bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
Authors: Recinella Lucia , Chiavaroli Annalisa , Di Valerio Valentina , Veschi Serena , Orlando Giustino , Ferrante Claudio , Gesmundo Iacopo , Granata Riccarda , Cai Renzhi , Sha Wei , Schally Andrew V. , Lattanzio Rossano , Brunetti Luigi , Leone Sheila
Published: January 2021

Besides its metabolic and endocrine effects, growth hormone (GH)-releasing hormone (GHRH) is involved in the modulation of inflammation. Recently synthetized GHRH antagonist MIA-690 and MR-409, GHRH agonist, developed by us have shown potent pharmacological effects in various experimental paradigms. However, whether their administration modify resistance to chronic inflammatory stimuli in colon is still unknown. Ex vivo results demonstrated that MIA-690 and MR-409 inhibited production of pro-inflammatory and oxidative markers induced by lipopolysaccharide on isolated mouse colon specimens. In vivo, both MIA-690 and MR-409 have also been able to decrease the responsiveness to nociceptive stimulus, in hot plate test. Additionally, both peptides also induced a decreased sensitivity to acute and persistent inflammatory stimuli in male mice, in formalin test and dextran sodium sulfate (DSS)-induced colitis model, respectively. MIA-690 and MR-409 attenuate DSS-induced colitis with particular regard to clinical manifestations, histopathological damage and release of pro-inflammatory and oxidative markers in colon specimens. Respect to MR-409, MIA-690 showed higher efficacy in inhibiting prostaglandin (PG)E2, 8-iso-PGF2α and serotonin (5-HT) levels, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide synthase gene expression in colon specimens of DSS-induced colitis. Furthermore, MIA-690 decreased serum insulin-like growth factor (IGF)-1 levels in mice DSS-treated, respect to MR-409. Thus, our findings highlight the protective effects of MIA-690 and MR-409 on inflammation stimuli. The higher antinflammatory and antioxidant activities observed with MIA-690 could be related to decreased serum IGF-1 levels.
Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor
Authors: Webb James Luke , Troise Luca , Hansen Nikolaj Winther , Olsson Christoffer , Wojciechowski Adam M. , Achard Jocelyn , Brinza Ovidiu , Staacke Robert , Kieschnick Michael , Meijer Jan , Thielscher Axel , Perrier Jean-François , Berg-Sørensen Kirstine , Huck Alexander , Andersen Ulrik Lund
Published: January 2021

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/$$\sqrt{\text {Hz}}$$

Hz

sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.
Intergenerational sustainability is enhanced by taking the perspective of future generations
Authors: Shahen Mostafa E. , Kotani Koji , Saijo Tatsuyoshi
Published: January 2021

The intergenerational sustainability dilemma (ISD) is a situation of whether or not a person sacrifices herself for future sustainability. To examine the individual behaviors, one-person ISD game (ISDG) is instituted with strategy method where a queue of individuals is organized as a generational sequence. In ISDG, each individual chooses unsustainable (or sustainable) option with her payoff of $$X$$
X
($$X-D$$

X
-
D

) and an irreversible cost of $$D$$
D
(zero cost) to future generations in $$36$$

36

situations. Future ahead and back (FAB) mechanism is suggested as resolution for ISD by taking the perspective of future generation whereby each individual is first asked to take the next generation’s standpoint and request what she wants the current generation to choose, and, second, to make the actual decision from the original position. Results show that individuals choose unsustainable option as previous generations do so or $$\frac{X}{D}$$

X
D

is low (i.e., sustainability is endangered). However, FAB prevents individuals from choosing unsustainable option in such endangered situations. Overall, the results suggest that some new institutions, such as FAB mechanisms, which induce people to take the perspective of future generations, may be necessary to avoid intergenerational unsustainability, especially when intergenerational sustainability is highly endangered.
Novel hybrid method to additively manufacture denser graphite structures using Binder Jetting
Authors: Popov Vladimir , Fleisher Alexander , Muller-Kamskii Gary , Avraham Shaul , Shishkin Andrei , Katz-Demyanetz Alexander , Travitzky Nahum , Yacobi Yair , Goel Saurav
Published: January 2021

This study introduces two hybrid processes integrating an additive manufacturing technique with post-processing treatments namely (i) Binder Jetting Printing (BJP) + Cold Isostatic Pressing (CIP) + cycle and (ii) BJP + cycle where cycle refers to a sequence of Impregnation—Drying—Pyrolysis. These two new processes yielded additively manufactured parts with higher density and reduced defects/porosities. As a testbed, we used these new processes to fabricate graphite structures. The samples produced by both methods were compared with each other and benchmarked to the samples produced by (a) BJP alone and (b) Traditional uniaxial pressing like compaction moulding. Various characterisation methods were used to investigate the microstructure and mechanical properties which showed that the porosity of hybrid manufactured samples reduces from 55% to a record 7%. This technological pathway is expected to create a new avalanche of industrial applications that are hitherto unexplored in the arena of hybrid additive manufacturing with BJP method.
Novel method for scalable synthesis of wollastonite nanoparticle as nano-filler in composites for promotion of anti-corrosive property
Authors: Dordane Rouholah , Doroodmand Mohammad Mahdi
Published: January 2021

