bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-assisted fluoroscopy of bladder function in awake mice
Authors: De Bruyn Helene , Corthout Nikky , Munck Sebastian , Everaerts Wouter , Voets Thomas
Published: September 2022

Understanding the lower urinary tract (LUT) and development of highly needed novel therapies to treat LUT disorders depends on accurate techniques to monitor LUT (dys)function in preclinical models. We recently developed videocystometry in rodents, which combines intravesical pressure measurements with X-ray-based fluoroscopy of the LUT, allowing the in vivo analysis of the process of urine storage and voiding with unprecedented detail. Videocystometry relies on the precise contrast-based determination of the bladder volume at high temporal resolution, which can readily be achieved in anesthetized or otherwise motion-restricted mice but not in awake and freely moving animals. To overcome this limitation, we developed a machine-learning method, in which we trained a neural network to automatically detect the bladder in fluoroscopic images, allowing the automatic analysis of bladder filling and voiding cycles based on large sets of time-lapse fluoroscopic images (>3 hr at 30 images/s) from behaving mice and in a noninvasive manner. With this approach, we found that urethane, an injectable anesthetic that is commonly used in preclinical urological research, has a profound, dose-dependent effect on urethral relaxation and voiding duration. Moreover, both in awake and in anesthetized mice, the bladder capacity was decreased ~fourfold when cystometry was performed acutely after surgical implantation of a suprapubic catheter. Our findings provide a paradigm for the noninvasive, in vivo monitoring of a hollow organ in behaving animals and pinpoint important limitations of the current gold standard techniques to study the LUT in mice.
Academic Performance of Grade V Pupils Using Science Strategic Intervention Material in Zambales, Philippines
Authors: Villar Alex S. , Gabriel Evangeline R. , Farin Elizabeth N.
Published: September 2022

Teachers in Science are challenged to use Strategic intervention materials to improve students’ academic performance. The objective of the study was to improve the academic performance of Grade V pupils through SIM (Strategic Intervention Material) in Science. The researcher used descriptive and quasi-experimental research methods to determine the effectiveness of SIM. Respondents were given sets of SIM to be utilized and answered. A pretest-post test design was used for comparison. The data collected were statistically treated through the mean, standard deviation, and T-test and Analysis of Variance. The results showed that the students were rated poor and “Did not meet the expectation” in the pre-test, while “Outstanding “in the post-test. There was a significant difference on the performance of the students based on the results of the pre-test and post-test. The teacher-respondents “Strongly Agreed” that the contents, interventional design and organizational presentation were acceptable. There was no significant difference in the assessment of acceptability as to contents, interventional design, organizational presentation, and assessment, respectively. SIM may be adopted as an “aid” for instructional materials in teaching to facilitate learning and improve performance of students. SIM made by the researcher can be used by teachers to re-teach the concepts and skills.
Heat is a Cause of the Global Climate Warming
Authors: Prisyazhniuk Vitaly A.
Published: September 2022

Experimental-statistical equations are proposed for calculating the results of fossil fuel combustion. The calculation is illustrated by the example of fuel combustion by engines of a Boeing series aircraft. The main supplier of energy to the ecological system of Planet Earth is the Sun. The atmosphere of Planet Earth retains about 50% of the thermal (infrared) radiation of the Sun. This casts doubt on the role of CO2, whose concentration in the Earth's atmosphere is about 0.05%, in Global Climate Warming. Knowing how much fuel humanity produces per year, it is possible to calculate the amount of thermal energy produced per year. If in 2000 humanity produced 412*106 TJ of thermal energy, then the Sun supplied 38286*106 TJ of thermal energy to the Earth in 365 hours a year. It is expedient to reduce Global Warming by 1.5 - 2.0 degrees by installing a "Solar Umbrella" in the stratosphere - a filter for infrared (thermal) radiation from the Sun.
Diabetes and Daytime Sleeping: Systematic Review
Authors: Alanazi Yasser Wadi
Published: September 2022

Background: The relationship between sleep disturbance and diabetes is dual-sided. Chronic sleep disturbance increases the chance of developing insulin resistance, while diabetes reduces sleep quality.

Objective: To address the aspects of insufficient sleep, diabetes mellitus, and their mutual interactions and interlinkages. The main objectives is to address the role and effect of diabetes on sleep. Methods: systematic review. A systematic search was done in PubMed, MEDLINE through Clarivate, Web of Science through Clarivate, and EBSCO. Studies retrieved were managed in Rayyan–Intelligent systematic reviews website for duplicate removal and screening. 

Results: DM is one of the most widespread illnesses in the world. In addition to directly disrupting sleep due to nocturia, polyuria, diabetic neuropathy, and neuropathy pain, DM has also been linked to a number of chronic illnesses, including obstructive sleep apnea, cardiovascular issues, hypertension, cerebrovascular accidents, and depression, all of which can lower quality of life and negatively affect sleep.  The patient may not bring the sleep issues during their visit to healthcare providers, with acute issues taking precedence during their visit.

