bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral blood flow impairment and cognitive decline in heart failure
Authors: Ovsenik Ana , Podbregar Matej , Fabjan Andrej
Published: May 2021

Background and Purpose

Cognitive decline is an important contributor to disability in patients with chronic heart failure, affecting 25%–50% of patients. The aim of this review is to stress the importance of understanding pathophysiological mechanisms of heart failure involved in cognitive decline.

Methods

An extensive PubMed search was conducted for the literature on the basic mechanisms of cerebral blood flow regulation, the effect of cardiac dysfunction on cerebral blood flow, and possible mechanisms underlying the association between cardiac dysfunction and cognitive decline.

Results

Published literature supports the thesis that cardiac dysfunction leads to cerebral blood flow impairment and predisposes to cognitive decline. One of the postulated mechanisms underlying cognitive decline in chronic heart failure is chronic regional hypoperfusion of critical brain areas. Cognitive function may be further compromised by microvascular damage due to cardiovascular risk factors. Furthermore, it is implied that cerebral blood flow assessment could enable early recognition of patients at risk and help guide appropriate therapeutic strategies.

Conclusion

Interdisciplinary knowledge in the fields of neurology and cardiology is essential to clarify heart and brain interconnections in chronic heart failure. Understanding and identifying the basic neuropathophysiological changes in chronic heart failure could help with developing methods for early recognition of patients at risk, followed by institution of therapeutic actions to prevent or decrease cognitive decline.
Transparency of cognitive complexity in performance assessments: A validity study
Authors: Hayes Heather , Demeter Marylee , Morris John G. , Trajkovski Goran
Published: May 2021

Performance assessments (PAs) offer a more authentic measure of higher order skills, which is ideal for competency‐based education (CBE) especially for students already in the workplace and striving to advance their careers. The goal of the current study was to examine the validity of undergraduate PA score interpretation in the college of IT at a CBE online, higher education institute by evaluating (a) the transparency of cognitive complexity or demands of the task as communicated through the task prompt versus expected cognitive complexity based on its associated rubric aspect and (b) the impact of cognitive complexity on task difficulty. We found that there is a discrepancy in the communicated versus expected cognitive complexity of PA tasks (i.e., prompt vs. rubric) where rubric complexity is higher, on average, than task prompt complexity. This discrepancy negatively impacts reliability but does not affect the difficulty of PA tasks. Moreover, the cognitive complexity of both the task prompt and the rubric aspect significantly impacts the difficulty of PA tasks based on Bloom's taxonomy but not Webb's DOK, and this effect is slightly stronger for the rubric aspect than the task prompt. Discussion centers on how these findings can be used to better inform and improve PA task writing and review procedures for assessment developers as well as customize PAs (their difficulty levels) to different course levels or individual students to improve learning.
Pseudoacromegaly with acromegalic features in radiography
Authors: Yamamoto Koichiro , Oka Kosuke , Honda Hiroyuki , Hasegawa Kou , Otsuka Fumio
Published: May 2021

Pseudoacromegaly is a condition characterized by acromegalic physical features without growth hormone excess, for which radiographic observation has seldom been reported. This is a rare case of pseudoacromegaly.
The effect of topical nitroglycerin on symmetrical peripheral gangrene in a pediatric patient
Authors: Alfraij Abdulla , Elseadawy Mohammad , Alghounaim Mohammad
Published: May 2021

Symmetrical peripheral gangrene is a rare condition associated with significant morbidity and mortality. The use of topical nitroglycerin may have a role in improving patient outcomes and opens a new area for future research regarding the use of topical nitroglycerin in SPG.
Not all that is miliary is tuberculosis: Metastatic medullary thyroid carcinoma mimicking miliary tuberculosis
Authors: Askari Elham , Pourabdollah Toutkaboni Mihan , Haseli Sara , Rezaei Mitrasadat , Tabarsi Payam , Marjani Majid , Moniri Afshin , Khalili Neda
Published: May 2021

Medullary carcinoma of the thyroid should be considered in the differential diagnosis of miliary pattern of micronodules on chest imaging, irrespective of clinical features.
Recombinant tissue‐type plasminogen activator treatment in an extremely low birth weight infant
Authors: Kurimoto Tomonori , Shimoji Yoshikazu , Shimabukuro Atsuya , Ohshiro Tatsuo
Published: May 2021

Tissue plasminogen activator can effectively treat clinical thrombosis in premature infants 11 hours after birth.
Small bowel GIST with hemorrhagic shock diagnosed by capsule endoscopy and double‐balloon endoscopy, angiography‐guided hemostasis, and laparoscopic‐assisted resection
Authors: Kogo Hideki , Shimanuki Kimiyoshi , Iwao Toshiyasu , Yoshida Hiroshi
Published: May 2021

Small bowel tumors presenting with hemorrhagic shock require urgent treatment with angiographic embolization to achieve hemostasis. Capsule endoscopy and double‐balloon endoscopy are useful for localizing the tumor, diagnosis, and guiding surgery.
Orthodontic treatment of an adolescent patient with Class II division 1 malocclusion with consideration of growth pattern and occlusal plane: A case report
Authors: Hou Jianhua , Sun Mengyao , Meng Xiuping
Published: May 2021

