead athletes; 13 non‐overhead athletes, age = 27.8 ± 5.2 years).

Results

Intra‐rater reliability (ICC3,1 0.996) was excellent. Inter‐rater reliability for the AHD defined as shortest distance between the most infero‐lateral edge of the acromion and the most superior aspect of the humerus (ICC2,1 0.997) was minimally higher than for the AHD defined as perpendicular distance (ICC2,1 0.959). Increased shoulder muscle activity led to larger AHD reductions with abduction. Higher shoulder strength was associated with larger AHD, while larger shoulder ROM led to shorter AHD, dependent on measurement position and population.

Conclusion

While shoulder muscle activity and ROM had a pronounced effect on AHD, effects of shoulder strength and population appeared to be marginal.
Magnetic resonance imaging of the normal canine eye using a T1‐weighted volumetric acquisition
Authors: Manchip Katherine Edith Leonora , Sansom Philip George , Donaldson David , Warren‐Smith Chris
Published: May 2021

Purpose: MRI is becoming increasingly available within the veterinary profession, and eyes are frequently included as part of a cranial study. The advantages of volumetric imaging are numerous, when compared to traditional two‐dimensional imaging, and could be utilised within the veterinary setting. This report describing the normal MRI appearance of the canine eye, aimed to establish a standard reference range on a T1w volumetric acquisition.

Method: This study retrospectively assessed 62 eyes from 31 dogs that had undergone MRI at the Small Animal Hospital, Langford Vets, University of Bristol between 2016 and 2018 using a standardised MRI protocol. Dogs were excluded if they had presented with any reported ocular or orbital abnormalities. Measurements were performed from the 3D T1w volumetric sequence by a single observer using a previously published technique.

Results: Mean axial globe length was 2.13 cm and equatorial width 2.16 cm. Mean anteroposterior depth of the anterior chamber was 0.40 cm and 0.97 cm for the vitreous chamber. The mean anteroposterior and equatorial distance of the lens was 0.75 cm and 1.15 cm, respectively. Mean optic nerve width was 0.15 cm, and the mean width of the entire optic nerve sheath was 0.43 cm. Statistically significant relationships were noted between age and axial globe length and both lens dimensions. Highly significant relationships were noted between all variables, except lens dimensions and body weight

Conclusion: This study provides reference values to assist in the interpretation of ocular structures during MRI on a T1w volumetric acquisition
Avian malaria affecting penguins in zoological gardens, aquariums and wildlife parks in the UK
Authors: Hernandez‐Colina Arturo , Gonzalez‐Olvera Merit , Eckley Lindsay , Lopez Javier , Baylis Matthew
Published: May 2021

Background

Avian malaria has caused mortalities in captive penguins worldwide and it is a conservation threat for some wild penguins. The experience of staff working on penguins is highly valuable for the improvement of captivity conditions.

Methods

An online questionnaire was designed to collect avian malaria information in penguins in the UK. Volunteers with diverse experience reviewed it for scientific value and clarity, and it was supported by the British and Irish Association of Zoos and Aquariums.

Results

Forty‐two institutions were contacted by email, obtaining 27 complete and five partial responses. Eighteen institutions reported avian malaria in 38 suspected and 37 confirmed outbreaks in the past 20 years, mainly occurring in the summer and recent years. Proportional risk was higher in the south east region of England. Humboldt and African penguins were more commonly affected, and prevalence was mostly low or medium, but lethality was high. Different treatment protocols were reported with inconsistent outcomes.