Conclusion: DM causes night sleep disturbances which eventually lead to daytime sleeping. Sleep education should be considered an essential part in the diabetic management armamentarium.
Notes on a 20‐Year Partnership: Challenging Architecture and Each Other
Authors: Lyall John
Published: September 2022

Alsop's first business partner of two decades, John Lyall describes their formative years as students at the Architectural Association in London, the influence of various members of Archigram, and sharing a house in Southeast London's not‐so‐salubrious Ladywell district. He recounts a world of music gigs, designing events and parties, and the offices they worked for as young architects before forming their fledgling practice in the 1970s.
A Second Course in Architecture
Authors: Hardingham Samantha
Published: September 2022

The milieu in which Alsop was educated, mixed and worked was crucial to the original architect he became. Samantha Hardingham describes those heady days, particularly the influence of the Architectural Association in the early 1970s and its rich menagerie of denizens of the period. She focuses on a critical and enigmatic mentor, Cedric Price, for whom Alsop worked and asserted as a profound influence on his design thinking.
Willie Wonky and the Arty‐tecture Factory
Authors: Coates Nigel
Published: September 2022

Nigel Coates lets us into the creative world of messy play that Alsop favoured as a way to teach architecture – the live‐in, eat‐in, drink‐in workshop. Such practices disrupted assumed modes of operation for architects and provoked new spatial and formal opportunities. His workshops, studios and lectures were a challenging mixture of kindergarten, party and questioning observations, all conducted with critical and colourful exuberance.
Yes, This Is Architecture
Authors: Thomas Neil
Published: September 2022

Structural engineer Neil Thomas describes some of the memorable encounters and collaborations with Alsop, particularly the Cardiff Bay Visitor Centre that Alsop maintained was inspired by his disposable cigarette lighter. A creative relationship maintained over a timeline that spanned nearly 30 years, Thomas conveys their way of working together that was fuelled by a deep desire to dare to dream met with breathtaking and credible design solutions.
Building Knowledge: Reflections on Peckham Library
Authors: Aquilina Thomas
Published: September 2022

Describing the making and thinking behind a film shot at Alsop & Störmer's Stirling Prize‐winning Peckham Library, Thomas Aquilina portrays how the building and its public piazza has democratised a previously neglected patch of South London, providing not just reading materials but much needed community functions for a diverse part of the capital. Much of the building's formal dexterity happens above its users’ heads, deploying the familiar Alsop trope of touching the ground lightly.
Tailoring Biotribological Performance of Polytetrafluoroethylene Nanocomposites through Control of Diameters and Aspect Ratios of In Situ Filled Hydroxyapatite Nanowires
Authors: Xu Yingxuan , Yan Xiaotian , Zhou Hongyu , Wang Bao , Shi Guojun
Published: September 2022

Excellent biocompatibility and biotribological performance are necessary for artificial acetabular cups in total hip replacement. Herein, polytetrafluoroethylene (PTFE) nanocomposites are fabricated via an in situ filling of hydroxyapatite nanowires. The resulting nanocomposites are characterized and evaluated by sliding friction against a high‐speed steel ring in the presence of simulated body fluid. Markedly enhanced hydrophobicity, heat resistance, and stiffness are observed for the fabricated nanocomposites in comparison with the matrix PTFE. The ethanol/water ratios for the in situ fabrication of the nanocomposites showed a predominant role in the diameters and aspect ratios of the hydroxyapatite nanowires filled in the nanocomposites. This might be related to the competition between the nucleation and growth of the hydroxyapatite crystals under applied synthetic conditions because the concentration of ethanol can influence the size and morphology of the oleic acid micelles. Furthermore, the diameters and aspect ratios of the nanofiller are found a decisive role in the tribological performance of the resulting PTFE nanocomposites, and those fabricated using a low ethanol/water ratio showed an enhanced diameter and aspect ratio and remarkable improvement in biotribological performance. The fabrication method is believed promising for the design and controllable synthesis of artificial acetabular cups or other artificial tissues.
Mitochondria‐Driven Dye Rearrangement That Enables Spatiotemporally Controlled Photomedicine
Authors: Luo Pei , Zhang Yongkang , Zhang Junqing , Zhang Hao , Yang Chun , Li Changhua
Published: September 2022

Reversibly controlling the dye arrangements in living systems has great potential to realize spatiotemporally controlled photomedicine. However, tuning or even maintaining a certain arrangement of dyes in a complex living environments is extremely challenging due to the interference of the various biological species. Herein, a conceptual supramolecular strategy to engineer a switchable photosensitizer (PS) via mitochondria‐mediated dynamic interconversion between monomer and J‐aggregation, enabling specific activation of the mitochondria‐targeting photodynamic therapy (PDT) and hibernation after mitochondria damage is presented. The presented mitochondria‐mediated “activate‐then‐hibernate” PS design enables a fascinating spatiotemporally controlled PDT in which spatially controlled mitochondrial‐targeting enhances therapeutic efficacy and temporally controlled activation‐then‐hibernation averts off‐target damage during PDT and tissue damage after clinical treatment, thus offering significant potential for biological research and clinical needs.
Transparent Lead‐Free Ferroelectric (K, Na)NbO3 Single Crystal with Giant Second Harmonic Generation and Wide Mid‐Infrared Transparency Window
Authors: Yin Fangyi , Liu Lei , Zhu Menghua , Lv Junai , Guan Xin , Zhang Jian , Lin Na , Fu Xiuwei , Jia Zhitai , Tao Xutang
Published: September 2022

