bluuebunny/crossref_metadata_2025 huggingface dataset:
Bisphosphonate Use May Reduce the Risk of Urolithiasis in Astronauts on Long‐Term Spaceflights
Authors: Okada Atsushi , Matsumoto Toshio , Ohshima Hiroshi , Isomura Tatsuya , Koga Tadashi , Yasui Takahiro , Kohri Kenjiro , LeBlanc Adrian , Spector Elisabeth , Jones Jeffrey , Shackelford Linda , Sibonga Jean
Published: September 2021

Long‐duration spaceflight is associated with an increased risk of urolithiasis, and the pain caused by urinary calculi could result in loss of human performance and mission objectives. The present study investigated the risk of urolithiasis in astronauts during 6 months on the International Space Station, and evaluated whether the suppression of bone resorption by the bisphosphonate, alendronate (ALN), can reduce the risk. A total of 17 astronauts were included into the analysis: exercise using the advanced resistive exercise device (ARED) plus weekly oral 70 mg alendronate (ARED+ALN group, n = 7) was compared to resistive exercise alone (ARED group, n = 10). Urine volume decreased in both groups during spaceflight but recovered after return. The ARED group showed increased urinary calcium excretion from the 15th to 30th day of spaceflight, whereas urinary calcium was slightly decreased in the ARED+ALN group. Urinary N‐terminal telopeptide (NTX) and helical peptide (HP) of type I collagen, as bone resorption markers, were elevated in the ARED group during and until 0 days after spaceflight, while there was no elevation in these parameters in the ARED+ALN group. Urinary oxalate and uric acid excretion tended to be higher in the ARED group than in the ARED+ALN group during spaceflight. These results demonstrate that astronauts on long‐duration spaceflights may be at high risk for the formation of urinary calcium oxalate and calcium phosphate stones through increased urinary excretion of oxalate and uric acid, from degraded type I collagen, as well as of calcium from enhanced bone resorption. Our findings suggest that increased bone resorption during spaceflight, as a risk factor for urinary calculus formation, could be effectively prevented by an inhibitor of bone resorption. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Pharmacological inhibition of BAG3‐HSP70 with the proposed cancer therapeutic JG‐98 is toxic for cardiomyocytes
Authors: Martin Thomas G. , Delligatti Christine E. , Muntu Nitha Aima , Stachowski‐Doll Marisa J. , Kirk Jonathan A.
Published: September 2021

The co‐chaperone Bcl2‐associated athanogene‐3 (BAG3) maintains cellular protein quality control through the regulation of heat shock protein 70 (HSP70). Cancer cells manipulate BAG3‐HSP70‐regulated pathways for tumor initiation and proliferation, which has led to the development of promising small molecule therapies, such as JG‐98, which inhibit the BAG3‐HSP70 interaction and mitigate tumor growth. However, it is not known how these broad therapies impact cardiomyocytes, where the BAG3‐HSP70 complex is a key regulator of protein turnover and contractility. Here, we show that JG‐98 exposure is toxic in neonatal rat ventricular myocytes (NRVMs). Using immunofluorescence microscopy to assess cell death, we found that apoptosis increased in NRVMs treated with JG‐98 doses as low as 10 nM. JG‐98 treatment also reduced autophagy flux and altered expression of BAG3 and several binding partners involved in BAG3‐dependent autophagy, including SYNPO2 and HSPB8. We next assessed protein half‐life with disruption of the BAG3‐HSP70 complex by treating with JG‐98 in the presence of cycloheximide and found BAG3, HSPB5, and HSPB8 half‐lives were reduced, indicating that complex formation with HSP70 is important for their stability. Next, we assessed sarcomere structure using super‐resolution microscopy and found that disrupting the interaction with HSP70 leads to sarcomere structural disintegration. To determine whether the effects of JG‐98 could be mitigated by pharmacological autophagy induction, we cotreated NRVMs with rapamycin, which partially reduced the extent of apoptosis and sarcomere disarray. Finally, we investigated whether the effects of JG‐98 extended to skeletal myocytes using C2C12 myotubes and found again increased apoptosis and reduced autophagic flux. Together, our data suggest that nonspecific targeting of the BAG3‐HSP70 complex to treat cancer may be detrimental for cardiac and skeletal myocytes.
Extraction of microalgal starch and pigments by using different cell disruption methods and aqueous two‐phase system
Authors: Di Caprio Fabrizio , Chelucci Rachele , Francolini Iolanda , Altimari Pietro , Pagnanelli Francesca
Published: September 2021

BACKGROUND

Microalgae can synthesize starch with productivity higher than conventional terrestrial crops, without the need for arable land. However, little is known about processes to extract starch from microalgae. Here, a biorefinery process is described including microalgal cell disruption followed by extraction of starch and pigments with aqueous two‐phase system (ATPS) using choline chloride and polypropylene glycol 400. Sonication and bead milling were compared for cell disruption rate and starch extraction efficiency.

RESULTS

A first order kinetic model described well the cell disruption for both the methods, with a rate 2.6 times higher for bead milling than sonication. By applying ATPS on samples with comparable cell disruption (>93%), starch was separated better after sonication (67% recovery in the pellet) than after bead milling, for which it remained equally distributed between pellet (40%) and choline chloride phase. Pigments were extracted with 42–66% yield irrespective of the cell disruption method. Microalgal starch granules had a normal and narrow distribution for size (0.93 ± 0.14 μm) and a gelatinization temperature between 45–55 °C.