Conclusions

Penguins’ susceptibility, their translocation across institutions, and the wide distribution of avian malaria make this disease a constant threat. Preventive and control measures are recommended, including testing for early diagnosis and treatment, avoiding prolonged stressful events in penguins, and monitoring and controlling mosquito vectors.
Anisotropic thermomagnetic effects on the universal stability of a diffusive state in porous media
Authors: Saravanan S. , Brindha D. , Yamaguchi H.
Published: May 2021

A nonlinear study is made to find the influence of transverse anisotropy on the onset of thermomagnetic convection in a homogeneous and rotating porous medium. The medium is filled with a magnetic fluid and is subjected to centrifugal force with alternating directions. Unconditional nonlinear stability bounds are found by exploiting the variational principles. Effects of various parameters on the stability threshold are discussed. The overpredicting nature of the linear theory is demonstrated by isolating the subcritical region which cannot be obtained a priori.
A thick‐point approximation of a small body embedded in an elastic medium: justification with an asymptotic analysis
Authors: Heibig Arnaud , Mannai Nidhal , Petrov Adrien , Renard Yves
Published: May 2021

The present paper proposes an approximation of the influence of a small inhomogeneity, having different stiffness, in an elastic medium restricting its cinematics to a finite dimensional space. The problem, for the unknown displacement, is written in accordance of transmission conditions between elastic medium and inhomogeneity. The multi‐scale asymptotic expansions techniques, by using some corrective terms, are introduced to analyze the inhomogeneity influence in both initial and approximated problems. Finally, some error estimates for asymptotic expansions are presented and different strategies are compared.
Quantum information probes of charge fractionalization in large-N gauge theories
Authors: DiNunno Brandon S. , Jokela Niko , Pedraza Juan F. , Pönni Arttu
Published: May 2021

Abstract

We study in detail various information theoretic quantities with the intent of distinguishing between different charged sectors in fractionalized states of large-N gauge theories. For concreteness, we focus on a simple holographic (2 + 1)-dimensional strongly coupled electron fluid whose charged states organize themselves into fractionalized and coherent patterns at sufficiently low temperatures. However, we expect that our results are quite generic and applicable to a wide range of systems, including non-holographic. The probes we consider include the entanglement entropy, mutual information, entanglement of purification and the butterfly velocity. The latter turns out to be particularly useful, given the universal connection between momentum and charge diffusion in the vicinity of a black hole horizon. The RT surfaces used to compute the above quantities, though, are largely insensitive to the electric flux in the bulk. To address this deficiency, we propose a generalized entanglement functional that is motivated through the Iyer-Wald formalism, applied to a gravity theory coupled to a U(1) gauge field. We argue that this functional gives rise to a coarse grained measure of entanglement in the boundary theory which is obtained by tracing over (part) of the fractionalized and cohesive charge degrees of freedom. Based on the above, we construct a candidate for an entropic c-function that accounts for the existence of bulk charges. We explore some of its general properties and their significance, and discuss how it can be used to efficiently account for charged degrees of freedom across different energy scales.
Supergravity solution-generating techniques and canonical transformations of σ-models from O(D, D)
Authors: Borsato Riccardo , Driezen Sibylle
Published: May 2021

Abstract

Within the framework of the flux formulation of Double Field Theory (DFT) we employ a generalised Scherk-Schwarz ansatz and discuss the classification of the twists that in the presence of the strong constraint give rise to constant generalised fluxes interpreted as gaugings. We analyse the various possibilities of turning on the fluxes Hijk, Fijk, Qijk and Rijk, and the solutions for the twists allowed in each case. While we do not impose the DFT (or equivalently supergravity) equations of motion, our results provide solution-generating techniques in supergravity when applied to a background that does solve the DFT equations. At the same time, our results give rise also to canonical transformations of 2-dimensional σ-models, a fact which is interesting especially because these are integrability-preserving transformations on the worldsheet. Both the solution-generating techniques of supergravity and the canonical transformations of 2-dimensional σ-models arise as maps that leave the generalised fluxes of DFT and their flat derivatives invariant. These maps include the known abelian/non-abelian/Poisson-Lie T-duality transformations, Yang-Baxter deformations, as well as novel generalisations of them.
An even lighter QCD axion
Authors: Di Luzio Luca , Gavela Belen , Quilez Pablo , Ringwald Andreas
Published: May 2021

Abstract

We explore whether the axion which solves the strong CP problem can naturally be much lighter than the canonical QCD axion. The $$ {Z}_{\mathcal{N}} $$

