bluuebunny/crossref_metadata_2025 huggingface dataset:
The protective effect of curcumin on cardiac markers and fibrosis in abemaciclib‐induced cardiac damage in rats
Authors: Huyut Zübeyir , Uçar Bünyamin , Yıldızhan Kenan , Altındağ Fikret
Published: September 2022

Abemaciclib (ABE) is a cyclin‐dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin‐I, total cholesterol, and creatine kinase myocardial band (CK‐MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK‐MB, troponin‐I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.
Density functional theory studies on molecular geometry, spectroscopy, HOMO–LUMO and reactivity descriptors of titanium(IV) and oxidozirconium(IV) complexes of phenylacetohydroxamic acid
Authors: Choudhary Vineet Kumar , Mandhan Kanika , Dash Dibyajit , Bhardwaj Sachin , Kumari Meena , Sharma Neeraj
Published: September 2022

The molecular geometry of new titanium(IV) and oxidozirconium(IV) phenylacetohydroxamate complexes [TiCl2(L1)2] (I) and [ZrO(L1)2] (II) (where L1 = Potassium phenylacetohydroxamate = C6H5CH2CONHOK) computed by B3LYP/6‐311++G(d,p) method has shown these to be distorted octahedral and square pyramidal, respectively. A comparison of computed characteristic bond lengths (CO, CN, and NO) of complexes with that of free ligand has shown chelation through carbonyl and hydroxamic oxygen atoms (O, O coordination). The TiO/ZrO bond lengths in complexes are suggestive of weak coordination through (carbonyl CO) and strong covalent (hydroxamic NO) bonding of the ligand. The magnitude of ClTiCl bond angle involving two chloride atoms is suggestive of cis‐conformation at titanium metal in (I). The thermodynamic parameters Gibbs free energy, enthalpy, entropy, nuclear internal energy, constant volume heat capacity, and internal energy of ligand and complexes have been computed. From the energies of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), the global reactivity descriptors such as ionization potential (IP), electron affinity (EA), chemical potential (μ), hardness (η), softness (S), electronegativity (χ), electrophilicity index (ω), and dipole moment have been calculated. The computed vibrational frequencies, 1H and 13C NMR spectra have substantiated the molecular structure of complexes. The thermal behavior of complexes has been studied by thermogravimetric techniques (TGA, DTG, and DTA) in N2 atmosphere has shown complexes are thermally stable.
Faculty diversity, equity, and inclusion in academic dentistry: Revisiting the past and analyzing the present to create the future
Authors: Cain Lisa , Brady Michelle , Inglehart Marita R. , Istrate Emilia C.
Published: September 2022

Aim

In 2021, NIDCR published the landmark report “Oral Health in America.” It described that while oral health‐related research and care has seen amazing progress, oral health inequities and lack of oral care for large segments of the US population have not improved. This situation plus the predicted increase of the diversification of the US population requires decisive actions to ensure that future dentists will be optimally prepared to provide the best possible care for all patients. A diverse dental educator workforce plays a crucial role in obtaining this goal. The objectives of this document were threefold. Aim 1 was to analyze past and current trends in the diversity and inclusion of historically underrepresented ethnic/racial (HURE) and marginalized (HURM) dental faculty members. Aim 2 focused on reviewing best practices and challenges related to achieving dental faculty and leadership diversity and inclusion. Aim 3 was to develop recommendations for increasing the diversity and inclusion of dental faculty in the present and future.

Methods

An analysis of ethnicity/race and gender faculty data collected by the American Dental Education Association (ADEA) in 2011–2012 and 2018–2019 showed that achieving faculty diversity and inclusion has been an ongoing challenge, with limited success for faculty from HURE backgrounds. In order to create this much‐needed change, best practices to increase the applicant pool, change recruitment strategies, and develop solid retention and promotion efforts were described. Research discussing the challenges to creating such changes was analyzed, and strategies for interventions were discussed.