Key Clinical Message

Consideration of growth pattern and occlusal plane is critical in orthodontic treatment planning to achieve optimal dentofacial esthetics and long‐term stability in adolescent patients, which is illustrated by success in orthodontic treatment of an adolescent Class II division 1 malocclusion with nonextraction.
Macular hole after Nd‐YAG laser capsulotomy with OCT findings
Authors: Ohashi Tsutomu , Fujiya Akio , Kojima Takashi
Published: May 2021

Patients with incomplete posterior vitreous detachment, especially with vitreomacular adhesion, can form a macular hole after Nd‐YAG laser capsulotomy. It is recommended to inform the risk of forming a macular hole before Nd‐YAG laser treatment.
Change in cycle length during pacemaker‐mediated tachycardia: What is the mechanism?
Authors: Fenelon Guilherme , Paul Luiz Carlos , Scuotto Frederico , Cirenza Claudio , Franken Marcelo
Published: May 2021

A thorough understanding of advanced device algorithms designed to promote intrinsic atrioventricular conduction is mandatory to allow appropriate management of arrhythmias induced by pacing, particularly when other types of tachycardia are involved.
Modulating charge carriers in carbon dots toward efficient solar‐to‐energy conversion
Authors: Kim Namhee , Lee Jiyoung , Gu Minsu , Kim Byeong‐Su
Published: May 2021

Growing attention to the development of sustainable solar‐to‐energy conversion applications has resulted in the synthesis of promising and environment‐friendly nanomaterials as energy harvesters. Among various carbon nanomaterials, carbon dots (CDs) have received significant attention due to their excellent light absorption capability, broad absorption region, and superior photostability with enormous potential for solar energy applications. Therefore, utilizing and modulating the charge carriers generated from CDs is critical for achieving a high energy conversion efficiency of CDs. Herein, we focus on the distinct characteristics of CDs as energy converters from charge excitation to charge separation and transfer for various solar‐to‐energy applications, including photovoltaic cells, photocatalysts, and photoelectrocatalysts. We anticipate that this review will offer insight into the synthesis and design of novel nanocomposites with a fundamental analysis of the photochemical properties and future development of energy conversion devices.
Comparative Investigation into the Complexation and Extraction Properties of Tridentate and Tetradentate Phosphine Oxide‐Functionalized 1,10‐Phenanthroline Ligands toward Lanthanides and Actinides
Authors: Xu Lei , Hao Yuxun , Yang Xiao , Wang Zhipeng , Xu Chao , Borisova Nataliya E. , Sun Mingze , Zhang Xingwang , Lei Lecheng , Xiao Chengliang
Published: May 2021

Two new phosphine oxide‐functionalized 1,10‐phenanthroline ligands, tetradentate 2,9‐bis(butylphenylphosphine oxide)‐1,10‐phenanthroline (BuPh‐BPPhen, L1) and tridentate 2‐(butylphenylphosphine oxide)‐1,10‐phenanthroline (BuPh‐MPPhen, L2), were synthesized and studied comparatively for their coordination with trivalent actinides and lanthanides. The complexation mechanisms of these two ligands toward trivalent f‐block elements were thoroughly elucidated by NMR spectroscopy, UV/vis spectrophotometry, fluorescence spectrometry, single‐crystal X‐ray diffraction, solvent extraction, and theoretical calculation methods. NMR titration results demonstrated that 1 : 1 and 1 : 2 (metal to ligand) lanthanides complexes formed for L1, whereas 1 : 1, 1 : 2 and 1 : 3 lanthanide complexes formed for L2 in methanol. The formation of these species was validated by fluorescence spectrometry, and the corresponding stability constants for the complexes of NdIII with L1 and L2 were determined by using UV/vis spectrophotometry. Structures of the 10‐coordinated 1 : 1‐type complexes of EuL1(NO3)3 and [EuL2(NO3)3(H2O)] Et2O in the solid state were characterized by X‐ray crystallography. In solvent‐extraction experiments, L1 exhibited extremely strong extraction ability for both AmIII and EuIII, whereas L2 showed nearly no extraction toward AmIII or EuIII due to its high hydrophilicity. Finally, the structures and bonding natures of the complex species formed between AmIII/EuIII and L1/L2 were analyzed in DFT calculations.
High‐performance anomaly intrusion detection system with ensemble neural networks on reconfigurable hardware
Authors: Thinh Tran Ngoc , Bao Tran Hoang Quoc , Ngo Duc‐Minh , Pham‐Quoc Cuong
Published: May 2021

In this article, we propose an ensemble neural network approach so that multiple neuron network models can be deployed concurrently for detecting anomalies in a system. Additionally, a high‐performance architecture integrating the neural networks for reconfigurable hardware is also designed to exploit the parallelism of the technology. We carefully implement four different models for detecting SYN, DNS, UNP, and ICMP attacks with the same configuration of neural networks on the NetFPGA platform. The neural networks can be executed in the pipeline to improve performance. Experiments with the generated dataset are conducted to test both performance in terms of throughput and accuracy. Our experimental results show that the system can process packets with throughput up to 30.48Gbps and is able to recognize 99.98% attacking packets with only 0.98% false alarms.
Controlled Fabrication and Characterization of Coronene Diimide‐Based Insoluble Thin Films Produced by Photoinduced Cyclization
Authors: Ogawa Tomoya , Kuzuhara Daiki
Published: May 2021