Z
N

symmetry proposed by Hook, with $$ \mathcal{N} $$
N
mirror and degenerate worlds coexisting in Nature and linked by the axion field, is considered in terms of generic effective axion couplings. We show that the total potential is safely approximated by a single cosine in the large $$ \mathcal{N} $$
N
limit, and we determine the analytical formula for the exponentially suppressed axion mass. The resulting universal enhancement of all axion interactions relative to those of the canonical QCD axion has a strong impact on the prospects of axion-like particle experiments such as ALPS II, IAXO and many others: experiments searching for generic axion-like particles have in fact discovery potential to solve the strong CP problem. The finite density axion potential is also analyzed and we show that the $$ {Z}_{\mathcal{N}} $$

Z
N

asymmetric background of high-density stellar environments sets already significant model-independent constraints: 3 ≤ $$ \mathcal{N} $$
N
≲ 47 for an axion scale fa ≲ 2.4 × 1015 GeV, with tantalizing discovery prospects for any value of fa and down to $$ \mathcal{N} $$
N
∼ 9 with future neutron star and gravitational wave data, down to the ultra-light mass region. In addition, two specific ultraviolet $$ {Z}_{\mathcal{N}} $$

Z
N

completions are developed: a composite axion one and a KSVZ-like model with improved Peccei-Quinn quality.
Adamantinomatous craniopharyngioma as a model to understand paracrine and senescence-induced tumourigenesis
Authors: Gonzalez-Meljem Jose Mario , Martinez-Barbera Juan Pedro
Published: May 2021

Cellular senescence is a process that can prevent tumour development in a cell autonomous manner by imposing a stable cell cycle arrest after oncogene activation. Paradoxically, senescence can also promote tumour growth cell non-autonomously by creating a permissive tumour microenvironment that fuels tumour initiation, progression to malignancy and metastasis. In a pituitary tumour known as adamantinomatous craniopharyngioma (ACP), cells that carry oncogenic β-catenin mutations and overactivate the WNT signalling pathway form cell clusters that become senescent and activate a senescence-associated secretory phenotype (SASP). Research in mouse models of ACP has provided insights into the function of the senescent cell clusters and revealed a critical role for SASP-mediated activities in paracrine tumour initiation. In this review, we first discuss this research on ACP and subsequently explore the theme of paracrine tumourigenesis in other tumour models available in the literature. Evidence is accumulating supporting the notion that paracrine signalling brought about by senescent cells may underlie tumourigenesis across different tumours and cancer models.
Salvage laryngectomy after primary radio- and radiochemotherapy
Authors: Sievert Matti , Goncalves Miguel , Binder Benedicta , Mueller Sarina K. , Rupp Robin , Koch Michael , Dürr Stephan , Traxdorf Maximilian , Hecht Markus , Iro Heinrich , Gostian Antoniu-Oreste
Published: May 2021

Background

Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases.

Objective

The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors’ academic cancer center.

Materials and methods

A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted.

Results

A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days.

Conclusion

Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.
Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy
Authors: Ben-Kraiem Adel , Sauer Reine-Solange , Norwig Carla , Popp Maria , Bettenhausen Anna-Lena , Atalla Mariam Sobhy , Brack Alexander , Blum Robert , Doppler Kathrin , Rittner Heike Lydia
Published: May 2021

Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.

Key messages

• In diabetic painful neuropathy in rats:

• Blood nerve barrier and blood DRG barrier are leaky for micromolecules.

• Perineurial Cldn1 sealing the blood nerve barrier is specifically downregulated.

• Endoneurial vessel-associated macrophages are also decreased.

• These changes occur after onset of hyperalgesia thereby maintaining rather than inducing pain.