Conclusion

In conclusion, evaluations of efforts designed to create a more diverse and inclusive work force is crucial. Institutions must evaluate their diversity data, practices utilized, and the policies implemented to determine whether the desired outcomes are achieved. Only then will the future dental workforce be optimally prepared to provide the best possible care for all patients in the United States.
Bringing structural competency to the forefront of dental education
Authors: Alarcon Bertha O. , O'Connor Lucian , Rowan Sean , Henson Bradley S. , Doan Van Anne E. , Simeteys Paul , Watanabe Marisa K.
Published: September 2022

Cultural competency as introduced to the healthcare industry had the intention to alleviate and familiarize all healthcare providers with individuals of other cultures and backgrounds than “self”. It attempted to fill in the gaps and prepare providers to relate better with their patients and provide cross‐cultural care. Although it gave the impression of helping to decrease biases and stigma, it resulted in stronger biases, stereotypes of different ethnic groups, and racial profiling. It never acknowledged the systemic barriers that are so ingrained in our society that determine who gets access to care, and who gets the best outcomes in our healthcare system. Starting with the premise of our Surgeon General Reports, we reviewed the Social Determinants of Health and the relationship to structural barriers. This manuscript describes the numerous barriers that affect the access to care, and outcomes of the most marginalized population in the US. Numerous of which are so prevalent amongst all of us that they “feel normal” that there is a degree of structural blindness. We share the experience and frameworks to assess the structural vulnerability of our patients and introduce the different aspects of the curriculum and research that are currently in place to address and bring structural competency to the forefront of dental education at WesternU College of Dental Medicine in Pomona CA.
Diversity in allied dental programs and community colleges
Authors: Jenkins Quincy , Moore Tracye A.
Published: September 2022

Background

Student retention is the most critical challenge facing most traditional 4‐ and 2‐year institutions. Challenges related to student belonging and retention are among many that colleges must contend with daily. Once students arrive, they are met with an academic environment that may greatly differ from their high school and home experiences.

Discussion

There is evidence that classroom success is influenced by faculty tone setting and the overall campus climate. Other studies have shown that creating a sense of belonging on college campuses is essential. Classroom success can be moderated by relationships with faculty, especially with faculty of color and other minoritized groups.

Aims

Given the predicted shortages of minority dental healthcare providers in the United States and the expanding diversity of the general population, it is important to recruit and retain an ethnically and culturally diverse allied dental workforce.

Conclusions

The objectives of this research were to identify strategies to recruit underrepresented (underrepresented minority [URM]) students into health professions, understand the significance of underrepresented (URM) faculty's influence on the number of URM student recruitment, retention, and graduation rates, and how to implement best practices for overall minority student success.
Can academic dentistry become an anti‐racist institution?: Addressing racial battle fatigue and building belonging
Authors: Fleming Eleanor , Smith Carlos S. , Ware Tawana K. , Gordon Nicholas B.
Published: September 2022

Racism, oppression, and marginalization are unfortunate hallmarks that Black individuals face in the United States. While dental schools serve as institutions of both learning and patient care, applying humanistic principles, they are not immune to racism, specifically anti‐Black racism. In this paper, the theoretical framework of racial battle fatigue is applied to academic dentistry to consider how it may impact faculty who have experiences with racism and discrimination. The framework of racial battle fatigue allows for a critique of academic dentistry as an institution that may be toxic, neither welcoming Black faculty members nor supporting their professional and career advancement, despite accreditation standards that call on these institutions to be humanistic environments for diversity and inclusion. Black faculty members may face unique challenges in academic dentistry because of racial battle fatigue. The cumulative stress may warrant unique strategies to both recruit and retain them in academic dental institutions. Specifically, pathways may need to be funded to insure that they have support and time allocations for professional development and career promotion. With understanding the effects of racial battle fatigue, dental schools may want to adopt policies and practices that support the professional and personal well‐being and success of faculty, especially those faculty members who are Black.
Oral health inequities: Recommended public policies to achieve health equity
Authors: López Ana N. , Mutis Martha J. , Morón Elías M. , Beltrán‐Aguilar Eugenio D. , Borrell Luisa N.
Published: September 2022