CONCLUSION

For the same cell disruption yield, different starch separation efficiencies can be achieved, depending on the cell disruption method applied. Although bead milling was faster than sonication in disrupting cells, it gave worst starch separation efficiency. The properties of the extracted microalgal starch indicate potential technical advantages, with respect to conventional starch sources, for applications in the bioplastic and food sector. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Seminal fluid and sperm diluent affect sperm metabolism in an insect: Evidence from NAD(P)H and flavin adenine dinucleotide autofluorescence lifetime imaging
Authors: Massino Christian , Wetzker Cornelia , Balvin Ondřej , Bartonicka Tomáš , Kremenova Jana , Sasinkova Markéta , Otti Oliver , Reinhardt Klaus
Published: September 2021

Sperm metabolism is fundamental to sperm motility and male fertility. Its measurement is still in its infancy, and recommendations do not exist as to whether or how to standardize laboratory procedures. Here, using the sperm of an insect, the common bedbug, Cimex lectularius, we demonstrate that standardization of sperm metabolism is required with respect to the artificial sperm storage medium and a natural medium, the seminal fluid. We used fluorescence lifetime imaging microscopy (FLIM) in combination with time‐correlated single‐photon counting (TCSPC) to quantify sperm metabolism based on the fluorescent properties of autofluorescent coenzymes, NAD(P)H and flavin adenine dinucleotide. Autofluorescence lifetimes (decay times) differ for the free and protein‐bound state of the co‐enzymes, and their relative contributions to the lifetime signal serve to characterize the metabolic state of cells. We found that artificial storage medium and seminal fluid separately, and additively, affected sperm metabolism. In a medium containing sugars and amino acids (Grace's Insect medium), sperm showed increased glycolysis compared with a commonly used storage medium, phosphate‐buffered saline (PBS). Adding seminal fluid to the sperm additionally increased oxidative phosphorylation, likely reflecting increased energy production of sperm during activation. Our study provides a protocol to measure sperm metabolism independently from motility, stresses that protocol standardizations for sperm measurements should be implemented and, for the first time, demonstrates that seminal fluid alters sperm metabolism. Equivalent protocol standardizations should be imposed on metabolic investigations of human sperm samples.
A protocol for single‐source dual‐pulse stimulated emission depletion setup with Bessel modulation
Authors: Xu Xinzhu , Zhao Kun , Ren Wei , Wu Zhaoyang , Yu Wentao , Shao Chendi , Shi Kebin , Xi Peng
Published: September 2021

STimulated Emission Depletion (STED) microscopy attains super‐resolution in biological imaging beyond the diffraction limit. Here, we give a concise protocol to construct a dual‐pulse STED setup with one super‐continuum laser. Moreover, a flexible and dismountable Bessel modulation module is introduced for potential 2D‐stack STED imaging. Experiments and notices are introduced in detail, with discussion on some important check‐points for STED, such as detector saturation. Finally, the results validate the system working.
Synthesis of new 1,4‐ and 1,5‐disubstituted N‐ethyl acetate and N‐α‐butyro‐γ‐lactone alkylimidazole derivatives as N‐acylhomoserine lactone analogs
Authors: Zhang Qiang , Li Si‐Zhe , Queneau Yves , Soulère Laurent
Published: September 2021

New alkylimidazoles functionalized with a homoserine lactone or an alkyloxycarbonyl moiety have been synthesized as N‐acylhomoserine lactones (AHLs) analogs. The 1,4‐disubstituted imidazole derivatives were prepared by alkylation of 4(5)‐alkylimidazoles with α‐bromo‐γ‐butyrolactone or ethyl α‐bromoacetate. An alternative route was preferred for the synthesis of their 1,5‐disubstituted counterparts based on the use of a N1‐protected alkylimidazole, its alkylation to an N3‐imidazolyl‐α‐acetate and deprotection to the desired 1,5‐disubstituted esters and subsequent alkylation of the acetate moiety with cyclic ethylene sulfate followed by acid‐catalyzed cyclization. The ability to modulate bacterial quorum sensing of all new compounds was compared to that of previously reported AHL analogs in which the amide bond is replaced by a heterocyclic group.
Absence of first‐pass isolation is associated with poor pulmonary vein isolation durability and atrial fibrillation ablation outcomes
Authors: Ninomiya Yuichi , Inoue Koichi , Tanaka Nobuaki , Okada Masato , Tanaka Koji , Onishi Toshinari , Hirao Yuko , Oka Takafumi , Inoue Hiroyuki , Takayasu Kohtaro , Nakamaru Ryo , Kitagaki Ryo , Koyama Yasushi , Okamura Atsunori , Iwakura Katsuomi , Ohishi Mitsuru , Fujii Kenshi
Published: September 2021

Background

Pulmonary vein (PV) reconnection is the main cause of atrial fibrillation (AF) recurrence. This study aimed to examine the effect of first‐pass PV isolation (PVI) on PV reconnection frequency during the procedure and on AF ablation outcomes.

Methods

This retrospective study included 446 patients with drug‐refractory AF (370 men, aged 64 ± 10 years) who underwent initial PVI using an open‐irrigated contact force catheter between January 2015 and October 2016. We investigated the effect of first‐pass PVI on PV reconnection during spontaneous PV reconnection and dormant conduction after an adenosine triphosphate challenge.