An insoluble thin film of a coronene diimide (CDI) derivative was fabricated from a soluble precursor of perylene diimide (PDI) by photoirradiation. We prepared a 1,7‐diarylated PDI (TP‐PDI) that can be converted into a coronene diimide (TP‐CDI) derivative via a Scholl‐type photocyclization reaction. This reaction was accompanied by structural changes from a twisted structure to a π‐extended planar molecule. It was found that this photoconversion reaction occurs for both solution‐based and thin‐film‐based reactants investigated by the changes of UV‐vis absorption spectra and 1H NMR spectra. The photocyclization reactions were found to proceed smoothly in polar solvents. In the thin‐film state, the solvent vapor annealing method is a key process for achieving photoconversion reaction. Additionally, the fabrication of multi‐layered thin films was achieved without undesirable dissolution of the underlying layers because of different solubilities of TP‐PDI and TP‐CDI.
Visible‐Light‐Driven Competitive Stereo‐ and Regioisomerization of (E)‐β‐Nitroenones
Authors: Raviola Carlotta , Carrera Cristina , Serra Massimo , Palmieri Alessandro , Lupidi Gabriele , Maestri Giovanni , Protti Stefano
Published: May 2021

A combined experimental and computational investigation of the photoreactivity of (E)‐β‐nitroenones pointed out the occurrence of competitive pathways namely stereoisomerisation to (E)‐β‐nitroenones and deconjugation to β‐nitro‐β,γ‐enones. Both processes are generated from the triplet excited state of the starting substrates.
Students’ experiences of a first‐year block model curriculum in higher education
Authors: Ambler Trudy , Solomonides Ian , Smallridge Andrew
Published: May 2021

The first year in Higher Education (HE) is an international priority because of its importance to the retention of students. While initiatives to improve students’ commencing experience continue to develop one area that has received limited consideration is the first‐year curriculum. The aim of the research reported in this paper was to enhance the student experience in HE by expanding understandings of the first‐year curriculum. Focus groups and an online questionnaire were the research methods used to, explore students’ experiences of learning in a newly developed First‐Year Block Model (FYBM) curriculum, implemented at a university in Australia. Findings from the research revealed that features in the design of the FYBM framed and permeated the students’ experiences of learning. The students explained that a sense of familiarity, curriculum leadership, teaching and teachers and curriculum customisation influenced their engagement and achievements. The study highlights that HE requires staff who possess deep knowledge and expertise in the first‐year curriculum because this valuable asset can positively influence student learning and success.
Interval‐based features of auditory ERPs for diagnosis of early Alzheimer's disease
Authors: Sabbaghi Neda , Sheikhani Ali , Noroozian Maryam , Sabbaghi Navide
Published: May 2021

Introduction

It has been demonstrated that event‐related potentials (ERPs) mirror the neurodegenerative process of Alzheimer's disease (AD) and may therefore qualify as diagnostic markers. The aim of this study was to explore the potential of interval‐based features as possible ERP biomarkers for early detection of AD patients.

Methods

The current results are based on 7‐channel ERP recordings of 95 healthy controls (HCs) and 75 subjects with mild AD acquired during a three‐stimulus auditory oddball task. To evaluate interval‐based features as diagnostic biomarkers in AD, two classifiers were applied to the selected features to distinguish AD and healthy control ERPs: RBFNN (radial basis function neural network) and MLP (multilayer perceptron).

Results

Using extracted features and a radial basis function neural network, a high overall diagnostic accuracy of 98.3% was achieved.

Discussion

Our findings demonstrate the great promise for scalp ERP and interval‐based features as non‐invasive, objective, and low‐cost biomarkers for early AD detection.
Repeated ecological and life cycle transitions make salamanders an ideal model for evolution and development
Authors: Bonett Ronald M. , Ledbetter Nicholus M. , Hess Alexander J. , Herrboldt Madison A. , Denoël Mathieu
Published: May 2021

Observations on the ontogeny and diversity of salamanders provided some of the earliest evidence that shifts in developmental trajectories have made a substantial contribution to the evolution of animal forms. Since the dawn of evo‐devo there have been major advances in understanding developmental mechanisms, phylogenetic relationships, evolutionary models, and an appreciation for the impact of ecology on patterns of development (eco‐evo‐devo). Molecular phylogenetic analyses have converged on strong support for the majority of branches in the Salamander Tree of Life, which includes 764 described species. Ancestral reconstructions reveal repeated transitions between life cycle modes and ecologies. The salamander fossil record is scant, but key Mesozoic species support the antiquity of life cycle transitions in some families. Colonization of diverse habitats has promoted phenotypic diversification and sometimes convergence when similar environments have been independently invaded. However, unrelated lineages may follow different developmental pathways to arrive at convergent phenotypes. This article summarizes ecological and endocrine‐based causes of life cycle transitions in salamanders, as well as consequences to body size, genome size, and skeletal structure. Salamanders offer a rich source of comparisons for understanding how the evolution of developmental patterns has led to phenotypic diversification following shifts to new adaptive zones.
Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism
Authors: Zamani Payman , Proto Elizabeth A. , Wilson Neil , Fazelinia Hossein , Ding Hua , Spruce Lynn A. , Davila Antonio , Hanff Thomas C. , Mazurek Jeremy A. , Prenner Stuart B. , Desjardins Benoit , Margulies Kenneth B. , Kelly Daniel P. , Arany Zoltan , Doulias Paschalis‐Thomas , Elrod John W. , Allen Mitchell E. , McCormack Shana E. , Schur Gayatri Maria , D'Aquilla Kevin , Kumar Dushyant , Thakuri Deepa , Prabhakaran Karthik , Langham Michael C. , Poole David C. , Seeholzer Steven H. , Reddy Ravinder , Ischiropoulos Harry , Chirinos Julio A.
Published: May 2021

Aims

Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants.