In the United States (US), racial and ethnic minority populations experience poorer oral health than the general population. Social and commercial determinants of health embedded in structural and institutional racism and/or discrimination generate and exacerbate oral health inequities. We provide examples of oral health disparities (including oral health status and workforce issues) among selected racial and ethnic minority groups in the US. In addition, we compiled four priority areas based on research over the last two decades to guide actions to improve oral health equity. These four priority areas aim to improve health care models, interventions, and policies to help close gaps and reduce disparities in oral health and access to dental care.
Establishing an antiracism framework for dental education through critical assessment of accreditation standards
Authors: Smith Patrick D. , Evans Caswell A. , Fleming Eleanor , Mays Keith A. , Rouse Leo E. , Sinkford Jeanne
Published: September 2022

Purpose

The purpose of this manuscript is to establish an antiracism framework for dental education. Since the accreditation process is an influential driver of institutional culture and policy in dental education, the focus of the framework is the Commission on Dental Accreditation (CODA) standards for predoctoral education.

Methods

The authors of this manuscript reviewed each CODA predoctoral standard for opportunities to incorporate antiracism strategies. Eight standards were identified under themes of diversity (Standards 1‐3, 1‐4, 4‐4), curriculum development (Standards 2‐17, 2‐26), and faculty recruitment and promotion (Standards 3‐1, 3‐4, 3‐5). Guided primarily by National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care, a logic model approach was used to critically assess those standards for opportunities to establish antiracism strategies, with anticipated outcomes and impacts.

Results

Strategies highlighted a need to improve recruitment, admissions, and accountability among dental schools to address the low numbers of historically underrepresented racial and ethnic (HURE) students and faculty. They emphasized the inclusion of racism in curricula geared toward training dental students to provide care to HURE populations. Finally, there are opportunities to improve accountability that dental schools are providing equitable opportunities for career advancement among HURE faculty, with consideration of conflicting demands for scholarship with HURE student mentoring, role modeling, teaching, and/or service.

Conclusions

The framework identifies gaps in CODA standards where racism may be allowed to fester, provides specific antiracism strategies to strengthen antiracism through the accreditation process, and offers dental education programs, a process for evaluating and establishing their own antiracism strategies.
Characteristics of students in International Dentist Training Programs versus applicants who are not yet successful in matriculating
Authors: Nalliah Romesh P. , Timothé Peggy
Published: September 2022

Purpose/objectives

For foreign‐trained dentists who seek requalification in United States dental schools, the acceptance rate is half that of applicants to traditional 4‐year DDS/DMD programs. Unsuccessful applicants also lack clarity on how to strengthen their re‐application. This is a comparison of foreign‐trained dentists who successfully matriculated into the University of Michigan's advanced standing program and prospective students who have yet to matriculate into any advanced standing program.

Methods

We collected data through a survey on the website of the University of Michigan program for foreign‐trained dentists—the Synergy Program is tuition‐free and helps International Dental Program (IDP) applicants navigate the application process. Secondly, we surveyed those enrolled in the University of Michigan's IDP. We compared various characteristics of these two groups. Thirdly, we convened focus groups among the University of Michigan IDP and had unstructured discussions about barriers faced by internationally trained dentists in entering an IDP. University of Michigan Medical School Committee on Human Studies determined this research is “not regulated”.

Results

There were 2400 unique visitors to the Synergy website. Among respondents, 1490 were female (62.1%). A total of 10.1% reported spending over $30,000 on strengthening their application. There were 38 individuals (out of a possible 60) in the University of Michigan's IDP who responded to the survey and 28 were female (73.7%). A total of 31.6% reported spending more than $30,000 on strengthening their application. We had focus groups with 12 IDP students. Regarding perceived differences that led to acceptance, all participants described the advantage in having a greater familiarity with American culture.