Results

First‐pass PVI was achieved in 69% (617/892) of ipsilateral PVs, of which we observed PV reconnection during the procedure in 134 (22%) PVs. This value was significantly lower than that observed in those without first‐pass PVI (50%, 138/275) (P < .0001). We divided the subjects into two groups based on the presence or absence of first‐pass PVI in at least one of two ipsilateral PVs: first‐pass (n = 383, 86%) and non‐first‐pass groups (n = 63, 14%). The 2‐year AF recurrence‐free rate was significantly higher in the first‐pass group than in the other group (75% vs 59%, log‐rank P = .032). In 78 patients with repeat AF ablation, the PV reconnection rate in the second procedure was significantly lower in PVs that had first‐pass isolation in the first procedure (34% vs 73%, P < .0001).

Conclusions

Absence of first‐pass PVI was associated with a higher frequency of spontaneous PV reconnection and dormant conduction and poor ablation outcomes. First‐pass isolation may be a useful marker for better PVI durability.
YfiF, an unknown protein, affects initiation timing of chromosome replication in Escherichia coli
Authors: GeZi GeZi , Liu Rui , Du Dongdong , Wu Nier , Bao Narisu , Fan Lifei , Morigen Morigen
Published: September 2021

The Escherichia coli YfiF protein is functionally unknown, being predicted as a transfer RNA/ribosomal RNA (tRNA/rRNA) methyltransferase. We find that absence of the yfiF gene delays initiation of chromosome replication and the delay is reversed by ectopic expression of YfiF, whereas excess YfiF causes an early initiation. A slight decrease in both cell size and number of origin per mass is observed in ΔyfiF cells. YfiF does not genetically interact with replication proteins such as DnaA, DnaB, and DnaC. Interestingly, YfiF is associated with ribosome modulation factor (RMF), hibernation promotion factor (HPF), and the tRNA methyltransferase TrmL. Defects in replication initiation of Δrmf, Δhpf, and ΔtrmL can be rescued by overexpression of YfiF, indicating that YfiF is functionally identical to RMF, HPF, and TrmL in terms of replication initiation. Also, YfiF interacts with the rRNA methyltransferase RsmC. Moreover, the total amount of proteins and DnaA content per cell decreases or increases in the absence of YfiF or the presence of excess YfiF. These facts suggest that YfiF is a ribosomal dormancy‐like factor, affecting ribosome function. Thus, we propose that YfiF is involved in the correct timing of chromosome replication by changing the DnaA content per cell as a result of affecting ribosome function.
Characterizing the tail behaviour of daily precipitation probability distributions over India using the obesity index
Authors: Gupta Neha , Chavan Sagar Rohidas
Published: September 2021

Extreme precipitation events lie in the upper part of the probability distribution of daily precipitation data, that is, the tail. Depending upon the tail behaviour, various probability distributions are partitioned into heavy‐tailed and light‐tailed distributions. Heavy‐tails tend to approach zero less rapidly than light‐tails, signifying a higher frequency of occurrences for extreme precipitation events. Prediction of extreme precipitation depends on how reliably the distribution tail is modelled. Tail behaviour can be studied by graphical as well as threshold‐based fitting approaches. However, the graphical methods are time‐consuming and do not provide quantitative comparisons between two distributions, whereas the threshold‐based approaches possess limitations such as ambiguity in selecting an optimum threshold for demarcation of the tail. This article assesses the utility of a simple empirical index, that is, the “Obesity Index” (OB) to discern the probability distributions of daily gridded precipitation data with a resolution of 0.25° for historical (1951–2004) and future (2006–2099) periods over India into light‐ and heavy‐tailed. The OB‐based approach is an easy‐to‐use empirical approach that can quantitatively diagnose the heaviness of distribution tails without assuming any threshold for segregating the tails. Future projections of daily precipitation were obtained by downscaling simulations of the Coordinated Regional Climate Downscaling Experiment. Subsequently, a comparative analysis between the OB‐based approach and threshold‐based approaches by Nerantzaki and Papalexiou and Papalexiou et al. was conducted. Finally, the application of the OB‐based approach is extended to characterize daily precipitation in Indian Meteorological Subdivisions. Furthermore, we explored the dependence of the OB on the elevation of grids. Results indicated the applicability of heavy‐tailed distributions in the representation of daily precipitation over India and suggest an OB‐based approach as a good alternative diagnostic tool for assessing tail behaviour.
Barriers to nutrition therapy in the critically ill patient with COVID‐19
Authors: Suliman, Sally , McClave Stephen A. , Taylor Beth E. , Patel, Jayshil , Omer, Endashaw , Martindale, Robert G.
Published: September 2021

Background

Coronavirus disease 2019 (COVID‐19) has created challenges for intensivists, as high ventilatory demands and prolonged hypermetabolism make it difficult to sustain nutrition status. The purpose of this survey was to determine current practices in nutrition therapy and identify barriers to its delivery.

Methods

A survey about delivering nutrition therapy to critically ill patients with COVID‐19 was sent to clinicians at academic and community hospitals from September to December 2020.

Results

Of 440 who viewed the survey, 199 (45%) completed the questionnaire. Respondents were composed of 30%, physicians and 70% registered dietitians, with 51% representing community programs, 43% academic institutions, and 6% Veterans Affairs centers. Half (49%) had protocols for managing critically ill patients with COVID‐19, and 21% had a protocol for nutrition therapy. Although most respondents (83%) attempted to feed by the intragastric route, only 9% indicated that energy/protein needs were met. The biggest barriers to delivery of enteral nutrition (EN) involved the patients unpredictable clinical course and fear of aspiration given the lack of respiratory reserve. Intensivists were reluctant to add supplemental parenteral nutrition (PN) because of perceived lack of benefit.