Methods and results

Fifty‐nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal‐effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical‐Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half‐time of Cr recovery (t1/2, Cr) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak, VT, and VO2 efficiency than either control group (all P < 0.05). The t1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF.

Conclusions

Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF.
Perhexiline treatment improves toxic effects of β‐adrenergic receptor stimulation in experimental peripartum cardiomyopathy
Authors: Pfeffer Tobias J. , List Manuel , Müller Julia H. , Scherr Michaela , Bauersachs Johann , Hilfiker‐Kleiner Denise , Ricke‐Hoch Melanie
Published: May 2021

Aims

Peripartum cardiomyopathy (PPCM) is a pregnancy‐associated cardiomyopathy that occurs in previously heart‐healthy women towards the end of pregnancy or in the first months after delivery and is characterized by heart failure due to systolic dysfunction. The clinical course of PPCM differs between mild symptoms and severe forms with acute heart failure complicated by cardiogenic shock (CS). Treatment of CS complicating PPCM is challenging, as β‐adrenergic receptor (β‐AR) stimulation seems to be associated with progression of heart failure and adverse outcome. This experimental study aims to examine whether postpartum treatment with the glucose uptake‐promoting drug perhexiline alone or as co‐treatment with β‐AR stimulation prevents heart failure in the experimental PPCM mouse model.

Methods and results

Postpartum (PP) female PPCM‐prone mice with a cardiomyocyte‐restricted STAT3‐deficiency (αMHC‐Cretg/+;Stat3fl/fl; CKO) were treated with perhexiline over two to three pregnancies and nursing periods (2/3PP) or were co‐treated with perhexiline after one pregnancy (1PP) under chronic β‐AR stimulation using isoproterenol (Iso) infusion. Perhexiline was not able to prevent onset of PPCM in CKO mice (FS: CKO Pexsig‐2/3PP: 25 ± 12% vs. CKO Ctrl‐2/3PP: 24 ± 9%, n.s.) but attenuated worsening of left ventricular function in response to treatment with the β‐AR agonist Iso (FS: CKO Pexsig‐Iso‐1PP: 19 ± 4% vs. CKO Ctrl‐Iso‐1PP: 11 ± 5%, P < 0.05).

Conclusions

Treatment of PPCM patients with β‐AR agonists should be avoided whenever possible. In cases with CS complicating PPCM, when treatment with β‐AR agonists cannot be prevented, co‐medication with perhexiline might help to reduce the cardiotoxic side effects of β‐AR stimulation. Clinical data are necessary to further validate this therapeutic approach.
Right‐ventricular dysfunction in HFpEF is linked to altered cardiomyocyte Ca2+ homeostasis and myofilament sensitivity
Authors: Hegemann Niklas , Primessnig Uwe , Bode David , Wakula Paulina , Beindorff Nicola , Klopfleisch Robert , Michalick Laura , Grune Jana , Hohendanner Felix , Messroghli Daniel , Pieske Burkert , Kuebler Wolfgang M. , Heinzel Frank R.
Published: May 2021

Aims

Heart failure with preserved ejection fraction (HFpEF) is frequently (30%) associated with right ventricular (RV) dysfunction, which increases morbidity and mortality in these patients. Yet cellular mechanisms of RV remodelling and RV dysfunction in HFpEF are not well understood. Here, we evaluated RV cardiomyocyte function in a rat model of metabolically induced HFpEF.

Methods and results

Heart failure with preserved ejection fraction‐prone animals (ZSF‐1 obese) and control rats (Wistar Kyoto) were fed a high‐caloric diet for 13 weeks. Haemodynamic characterization by echocardiography and invasive catheterization was performed at 22 and 23 weeks of age, respectively. After sacrifice, organ morphometry, RV histology, isolated RV cardiomyocyte function, and calcium (Ca2+) transients were assessed. ZSF‐1 obese rats showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV diastolic dysfunction (including increased LV end‐diastolic pressures and E/e′ ratio), and preserved LV ejection fraction. ZSF‐1 obese animals developed RV dilatation (50% increased end‐diastolic area) and mildly impaired RV ejection fraction (42%) with evidence of RV hypertrophy. In isolated RV cardiomyocytes from ZSF‐1 obese rats, cell shortening amplitude was preserved, but cytosolic Ca2+ transient amplitude was reduced. In addition, augmentation of cytosolic Ca2+ release with increased stimulation frequency was lost in ZSF‐1 obese rats. Myofilament sensitivity was increased, while contractile kinetics were largely unaffected in intact isolated RV cardiomyocytes from ZSF‐1 obese rats. Western blot analysis revealed significantly increased phosphorylation of cardiac myosin‐binding protein C (Ser282 cMyBP‐C) but no change in phosphorylation of troponin I (Ser23, 24 TnI) in RV myocardium from ZSF‐1 obese rats.