This study is focused on novel anti-corrosive support. This coating is based on the mixed matrix (MM) including epoxy and its hardener as thermoset polymer, melamine–formaldehyde as the organic phase, activated graphite as both inorganic and conductive phases, as well as wollastonite nanoparticles as filler. The wollastonite nanoparticles are synthesized by the new and novel method as suitable etching using hydrofluoric acid, “HF” at room temperature (25 ℃). The synthesized wollastonite nanoparticles are then adapted as a suitable filler during the formation of a new type of MM anti-corrosive coating for the preservation of metals form any corrosion. According to the results, during coating the MM, significant positive characteristics such as enough positive open circuit potential (OCP), small enough (icorr), low cost, significant chemical/mechanical stability and acceptable flexibility are observed. Based on to the weight-loss analysis test on the MM-modified stainless steel during a 42-day time interval, the corrosion rate % is decreased from 74.86 to 0.34. In addition, the electrochemical impedance spectroscopy reveals major enhancements in the double-layer resistance and solution resistance of the cell system. Based on the electrochemical measurements, noticeable reduction and enhancement are observed in the correction rate and potential, respectively, during introducing hard corrosive conditions such as NaCl (3.0%, w/v) and HCl (1.0 mol L−1) environments that reveal the acceptable anti-corrosive behavior of the synthesized MM. The introduced MM is therefore considered as low cost, safe, eco-friendly, industrial-justified anti-corrosion support.
Multi-functionality of a tryptophan residue conserved in substrate-binding groove of GH19 chitinases
Authors: Nagata Takuya , Shinya Shoko , Ohnuma Takayuki , Fukamizo Tamo
Published: January 2021

GH19 and GH22 glycoside hydrolases belonging to the lysozyme superfamily have a related structure/function. A highly conserved tryptophan residue, Trp103, located in the binding groove of a GH19 chitinase from moss Bryum coronatum (BcChi-A) appears to have a function similar to that of well-known Trp62 in GH22 lysozymes. Here, we found that mutation of Trp103 to phenylalanine (W103F) or alanine (W103A) strongly reduced the enzymatic activity of BcChi-A. NMR experiments and the X-ray crystal structure suggested a hydrogen bond between the Trp103 side chain and the -2 sugar. Chitooligosaccharide binding experiments using NMR indicated that the W103F mutation reduced the sugar-binding abilities of nearby amino acid residues (Tyr105/Asn106) in addition to Trp103. This appeared to be derived from enhanced aromatic stacking of Phe103 with Tyr105 induced by disruption of the Trp103 hydrogen bond with the -2 sugar. Since the stacking with Tyr105 was unlikely in W103A, Tyr105/Asn106 of W103A was not so affected as in W103F. However, the W103A mutation appeared to reduce the catalytic potency, resulting in the lowest enzymatic activity in W103A. We concluded that Trp103 does not only interact with the sugar, but also controls other amino acids responsible for substrate binding and catalysis. Trp103 (GH19) and Trp62 (GH22) with such a multi-functionality may be advantageous for enzyme action and conserved in the divergent evolution in the lysozyme superfamily.
Expression profile of protein fractions in the developing kernel of normal, Opaque-2 and quality protein maize
Authors: Sethi Mehak , Singh Alla , Kaur Harmanjot , Phagna Ramesh Kumar , Rakshit Sujay , Chaudhary Dharam Paul
Published: January 2021

Maize protein quality is determined by the composition of its endosperm proteins, which are classified as nutritionally poor zeins (prolamin and prolamin-like) and nutritionally rich non-zeins (albumin, globulin, glutelin-like, and glutelin). Protein quality is considerably higher in opaque-2 mutants due to increased content of non-zeins over zeins. However, the opaque-2 endosperm is soft, which leads to poor agronomic performance and post-harvest infestation. Endosperm modification of opaque-2 had led to the development of Quality Protein Maize (QPM), which has higher protein quality along with hard kernel endosperm. The present study was planned to analyze the expression dynamics of different protein fractions in the endospem of developing maize kernel in normal, opaque-2 and QPM in response to the introgression of endosperm modifiers. Results revealed that albumin and globulin content decreases, whereas, prolamin, prolamin-like, glutelin-like, and glutelin content increases with kernel maturity. It has been observed that opaque-2 mutation affects protein expression at initial stages, whereas, the effect of endosperm modifiers was observed at the intermediate and later stages of kernel development. It has also been noted that prolamin, glutelin, and glutelin-like fractions can be used as quick markers for quality assessment for differentiating QPM varieties, even at the immature stage of kernel development. Overall, the present study implicates the role of different protein fractions in developing and utilizing nutritionally improved maize varieties.
Human amnion-derived mesenchymal stem cells attenuate xenogeneic graft-versus-host disease by preventing T cell activation and proliferation
Authors: Tago Yoshiyuki , Kobayashi Chiho , Ogura Mineko , Wada Jutaro , Yamaguchi Sho , Yamaguchi Takashi , Hayashi Masahiro , Nakaishi Tomoyuki , Kubo Hiroshi , Ueda Yasuyoshi
Published: January 2021