Environment‐friendly lead‐free potassium‐sodium niobate (KNN) has become one of the most extensively investigated ferroelectrics in the past decade, while high transparency KNN single crystal has never been realized yet. Here, a transparent KNN single crystal is successfully grown by the top seeded solution growth method. The KNN crystal possesses a very wide transmittance range of 0.37–8 µm, completely covering the important mid‐infrared atmospheric transparent window (3–5 µm). Noticeably, the KNN crystal exhibits the largest second‐harmonic generation efficiency (7.6× that of potassium‐titanyl phosphate (KTP)) with type‐I phase matchability under the fundamental wavelength of 1064 nm among all of the studied mid‐infrared oxide nonlinear optical crystals reported so far. This work demonstrates a novel mid‐infrared nonlinear optical oxide crystal with a giant second‐harmonic generation and wide transparency range, providing a new idea for the exploration of nonlinear oxide crystals.
Cascade Cyclopolymerization of 5‐Ethynyl‐1,8‐Nonadiyne Derivatives to Synthesize Low Band Gap Conjugated Polyacetylenes Containing a Fused Bicyclic Structure
Authors: Ryu Hanseul , Sung Jong‐Chan , Kim Gangme , Xu Yan , Grubbs Robert H. , Choi Tae‐Lim
Published: September 2022

Cyclopolymerization is a powerful method for synthesizing polyacetylenes containing four‐ to seven‐membered rings. However, the structure of the repeat unit only consists of mono‐cycloalkene due to the single cyclization of diyne monomers. Herein, we demonstrate a novel cascade cyclopolymerization to synthesize polyacetylenes containing fused bicyclic rings from triyne monomers containing bulky dendrons via sequential cascade ring‐closing metathesis. These dendrons provided solubility and stability to the rigid bicyclic polyacetylene backbone. In addition, we controlled the regioselectivity of the catalyst approach by altering its structure and synthesized polymers containing fused bicyclo[4,3,0] or [4,4,0] rings with high molecular weights of up to 120 kg mol−1. Interestingly, the resulting polymers showed narrower band gaps (down to 1.6 eV) than polymers with mono‐cycloalkene repeat units due to the planarization of the conjugated segment resulting from the fused bicyclic structure.
Phase Transitions in Chemically Fueled, Multiphase Complex Coacervate Droplets
Authors: Donau Carsten , Späth Fabian , Stasi Michele , Bergmann Alexander M. , Boekhoven Job
Published: September 2022

Membraneless organelles are droplets in the cytosol that are regulated by chemical reactions. Increasing studies suggest that they are internally organized. However, how these subcompartments are regulated remains elusive. Herein, we describe a complex coacervate‐based model composed of two polyanions and a short peptide. With a chemical reaction cycle, we control the affinity of the peptide for the polyelectrolytes leading to distinct regimes inside the phase diagram. We study the transitions from one regime to another and identify new transitions that can only occur under kinetic control. Finally, we show that the chemical reaction cycle controls the liquidity of the droplets offering insights into how active processes inside cells play an important role in tuning the liquid state of membraneless organelles. Our work demonstrates that not only thermodynamic properties but also kinetics should be considered in the organization of multiple phases in droplets.
Ultrastable Anti‐Acid “Shield” in Layered Silver Coordination Polymers
Authors: Sun Peipei , Xie Mo , Zhang Lin‐Mei , Liu Jia‐Xing , Wu Jin , Li Dong‐Sheng , Yuan Shang‐Fu , Wu Tao , Li Dan
Published: September 2022

Surface passivation technology provides noble‐metal materials with limited chemical stability, especially under highly acidic condition. To design effective strategy to enhance stability of noble‐metal particles, an understanding of their surface anticorrosion mechanism at the atomic level is desirable by using two‐dimensional (2D) noble‐metal coordination polymer (CP) as an ideal model for their interfacial region. With the protection of 2‐thiobenzimidazole (TBI), we isolated two Ag‐based 2D CPs, {Ag14(TBI)12X2}n (S−X, where S denotes sheet and X=Cl or Br). These compounds exhibited excellent chemical stability upon immersion in various common solvents, boiling water, boiling ethanol, 10 % hydrogen peroxide, concentrated acid (12 M HCl), and concentrated alkali (19 M NaOH). Systematic characterization and DFT analyses demonstrate that the superior stability of S−X was attributed to the hydrophobic organic shell and dynamic proton buffer layer acting as a double protective “shield”.
Molecular Self‐Assembly Regulated Dopant‐Free Hole Transport Materials for Efficient and Stablen‐i‐pPerovskite Solar Cells and Scalable Modules
Authors: Cheng Qinrong , Chen Haiyang , Yang Fu , Chen Ziyuan , Chen Weijie , Yang Heyi , Shen Yunxiu , Ou Xue‐Mei , Wu Yeyong , Li Yaowen , Li Yongfang
Published: September 2022

Dopant‐free organic hole transport materials (HTMs) remain highly desirable for stable and efficientn‐i‐pperovskite solar cells (pero‐SCs) but rarely succeed. Here, we propose a molecular assembly strategy to overcome the limited optoelectronic properties of organic HTMs by precisely designing a linear organic small molecule BDT‐DPA‐F from the atomic to the molecular levels. BDT‐DPA‐F can assemble into a fibril network, showing an obviously improved hole mobility and decreased energy disorder. The resultant pero‐SCs showed a promising efficiency of 23.12 % (certified 22.48 %), which is the highest certified value of pero‐SCs with dopant‐free HTMs, to date. These devices also showed a weak‐dependence of efficiency on size, enabling a state‐of‐the‐art efficiency of 22.50 % for 1‐cm2device and 20.17 % for 15.64‐cm2module. For the first time, the pero‐SCs based on dopant‐free HTMs realized ultralong stabilities withT80lifetimes over 1200 h under operation or thermal aging at 85 °C.
Diterpene Biosynthesis from Geranylgeranyl Diphosphate Analogues with Changed Reactivities Expands Skeletal Diversity
Authors: Li Heng , Dickschat Jeroen S.
Published: September 2022