Conclusions

Right ventricular dysfunction in obese ZSF‐1 rats with HFpEF is associated with intrinsic RV cardiomyocyte remodelling including reduced cytosolic Ca2+ amplitudes, loss of frequency‐dependent augmentation of Ca2+ release, and increased myofilament Ca2+ sensitivity.
Does renin‐angiotensin system inhibition have impacts on muscle mass and bone mineral density in heart failure patients?
Authors: Katano Satoshi , Yano Toshiyuki , Shimizu Masaki , Ohori Katsuhiko , Kouzu Hidemichi , Koyama Masayuki , Nagaoka Ryohei , Inoue Takuya , Takamura Yuhei , Ishigo Tomoyuki , Takashima Hiroyuki , Katayose Masaki , Ohnishi Hirofumi , Miura Tetsuji
Published: May 2021

Aims

Results of experimental studies have indicated the possibility of muscle and bone mass being negatively regulated by renin‐angiotensin system (RAS) activation, but that possibility has not been analysed in patients with heart failure (HF).

Methods and results

Data for HF patients who received a dual‐energy X‐ray absorptiometry scan in our hospital were reviewed. Propensity scores for the use of RAS inhibitors (RASIs) were calculated using a multivariate logistic regression model to minimize selection bias. One hundred sixty pairs of patients were extracted. Plasma aldosterone concentration was significantly lower in the RASIs group than in the no‐RASIs group (119 [IQR 71–185] vs. 94 [IQR 60–131] pg/mL, P = 0.003), confirming RAS inhibition in the RASIs group. Skeletal muscle mass index tended to be higher in the RASIs group than in the non‐RASIs group (15.6 [IQR 14.0–17.2] vs. 15.0 [IQR 13.3–16.6] pg/mL, P = 0.065). The proportion of patients with muscle wasting, defined as appendicular skeletal muscle mass indexes of <7.00 and <5.40 kg/m2 for males and females, respectively, was significantly lower in the RASIs group than in the non‐RASIs group (53% vs. 64%, P = 0.041). Multivariate logistic regression analysis showed that the no use of RASIs was associated with presence of muscle wasting independently of age, presence of diabetes, renal function, and severity of HF. Bone mineral densities and proportions of patients with osteoporosis were similar in the two groups.

Conclusions

Renin‐angiotensin system inhibition is associated with a lower prevalence of muscle wasting in HF patients independently of established risk factors.
Unexpected Formation of the Highly Symmetric Borate Ion [B(SiCl3)4]−
Authors: Bochmann Sebastian , Böhme Uwe , Brendler Erica , Friebel Mike , Gerwig Maik , Gründler Franziska , Günther Betty , Kroke Edwin , Lehnert Robert , Ruppel Lars
Published: May 2021

Disproportionation reactions of chlorosilane compounds in the presence of boron trichloride yield the compound H[B(SiCl3)4]. Spectroscopic analyses of the yellow‐whitish solid with IR‐, Raman‐, and NMR‐spectroscopy (29Si, 11B) show the presence of a highly symmetric anion containing boron, which is fourfold coordinated with silicon. Due to the high symmetry 1J(11B,29Si) and even 1J (10B, 29Si) couplings can be observed in the NMR spectra of the dissolved compound. The crystal structure analysis with a crystal obtained from toluene solution proves the existence of a highly symmetric borate anion, which is stabilized by four trichlorosilyl groups. The molecular structure consists of a para‐protonated toluene cation and the weakly coordinating borate anion [B(SiCl3)4]−. Quantum chemical analysis of the tetrakis(trichlorosilyl)borate ion shows a negatively charged boron atom and the presence of polar Si−Cl and Si−B bonds. Highly reactive compounds [E(SiCl3)n]− which are stabilized solely by trichlorosilyl groups have been prepared with E=C, Si, Ge, P, S in recent years. The superacid H[B(SiCl3)4] represents a new member in this elusive compound family.
Direct Trifluoromethoxylation without OCF3‐Carrier through In Situ Generation of Fluorophosgene
Authors: Saiter Jérémy , Guérin Thomas , Donnard Morgan , Panossian Armen , Hanquet Gilles , Leroux Frédéric R.
Published: May 2021

Owing to the high interest in the OCF3 group for pharmaceutical and agrochemical applications, trifluoromethoxylation received great attention in the last years with several new methods for this approach towards OCF3‐comprising compounds. Yet, it most often requires the beforehand preparation of specific F3CO− transfer reagents, which can be toxic, expensive, unstable, and/or generate undesired side‐products upon consumption. To circumvent this, the in‐situ generation of gaseous fluorophosgene from triphosgene, its conversion by fluoride into the OCF3 anion, and the direct use of the latter in nucleophilic substitutions is an appealing strategy, which, although recently approached, has not been fully exploited. We disclose herein our efforts towards this aim.
Dimeric Indenofluorene‐Extended Tetrathiafulvalene Motif for Enhanced Intramolecular Complexation
Authors: Broløs Line , Kilde Martin Drøhse , Brock‐Nannestad Theis , Nielsen Mogens Brøndsted
Published: May 2021