Acute graft-versus-host disease (GVHD) is characterized by severe tissue damage that is a life-threatening complication of allogeneic hematopoietic stem cell transplantation. Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been increasingly examined for the treatment of immune-related diseases. We aimed to assess the immunosuppressive effects of human amnion-derived MSC (AMSC) in a xenogeneic GVHD NOD/Shi-scid IL2rγnull mouse model using human peripheral blood mononuclear cells (PBMC). Additionally, we used human bone marrow-derived MSC (BMSC) as comparative controls to determine differences in immunomodulatory functions depending on the MSC origin. Administration of AMSC significantly prolonged survival, and reduced human tumor necrosis factor-α (TNF-α) concentration and percentage of programmed cell death protein-1 receptor (PD-1)+CD8+ T cell populations compared with in GVHD control mice. Furthermore, colonic inflammation score and percentage of human CD8+ T cell populations in AMSC-treated mice were significantly lower than in GVHD control and BMSC-treated mice. Interestingly, gene expression and protein secretion of the PD-1 ligands were higher in AMSC than in BMSC. These findings are the first to demonstrate that AMSC exhibit marked immunosuppression and delay acute GVHD progression by preventing T cell activation and proliferation via the PD-1 pathway.
Higher cardiorespiratory fitness is strongly associated with lower cardiovascular risk factors in firefighters: a cross-sectional study in a German fire brigade
Authors: Strauss Markus , Foshag Peter , Jehn Ulrich , Brzęk Anna , Littwitz Henning , Leischik Roman
Published: January 2021

Previous studies have shown significant cardiovascular risks in firefighters and that they suffer from cardiovascular events, especially on duty. Otherwise, adequate cardiorespiratory fitness is considered to have a protective effect in reducing cardiovascular complications. Therefore, the study aimed to evaluate the association between cardiorespiratory fitness and cardiovascular risks factors in firefighters. We enrolled ninety-seven male German firefighters in this cross-sectional study of cardiorespiratory fitness and cardiovascular risk factors. We used spiroergometry testing to estimate oxygen consumption to determine cardiorespiratory fitness and to calculate metabolic equivalents. We evaluated cardiovascular risk factors included nicotine consumption, lipid profiles, body composition, resting blood pressure, and heart rate. We evaluated cardiovascular risk factors included nicotine consumption, lipid profiles, body composition, resting blood pressure and heart rate. The comparison of association between cardiorespiratory fitness and cardiovascular risk factors was performed by using χ2-test, analysis of variance, general linear regression with/without adjustment for age and body mass index (BMI). This study demonstrated a strong association between lower cardiovascular risk factors and higher cardiorespiratory fitness. There were significantly lower values for BMI, waist circumference, body fat percentage and resting systolic blood pressure, triglycerides, and total cholesterol (all p < 0.0443, age-adjusted) with increased cardiorespiratory fitness. Only 19.6% (n = 19) of the examined firefighters were classified as “fit and not obese”, 48.4% (n = 47) were “low fit and not obese” and 30.9% (n = 30) were “low fit and obese”. The results clarify that increasing cardiorespiratory fitness is a fundamental point for the reduction and prevention of cardiovascular complications in firefighters. It could be demonstrated, especially for central risk factors, particularly BMI, waist circumference, sytolic resting blood pressure and triglyceride values. Therefore, firefighters should be motivated to increase their cardiorespiratory fitness for the beneficial effect of decreasing cardiovascular risk profile.
Simultaneously enhanced dielectric properties and through-plane thermal conductivity of epoxy composites with alumina and boron nitride nanosheets
Authors: Wang Zhengdong , Meng Guodong , Wang Liangliang , Tian Liliang , Chen Siyu , Wu Guanglei , Kong Bo , Cheng Yonghong
Published: January 2021

Dielectric materials with good thermal transport performance and desirable dielectric properties have significant potential to address the critical challenges of heat dissipation for microelectronic devices and power equipment under high electric field. This work reported the role of synergistic effect and interface on through-plane thermal conductivity and dielectric properties by intercalating the hybrid fillers of the alumina and boron nitride nanosheets (BNNs) into epoxy resin. For instance, epoxy composite with hybrid fillers at a relatively low loading shows an increase of around 3 times in through-plane thermal conductivity and maintains a close dielectric breakdown strength compared to pure epoxy. Meanwhile, the epoxy composite shows extremely low dielectric loss of 0.0024 at room temperature and 0.022 at 100 ℃ and 10−1 Hz. And covalent bonding and hydrogen-bond interaction models were presented for analyzing the thermal conductivity and dielectric properties.
Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study
Authors: Middleton Paul , Perez-Guzman Pablo N. , Cheng Alexandra , Kumar Naveenta , Kont Mara D. , Daunt Anna , Mukherjee Sujit , Cooke Graham , Hallett Timothy B. , Hauck Katharina , White Peter J. , Thursz Mark R. , Nayagam Shevanthi
Published: January 2021

Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for > 60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.
A clinical pilot study on the effect of the probiotic Lacticaseibacillus rhamnosus TOM 22.8 strain in women with vaginal dysbiosis
Authors: Pino Alessandra , Rapisarda Agnese Maria Chiara , Vitale Salvatore Giovanni , Cianci Stefano , Caggia Cinzia , Randazzo Cinzia Lucia , Cianci Antonio
Published: January 2021

Lactobacilli with probiotic features play an essential role in maintaining a balanced vaginal microbiota and their administration has been suggested for the treatment and prevention of vaginal dysbiosis. The present study was aimed to in vitro and in vivo investigate the probiotic potential of the Lacticaseibacillus rhamnosus TOM 22.8 strain, isolated from the vaginal ecosystem of a healthy woman. For this purpose, safety and functional properties were in depth evaluated. The strain exhibited a broad spectrum of antagonistic activity against vaginal pathogens; adhesion capacity to both the vaginal VK2/E6E7 and the intestinal Caco-2 cells; anti-inflammatory and antioxidant activities, suggesting its promising probiotic features. In addition, an in vivo pilot-study was planned. Based on both clinical and microbiological parameters, the oral or vaginal strain administration, determined a significant pathogens reduction after 10 days of administration and a maintenance of eubiosis up to 30 days after the end of the treatment. Therefore, the L. rhamnosus TOM 22.8 strain can be proposed as valuable oral and/or vaginal treatment for vaginal dysbiosis.
Particulate matter (PM2.5) as a potential SARS-CoV-2 carrier
Authors: Nor Norefrina Shafinaz Md , Yip Chee Wai , Ibrahim Nazlina , Jaafar Mohd Hasni , Rashid Zetti Zainol , Mustafa Norlaila , Hamid Haris Hafizal Abd , Chandru Kuhan , Latif Mohd Talib , Saw Phei Er , Lin Chin Yik , Alhasa Kemal Maulana , Hashim Jamal Hisham , Nadzir Mohd Shahrul Mohd
Published: January 2021

The rapid spread of the SARS-CoV-2 in the COVID-19 pandemic had raised questions on the route of transmission of this disease. Initial understanding was that transmission originated from respiratory droplets from an infected host to a susceptible host. However, indirect contact transmission of viable virus by fomites and through aerosols has also been suggested. Herein, we report the involvement of fine indoor air particulates with a diameter of ≤ 2.5 µm (PM2.5) as the virus’s transport agent. PM2.5 was collected over four weeks during 48-h measurement intervals in four separate hospital wards containing different infected clusters in a teaching hospital in Kuala Lumpur, Malaysia. Our results indicated the highest SARS-CoV-2 RNA on PM2.5 in the ward with number of occupants. We suggest a link between the virus-laden PM2.5 and the ward’s design. Patients’ symptoms and numbers influence the number of airborne SARS-CoV-2 RNA with PM2.5 in an enclosed environment.
Multiple maternal risk-management adaptations in the loggerhead sea turtle (Caretta caretta) mitigate clutch failure caused by catastrophic storms and predators
Authors: Cassill Deby L.
Published: January 2021

Maternal risk-management, an extension ofr/Kselection, is an indispensable tool for understanding the natural selection pressures that shape the evolution of reproduction. Central to the construct of maternal risk-management is its definition of reproductive success as replacement fitness (w = 2), the survival of one breeding daughter to replace the female and one outbreeding son to replace her mate. Here, I apply maternal risk-management as a theoretical framework to explain multiple reproductive adaptations by loggerhead sea turtles nesting on a barrier island off the southern coast of Florida, US, from 1988 to 2004. Extrapolated over a 30-year reproductive span, nesting females averaged 4000–4500 eggs. I show that, rather than “putting all their eggs in one basket,” females divided eggs into 40 clutches of variable size (50–165 eggs). To deposit clutches, females migrated to the barrier island 10–12 times at unpredictable intervals of 2–8 years. Each nesting season, females deposited 1–7 clutches over diversified time intervals at diversified locations on the beach. Despite devastating clutch losses caused by ten catastrophic hurricanes, hundreds of erratic thunderstorms and dozens of predation events during this study, 72% of clutches produced by nesting females on this barrier island were undisturbed—median hatching success for these clutches was an astonishing 92%. I conclude that diversified maternal investments over time and space by nesting females are reproductive adaptations that have successfully offset clutch losses, thus enabling populations of loggerhead females to meet or exceed their reproductive goal of replacement fitness.
Epigenetic silencing directs expression heterogeneity of stably integrated multi-transcript unit genetic circuits
Authors: Zimak Jan , Wagoner Zachary W. , Nelson Nellie , Waechtler Brooke , Schlosser Hana , Kopecky Morgan , Wu Jie , Zhao Weian
Published: January 2021