Conclusion

The survey results would suggest that strategies for nutrition therapy based on the intragastric infusion of EN are unsuccessful in meeting the energy/protein needs of critically ill patients with COVID‐19. It is likely these barriers exist in providing nutrition to non‐Covid‐19 critically ill patients. Intensivists need protocols that optimally deliver intragastric EN, consider early postpyloric infusion, and address adding supplemental PN in a deteriorating nutrition status.
Cytotoxic effects of dental calculus particles and freeze‐dried Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum on HSC‐2 oral epithelial cells and THP‐1 macrophages
Authors: Ziauddin S.M. , Alam Mohammad Ibtehaz , Mae Megumi , Oohira Masayuki , Higuchi Kanako , Yamashita Yasunori , Ozaki Yukio , Yoshimura Atsutoshi
Published: September 2021

Background

Periodontitis is an inflammatory disease initiated by dental deposits. Microorganisms in the dental biofilm induce cell death in epithelial cells, contributing to the breakdown of epithelial barrier function. Recently, dental calculus has also been implicated in pyroptotic cell death in oral epithelium. We analyzed the cytotoxic effects of dental calculus and freeze‐dried periodontopathic bacteria on oral epithelial cells and macrophages.

Methods

HSC‐2 (human oral squamous carcinoma cells) and phorbol 12‐myristate 13‐acetate‒differentiated THP‐1 macrophages were exposed to dental calculus or one of two species of freeze‐dried bacterium, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. Following incubation for 24 hours, we measured cytotoxicity via lactate dehydrogenase release. Cells were then incubated with glyburide, an NLRP3 inflammasome inhibitor, to assess the potential role of pyroptosis. We also conducted a permeability assay to analyze the effects on epithelial barrier function.

Results

Dental calculus induced dose‐dependent cell death in HSC‐2 cells, whereas cell death induced by freeze‐dried bacteria was insignificant. Conversely, freeze‐dried bacteria induced more cell death than dental calculus in THP‐1 macrophages. Cell death induced by dental calculus but not by freeze‐dried bacteria was inhibited by glyburide, indicating that these are different types of cell death. In the permeability assays, dental calculus but not freeze‐dried bacteria attenuated the barrier function of HSC‐2 cell monolayers.

Conclusion

Due to the low sensitivity of HSC‐2 cells to microbial cytotoxicity, dental calculus had stronger cytotoxic effects on HSC‐2 cell monolayers than freeze‐dried A. actinomycetemcomitans and F. nucleatum, suggesting that it plays a critical role in the breakdown of crevicular/pocket epithelium integrity.
Cathodoluminescence, Raman and scanning electron microscopy with energy dispersion system mapping to unravel the mineralogy and texture of an altered CaAl‐rich inclusion in Renazzo CR2 carbonaceous chondrite
Authors: Tribaudino Mario , Bersani Danilo , Mantovani Luciana , Pizzati Mattia , Salviati Giancarlo
Published: September 2021

An altered fluffy type A CaAl‐rich inclusion in the CR2 Renazzo carbonaceous chondrite was examined by combined Raman, scanning electron microscopy with energy dispersion system (SEM‐EDS) and cathodoluminescence (CL) mapping. Blue CL at 450 nm and orange emission at 600 nm were related to anorthite and calcite, respectively. Raman spectra were highly fluorescent, and only the stronger peaks of anorthite, clinopyroxene and calcite were observed. Raman‐induced fluorescence emission was measured using the 632‐nm Raman laser source, up to 850 nm, and used to chart the mineral phases. A fluorescence structured peak at 690 nm, split in three subpeaks at 678, 689 and 693 nm, was found; it is likely related to the fluorescence emission of Cr3+ from a fassaitic pyroxene in anorthite. Secondary pyroxene in the Wark–Lovering rim does not show the peak at 690 nm; the different fluorescence emission from the secondary rim and the pyroxene patches within anorthite could be a marker to spot the primary pyroxene. From combined imaging, the events in the altered chondrite could be sequenced. Starting from a pristine assemblage of spinel and melilite, with little fassaite, several alteration episodes occurred. Alteration in secondary anorthite, which could be mapped by the blue CL emission at 450 nm, was followed by alkalization, with rims of sodalite and nepheline, and subsequent formation of secondary clinopyroxene, encircling the inclusion. Widespread calcite alteration, present also in the matrix between chondrules, was the last recorded event.
Stratifying the Risk of Cardiovascular Disease in Obstructive Sleep Apnea Using Machine Learning
Authors: Gourishetti Saikrishna C. , Taylor Rodney , Isaiah Amal
Published: September 2021

Objectives/Hypothesis

Obstructive sleep apnea (OSA) is associated with higher risk of morbidity and mortality related to cardiovascular disease (CVD). Due to overlapping clinical risk factors, identifying high‐risk patients with OSA who are likely to develop CVD remains challenging. We aimed to identify baseline clinical factors associated with the future development of CVD in patients with OSA.

Study Design

Retrospective analysis of prospectively collected data.