Tetrathiafulvalene (TTF) is a redox‐active compound, which reversibly undergoes two one‐electron oxidations to give stable species. Several features of TTF, such as redox and optical properties as well as geometry and self‐associating nature, can be tuned by extension of the conjugated system with an aromatic linker such as an indenofluorene (IF) moiety. In this work we present the synthesis of a novel dimeric scaffold of IF‐extended TTF (IF‐TTF) in which the units are linked by a rigid 1,4‐bis(2‐ethynylphenyl)buta‐1,3‐diyne moiety. 1H‐NMR spectroscopic studies reveal that the scaffold is highly prone to form intramolecular IF‐TTF dimer complexes even in the neutral form, and stable radical cation species were formed in solution upon chemical oxidation with tris(4‐bromophenyl)ammoniumyl hexachloroantimonate (‘magic blue’). Electrocrystallization of the rigid scaffold yielded a semi‐conducting material, which proved to be stable at ambient temperature and air.
Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis—the effects on pain and sensitization
Authors: Holm Pætur M. , Petersen Kristian K. , Wernbom Mathias , Schrøder Henrik M. , Arendt‐Nielsen Lars , Skou Søren T.
Published: May 2021

Background

There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA).

Methods

Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice‐weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX‐EDU) or neuromuscular exercise and education alone (NEMEX‐EDU). Outcomes were bilateral, lower‐leg, cuff pressure pain‐ and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self‐reported knee pain intensity and number of painful body sites.

Results

After 12 weeks of exercise, we found significant differences in increases in PPT (−5.01 kPa (−8.29 to −1.73, p = .0028)) and PTT (−8.02 kPa (−12.22 to −3.82, p = .0002)) in the KOA leg in favour of ST+NEMEX‐EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain‐relieving effects on VAS mean knee pain during the last week (−8.4 mm (−16.2 to −0.5, p = .0364) and during function (−16.0 mm (−24.8 to −7.3, p = .0004)) in favour of NEMEX‐EDU after 12 weeks of exercise.

Conclusion

Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose‐ and type‐specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes.

Significance

This study is an important step towards better understanding the effects of exercise in pain management of chronic musculoskeletal conditions. We found that strength training in addition to neuromuscular exercise and education compared with neuromuscular exercise and education only had a differential impact on pain sensitization and pain intensity, but also that regardless of the exercise mode, the positive effects on pain sensitization and pain intensity were comparable to the effects of other therapeutic interventions for individuals with knee osteoarthritis.
Automatic medium exchange for micro‐volume cell samples based on dielectrophoresis
Authors: Ma Zhouyang , Zhao Hongwang , Shi Liujia , Yu Duli , Guo Xiaoliang
Published: May 2021

Cell medium exchange is a crucial step for life science and medicine. However, conventional cell medium exchange methods, including centrifuging and filtering, show limited ability for micro‐volume cell samples such as circulating tumor cell (CTC) and circulating fetal cell (CFC). In this paper, we proposed an automatic medium exchange method for micro‐volume cell samples based on dielectrophoresis (DEP) in microfluidic chip. Fresh medium and cell suspension were introduced into the microfluidic channel as the laminar flow. Plane stair‐shaped interdigital electrodes were employed to drive the cells from the cell suspension to fresh media directly by DEP force. Additionally, we characterized and optimized the cell medium exchange according to both the theory and experiments. In the end, we achieved a 96.9% harvest rate of medium exchange for 0.3 μL samples containing micro‐volume cells. For implementing an automatic continuous cell medium exchange, the proposed method can be integrated into the automatic cell processing system conveniently. Furthermore, the proposed method is a great candidate in micro‐volume cell analysis and processing, cell electroporation, single cell sequencing, and other scenarios.
Philadelphia ‐ Tianjin Economic‐technological Development Area urban clean energy infrastructures EcoPartnership
Authors: Cooke Merritt
Published: May 2021

Among U.S.‐China EcoPartnerships, the PHL‐TEDA EcoPartnership is unique in its design as an open platform to facilitate collaboration among businesses, local governments, universities and non‐governmental organizations (NGO). On the U.S. side, the platform consists of China Partnership of Greater Philadelphia (CPGP, a 501c3 non‐profit) and its public sector partner, the Commerce Department of the City of Philadelphia. The objective of this collaboration is to bring to scale sustainable‐city‐type BE Better technologies (built environment technologies that are more energy‐efficient, smarter and healthier) in China and, by doing so, to promote sustainable economic development in the U.S. The mechanism for scaling these BE Better technologies is through China's national‐level industrial parks. The initial stage focuses on China's northeastern Jing‐Jin‐Ji region (comprising Beijing, Tianjin and Hebei Province) through collaborations with Green Development League‐member National Economic‐Technological Development Zones (NETDZ) in Beijing, Tianjin and Langfang. The larger goal is to position for second‐stage, nation‐wide expansion of the BE Better model through the Green Development League's 36 member‐NETDZs nationwide and through the Ministry of Commerce's national Eco Park program.
Hypoxia‐Inducible Factor 1 Alpha–Mediated RelB/APOBEC3B Down‐regulation Allows Hepatitis B Virus Persistence
Authors: Riedl Tobias , Faure‐Dupuy Suzanne , Rolland Maude , Schuehle Svenja , Hizir Zohier , Calderazzo Silvia , Zhuang Xiaodong , Wettengel Jochen , Lopez Martin Alexander , Barnault Romain , Mirakaj Valbona , Prokosch Sandra , Heide Danijela , Leuchtenberger Corinna , Schneider Martin , Heßling Bernd , Stottmeier Benjamin , Wessbecher Isabel M. , Schirmacher Peter , McKeating Jane A , Protzer Ulrike , Durantel David , Lucifora Julie , Dejardin Emmanuel , Heikenwalder Mathias
Published: May 2021

Background and Aims

Therapeutic strategies against HBV focus, among others, on the activation of the immune system to enable the infected host to eliminate HBV. Hypoxia‐inducible factor 1 alpha (HIF1α) stabilization has been associated with impaired immune responses. HBV pathogenesis triggers chronic hepatitis‐related scaring, leading inter alia to modulation of liver oxygenation and transient immune activation, both factors playing a role in HIF1α stabilization.