Graphical abstract
Flat F-Manifolds, F-CohFTs, and Integrable Hierarchies
Authors: Arsie Alessandro , Buryak Alexandr , Lorenzoni Paolo , Rossi Paolo
Published: May 2021

We define the double ramification hierarchy associated to an F-cohomological field theory and use this construction to prove that the principal hierarchy of any semisimple (homogeneous) flat F-manifold possesses a (homogeneous) integrable dispersive deformation at all orders in the dispersion parameter. The proof is based on the reconstruction of an F-CohFT starting from a semisimple flat F-manifold and additional data in genus 1, obtained in our previous work. Our construction of these dispersive deformations is quite explicit and we compute several examples. In particular, we provide a complete classification of rank 1 hierarchies of DR type at the order 9 approximation in the dispersion parameter and of homogeneous DR hierarchies associated with all 2-dimensional homogeneous flat F-manifolds at genus 1 approximation.
Within- and across-network alterations of the sensorimotor network in Parkinson’s disease
Authors: Caspers Julian , Rubbert Christian , Eickhoff Simon B. , Hoffstaedter Felix , Südmeyer Martin , Hartmann Christian J. , Sigl Benjamin , Teichert Nikolas , Aissa Joel , Turowski Bernd , Schnitzler Alfons , Mathys Christian
Published: May 2021

Purpose

Parkinson’s disease (PD) is primarily defined by motor symptoms and is associated with alterations of sensorimotor areas. Evidence for network changes of the sensorimotor network (SMN) in PD is inconsistent and a systematic evaluation of SMN in PD yet missing. We investigate functional connectivity changes of the SMN in PD, both, within the network, and to other large-scale connectivity networks.

Methods

Resting-state fMRI was assessed in 38 PD patients under long-term dopaminergic treatment and 43 matched healthy controls (HC). Independent component analysis (ICA) into 20 components was conducted and the SMN was identified within the resulting networks. Functional connectivity within the SMN was analyzed using a dual regression approach. Connectivity between the SMN and the other networks from group ICA was investigated with FSLNets. We investigated for functional connectivity changes between patients and controls as well as between medication states (OFF vs. ON) in PD and for correlations with clinical parameters.

Results

There was decreased functional connectivity within the SMN in left inferior parietal and primary somatosensory cortex in PD OFF. Across networks, connectivity between SMN and two motor networks as well as two visual networks was diminished in PD OFF. All connectivity decreases partially normalized in PD ON.

Conclusion

PD is accompanied by functional connectivity losses of the SMN, both, within the network and in interaction to other networks. The connectivity changes in short- and long-range connections are probably related to impaired sensory integration for motor function in PD. SMN decoupling can be partially compensated by dopaminergic therapy.
Glue Embolization of Gastroesophageal Varices during Transjugular Intrahepatic Portosystemic Shunt (TIPS) Improves Survival Compared to Coil-only Embolization—A Single-Center Retrospective Study
Authors: Wolter Karsten , Praktiknjo Michael , Boie Julia , Decker Georges , Nadal Jennifer , Jansen Christian , Keller Wiebke I. Y. , Meyer Carsten , Trebicka Jonel , Attenberger Ulrike , Thomas Daniel
Published: May 2021

Purpose

To compare the safety and effectiveness of coil versus glue embolization of gastroesophageal varices during transjugular intrahepatic portosystemic shunt (TIPS) creation.

Materials and Methods

In this monocentric retrospective study 104 (males: 67 (64%)) patients receiving TIPS with concomitant embolization of GEV and a minimum follow-up of one year (2008—2017) were included. Primary outcome parameter was overall survival (6 week; 1 year). Six-week overall survival was assessed as a surrogate for treatment failure as proposed by the international Baveno working group. Secondary outcome parameters were development of acute-on-chronic liver failure (ACLF), variceal rebleeding and hepatic encephalopathy (HE). Survival analysis was performed using Kaplan–Meier with log-rank test and adjusted Cox regression analysis.

Results

Indications for TIPS were refractory ascites (n = 33) or variceal bleeding (n = 71). Embolization was performed using glue with or without coils (n = 40) (Group G) or coil-only (n = 64) (Group NG).

Overall survival was significantly better in group G (p = 0.022; HR = -3.333). Six-week survival was significantly lower in group NG (p = 0.014; HR = 6.945).