We report that epigenetic silencing causes the loss of function of multi-transcript unit constructs that are integrated using CRISPR-Cas9. Using a modular two color reporter system flanked by selection markers, we demonstrate that expression heterogeneity does not correlate with sequence alteration but instead correlates with chromosomal accessibility. We partially reverse this epigenetic silencing via small-molecule inhibitors of methylation and histone deacetylation. We then correlate each heterogeneously-expressing phenotype with its expected epigenetic state by employing ATAC-seq. The stability of each expression phenotype is reinforced by selective pressure, which indicates that ongoing epigenetic remodeling can occur for over one month after integration. Collectively, our data suggests that epigenetic silencing limits the utility of multi-transcript unit constructs that are integrated via double-strand repair pathways. Our research implies that mammalian synthetic biologists should consider localized epigenetic outcomes when designing complex genetic circuits.
Bacterial communities of the upper respiratory tract of turkeys
Authors: Kursa Olimpia , Tomczyk Grzegorz , Sawicka-Durkalec Anna , Giza Aleksandra , Słomiany-Szwarc Magdalena
Published: January 2021

The respiratory tracts of turkeys play important roles in the overall health and performance of the birds. Understanding the bacterial communities present in the respiratory tracts of turkeys can be helpful to better understand the interactions between commensal or symbiotic microorganisms and other pathogenic bacteria or viral infections. The aim of this study was the characterization of the bacterial communities of upper respiratory tracks in commercial turkeys using NGS sequencing by the amplification of 16S rRNA gene with primers designed for hypervariable regions V3 and V4 (MiSeq, Illumina). From 10 phyla identified in upper respiratory tract in turkeys, the most dominated phyla were Firmicutes and Proteobacteria. Differences in composition of bacterial diversity were found at the family and genus level. At the genus level, the turkey sequences present in respiratory tract represent 144 established bacteria. Several respiratory pathogens that contribute to the development of infections in the respiratory system of birds were identified, including the presence of Ornithobacterium and Mycoplasma OTUs. These results obtained in this study supply information about bacterial composition and diversity of the turkey upper respiratory tract. Knowledge about bacteria present in the respiratory tract and the roles they can play in infections can be useful in controlling, diagnosing and treating commercial turkey flocks.
Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
Authors: Morito Takahiro , Harada Ryuichi , Iwata Ren , Du Yiqing , Okamura Nobuyuki , Kudo Yukitsuka , Yanai Kazuhiko
Published: January 2021

Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.
Post-acute pre-discharge echocardiography in the long-term prognostic assessment of pulmonary thrombembolism
Authors: Kokalj Nataša , Kozak Matija , Jug Borut
Published: January 2021

The aim of our study was to asses the long-term prognostic impact of post-acute, pre-discharge echocardiographic assessment of right ventricular (RV) dysfunction in patients with low- and intermediate-risk pulmonary embolism (PE). Consecutive patients with acute PE underwent post-acute, pre-discharge echocardiographic assessment of RV dysfunction (defined by: RV dilation, tricuspid anulus peak systolic excursion, or tricuspid regurgitation systolic velocity). A Cox multivariate survival mode was constructed to determine the prognostic impact of post-acute, pred-discharge RV dysfunction on all-cause mortality. 615 patients were included: 330 (54%) women, mean age 64 ± 18 years, 265 (43.1%) with post-acute, predischarge RV dysfunction. During follow-up (median 1068 days), 88 (14.3%) patients died. On Cox multivariate analyis, pre-discharge post-acute tricuspid regurgitation systolic velocity emerged as the only independent echocardiographic predictor of mortality (HR 1.73 for every 1 m/s increase; 95% confidence interval 1.033–2.897; p = 0.037). RV dysfunction persists in almost one half of PE patients in the post-acute phase on pre-discharge echocardiography; however, only tricuspid regurgitation systolic velocity independently predicts long-term prognosis.
Changes in headache characteristics with oral appliance treatment for obstructive sleep apnea
Authors: Park Ji Woon , Mehta Sujay , Fastlicht Sandra , Lowe Alan A. , Almeida Fernanda R.
Published: January 2021