Approach and Results

We addressed whether HIF1α interferes with immune‐mediated induction of the cytidine deaminase, apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B; A3B), and subsequent covalently closed circular DNA (cccDNA) decay. Liver biopsies of chronic HBV (CHB) patients were analyzed by immunohistochemistry and in situ hybridization. The effect of HIF1α induction/stabilization on differentiated HepaRG or mice ± HBV ± LTβR‐agonist (BS1) was assessed in vitro and in vivo. Induction of A3B and subsequent effects were analyzed by RT‐qPCR, immunoblotting, chromatin immunoprecipitation, immunocytochemistry, and mass spectrometry. Analyzing CHB highlighted that areas with high HIF1α levels and low A3B expression correlated with high HBcAg, potentially representing a reservoir for HBV survival in immune‐active patients. In vitro, HIF1α stabilization strongly impaired A3B expression and anti‐HBV effect. Interestingly, HIF1α knockdown was sufficient to rescue the inhibition of A3B up‐regulation and ‐mediated antiviral effects, whereas HIF2α knockdown had no effect. HIF1α stabilization decreased the level of v‐rel reticuloendotheliosis viral oncogene homolog B protein, but not its mRNA, which was confirmed in vivo. Noteworthy, this function of HIF1α was independent of its partner, aryl hydrocarbon receptor nuclear translocator.

Conclusions

In conclusion, inhibiting HIF1α expression or stabilization represents an anti‐HBV strategy in the context of immune‐mediated A3B induction. High HIF1α, mediated by hypoxia or inflammation, offers a reservoir for HBV survival in vivo and should be considered as a restricting factor in the development of immune therapies.
Population‐based cancer staging for oesophageal, gastric, and pancreatic cancer 2012‐2014: International Cancer Benchmarking Partnership SurvMark‐2
Authors: Cabasag Citadel J. , Arnold Melina , Piñeros Marion , Morgan Eileen , Brierley James , Hofferkamp Jim , Kehoe Sean , Butler John , Bucher Oliver , Bray Freddie , Soerjomataram Isabelle , Parkin D Maxwell
Published: May 2021

Cancer stage at diagnosis is important information for management and treatment of individual patients as well as in epidemiological studies to evaluate effectiveness of health care system in managing cancer patients. Population‐based studies to examine international disparities on cancer survival by stage, however, has been challenging due to the lack of international standardization on recording stage information and variation in stage completeness across regions and countries. The International Cancer Benchmarking Partnership (ICBP) previously assessed the availability and comparability of staging information for colorectal, lung, female breast and ovarian cancers. Stage conversion algorithms were developed to aggregate and map all stage information into a single staging system to allow international comparison by stage at diagnosis. In this article, we developed stage conversion algorithms for three additional cancers, namely oesophageal, gastric and pancreatic cancers. We examined all stage information available, evaluated stage completeness, applied each stage conversion algorithm, and assessed the magnitude of misclassification using data from six Canadian cancer registries (Alberta, Manitoba, Newfoundland, Nova Scotia, Prince Edward Island and Saskatchewan). In addition, we discussed five recommendations for registries to improve international cancer survival comparison by stage: (a) improve collection and completeness of staging data; (b) promote a comparable definition for stage at diagnosis; (c) promote the use of a common stage classification system; (d) record versions of staging classifications and (e) use multiple data sources for valid staging data.
Transcription of human papillomaviruses in nonmelanoma skin cancers of the immunosuppressed
Authors: Arroyo Mühr Laila Sara , Hultin Emilie , Dillner Joakim
Published: May 2021

Nonmelanoma skin cancer (NMSC) has a greatly increased incidence among the immunosuppressed and the DNA of human papillomavirus (HPV) is commonly found in these tumors. To investigate if there are any actively transcribed HPV infections in these tumors, we identified all skin cancers diagnosed after solid organ transplantation in Sweden during 1964‐2011 (n = 7614 NMSCs) and requested the diagnostic tumor blocks from the corresponding pathology archives. For the present study, we selected diagnostic specimens from 345 NMSC and performed whole genome transcriptome analysis using NovaSeq (Illumina), in comparison with three cervical cancers. Although we obtained an abundance of high‐quality paired reads per sample (median of 35 million reads), only 15 NMSC specimens contained HPV transcription. Three specimens had transcription of oncogenic anogenital HPVs (HPV16 and 56), six tumors had transcription of HPVs from the beta‐2 species (three HPV38, two with HPV23 and one with HPV107) and then there was one observation each of transcription of HPVs 3, 26, 57, 147, 158, 168 and of two nonestablished HPV types belonging to the gamma genus. In conclusion, transcription of specific HPV types can be found in NMSC among the immunosuppressed, but this is not common.
On the mechanism of tumor cell entry of aloe‐emodin, a natural compound endowed with anticancer activity
Authors: Pecere Teresa , Ponterio Eleonora , Di Iorio Enzo , Carli Modesto , Fassan Matteo , Santoro Luisa , Bissaro Maicol , Bernabè Giulia , Moro Stefano , Castagliuolo Ignazio , Palù Giorgio
Published: May 2021