Two analogues of the diterpene precursor geranylgeranyl diphosphate with shifted double bonds, named iso‐GGPP I and iso‐GGPP II, were enzymatically converted with twelve diterpene synthases from bacteria, fungi and protists. The changed reactivity in the substrate analogues resulted in the formation of 28 new diterpenes, many of which exhibit novel skeletons.
Synthesis, Structure, and Bonding of a XeIV Transition‐Metal Coordination Complex, F3XeFb‐ ‐ ‐WOF4
Authors: Bortolus Mark R. , Mercier Hélène P. A. , Schrobilgen Gary J.
Published: September 2022

The coordination complex, F3XeFb‐ ‐ ‐WOF4, was synthesized in CFCl3 solvent by reaction of the weak fluoride‐ion donor and strong oxidative fluorinating agent, XeF4, with the moderate‐strength fluoride‐ion acceptor, WOF4. The compound is the only transition‐metal coordination complex of XeIV and was characterized at low temperatures by single‐crystal X‐ray diffraction and Raman spectroscopy. Xenon tetrafluoride and WOF4 coordinate trans to the W=O bond through a W‐ ‐ ‐Fb bond. The XeF3 moiety of F3XeFb‐ ‐ ‐WOF4 acquires a degree of [XeF3]+ character upon coordination that is reflected by its Xe−F stretching frequencies which are intermediate with respect to those of XeF4 and [XeF3]+. Calculations show W‐ ‐ ‐Fb is predominantly an electrostatic, σ‐hole bond with a significant orbital contribution that accounts for the bent Xe−Fb‐ ‐ ‐W angle. The calculations show F3XeFb‐ ‐ ‐MOF4 (M=Cr, Mo) are less stable than their W analogue, consistent with failed attempts to synthesize F3XeFb‐ ‐ ‐MoOF4.
DNA‐Based Biosensors for Imaging of Subcellular Enzymatic Activity
Authors: Zhao Hengzhi , Yu Fangzhi , Yu Mingming , Li Lele
Published: September 2022

As one kind of the most important biomolecules, enzymes participate in nearly all biochemical reactions. Dysregulation of enzymes’ spatial distributions and activities is often associated with many diseases. In situ imaging of enzymatic activity at the subcellular level is extremely challenging due to the lack of spatiotemporal precision of sensor probes. In this concept, we introduce several recent works in which DNA‐based biosensors with controllable localization ability were constructed for imaging of specific enzymatic activities and dynamics in a subcellular compartment of interest. These DNA‐based biosensors are classified into two types, in which DNA molecules serve as a subcellular targeting scaffold and an enzyme responsive sensing unit, respectively. We highlight the working principles of these DNA‐based biosensors and briefly introduce their biological applications. Finally, we discuss current limitations and future opportunities in this emerging field.
Renewable low viscosity polyester‐polyols for biodegradable thermoplastic polyurethanes
Authors: Rajput Bhausaheb S. , Hai Thien An Phung , Gunawan Natasha R. , Tessman Marissa , Neelakantan Nitin , Scofield Gordon B. , Brizuela Jose , Samoylov Anton A. , Modi Miheer , Shepherd Jenna , Patel Amal , Pomeroy Robert S. , Pourahmady Naser , Mayfield Stephen P. , Burkart Michael D.
Published: September 2022

In the transition to renewably sourced, biodegradable polymers, the preparation of low viscosity polyester‐polyols has posed a challenge for renewable polyurethane (PU) development. Low viscosity polyols not only reduce the requirement for high process temperatures but also decrease manufacturing time. In our efforts to incorporate increasing ratios of bio‐based monomers into renewable PUs, we mixed diacids such as even carbon sebacic acid and odd carbon azelaic acid along with a renewable diol. This provided library of 2000 g/mol molecular weight polyester‐polyols, and structures were established by 1H and 13C NMR analysis. The prepared polyester‐polyols offered lower viscosity and enable lower fabrication temperatures to make TPUs, and their structure and material metrics were evaluated. The formation of TPUs is ascertained from FTIR and NMR analysis. The final TPUs displayed good physical and mechanical properties. These TPUs exhibited Tg in the range of −56.5 to −39.7°C, corresponding to TPU soft block structure, and Tm between 98.3 and 105.1°C originating from the hard segment. Prepared TPUs exhibit excellent biodegradation under compost environmental conditions. These TPUs showed up to 57% decrease in molecular weight by GPC analysis after 9 weeks of biodegradation, and respirometer analysis displayed up to 97% biodegradation over 120 days.
Impact of fetal treatments for congenital diaphragmatic hernia on lung development
Authors: Dahl Mar Janna , Lavizzari Anna , Davis Jonathan W. , Noble Peter B. , Dellacà Raffaele , Pillow J. Jane
Published: September 2022

The extent of lung hypoplasia impacts the survival and severity of morbidities associated with congenital diaphragmatic hernia (CDH). The alveoli of CDH infants and in experimental models of CDH have thickened septa with fewer type II pneumocytes and capillaries. Fetal treatments of CDH‐risk preterm birth. Therefore, treatments must aim to balance the need for increased gas exchange surface area with the restoration of pulmonary epithelial type II cells and the long‐term respiratory and neurodevelopmental consequences of prematurity. Achievement of sufficient lung development in utero for successful postnatal transition requires adequate intra‐thoracic space for lung growth, maintenance of sufficient volume and appropriate composition of fetal lung fluid, regular fetal breathing movements, appropriate gas exchange area, and ample surfactant production. The review aims to examine the rationale for current and future therapeutic strategies to improve postnatal outcomes of infants with CDH.
Palladium‐catalyzed Synthesis of Fused Carbo‐ and Heterocycles
Authors: Ghosh Tapas , Biswas Diptam , Bhakta Sayantika
Published: September 2022