Rates of development of ACLF were significantly higher in group NG after 6 months (NG = 14; G = 6; p = 0.039; HR = 3.243). Rebleeding rates (NG = 6; G = 3; p = 0.74) and development of HE (NG = 22; G = 15; p = 0.75) did not differ significantly between groups.

Conclusion

Usage of glue in embolization of GEV may improve overall survival, reduce treatment failure and may be preferable over coil embolization alone.
Innate immunity in hepatitis B and D virus infection: consequences for viral persistence, inflammation, and T cell recognition
Authors: Dandri Maura , Bertoletti Antonio , Lütgehetmann Marc
Published: May 2021

Chronic infections with human hepatitis viruses continue to be a major health burden worldwide. Despite the availability of an effective prophylactic vaccine against the hepatitis B virus (HBV) and of antiviral agents efficiently suppressing HBV replication, more than 250 million people are currently chronically infected with this hepatotropic DNA virus, and resolution of chronic hepatitis B (CHB) is rarely achieved. Moreover, coinfection with the hepatitis D virus (HDV), a human RNA satellite virus requiring the envelope proteins of HBV for productive viral spreading, substantially aggravates the disease course of CHB. The molecular mechanisms by which these viruses interact with each other and with the intrinsic innate responses of the hepatocytes are not fully understood. While HBV appears to avoid innate immune recognition, HDV elicits a strong enhancement of innate responses. Notwithstanding, such induction does not hamper HDV replication but contributes to liver inflammation and pathogenesis. Intriguingly, HDV appears to influence the ability of T cells to recognize infected hepatocytes by boosting antigen presentation. This review focuses on current knowledge regarding how these viruses can shape and counteract the intrinsic innate responses of the hepatocytes, thus affecting the immune system and pathogenesis. Understanding the distinct strategies of persistence that HBV and HDV have evolved is central for advancing the development of curative therapies.
The structure of infinitesimal homeostasis in input–output networks
Authors: Wang Yangyang , Huang Zhengyuan , Antoneli Fernando , Golubitsky Martin
Published: May 2021

Homeostasis refers to a phenomenon whereby the output $$x_o$$

x
o

of a system is approximately constant on variation of an input $${{\mathcal {I}}}$$
I
. Homeostasis occurs frequently in biochemical networks and in other networks of interacting elements where mathematical models are based on differential equations associated to the network. These networks can be abstracted as digraphs $${{\mathcal {G}}}$$
G
with a distinguished input node $$\iota $$
ι
, a different distinguished output node o, and a number of regulatory nodes $$\rho _1,\ldots ,\rho _n$$

ρ
1

,
…
,

ρ
n

. In these models the input–output map $$x_o({{\mathcal {I}}})$$

x
o

(
I
)

is defined by a stable equilibrium $$X_0$$

X
0

at $${{\mathcal {I}}}_0$$

I
0

. Stability implies that there is a stable equilibrium $$X({{\mathcal {I}}})$$

X
(
I
)

for each $${{\mathcal {I}}}$$
I
near $${{\mathcal {I}}}_0$$

I
0

and infinitesimal homeostasis occurs at $${{\mathcal {I}}}_0$$

I
0

when $$(dx_o/d{{\mathcal {I}}})({{\mathcal {I}}}_0) = 0$$

(
d

x
o

/
d
I
)

(

I
0

)

=
0

. We show that there is an $$(n+1)\times (n+1)$$

(
n
+
1
)
×
(
n
+
1
)

homeostasis matrix$$H({{\mathcal {I}}})$$

H
(
I
)

for which $$dx_o/d{{\mathcal {I}}}= 0$$

d

x
o

/
d
I
=
0

if and only if $$\det (H) = 0$$

det
(
H
)
=
0

. We note that the entries in H are linearized couplings and $$\det (H)$$

det
(
H
)

is a homogeneous polynomial of degree $$n+1$$

n
+
1

in these entries. We use combinatorial matrix theory to factor the polynomial $$\det (H)$$