Methods

We performed a retrospective analysis of 967 adults aged 45 to 84 years and enrolled in the Multi‐Ethnic Study of Atherosclerosis. Six machine learning models were created using baseline clinical factors initially identified by stepwise variable selection. The performance of these models for the prediction of additional risk of CVD in OSA was calculated. Additionally, these models were evaluated for interpretability using locally interpretable model‐agnostic explanations.

Results

Of the 967 adults without baseline OSA or CVD, 116 were diagnosed with OSA and CVD and 851 with OSA alone 10 years after enrollment. The best performing models included random forest (sensitivity 84%, specificity 99%, balanced accuracy 91%) and bootstrap aggregation (sensitivity 84%, specificity 100%, balanced accuracy 92%). The strongest predictors of OSA and CVD versus OSA alone were fasting glucose >91 mg/dL, diastolic pressure >73 mm Hg, and age >59 years.

Conclusion

In the selected study population of adults without OSA or CVD at baseline, the strongest predictors of CVD in patients with OSA include fasting glucose, diastolic pressure, and age. These results may shape a strategy for cardiovascular risk stratification in patients with OSA and early intervention to mitigate CVD‐related morbidity.

Level of Evidence

3 Laryngoscope, 132:234–241, 2022
Enzyme‐ and UV‐Mediated Double‐Network Hybrid Hydrogels for 3D Cell Culture application
Authors: Li Xiao‐Pei , Zou Lin , Abodunrin Oluwatosin David , Wang Xiao‐Wei , Huang Ning‐Ping
Published: September 2021

Three‐dimensional (3D) cell culture using hydrogel scaffolds can closely resemble the natural extracellular matrix (ECM), which offers appropriate mechanical support for cells and regulates cellular behavior. In this study, a bacterial transpeptidase sortase A (SA) is used to prepare enzymatically cross‐linked methacrylated hyaluronic acid (HA) peptides (HAMA‐P) hydrogel, which reveals fast gel kinetics under high SA cross‐linking concentrations and can be used as an injection hydrogel for tissue repair or extrusive 3D bioprinting. Furthermore, methacrylated gelatin (GelMA) is introduced to build the hybrid hydrogel (HAMA‐P‐GelMA) with double cross‐linking of enzyme‐UV, which has shown proper physical properties (mechanical properties, swelling, degradation rate, etc.) of the hydrogel matrix, and displayed desirable effects on cell viability, adhesion, and cell spreading, when compared to GelMA or HAMA‐P single‐network hydrogels. The HAMA‐P‐GelMA hybrid hydrogels provide a favorable 3D milieu for cell growth and can be used as a 3D bio‐ink or a carrier of stem cells/cytokines for injectable tissue repair and filling.
An Epoxy Adhesive Crosslinked through Radical‐Induced Cationic Frontal Polymerization
Authors: Turani Matteo , Baggio Andrea , Casalegno Valentina , Salvo Milena , Sangermano Marco
Published: September 2021

UV‐initiated cationic frontal polymerization is exploited as a solvent‐free, extremely fast, and low‐temperature technique to obtain epoxy‐based adhesives. Epoxy formulations are prepared by blending commercial resins at different weight ratios and adding photo and thermal initiators at different percentages. In addition, the influence of other critical parameters, including the joint thickness, the nature of the adherends, and the temperature, is studied. As the reaction front is thermally sustained, the boundary conditions play a key role during the curing process and heat dissipation through the adherends in particular. The thermal properties of the epoxy formulation are studied through differential scanning calorimetry analysis, and the joint strengths are investigated by carrying out single lap off‐set shear tests under compression. The results demonstrate the feasibility of obtaining joints by means of the radical induced cationic frontal polymerization of the epoxy adhesives, which exhibit comparable epoxy group conversion and mechanical performances to the ones cured by traditional energy‐intensive techniques.
Enhancing adversarial defense for medical image analysis systems with pruning and attention mechanism
Authors: Chen Lun , Zhao Lu , Chen Calvin Yu‐Chian
Published: September 2021

Purpose

Deep learning has achieved impressive performance across a variety of tasks, including medical image processing. However, recent research has shown that deep neural networks (DNNs) are susceptible to small adversarial perturbations in the image, which raise safety concerns about the deployment of these systems in clinical settings.

Methods

To improve the defense of the medical imaging system against adversarial examples, we propose a new model‐based defense framework for medical image DNNs model equipped with pruning and attention mechanism module based on the analysis of the reason why existing medical image DNNs models are vulnerable to attacks from adversarial examples is that complex biological texture of medical imaging and overparameterized medical image DNNs model.

Results

Three benchmark medical image datasets have verified the effectiveness of our method in improving the robustness of medical image DNNs models. In the chest X‐ray datasets, our defending method can even achieve up 77.18% defense rate for projected gradient descent attack and 69.49% defense rate for DeepFool attack. And through ablation experiments on the pruning module and the attention mechanism module, it is verified that the use of pruning and attention mechanism can effectively improve the robustness of the medical image DNNs model.