Changes in headache characteristics in obstructive sleep apnea (OSA) patients following oral appliance treatment was investigated for the first time. Thirteen OSA patients with headaches treated with a mandibular advancement device were investigated. Level I polysomnography and Migraine Disability Assessment Questionnaire were completed before and after treatment. Various headache characteristics and concomitant conditions were analyzed. The patient was considered a headache responder when ≥ 30% reduction in headache frequency following treatment. Differences in headache and polysomnographic parameters were compared between headache responder groups. Eight patients (62%) were headache responders. Eleven patients (85%) before and 7 (54%) after treatment reported morning headaches. Significantly more patients had bilateral headache in the responder group before treatment (P = 0.035). The severest headache intensity (P = 0.018) at baseline showed a significant decrease in the headache responder group after treatment. The time spent in N2 (r = − 0.663, P = 0.014), REM sleep (r = 0.704, P = 0.007) and mean oxygen saturation (r = 0.566, P = 0.044) showed a significant correlation with post-treatment average headache intensity. Pre-treatment lower PLM index (r = − 0.632, P = 0.027) and higher mean oxygen saturation levels (r = 0.592, P = 0.043) were significantly correlated with higher post-treatment severest headache intensity. Treatment with an oral appliance is beneficial for many OSA patients with headaches. It should be considered as an alternative treatment in headache patients with mild to moderate OSA.
Development and validation of a nomogram to predict drainage duration in patients with breast cancer treated with modified radical mastectomy
Authors: Wu Song , Xin Zechang , Sui Daxing , Ou Zhengli , Bai Haotian , Zhu Shenzhen , Wang Xueying , Zhang Jiaxin
Published: January 2021

Appropriate drainage duration is vital for the postoperative rehabilitation of patients with breast cancer (BC) undergoing modified radical mastectomy (MRM). To provide better and individualized postoperative management for these patients, this study explored independent predictors of postoperative drainage duration in patients with BC. This was a single-center retrospective cohort study. Patients diagnosed with BC and treated with MRM from May 2016 to April 2020 were randomly divided into training (n = 729) and validation (n = 243) cohorts. Univariate and multivariate Cox analyses revealed that the body mass index, serum albumin level, hypertension, number of total dissected axillary lymph nodes, and ratio of positive axillary lymph nodes were independent predictors of postoperative drainage duration in the training cohort. Based on independent predictors, a nomogram was constructed to predict the median postoperative drainage duration and the probability of retaining the suction drain during this period. This nomogram had good concordance and discrimination both in the training and validation cohorts and could effectively predict the probability of retaining the suction drain during drainage, thus assisting clinicians in predicting postoperative drainage duration and providing individualized postoperative management for patients with BC.
Multiparametric ultrasound examination for response assessment in breast cancer patients undergoing neoadjuvant therapy
Authors: Dobruch-Sobczak K. , Piotrzkowska-Wróblewska H. , Klimonda Z. , Karwat P. , Roszkowska-Purska K. , Clauser P. , Baltzer P. A. T. , Litniewski J.
Published: January 2021

To investigate the performance of multiparametric ultrasound for the evaluation of treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Breast cancer patients who were scheduled to undergo NAC were invited to participate in this study. Changes in tumour echogenicity, stiffness, maximum diameter, vascularity and integrated backscatter coefficient (IBC) were assessed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was considered as standard of reference. RMC < 30% was considered a good response and > 70% a poor response. The correlation coefficients of these parameters were compared with RMC from post-operative histology. Linear Discriminant Analysis (LDA), cross-validation and Receiver Operating Characteristic curve (ROC) analysis were performed. Thirty patients (mean age 56.4 year) with 42 lesions were included. There was a significant correlation between RMC and echogenicity and tumour diameter after the 3rd course of NAC and average stiffness after the 2nd course. The correlation coefficient for IBC and echogenicity calculated after the first four doses of NAC were 0.27, 0.35, 0.41 and 0.30, respectively. Multivariate analysis of the echogenicity and stiffness after the third NAC revealed a sensitivity of 82%, specificity of 90%, PPV = 75%, NPV = 93%, accuracy = 88% and AUC of 0.88 for non-responding tumours (RMC > 70%). High tumour stiffness and persistent hypoechogenicity after the third NAC course allowed to accurately predict a group of non-responding tumours. A correlation between echogenicity and IBC was demonstrated as well.
Central aortic hemodynamics following acute lower and upper-body exercise in a cold environment among patients with coronary artery disease
Authors: Hintsala Heidi E. , Valtonen Rasmus I. P. , Kiviniemi Antti , Crandall Craig , Perkiömäki Juha , Hautala Arto , Mäntysaari Matti , Alén Markku , Ryti Niilo , Jaakkola Jouni J. K. , Ikäheimo Tiina M.
Published: January 2021