The use of palladium catalysts in fused ring synthesis has been increasingly noteworthy in recent years in organic synthesis. It has a lot of potential compared to other transition metal catalysts, because of its one‐of‐a‐kind feature that makes them more widely applicable in a variety of disciplines application. Palladium is important in a variety of Heck processes, including intramolecular, intermolecular, and reductive Heck reactions, which produce diverse carbocycles and heterocycles of biological importance. Under optimal reaction conditions, carbocyclization or heterocyclization occurs, resulting in the production of numerous structural building blocks of naturally occurring compounds. Beside intramolecular Heck‐type reactions, cycloaddition, cycloalkylation, oxidative coupling, C−H functionalization, cross‐coupling reactions, and carboamidation reactions have also been employed extensively to access fused carbo‐ and heterocycles of immense biological importance. This review article provides a well‐summarized discussion (since 2001) on fused carbo‐ and heterocycle ring synthesis using palladium catalysts, overviewing their applications, and mechanistic insights.
Probable nature of HD 196821: Is the star a cool HgMn?
Authors: Çalışkan Şeyma , Ünal Kübraözge , Özuyar Doğus , Kılıçoğlu Tolgahan , Elmaslı Aslı , Özgür Ergün , Nasolo Yahya
Published: September 2022

The abundance and detailed chemical analysis of HD 196821 are discussed, based on medium‐ and high‐resolution spectra. The nature of this star is controversial: it has been classified variously as Bootis, Ap of the Si‐Cr group, and HgMn. The atmospheric parameters are determined from the Hβ profile line from the medium‐resolution spectra. We measure the chemical abundances of 19 atomic species from the high‐resolution spectrum. The atmosphere of this star has slightly lower abundances of the light elements oxygen and magnesium with respect to solar values. Nevertheless, phosphorus, scandium, and chromium, as well as the heavy elements Sr, Y, Ba, and Yb, are enhanced compared to the solar values. The abundances of silicon, titanium, iron, and nickel are close to solar. HD 196821 shows an obvious overabundance of Mn II (2.11 dex) and Hg II (5.32 dex). Such a pattern is characteristic of chemically peculiar stars, particularly mercury‐manganese stars. We also investigate the possible photometric variability of the star. The transiting exoplanet survey satellite light curve of HD 196821 reveals a rotational period of 5.7182 days and a harmonic of 2.8286 days, indicating the presence of high‐contrast star‐spots on its surface. According to these indicators, we conclude that the star is a mercury‐manganese star.
3‐Chloro‐5‐Substituted‐1,2,4‐Thiadiazoles (TDZs) as Selective and Efficient Protein Thiol Modifiers
Authors: Jänsch Niklas , Frühauf Anton , Schweipert Markus , Debarnot Cécile , Erhardt Miriam , Brenner‐Weiss Gerald , Kirschhöfer Frank , Jasionis Tomas , Čapkauskaitė Edita , Zubrienė Asta , Matulis Daumantas , Meyer‐Almes Franz‐Josef
Published: September 2022

The study of cysteine modifications has gained much attention in recent years. This includes detailed investigations in the field of redox biology with focus on numerous redox derivatives like nitrosothiols, sulfenic acids, sulfinic acids and sulfonic acids resulting from increasing oxidation, S‐lipidation, and perthiols. For these studies selective and rapid blocking of free protein thiols is required to prevent disulfide rearrangement. In our attempt to find new inhibitors of human histone deacetylase 8 (HDAC8) we discovered 5‐sulfonyl and 5‐sulfinyl substituted 1,2,4‐thiadiazoles (TDZ), which surprisingly show an outstanding reactivity against thiols in aqueous solution. Encouraged by these observations we investigated the mechanism of action in detail and show that these compounds react more specifically and faster than commonly used N‐ethyl maleimide, making them superior alternatives for efficient blocking of free thiols in proteins. We show that 5‐sulfonyl‐TDZ can be readily applied in commonly used biotin switch assays. Using the example of human HDAC8, we demonstrate that cysteine modification by a 5‐sulfonyl‐TDZ is easily measurable using quantitative HPLC/ESI‐QTOF‐MS/MS, and allows for the simultaneous measurement of the modification kinetics of seven solvent‐accessible cysteines in HDAC8.
Fusion of Formate Dehydrogenase and Alanine Dehydrogenase as an Amino Donor Regenerating System Coupled to Transaminases
Authors: Marchini Valentina , Benítez‐Mateos Ana I. , Hutter Sofia L. , Paradisi Francesca
Published: September 2022

Fusion enzymes are attractive tools for facilitating the assembly of biocatalytic cascades for chemical synthesis. This approach can offer great advantages for cooperative redox cascades that need the constant supply of a donor molecule. In this work, we have developed a self‐sufficient bifunctional enzyme that can be coupled to transaminase‐catalyzed reactions for the efficient recycling of the amino donor (L‐alanine). By genetic fusion of an alanine dehydrogenase (AlaDH) and a formate dehydrogenase (FDH), a redox‐complementary system was applied to recycle the amino donor and the cofactor (NADH), respectively. AlaDH and FDH were assembled in both combinations (FDH‐AlaDH and AlaDH‐FDH), with a 2.5‐fold higher enzymatic activity of the latter system. Then, AlaDH‐FDH was coupled to two different S‐selective transaminases for the synthesis of vanillyl amine (10 mM) reaching up to 99 % conversion in 24 h in both cases. Finally, the multienzyme system was reused for at least 3 consecutive cycles when implemented in dialysis‐assisted biotransformations.
Underrepresentation of Asians in pediatric health services research
Authors: Thamotharan Sneha , Collibee Charlene
Published: September 2022