det
(
H
)

and thereby determine a menu of different types of possible homeostasis associated with each digraph $${{\mathcal {G}}}$$
G
. Specifically, we prove that each factor corresponds to a subnetwork of $${{\mathcal {G}}}$$
G
. The factors divide into two combinatorially defined classes: structural and appendage. Structural factors correspond to feedforward motifs and appendage factors correspond to feedback motifs. Finally, we discover an algorithm for determining the homeostasis subnetwork motif corresponding to each factor of $$\det (H)$$

det
(
H
)

without performing numerical simulations on model equations. The algorithm allows us to classify low degree factors of $$\det (H)$$

det
(
H
)

. There are two types of degree 1 homeostasis (negative feedback loops and kinetic or Haldane motifs) and there are two types of degree 2 homeostasis (feedforward loops and a degree two appendage motif).
Whole-body MRI versus an [18F]FDG-PET/CT-based reference standard for early response assessment and restaging of paediatric Hodgkin’s lymphoma: a prospective multicentre study
Authors: Spijkers Suzanne , Littooij Annemieke S. , Kwee Thomas C. , Tolboom Nelleke , Beishuizen Auke , Bruin Marrie C. A. , Enríquez Goya , Sábado Constantino , Miller Elka , Granata Claudio , de Lange Charlotte , Verzegnassi Federico , de Keizer Bart , Nievelstein Rutger A. J.
Published: May 2021

Objectives

To compare WB-MRI with an [18F]FDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin’s lymphoma (HL).

Methods

Fifty-one children (ages 10–17) with HL were included in this prospective, multicentre study. All participants underwent WB-MRI and [18F]FDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and [18F]FDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The [18F]FDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and [18F]FDG-PET/CT to derive the [18F]FDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation.

Results

Inter-observer agreement of WB-MRI including DWI between both readers was moderate (κ 0.46–0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51–77%) versus 15/51 (29%, 95% CI 19–43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42–87%) versus 5/13 patients (38%, 95% CI 18–64%) for WB-MRI without DWI.

Conclusions

The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the [18F]FDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence.

Key Points

• Inter-observer agreement of WB-MRI including DWI between both readers was moderate for (early) response assessment of paediatric Hodgkin’s lymphoma.

• The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric Hodgkin’s lymphoma improved agreement with the [18F]FDG-PET/CT-based reference standard.

• WB-MRI including DWI agreed with the reference standard in respectively 65% and 69% of the patients for early response assessment and restaging.
Altered oligodendroglia and astroglia in chronic traumatic encephalopathy
Authors: Chancellor K. Blake , Chancellor Sarah E. , Duke-Cohan Joseph E. , Huber Bertrand R. , Stein Thor D. , Alvarez Victor E. , Okaty Benjamin W. , Dymecki Susan M. , McKee Ann C.
Published: May 2021

Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts. White matter rarefaction and axonal loss have been reported in CTE but have not been characterized on a molecular or cellular level. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white matter from eight individuals with neuropathologically confirmed CTE and eight age- and sex-matched controls. Analyzing these profiles using unbiased clustering approaches, we identified eighteen transcriptomically distinct cell groups (clusters), reflecting cell types and/or cell states, of which a subset showed differences between CTE and control tissue. Independent in situ methods applied on tissue sections adjacent to that used in the single-nucleus RNA-seq work yielded similar findings. Oligodendrocytes were found to be most severely affected in the CTE white matter samples; they were diminished in number and altered in relative proportions across subtype clusters. Further, the CTE-enriched oligodendrocyte population showed greater abundance of transcripts relevant to iron metabolism and cellular stress response. CTE tissue also demonstrated excessive iron accumulation histologically. In astrocytes, total cell numbers were indistinguishable between CTE and control samples, but transcripts associated with neuroinflammation were elevated in the CTE astrocyte groups compared to controls. These results demonstrate specific molecular and cellular differences in CTE oligodendrocytes and astrocytes and suggest that white matter alterations are a critical aspect of CTE neurodegeneration.