Conclusions

We found that those from wealthier households, those who are willing to spend more on their application process, and those who obtained an additional US degree were more likely to be matriculants in IDPs.
Breast PET/MRI Hybrid Imaging and Targeted Tracers
Authors: Romeo Valeria , Helbich Thomas H. , Pinker Katja
Published: September 2022

The recent introduction of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) as a promising imaging modality for breast cancer assessment has prompted fervent research activity on its clinical applications. The current knowledge regarding the possible clinical applications of hybrid PET/MRI is constantly evolving, thanks to the development and clinical availability of hybrid scanners, the development of new PET tracers and the rise of artificial intelligence (AI) techniques. In this state‐of‐the‐art review on the use of hybrid breast PET/MRI, the most promising advanced MRI techniques (diffusion‐weighted imaging, dynamic contrast‐enhanced MRI, magnetic resonance spectroscopy, and chemical exchange saturation transfer) are discussed. Current and experimental PET tracers (18F‐FDG, 18F‐NaF, choline, 18F‐FES, 18F‐FES, 89Zr‐trastuzumab, choline derivatives, 18F‐FLT, and 68Ga‐FAPI‐46) are described in order to provide an overview on their molecular mechanisms of action and corresponding clinical applications. New perspectives represented by the use of radiomics and AI techniques are discussed. Furthermore, the current strengths and limitations of hybrid PET/MRI in the real world are highlighted.

Evidence Level

2

Technical Efficacy

Stage 2
SARS‐CoV‐2 ORF3a inhibits cGAS‐STING‐mediated autophagy flux and antiviral function
Authors: Su Jiaming , Shen Si , Hu Ying , Chen Shiqi , Cheng Leyi , Cai Yong , Wei Wei , Wang Yanpu , Rui Yajuan , Yu Xiao‐Fang
Published: September 2022

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS‐STING‐mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS‐CoV‐2 infection, responsible for the COVID‐19 pandemic, triggers cGAS‐STING activation. cGAS‐STING activation can trigger IRF3‐Type I interferon (IFN) and autophagy‐mediated antiviral activity. Although viral evasion of STING‐triggered IFN‐mediated antiviral function has been well studied, studies concerning viral evasion of STING‐triggered autophagy‐mediated antiviral function are scarce. In the present study, we have discovered that SARS‐CoV‐2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING‐LC3 interaction, thus blocking cGAS‐STING‐induced autophagy but not IRF3‐Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome‐lysosome fusion, is a selective inhibition of STING‐triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING‐triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING‐induced autophagy appears to be an acquired function of SARS‐CoV‐2 ORF3a, since SARS‐CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID‐19.
Cell‐based experimental strategies for myelin repair in multiple sclerosis
Authors: Borda Maximiliano , Aquino Jorge B. , Mazzone Graciela L.
Published: September 2022

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS), diagnosed at a mean age of 32 years. CNS glia are crucial players in the onset of MS, primarily involving astrocytes and microglia that can cause/allow massive oligodendroglial cells death, without immune cell infiltration. Current therapeutic approaches are aimed at modulating inflammatory reactions during relapsing episodes, but lack the ability to induce very significant repair mechanisms. In this review article, different experimental approaches based mainly on the application of different cell types as therapeutic strategies applied for the induction of myelin repair and/or the amelioration of the disease are discussed. Regarding this issue, different cell sources were applied in various experimental models of MS, with different results, both in significant improvements in remyelination and the reduction of neuroinflammation and glial activation, or in neuroprotection. All cell types tested have advantages and disadvantages, which makes it difficult to choose a better option for therapeutic application in MS. New strategies combining cell‐based treatment with other applications would result in further improvements and would be good candidates for MS cell therapy and myelin repair.
Early intervention and disease memory in psoriasis: A literature review
Authors: Ben Abdallah Hakim , Emmanuel Thomas , Bregnhøj Anne , Johansen Claus , Iversen Lars
Published: September 2022