Pediatric health services research is a multidisciplinary field aimed at improving the health of youth. It examines how factors, structures, and systems can be improved to deliver high‐quality care to all youth and has the potential to eliminate health disparities. This comprises examinations of medical and cost effectiveness, clarification of health status concepts, modification of health services and delivery systems, and the evaluation of clinical procedures. Yet health and healthcare disparities in racially and ethnically minoritized youth remain pervasive and persistent, in large part due to the lack of representation and inclusion in health services research, including clinical trials. Indeed, a recent congressionally mandated report from the National Academies of Sciences (2022) called for the improved representation of racial and ethnic minoritized groups in health‐related research and clinical trials (1). In a concerted effort to increase diversity and inclusion in pediatric clinical trials, beginning in 2022, Medicaid will provide coverage for routine costs associated with clinical trial participation.
Keep your eye on…
Authors: Knopf Alison
Published: September 2022

The many ways SAMHSA's new 988 “lifeline” can help youth

Increase in resilience among adolescents as a result of COVID‐19

Effects of smartphone deprivations in psychiatric hospitals
Addiction treatment providers step up to help with mental illness care
Authors: Knopf Alison
Published: September 2022

The lack of adequate treatment for mental illness has been highlighted by the COVID‐19 pandemic, but addiction treatment providers have always recognized that the needs of patients go beyond merely treating the substance use disorder (SUD), and certainly go beyond achieving abstinence. A decade or so ago, the concept of trauma as a precipitating cause of SUDs emerged, with the realization that unless that trauma was treated, the addiction treatment wouldn't hold. Even before then, there were important concepts of self‐medication, in which patients who did not understand why they were addicted eventually learned — if they were fortunate enough to have helpful providers — that their problems were not just about using alcohol or drugs.
Sentinel node mapping and biopsy in ectopic axillary breast cancer: A case report and review of the literature
Authors: Harris Micah K. , Guo Marissa Z. , Mangino Ann , Taylor Clayton , Carson William E.
Published: September 2022

Sentinel lymph node mapping in patients with axillary breast carcinoma is technically challenging and poorly described in the literature. We report a patient with primary ectopic breast carcinoma of the axilla in whom concurrent peri‐tumoral and intra‐tumoral injection of radionuclide tracer allowed for identification and biopsy of sentinel lymph nodes.
A case of BNT162b2 COVID‐19 vaccine‐associated fulminant myocarditis in a very elderly woman
Authors: Otsuka Kaishi , Matsuo Takashi , Ishimatsu Takashi , Fukae Atsuki , Hamamoto Takuro , Oku Koji , Ito Masahiro
Published: September 2022

Coronavirus disease 2019 (COVID‐19) vaccination is reportedly safe and effective. The histologic features of post‐COVID‐19 vaccination myocarditis are unknown. We present a case of a 77‐year‐old Japanese woman diagnosed with eosinophilic myocarditis using endomyocardial biopsy, 7 days after the second dose of BNT162b2 COVID‐19 vaccine. Steroid pulse therapy was effective.
Hypoparathyroidism as one of the initial presentations of systemic lupus erythematosus
Authors: Gadakchi Leyla , Ebrahimi Ali‐Asghar , Sadra Vahideh , Moslemi Mohammadreza , Khabbazi Alireza
Published: September 2022

Systemic lupus erythematosus (SLE) is an autoimmune disease and may be associated with many autoimmune conditions. Hypoparathyroidism is a rare disease. The leading cause of hypoparathyroidism is postsurgical hypoparathyroidism. However, hypoparathyroidism as an initial presentation of SLE is still a rare condition. Here, we report a case of SLE presented with hypoparathyroidism and Hashimoto's thyroiditis.
N‐Heterocyclic Carbene‐Based Zinc Complexes: Same Precursors for Different Lactide Ring‐Opening Polymerization Mechanisms.
Authors: Tufano Federica , Santulli Federica , Grisi Fabia , Lamberti Marina
Published: September 2022

Two zinc complexes bearing NHC ligands were synthesized and fully characterized by NMR spectroscopy. Their behavior in the Ring‐Opening Polymerization (ROP) of lactides was investigated under several conditions of reaction. They showed to be efficient initiators, producing polylactides with molecular weights depending on the cocatalysts. Microstructural analysis of poly(rac‐LA) by1H NMR spectroscopy revealed a slightly enriched‐heterotactic PLAs withPrvalues up to 0.66. Inspection of the kinetic parameters for L‐LA andrac‐LA allowed to compare thekobsof the studied complexes1and2under different conditions, and showed that propagations present the usual pseudo‐first‐order dependence on monomer concentration. Hence, some reactivity studies were carried out, addressed to unravel the nature of the active species in the polymerization processes conducted in the presence of different catalytic systems, namely zinc complexes alone and in combination with neutral or ionic cocatalysts.
Stabilization of Extra‐Large‐Pore Zeolite by Boron Substitution for the Production of Commercially Applicable Catalysts
Authors: Chen Pohua , Xie Mingguan , Zhai Yunping , Wang Youju , Huang Zhehao , Yang Taimin , Sun Wenjia , Wang Yongrui , Sun Junliang
Published: September 2022