Exercise is beneficial to cardiovascular health, evidenced by reduced post-exercise central aortic blood pressure (BP) and wave reflection. We assessed if post-exercise central hemodynamics are modified due to an altered thermal state related to exercise in the cold in patients with coronary artery disease (CAD). CAD patients (n = 11) performed moderate-intensity lower-body exercise (walking at 65–70% of HRmax) and rested in neutral (+ 22 °C) and cold (− 15 °C) conditions. In another protocol, CAD patients (n = 15) performed static (five 1.5 min work cycles, 10–30% of maximal voluntary contraction) and dynamic (three 5 min workloads, 56–80% of HRmax) upper-body exercise at the same temperatures. Both datasets consisted of four 30-min exposures administered in random order. Central aortic BP and augmentation index (AI) were noninvasively assessed via pulse wave analyses prior to and 25 min after these interventions. Lower-body dynamic exercise decreased post-exercise central systolic BP (6–10 mmHg, p < 0.001) and AI (1–6%, p < 0.001) both after cold and neutral and conditions. Dynamic upper-body exercise lowered central systolic BP (2–4 mmHg, p < 0.001) after exposure to both temperatures. In contrast, static upper-body exercise increased central systolic BP after exposure to cold (7 ± 6 mmHg, p < 0.001). Acute dynamic lower and upper-body exercise mainly lowers post-exercise central BP in CAD patients irrespective of the environmental temperature. In contrast, central systolic BP was elevated after static exercise in cold. CAD patients likely benefit from year-round dynamic exercise, but hemodynamic responses following static exercise in a cold environment should be examined further.

Clinical trials.gov: NCT02855905 04/08/2016.
Extracting sub-cycle electronic and nuclear dynamics from high harmonic spectra
Authors: Austin Dane R. , Johnson Allan S. , McGrath Felicity , Wood David , Miseikis Lukas , Siegel Thomas , Hawkins Peter , Harvey Alex , Mašín Zdeněk , Patchkovskii Serguei , Vacher Morgane , Malhado João Pedro , Ivanov Misha Y. , Smirnova Olga , Marangos Jon P.
Published: January 2021

We present a new methodology for measuring few-femtosecond electronic and nuclear dynamics in both atoms and polyatomic molecules using multidimensional high harmonic generation (HHG) spectroscopy measurements, in which the spectra are recorded as a function of the laser intensity to form a two-dimensional data set. The method is applied to xenon atoms and to benzene molecules, the latter exhibiting significant fast nuclear dynamics following ionization. We uncover the signature of the sub-cycle evolution of the returning electron flux in strong-field ionized xenon atoms, implicit in the strong field approximation but not previously observed directly. We furthermore extract the nuclear autocorrelation function in strong field ionized benzene cations, which is determined to have a decay of $$\tau _0 = 4 \pm 1$$

τ
0

=
4
±
1

fs, in good agreement with the $$ \tau _0 = 3.5$$

τ
0

=
3.5

fs obtained from direct dynamics variational multi-configuration Gaussian calculations. Our method requires minimal assumptions about the system, and is applicable even to un-aligned polyatomic molecules.
Engineered biochar from wood apple shell waste for high-efficient removal of toxic phenolic compounds in wastewater
Authors: Kumar Nadavala Siva , Shaikh Hamid M. , Asif Mohammad , Al-Ghurabi Ebrahim H.
Published: January 2021

This study investigated a novel agricultural low-cost bio-waste biochar derived from wood apple fruit shell waste via the pyrolysis method, which is modified by ball milling and utilized to remove toxic phenol and chlorophenols (4-CPh and 2,4-DCPh) from contaminated aqueous media. The ball-milled wood apple fruit shell waste biochar (WAS-BC) sorbent was systematically analyzed by BET, CHN, and FTIR as well as particle size, SEM–EDS, XPS and TGA studies. The sorption equilibrium and kinetic studies exhibit that the sorption capacity was greater than 75% within the first 45 min of agitation at pH 6.0. The uptake capacity of 2,4-DCPh onto WAS-BC was greater than those of 4-CPh and phenol. Equilibrium results were consistent with the Langmuir isotherm model, while the kinetic data were best represented by the Elovich and pseudo-second-order model. The maximum uptake of phenol, 4-CPh, and 2,4-DCPh was 102.71, 172.24, and 226.55 mg/g, respectively, at 30 ± 1 °C. Thus, this study demonstrates that WAS-BC is an efficient, low-cost sorbent that can be used for the elimination of phenol and chlorophenol compounds from polluted wastewater.
Antifibrotic effect of novel neutrophil gelatinase-associated lipocalin inhibitors in cardiac and renal disease models
Authors: Bonnard Benjamin , Martínez-Martínez Ernesto , Fernández-Celis Amaya , Pieronne-Deperrois Marie , Do Quoc-Tuan , Ramos Isbaal , Rossignol Patrick , Zannad Faiez , Mulder Paul , Ouvrard-Pascaud Antoine , López-Andrés Natalia , Jaisser Frédéric
Published: January 2021