Psoriasis is a chronic inflammatory skin disease, in which molecular and cellular changes retain following clinical resolution of psoriatic lesions, a form of disease memory (‘molecular scar’) that may reestablish the psoriatic inflammation. The increasing evidence of the benefits from early intervention in other immune‐mediated diseases prompts the question of whether early systemic intervention, such as biologics, in new‐onset cutaneous psoriasis may lead to improved clinical response and sustained remission by averting an inflammatory disease memory. Herein, we review the current evidence on early intervention and disease memory in psoriasis. The evidence is sparse and inconsistent, although an early intervention within 2 years of disease‐onset may provide a more favourable long‐term prognosis in psoriasis. However, ongoing randomised clinical trials will explore whether early intervention with biologics in new‐onset psoriasis will be an effective treatment strategy, and whether it prevents the molecular and cellular changes potentially underlying the inflammatory disease memory.
Soil quality assessment of cropland in China and its relationships with climate and topography
Authors: Li Ting , Li Lulu , Chen Xiaoqin , Zhang Shirong , Wang Huoyan , Pu Yulin , Xu Xiaoxun , Wang Guiying , Jia Yongxia , Li Hao , Wu Xiaobo , Liu Xiaojing
Published: September 2022

Assessing soil quality (SQ) of cropland is fundamental for food security and sustainable land management. However, there is limited information regarding SQ assessment on a national scale, which is vital to answer important SQ‐related questions in quantitative terms on that scale. Here, the SQ of cropland in China was assessed by constructing a minimum data set (MDS) from 23 soil physicochemical properties based on principal component analysis. The interaction roles and relative contributions of climate and topography on SQ was evaluated by a structural equation model. The MDS comprised eight indicators: proportion of silt, bulk density, total phosphorus, total potassium, available nitrogen, exchangeable calcium, chlorite, and vermiculite. The soil quality index (SQI) varied from 0.245 to 0.705 and showed a clear pattern of decreasing quality from the north to the south of the country. Of the total cropland area in China, the largest share (27.91%) was of soils of high quality, followed by those of moderate quality (24.63%), low quality (20.37%), very high quality (14.18%), and very low quality (12.91%). The north and the south differed significantly in terms of total potassium, exchangeable calcium, chlorite, and vermiculite, which are the four most important indicators of SQ. Climate and elevation explained about 2.2%–30.1% of the variation in SQ on the national and regional scales. These findings suggest that croplands in southern China will benefit from potassium and calcium fertilizers, which will contribute to enhance food security and promote sustainable land management in China.
An experimental Stommel Retention Zone facility with an application to oil droplet dispersion
Authors: Gurung Sanjib , Smith Carlowen Andrew , Zeidi Seyedmohammadjavad , Tejada‐Martinez Andres E. , Murphy David W.
Published: September 2022

Stommel Retention Zones (SRZs) associated with wind‐driven Langmuir circulation (LC) facilitate the subsurface retention of particles and thus affect processes such as oil spill dispersion, sediment suspension, oil–particle aggregation, and plankton distribution. Since the effect of SRZs on these processes is difficult to study in the field, we present a novel laboratory facility designed to recreate the counterrotating vortex pair flow pattern associated with small‐scale SRZs of various strengths in two dimensions (2D). We then inject an oil jet into this facility to study buoyant oil droplet retention in these SRZs. 2D particle image velocimetry and hybrid Reynolds‐averaged Navier–Stokes/large eddy simulation are used to characterize the flow. Large‐scale oil droplet trajectories in the SRZs are visualized, and oil droplet statistics in the downwelling region and vortex core are measured using high‐magnification brightfield imaging and a droplet detection algorithm. Values of maximum velocity (7.7–32.2 mm s−1), turbulent kinetic energy (10−6 to 10−4 m2 s−2), and turbulent kinetic energy dissipation rate (10−7 to 10−5 m2 s−3) in the downwelling region of the facility fall within the range of values observed in the field. Flow field strength strongly influences oil droplet trajectories, the shape and size of the SRZ, and oil droplet statistics over time, with stronger flows retaining larger oil droplets in the downwelling region over longer periods of time. Indeed, droplets of almost 400 μm diameter are observed in the downwelling region after almost 10 min for the strongest flow. The facility may be used to study the behavior of microplastics, sediments, and zooplankton in LC in the future.
Increasing the scope of the resazurin‐resorufin smart tracer system in hydrologic and biogeochemical sciences: The effects of storage duration and temperature on preservation
Authors: Howard Ben Christopher , Baker Ian , Kettridge Nicholas , Ullah Sami , Krause Stefan
Published: September 2022