Conclusions

Compared with the existing model‐based defense methods proposed for natural images, our defense method is more suitable for medical images. Our method can be a general strategy to approach the design of more explainable and secure medical deep learning systems, and can be widely used in various medical image tasks to improve the robustness of medical models.
Dielectric polymer nanocomposites: Past advances and future prospects in electrical insulation perspective
Authors: Pandey Jeewan Chandra , Singh Manohar
Published: September 2021

Polymeric materials enjoy widespread acceptance among electrical insulation design engineers due to their multi‐functional attributes (e.g., excellent dielectric properties, high strength to weight ratio, and ease of molding). However, charge accumulation at the high DC field, poor discharge resistance, low thermal conductivity, limited‐service temperature range, and inadequate stiffness have proven to be severe obstructions to far‐reaching utilization of these materials. To ensure the reliability of today's electrical power systems, novel dielectric materials with enhanced functionalities are essential. An idea that originated under the name of polymer nanocomposites (PNCs) is supposed to provide a viable solution to the challenges mentioned earlier. PNCs are made by mixing a small quantity of nanometer‐sized fillers into a polymer matrix and dispersing them uniformly. To effectively use PNCs in electrical insulation for power apparatus, extensive research into the physical and chemical phenomena associated with these new materials is required. This article aims to provide a comprehensive review of previous research on dielectric PNCs, including synthesis, electrical and nonelectrical characterization, and attendant issues from an electrical insulation standpoint.
Molecular design strategies for high‐performance organic electrochemical transistors
Authors: Li Peiyun , Lei Ting
Published: September 2021

Organic electrochemical transistors (OECTs) utilize ion flow from the electrolyte to modulate the electrical conductivity of the whole bulk organic semiconductor channel. With the characteristic of mixed ionic‐electronic conducting in the entire volume, OECTs exhibit high transconductance and act as good transducers, particularly in bioelectronics. To gain high‐performance OECTs, developing novel high‐performance polymeric semiconductors is important. In this article, operation principles, performance evaluations, and polymerization methods are first discussed. We then analyze the molecular design strategies for high‐performance OECT materials and highlight the characteristics and effects of backbone design and side chain engineering. Finally, we discuss some neglected and unsolved issues and provide an outlook for the OECTs research and development.
Chest X‐ray lung imaging features in pediatric COVID‐19 and comparison with viral lower respiratory infections in young children
Authors: Nino Gustavo , Molto Jose , Aguilar Hector , Zember Jonathan , Sanchez‐Jacob Ramon , Diez Carlos T. , Tabrizi Pooneh R. , Mohammed Bilal , Weinstock Jered , Xuchen Xilei , Kahanowitch Ryan , Arroyo Maria , Linguraru Marius G.
Published: September 2021

Rationale

Chest radiography (CXR) is a noninvasive imaging approach commonly used to evaluate lower respiratory tract infections (LRTIs) in children. However, the specific imaging patterns of pediatric coronavirus disease 2019 (COVID‐19) on CXR, their relationship to clinical outcomes, and the possible differences from LRTIs caused by other viruses in children remain to be defined.

Methods

This is a cross‐sectional study of patients seen at a pediatric hospital with polymerase chain reaction (PCR)‐confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (n = 95). Patients were subdivided in infants (0–2 years, n = 27), children (3–10 years, n = 27), and adolescents (11–19 years, n = 41). A sample of young children (0–2 years, n = 68) with other viral lower respiratory infections (LRTI) was included to compare their CXR features with the subset of infants (0–2 years) with COVID‐19.

Results

Forty‐five percent of pediatric patients with COVID‐19 were hospitalized and 20% required admission to intensive care unit (ICU). The most common abnormalities identified were ground‐glass opacifications (GGO)/consolidations (35%) and increased peribronchial markings/cuffing (33%). GGO/consolidations were more common in older individuals and perihilar markings were more common in younger subjects. Subjects requiring hospitalization or ICU admission had significantly more GGO/consolidations in CXR (p < .05). Typical CXR features of pediatric viral LRTI (e.g., hyperinflation) were more common in non‐COVID‐19 viral LRTI cases than in COVID‐19 cases (p < .05).

Conclusions

CXR may be a complemental exam in the evaluation of moderate or severe pediatric COVID‐19 cases. The severity of GGO/consolidations seen in CXR is predictive of clinically relevant outcomes. Hyperinflation could potentially aid clinical assessment in distinguishing COVID‐19 from other types of viral LRTI in young children.
The first reported use of autologous blood pleurodesis for treatment of prolonged air leak in COVID‐19‐related spontaneous pneumomediastinum and pneumothorax: A case report
Authors: S. Rashid Ali Muhammad Redzwan
Published: September 2021

Spontaneous pneumomediastinum (SPM) and pneumothorax (PTX) have been described as rare complications of COVID‐19 pneumonia. We present a case of COVID‐19 pneumonia which was complicated by SPM on Day 13 of admission with progression to spontaneous PTX 2 days later which necessitated intercostal chest drainage. It was complicated by prolonged air leak (PAL) for the next 9 days despite being on continued low‐dose suction and another additional larger bore intercostal drain inserted. Surgical pleurodesis was not an option in view of anaesthesia and operative risk expected in COVID‐19. In view of this, autologous blood pleurodesis (ABP) to address the alveolar pleural leak was opted. ABP has been previously used for PAL in cases of non‐COVID‐19‐related intractable spontaneous PTX. The air leak ceased with subsequent lung re‐expansion, with good clinical and radiological improvement. He was discharged well after resolution of PTX which required intercostal drain for a total of 15 days.
Sustainable development of carbon sinks? Lessons from three types of peatland partnerships in Indonesia
Authors: Miller Michelle Ann , Tonoto Prayoto , Taylor David
Published: September 2021