Neutrophil gelatinase-associated lipocalin (NGAL) is involved in cardiovascular and renal diseases. Gene inactivation of NGAL blunts the pathophysiological consequences of cardiovascular and renal damage. We aimed to design chemical NGAL inhibitors and investigate its effects in experimental models of myocardial infarction (MI) and chronic kidney disease induced by 5/6 nephrectomy (CKD) on respectively 8–12 weeks old C57Bl6/j and FVB/N male mice. Among the 32 NGAL inhibitors tested, GPZ614741 and GPZ058225 fully blocked NGAL-induced inflammatory and profibrotic markers in human cardiac fibroblasts and primary mouse kidney fibroblasts. The administration of GPZ614741 (100 mg/kg/day) for three months, was able to improve cardiac function in MI mice and reduced myocardial fibrosis and inflammation. The administration of GPZ614741 (100 mg/kg/day) for two months resulting to no renal function improvement but prevented the increase in blood pressure, renal tubulointerstitial fibrosis and profibrotic marker expression in CKD mice. In conclusion, we have identified new compounds with potent inhibitory activity on NGAL-profibrotic and pro-inflammatory effects. GPZ614741 prevented interstitial fibrosis and dysfunction associated with MI, as well as tubulointerstitial fibrosis in a CKD model. These inhibitors could be used for other diseases that involve NGAL, such as cancer or metabolic diseases, creating new therapeutic options.
Locomotion of the C60-based nanomachines on graphene surfaces
Authors: Mofidi Seyedeh Mahsa , Nejat Pishkenari Hossein , Ejtehadi Mohammad Reza , Akimov Alexey V.
Published: January 2021

We provide a comprehensive computational characterization of surface motion of two types of nanomachines with four C60 “wheels”: a flexible chassis Nanocar and a rigid chassis Nanotruck. We study the nanocars’ lateral and rotational diffusion as well as the wheels’ rolling motion on two kinds of graphene substrates—flexible single-layer graphene which may form surface ripples and an ideally flat graphene monolayer. We find that the graphene surface ripples facilitate the translational diffusion of Nanocar and Nanotruck, but have little effect on their surface rotation or the rolling of their wheels. The latter two types of motion are strongly affected by the structure of the nanomachines instead. Surface diffusion of both nanomachines occurs preferentially via a sliding mechanism whereas the rolling of the “wheels” contributes little. The axial rotation of all “wheels” is uncorrelated.
Evaluation of the nano silica and nano waste materials on the corrosion protection of high strength steel embedded in ultra-high performance concrete
Authors: Mostafa Sahar A. , EL-Deeb Mohamed M. , Farghali Ahmed A. , Faried A. Serag
Published: January 2021

Corrosion resistance of high strength steel (HHS) embedded in ultra-high performance concrete (UHPC) immersed in 3.5% NaCl solution is evaluated in the absence and presence of nano silica (NS), nano glass waste (NGW), nano rice husk ash (NRHA) and nano metakaolin (NMK) using open circuit potential, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) under normal and accelerated conditions. Data showed that the corrosion rate in the accelerated conditions is higher compared by the normal conditions due to the increasing in the rate of both anodic and cathodic reactions in the presence of anodic current. On the other hand, the presence of the studied nano materials decreases both the anodic and cathodic overpotentials, and shifts both the open circuit potential (Eocp) and corrosion potential (Ecorr) of HSS to more noble values, as well as decreases the values of the corrosion current densities (Icorr) in both normal and accelerated conditions. Furthermore, EIS analysis illustrates that the presence of these materials enhances both the concrete bulk resistance and the charge transfer resistance at HSS/UHPC interface, which retards the flow of the electrons between the anodic and cathodic sites, thus impeding the propagation of the corrosion process. The inhibitory effect of the studied nano materials for the corrosion of HSS is interpreted on the basis of the change in the microstructure and the compressive strength of the UHPC.
Detecting neurodevelopmental trajectories in congenital heart diseases with a machine-learning approach
Authors: Cainelli Elisa , Bisiacchi Patrizia S. , Cogo Paola , Padalino Massimo , Simonato Manuela , Vergine Michela , Lanera Corrado , Vedovelli Luca
Published: January 2021

We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18 months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains: intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles: a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD.
Publisher Correction: Anatomical study of the coffee berry borer (Hypothenemus hampei) using micro-computed tomography
Authors: Alba-Alejandre Ignacio , Alba-Tercedor Javier , Vega Fernando E.
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mechanisms of slab avalanche release and impact in the Dyatlov Pass incident in 1959
Authors: Gaume Johan , Puzrin Alexander M.
Published: January 2021

The Dyatlov Pass incident is an intriguing unsolved mystery from the last century. In February 1959, a group of nine experienced Russian mountaineers perished during a difficult expedition in the northern Urals. A snow avalanche hypothesis was proposed, among other theories, but was found to be inconsistent with the evidence of a lower-than-usual slope angle, scarcity of avalanche signs, uncertainties about the trigger mechanism, and abnormal injuries of the victims. The challenge of explaining these observations has led us to a physical mechanism for a slab avalanche caused by progressive wind-blown snow accumulation on the slope above the hikers’ tent. Here we show how a combination of irregular topography, a cut made in the slope to install the tent and the subsequent deposition of snow induced by strong katabatic winds contributed after a suitable time to the slab release, which caused severe non-fatal injuries, in agreement with the autopsy results.