The resazurin (raz)‐resorufin (rru) smart tracer system has led to significant advances in hydrologic and biogeochemical sciences but its application has been limited in scope and geography by the short duration that it has been assumed samples can be reliably stored before analysis. For the first time, we quantify the effects of sample storage duration and temperature on measured raz and rru concentrations in order to identify robust storage protocols. Raz/rru concentrations equivalent to those typically used in field and laboratory applications were prepared in three different mediums (deionized water, groundwater, and surface water). Samples were stored at 20°C, 5°C, and −20°C, representing average room, refrigerator, and freezer temperatures. Analysis of raz/rru concentration changes were conducted systematically during an 84‐day period, with higher frequency of analysis in the first 7 d. For samples stored at room temperature, changes of up to 22.6% were observed over the initial 24 h. In contrast, for samples stored in the refrigerator and freezer, changes of up to 8.4% and 6.9% were observed in the same period, respectively. Freezing samples provided the best preservation, yielding a maximum of ~ 10% change after 14 d compared to a maximum of ~ 30% change when cooled. It is generally recommended that raz/rru samples be stored cooled for up to 48 h and frozen for up to 14 d. This offers exciting opportunities to broaden the application of the raz‐rru system to undertake measurements in wider geographical (remote) locations and at increased sampling frequencies.
Comparing methods for measuring egestion in aquatic animals
Authors: May Emily M. , El‐Sabaawi Rana W.
Published: September 2022

Most aquatic research on animal waste production evaluates excretion and not egestion, as it is difficult both to collect feces and to accurately analyze its nutrient content. This limits our understanding of how individuals process their dietary nutrients and how animal waste production impacts ecosystems. In this study, we systematically analyzed whether incubation experiments effectively quantify egestion (at high and low temperatures), estimated fecal phosphorus (P) leaching, and evaluated foregut‐hindgut analyses as a complementary method. Incubations were superficially effective but were flawed. Although 82% of fish in high‐temperature incubations and 75% of fish in low‐temperature incubations egested in 24 h, a minority of fish cleared their guts (38% at high temperatures and 6% at low temperatures), making analyzing full nutrient input and output impossible. Furthermore, feces leached P rapidly and variably; a field population's and an experimental population's feces leached 41% and 75% of their initial P respectively. This suggests that previous egestion research that does not measure leaching underestimates fecal nutrient content. Foregut‐hindgut analyses are unaffected by leaching and so effectively complemented incubations. These analyses provided enough hindgut material to estimate fecal %P and allowed us to estimate both dietary nutrient intake (when unknown) and the relative quantity of P in the diet and in the feces. Overall, we suggest that future researchers combine incubations and foregut‐hindgut analyses to estimate aquatic animal waste production.
Thiol‐Click Based Polyglycerol Hydrogels as Biosensing Platform with In Situ Encapsulated Streptavidin Probes
Authors: Thongrom Boonya , Dimde Mathias , Schedler Uwe , Haag Rainer
Published: September 2022