Stable extra‐large‐pore zeolites are desirable for industrial purposes due to their ability to accommodate bulky reactants and diffusion through channels. Although there are several extra‐large pore zeolites reported, stable ones are rare. Thus, their stabilization is a feasible strategy for industrial applications. Here, an extra‐large‐pore zeolite EWT with boron substitution is presented, and the resulting zeolite B‐RZM‐3 increased the thermal stability from 600 °C in its silica form to 850 °C. The crystal structure, determined by combining continuous rotation electron diffraction (cRED) and powder X‐ray diffraction (PXRD), shows that B atoms preferentially substitute the interrupted (HO)T(OT)3 (Q3) sites and are partially converted into 3‐coordination to relax framework deformation upon heating. After Al‐reinsertion post‐treatment, Al‐B‐RZM‐3 shows higher ethylbenzene selectivity and ethylene conversion rate per mol acid site than commercial ZSM‐5 and Beta zeolite in benzene alkylation reaction. Synthesizing extra‐large‐pore zeolite in borosilicate form is a potential approach to stabilize interrupted zeolites for commercial applications.
Palladium‐Catalyzed Cascade Reaction in Water to Imidazo[1,2‐a]pyridazines as Switchable DSEgens, AIEgens, and ACQgens**
Authors: Lao Jiaxin , Li Jinbiao , Zou Hongbin
Published: September 2022

Dual‐state emission (DSE) luminophores exhibit strong emissions in both solution and solid states, filling the gaps between aggregation‐induced emissions (AIE) and aggregation‐caused quenching (ACQ). However, limited design concepts and complicated synthetic strategies restrict the discovery of novel DSE molecules. Developing efficient and green methodologies to access novel DSE scaffolds via rational design remains highly desirable. In this work, we report a water‐promoted Pd‐catalyzed cascade reaction for the synthesis of multi‐substituted imidazo[1,2‐a]pyridazine derivatives with DSE properties. The intramolecular interactions of the neighboring benzene rings restrict molecular motion, leading to emissions in the solid state (quantum yield: 11 %), and the newly constructed core structure of imidazo[1,2‐a]pyridazine ensures considerable planarity, allowing for emissions in solution. Further removal of the neighboring phenyl groups resulted in ACQgens, while additional methyl groups led to AIEgens. Subsequent live cell imaging investigations suggested that the novel DSEgens could serve as specific lipid droplet (LD) probes in a wide concentration range.
Highly Efficient Au(I) Alkynyl Emitters: Thermally Activated Delayed Fluorescence and Solution‐Processed OLEDs
Authors: Yu Fei‐Hu , Song Xiu‐Fang , Liu Guan‐Hao , Chang Xiaoyong , Li Kai , Wang Ying , Cui Ganglong , Chen Yong
Published: September 2022

Two‐coordinate donor‐metal‐acceptor type coinage metal complexes displaying efficient thermally activated delayed fluorescence (TADF) have been unveiled to be highly appealing candidates as emitters for organic light‐emitting diodes (OLEDs). Herein a series of green to yellow TADF gold(I) complexes with alkynyl ligands has been developed for the first time. The complexes exhibit high photoluminescence quantum yields (PLQYs) of up to 0.76 in doped films (5 wt % in PMMA) at room temperature. The modifications of alkynyl ligands with electron‐donating amino groups together with the use of electron‐deficient carbene ligands induce ligand‐to‐ligand charge transfer excited states that give rise to TADF emission. Spectroscopic and density functional theory (DFT) calculations reveal the roles of electron‐donating capability of the alkynyl ligand in tuning the excited‐state properties. Solution‐processed organic light‐emitting diodes (OLEDs) using the present complexes as emitters achieve maximum external quantum efficiency (EQE) of up to 20 %.
In Situ Studies of the Formation of Tungsten and Niobium Oxide Nanoparticles: Towards Automated Analysis of Reaction Pathways from PDF Analysis using the Pearson Correlation Coefficient
Authors: Kjær Emil T. S. , Aalling‐Frederiksen Olivia , Yang Long , Thomas Nancy K. , Juelsholt Mikkel , Billinge Simon J. L. , Jensen Kirsten M. Ø.
Published: September 2022

Invited for this month's cover are the groups of Kirsten M. Ø. Jensen at the University of Copenhagen (Denmark) and Simon J. L. Billinge at Columbia University (US). The cover picture shows a sketch of the formation process of metal oxide nanoparticles, where nanocrystalline oxides form from fragments of e.g., polyoxometalates. In situ X‐ray total scattering studies with Pair Distribution Function analysis can give new insights into the formation process, as it provides structural information on all stages of the reaction – from precursor ions in solution, over amorphous or nanostructured intermediates to the final crystalline material. Here, it is show how the analysis of such data can be automated using structure mining and simple computational tools. Read the full text of their Research Article at 10.1002/cmtd.202200034.
The parabigeminal nucleus is a source of “retinogeniculate replacement terminals” in mice that lack retinofugal input
Authors: Whyland Kyle L. , Hernandez Yanio , Slusarczyk Arkadiusz S. , Guido William , Bickford Martha E.
Published: September 2022