Peatland conversion for agriculture is the leading cause of Indonesia's terrestrial carbon emissions that contribute substantially to global warming. Indonesia's peatlands contain 55–57 billion tonnes of carbon, the equivalent of almost 2 years of global carbon emissions at existing rates. This paper examines initiatives to retain soil‐based carbon in Indonesia's province of Riau, where over half the surface area is composed of agriculturally productive peatlands. We qualitatively evaluate three types of partnership programmes (bilateral, co‐governed and internationally funded local initiatives) in Riau aimed at the sustainable development of peatlands. The article finds that carbon loss is likely to persist in all case studies. Public, private and civil society actors in each partnership have exploited funding and political opportunities to advance agendas not directly related to the environment. The administrative category of the peatland hydrological unit as an ecologically meaningful scale of peatland governance is also under‐utilised by the partnerships studied.
Best practices in statistical computing
Authors: Sanchez Ricardo , Griffin Beth Ann , Pane Joseph , McCaffrey Daniel F.
Published: September 2021

The world is becoming increasingly complex, both in terms of the rich sources of data we have access to and the statistical and computational methods we can use on data. These factors create an ever‐increasing risk for errors in code and the sensitivity of findings to data preparation and the execution of complex statistical and computing methods. The consequences of coding and data mistakes can be substantial. In this paper, we describe the key steps for implementing a code quality assurance (QA) process that researchers can follow to improve their coding practices throughout a project to assure the quality of the final data, code, analyses, and results. These steps include: (i) adherence to principles for code writing and style that follow best practices; (ii) clear written documentation that describes code, workflow, and key analytic decisions; (iii) careful version control; (iv) good data management; and (v) regular testing and review. Following these steps will greatly improve the ability of a study to assure results are accurate and reproducible. The responsibility for code QA falls not only on individual researchers but institutions, journals, and funding agencies as well.
O‐Galactosylation of Diphenolic Compounds Using Boc Activation: A Convenient Chemical Synthesis
Authors: Rajendran Divya , Bhagavathsingh Jebasingh
Published: September 2021

Herein we report the convenient synthesis of O‐galactosylation of diphenolic systems such as Dopamine, L‐DOPA, and Fluorescein by the reaction of Boc‐activated diphenols with α‐bromoacetogalactose in the presence of AgOTf as a promoter and MS 3 Å as an acid scavenger. The Boc protected amine and diphenolic hydroxyl group using t‐butyl dicarbonate facilitates the formation of galactosylated products in the two steps such as Boc‐activation and followed by galactosylation. The protection of C‐terminal carboxylic acid is essential to isolate the β‐ isomer of L‐DOPA glycoside under the same condition. The Boc‐activation of the hydroxyl group in diphenols enhances the nucleophilicity of glycosyl acceptor and the corresponding yields of 72–84 % as β‐isomer through the formation of oxocarbenium intermediate.
High‐Rate Aqueous Aluminum‐Ion Batteries Enabled by Confined Iodine Conversion Chemistry
Authors: Yang Shuo , Li Chuan , Lv Haiming , Guo Xun , Wang Yanbo , Han Cuiping , Zhi Chunyi , Li Hongfei
Published: September 2021

Most reported cathode materials for rechargeable aqueous Al metal batteries are based on an intercalative‐type chemistry mechanism. Herein, iodine embedded in MOF‐derived N‐doped microporous carbon polyhedrons (I2@ZIF‐8‐C) is proposed to be a conversion‐type cathode material for aqueous aluminum‐ion batteries based on “water‐in‐salt” electrolytes. Compared with the conventional Al–I2 battery using ionic liquid electrolyte, the proposed aqueous Al–I2 battery delivers much enhanced electrochemical performance in terms of specific capacity and voltage plateaus. Benefitting from the confined liquid–solid conversion of iodine in hierarchical N‐doped microporous carbon polyhedrons and enhanced reaction kinetics of aqueous electrolytes, the I2@ZIF‐8‐C electrode delivers high reversibility, superior specific capacity (≈219.8 mAh g−1 at 2 A g−1), and high rate performance (≈102.6 mAh g−1 at 8 A g−1). The reversible reaction between I2 and I−, with I3− and I5− as intermediates, is confirmed via ex situ Raman spectra and X‐ray photoelectron spectroscopy. Furthermore, solid‐state hydrogel electrolyte is employed to fabricate a flexible Al–I2 battery, which shows performance comparable to batteries using liquid electrolyte and can be integrated to power wearable devices as a reliable energy supply.
Maintenance of Neural Stem-Progenitor Cells by the Lysosomal Biosynthesis Regulators TFEB and TFE3 in the Embryonic Mouse Telencephalon
Authors: Yuizumi Naoya , Harada Yujin , Kuniya Takaaki , Sunabori Takehiko , Koike Masato , Wakabayashi Masaki , Ishihama Yasushi , Suzuki Yutaka , Kawaguchi Daichi , Gotoh Yukiko
Published: September 2021