Aloe‐emodin (1,8‐dihydroxy‐3‐[hydroxymethyl]‐anthraquinone), AE, is one of the active constituents of a number of plant species used in traditional medicine. We have previously identified, for the first time, AE as a new antitumor agent and shown that its selective in vitro and in vivo killing of neuroblastoma cells was promoted by a cell‐specific drug uptake process. However, the molecular mechanism underlying the cell entry of AE has remained elusive as yet. In this report, we show that AE enters tumor cells via two of the five somatostatin receptors: SSTR2 and SSTR5. This observation was suggested by gene silencing, receptor competition, imaging and molecular modeling experiments. Furthermore, SSTR2 was expressed in all surgical neuroblastoma specimens we analyzed by immunohistochemistry. The above findings have strong implications for the clinical adoption of this natural anthraquinone molecule as an antitumor agent.
Aortic clamping for limiting blood loss at cesarean hysterectomy for placenta percreta: A case series
Authors: Joshi Vivek Madhusudan , Otiv Suhas Raghuvir , Sovani Yogesh Bhairav , Kulat Prasad Kisanrao
Published: May 2021

Objective

In women with placenta percreta, cesarean hysterectomy is associated with massive blood loss during dissection of bladder from lower uterine segment. We studied the safety and effectiveness of temporary aortic clamping as a method of limiting blood loss at cesarean hysterectomy in women with placenta percreta.

Methods

This was a retrospective case series of 15 women with placenta percreta who underwent cesarean section with total hysterectomy at KEM Hospital, Pune, India, with a technique of temporary clamping of the infra‐renal aorta for reducing blood loss during hysterectomy.

Results

Fifteen women with placenta percreta underwent classical cesarean section followed by total hysterectomy with temporary clamping of the aorta. The procedure was associated with median estimated intra‐operative blood loss of 650 ml. No woman had ureteric injury or needed post‐operative intensive care. Aortic clamping for 28–70 min was not associated with any intra‐operative vascular complications or post‐operative ischemic lesions in the lower limbs, kidneys, or bowel.

Conclusion

Aortic clamping safely and effectively limited blood loss during cesarean hysterectomy for placenta percreta and thereby reduced transfusion requirements. It compares favorably with reported outcomes of other strategies of managing placenta percreta.
LEAP‐2/ghrelin interplay in adult growth hormone deficiency: Cause or consequence? A pilot study
Authors: Vergani Edoardo , Bruno Carmine , Gavotti Cesare , Aversa Luigi Simone , Martire Maria , Mancini Antonio , Currò Diego
Published: May 2021

Ghrelin and its endogenous antagonist liver‐expressed antimicrobial peptide‐2 (LEAP‐2) are involved in GH secretion and glucose/lipids metabolism. LEAP‐2 expression in conditions of metabolic impairment may be upregulated, usually pairing with a concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD) is characterized by insulin resistance, weight gain, and increased fat mass. Therefore, the primary endpoint of this cross‐sectional observational pilot study was to compare circulating LEAP‐2 and ghrelin levels in aGHD and healthy controls. Thirty patients were included in the study. Group A included adult GHD: 15 patients, 8 females, and 7 males. Median and interquartile range age of the group was 53 (41–57) years, while BMI was 27.1 (25–35) kg/m2. Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (36–57) years, while BMI 22.9 (20.8–33.1) kg/m2. They were evaluated for serum glucose and insulin, HOMA‐index, QUICKI‐index, total/LDL/HDL cholesterol, triglycerides, IGF‐1, ghrelin, and LEAP‐2. Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP‐2 showed a trend toward higher levels, although the differences were not significant. However, the LEAP‐2/Ghrelin ratio was significantly higher in aGHD. No significant correlations between ghrelin and LEAP‐2 with BMI and HOMA index were found in aGHD population. However, a significant inverse correlation (r2 = 0.15, p = .047) between BMI and ghrelin was evidenced when considering the whole population. Taken together, these results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.
A spatial resolution evaluation method of endoscopic optical coherence tomography system using the annular phantom
Authors: Huang Ningning , Deng Zhichao , Hu Zhixiong , Mei Jianchun , Zhao Shiyong , Wu Xining , Jia Zongnan , Liu Yuyan , Wang Jin , Ye Qing , Tian Jianguo
Published: May 2021

As an important biomedical imaging method, endoscopic optical coherence tomography (OCT) is necessary to check its performance regularly. The ordinary plane phantoms are only able to evaluate part of image tangent to the probe. In this research, a spatial resolution estimate method of the endoscope OCT system is proposed. The annular phantom, made by uniformly distributing golden scattered microparticles in polydimethylsiloxane (PDMS), can provide dynamic scanning imaging evaluation of endoscopic OCT system, closer to its actual working status. The point spread function analysis method is used to analyze the imaging results of the annular phantom with the endoscopic OCT system. And many scattered particles are statistically analyzed to determine the spatial resolution of the endoscope OCT system. The method is low in cost, simple and convenient. It is valuable for the development of test standards for endoscope OCT systems.