In the dorsal lateral geniculate nucleus (LGN) of mice that lack retinal input, a population of large terminals supplants the synaptic arrangements normally made by the missing retinogeniculate terminals. To identify potential sources of these “retinogeniculate replacement terminals,” we used mutant mice (math5–/–) which lack retinofugal projections due to the failure of retinal ganglion cells to develop. In this line, we labeled LGN terminals that originate from the primary visual cortex (V1) or the parabigeminal nucleus (PBG), and compared their ultrastructure to retinogeniculate, V1 or PBG terminals in the dLGN of C57Blk6 (WT) mice (schematically depicted above graph). Corticogeniculate terminals labeled in WT and math5–/– mice were similar in size and both groups were significantly smaller than WT retinogeniculate terminals. In contrast, the PBG projection in math5–/– mice was extensive and there was considerable overlap in the sizes of retinogeniculate terminals in WT mice and PBG terminals in math5–/– mice (summarized in histogram). The data indicate that V1 is not a source of “retinogeniculate replacement terminals” and suggests that large PBG terminals expand their innervation territory to replace retinogeniculate terminals in their absence.
Detection of zero‐day attacks in computer networks using combined classification
Authors: Gavari Bami Hamid , Moharamkhani Elaheh , Zadmehr Behrouz , Najafpoor Vahid , Shokouhifar Mohammad
Published: September 2022

In today's world, many public and private services are provided virtually on the Internet. Due to the increasing dynamism and development of computer networks, intrusion detection systems, as one of the hottest topics in network security, has become an attractive area of research for researchers. The intrusion detection system tries to categorize the activity of the connections into two categories, normal and abnormal. In intrusion detection system, each connection is described based on a set of features, and decisions about whether that connection is normal or abnormal are made using those features. The act of determining the norm or abnormality of a connection is called classification. In this article, a method based on combined classification is proposed to detect zero‐day attacks. One of the most important innovations in this method is using a new version of the GRASP feature selection algorithm, which is used to diversify the base classifiers. In this method, an attempt is made to produce a subset of different features that have high accuracy; and variety to be used in the assembly stage. Experimental results showed that the method used to create feature subsets has high quality.
Low Loading and High Activity of Platinum Oxide Nanoclusters Formed by Defect Engineering of a Metal‐Organic Framework for Formaldehyde Degradation
Authors: Ren Lantian , Ma Qinglang , Yin Anxiang , Feng Xiao , Zhang Teng , Wang Bo
Published: September 2022

A distinct platinum oxide nanocluster (PtOx) was developed, consisting of only Pt−O bond by a defect‐engineered Al metal‐organic framework (MOF) (BIT‐72) with superior formaldehyde (HCHO) degradation activity and stability. With only 0.015 wt % Pt loading, PtOx@BIT‐72‐DE could degrade HCHO with 100 % conversion continuously for at least 200 h under HCHO concentration of 25 ppm and gas hourly space velocity of 60000 mL g−1 h−1 at room temperature. Furthermore, its specific rate (446 mmolHCHO gPt−1 h−1) was higher than for traditional Pt‐based catalysts and single‐atom Pt catalysts. Moreover, the cost of PtOx@BIT‐72‐DE was lowered to 0.0769 $ g−1, which could significantly facilitate its commercial application. This study demonstrates the promising potential of MOFs in the design of HCHO degradation catalysts.
Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial
Authors: Voors Adriaan A. , Damman Kevin , Teerlink John R. , Angermann Christiane E. , Collins Sean P. , Kosiborod Mikhail , Biegus Jan , Ferreira João Pedro , Nassif Michael E. , Psotka Mitchell A. , Tromp Jasper , Brueckmann Martina , Blatchford Jonathan P. , Salsali Afshin , Ponikowski Piotr ,   for the EMPULSE Trial Investigators
Published: September 2022

Aim

The sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown.

Methods and results

Between 1 and 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR >20 ml/min/1.73 m2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 ml/min/1.73 m2 in the empagliflozin group and 55.7 ml/min/1.73 m2 in the placebo group. Empagliflozin caused an initial decline in eGFR (−2 ml/min/1.73 m2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator‐reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all‐cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR.

Conclusion

In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function.
Particle surface functionalization affects mechanism of endocytosis and adverse effects of silver nanoparticles in mammalian kidney cells
Authors: Beus Maja , Pongrac Igor M. , Capjak Ivona , Ilić Krunoslav , Vrček Ena , Ćurlin Marija , Milić Mirta , Čermak Ana Marija Marjanović , Pavičić Ivan
Published: September 2022

Silver nanoparticles (AgNPs) show a plethora of possible applications due to their antimicrobial properties. Different coatings of AgNPs are used in order to increase stability, availability, and activity. However, the question about the toxicity after prolonged exposure still remains. Here, we show that different surface coatings affect in vitro toxicity and internalization of AgNPs in porcine kidney (PK15) cells. AgNPs coated with cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), sodium bis(2‐ethylhexyl)‐sulfosuccinate (AOT), poly‐L‐lysine (PLL), and bovine serum albumin (BSA) were toxic at the concentration of 10 mg Ag/L and higher. The toxicity increased in the following manner: PVP‐AgNPs < CTAB‐AgNPs < PLL‐AgNPs < AOT‐AgNPs < BSA‐AgNPs. All types of AgNPs were internalized by the PK15 cells in a dose‐dependent manner with greater internalization of AgNPs bearing positive surface charge. Transmission electron microscopy (TEM) experiments showed that AgNPs were located in the lysosomal compartments, while the co‐treatment with known inhibitors of endocytosis pathways suggested macropinocytosis as the preferred internalization pathway. When inside the cell, all types of AgNPs induced the formation of reactive oxygen species while decreasing the concentration of the cell's endogenous antioxidant glutathione. The comet assay indicated possible genotoxicity of tested AgNPs starting at the concentration of 2 mg Ag/L or higher, depending on the surface functionalization. This study demonstrates the toxicity of AgNPs pointing to the importance of biosafety evaluation when developing novel AgNPs‐containing materials.