Lysosomes have recently been implicated in regulation of quiescence in adult neural stem cells (NSCs). Whether lysosomes regulate the differentiation of neural stem-progenitor cells (NPCs) in the embryonic brain has remained unknown, however. We here show that lysosomes are more abundant in rapidly dividing NPCs than in differentiating neurons in the embryonic mouse neocortex and ganglionic eminence. The genes for TFEB and TFE3, master regulators of lysosomal biosynthesis, as well as other lysosome-related genes were also expressed at higher levels in NPCs than in differentiating neurons. Anatomic analysis revealed accumulation of lysosomes at the apical and basal endfeet of NPCs. Knockdown of TFEB and TFE3, or that of the lysosomal transporter Slc15a4, resulted in premature differentiation of neocortical NPCs. Conversely, forced expression of an active form of TFEB (TFEB-AA) suppressed neuronal differentiation of NPCs in association with upregulation of NPC-related genes. These results together point to a previously unappreciated role for TFEB and TFE3, and possibly for lysosomes, in maintenance of the undifferentiated state of embryonic NPCs. We further found that lysosomes are even more abundant in an NPC subpopulation that rarely divides and includes the embryonic origin of adult NSCs than in the majority of NPCs that divide frequently for construction of the embryonic brain, and that overexpression of TFEB-AA also suppressed the cell cycle of neocortical NPCs. Our results thus also implicate lysosomes in establishment of the slowly dividing, embryonic origin of adult NSCs.
Sars-Cov-2 Infects an Upper Airway Model Derived from Induced Pluripotent Stem Cells
Authors: Djidrovski Ivo , Georgiou Maria , Hughes Grant L. , Patterson Edward I. , Casas-Sanchez Aitor , Pennington Shaun H. , Biagini Giancarlo A. , Moya-Molina Marina , Bor Jelle , Smit Martine J. , Chung Git , Lako Majlinda , Armstrong Lyle
Published: September 2021

As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal-like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal-like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air-liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS-CoV-2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs.
Academics' perception of systems engineering and applied research projects
Authors: Honoré‐Livermore Evelyn , Fossum Knut Robert , Veitch Erik
Published: September 2021

There is an increased complexity in applied research projects that demand more researcher skills, especially in managing the research project and interdisciplinary work. Researchers receive little training in how to manage such projects, yet most manage to deliver project results. There is a tradition of project management and systems engineering which benefits complex development projects in industrial settings. Despite the apparent benefits, we found limited application of either project management or systems engineering practices in academia. Furthermore, we found barriers to applying these practices in the first place, such as a lack of clear guidance or tools for their execution. A case study based on 18 semi‐structured interviews provides a perspective on academic research projects, and how the application of project management and systems engineering in an academic setting shows promise to improve the realization of concept design.
Long‐term ketamine administration induces bladder damage and upregulates autophagy‐associated proteins in bladder smooth muscle tissue
Authors: Li Yanning , Dong Zhibin , Wen Gehua , Ren Xinghua , Ren Weishu , Yan Lei , Wang Xiaolong , Yu Hao , Wu Xue , Xia Xi , Lu Yan , Wu Xu
Published: September 2021

Long‐term ketamine abuse can cause significant lower urinary tract symptoms in humans, termed ketamine‐associated cystitis (KC). Here, we established a model of long‐term (6 months) ketamine administration in wild‐type (C57BL/6) mice. We elucidated the pathological effects of ketamine in the bladder and investigated changes in autophagy‐associated protein expression (i.e., LC3, Beclin‐1, and P62) and inflammatory cytokines (i.e., IL‐6 and IL‐1β) in the bladder smooth muscle tissue. Long‐term ketamine administration reduced the number of layers in the bladder mucosal epithelial cells (4–5 layers in the saline group vs. 2–3 layers in the ketamine groups), but increased the number of mast cells and collagen fibers. LC3‐II/LC3‐I, Beclin‐1, IL‐6, and IL‐1β protein expression in the bladder smooth muscle tissues of ketamine‐treated mice was significantly increased. The mRNA and protein levels of P62 in the Ket‐60 mg/kg group were also significantly increased, but not the Ket‐30 mg/kg group. Our results reveal that long‐term ketamine administration can cause cystitis‐like pathological changes in mice, and the disordered autophagy in the bladder tissue may be involved in the persistent bladder damage following long‐term administration of ketamine at 60 mg/kg.
Building Bridges: Curating Text Sets to Connect to Learners’ Lives
Authors: Opatz Margaret Osgood , Nelson Elizabeth Thackeray
Published: September 2021

The authors demonstrate how teachers can scaffold instruction that invites students into the learning process by presenting engaging, relevant material. Employing five steps, the authors describe how to curate and sequence text sets: access learners’ funds of knowledge, begin with the end in mind, consult the curriculum to determine areas that require additional resources, gather texts, and build a bridge. The authors provide an example text set based on Next Generation Science Standards to illustrate how the process of curating text sets builds bridges to help students develop background knowledge and foster meaningful connections to increase reading engagement.
Assessing leadership: Historical roots and contemporary considerations
Authors: Gigliotti Ralph A. , Shankman Marcy Levy
Published: September 2021

Leadership inventories and assessments have emerged and evolved to meet the needs of unique historical moments. The article raises questions for how assessments and instruments may be used for the different purposes of leadership training, education, and development. The article concludes with a summary of the broad categories of leadership assessments, inventories, and tools presented in this volume.
Co‐curricular leadership tools: The use of inventories outside of the college classroom
Authors: Maia Ana C.
Published: September 2021

Many college leadership educators use inventories as part of co‐curricular programs, outside the traditional classroom. This article will describe and critique the use of four instruments (Myers–Briggs Type Indicator, CliftonStrengths, Emotionally Intelligent Leadership Inventory, and EarthquakeTM Simulation) to support student development within the context of leadership as a relational, community‐oriented process. By using these tools intentionally, through a culturally relevant design and in line with students’ developmental readiness, co‐curricular educators can help foster leadership within each unique individual.