An in situ streptavidin‐encapsulated hydrogel based on dendritic polyglycerol (dPG) which is functionalized with either an acrylate, allyl or acrylamide group and dithiolated polyethylene glycol (PEG) is constructed via a thiol‐click chemistry approach and is investigated for biosensing applications. The hydrogel platform is screened for the encapsulation and release efficiencies of the model protein streptavidin under varying physicochemical conditions, for example, crosslinking chemistry reactions, the molar ratio between the two gel components, macromonomer concentrations or pH‐values. By that, tailor‐made hydrogels can be developed, which are able to encapsulate or release the model protein for several days based on its modality. Furthermore, the accessible binding site of encapsulated streptavidin or in other words, the biotin‐binding performance is quantified, and the stability of the various hydrogel types is studied by rheology measurements, 1H NMR, gel permeation chromatography (GPC), and mass loss experiments.
Uncommon posttranslational modifications in proteomics: ADP‐ribosylation, tyrosine nitration, and tyrosine sulfation
Authors: Bashyal Aarti , Brodbelt Jennifer S.
Published: September 2022

Posttranslational modifications (PTMs) are covalent modifications of proteins that modulate the structure and functions of proteins and regulate biological processes. The development of various mass spectrometry‐based proteomics workflows has facilitated the identification of hundreds of PTMs and aided the understanding of biological significance in a high throughput manner. Improvements in sample preparation and PTM enrichment techniques, instrumentation for liquid chromatography‐tandem mass spectrometry (LC‐MS/MS), and advanced data analysis tools enhance the specificity and sensitivity of PTM identification. Highly prevalent PTMs like phosphorylation, glycosylation, acetylation, ubiquitinylation, and methylation are extensively studied. However, the functions and impact of less abundant PTMs are not as well understood and underscore the need for analytical methods that aim to characterize these PTMs. This review focuses on the advancement and analytical challenges associated with the characterization of three less common but biologically relevant PTMs, specifically, adenosine diphosphate‐ribosylation, tyrosine sulfation, and tyrosine nitration. The advantages and disadvantages of various enrichment, separation, and MS/MS techniques utilized to identify and localize these PTMs are described.
Quantitative nuclear magnetic resonance of chloride by an accurate internal standard approach
Authors: Wood Jared S. , Dal Poggetto Guilherme , Wang Xiao , Reibarkh Mikhail , Williamson R. Thomas , Cohen Ryan D.
Published: September 2022

Chloride is the most common counterion used to improve aqueous solubility and enhance stability of small molecule active pharmaceutical ingredients. While several analytical techniques, such as titration, HPLC with charged aerosol detection, and ion chromatography, are currently utilized to assay the level of chloride, they have notable limitations, and these instruments may not be readily available. Here, we present a generally applicable 35Cl solution NMR method to assay the level of chloride in pharmaceutical compounds. The method uses KClO4 as an internal standard for improved accuracy in comparison with external standard methods, and it was found to be robust, linear over three orders of magnitude, precise (<3% RSD), and accurate (<0.5% absolute error).
Convective thermal conditions and the thermophoretic effect's impacts on a hybrid nanofluid over a moving thin needle
Authors: Madhukesh Javali Kotresh , Ramesh Gosikere Kenchappa , Prasannakumara Ballajja Chandrappa
Published: September 2022

This research focuses on the heat source/sink, chemical reaction, and thermophoretic particle deposition in the influence of hybrid nanofluid over a moving thin needle subjected to a magnetic field. Using the appropriate transformations, a group of nonlinear partial differential equations may be converted to ordinary differential equations. Additionally, with the aid of computational software, the RKF‐45 approach is used for the numerical assessment, as well as the shooting operation. It should be mentioned that the results' approval demonstrates a strong association with the previous findings. The resulting graphs mainly explain the fundamental characteristics of hybrid nanofluids and nanofluids, as well as the consequences of different restrictions. An increase in needle size enhances the velocity profile, temperature profile, and concentration profile. The radial and axial velocity profiles are reduced when the magnetic constraint is increased, whereas the thermal and concentration patterns are reversed. Improved heat source‐sink as well as Biot number values will enhance the thermal profile. The concentration profiles will decrease due to reaction rate restrictions and thermophoretic limits. The inclusion of solid volume fraction reduces surface drag forces while increasing the rate of mass transfer. In most circumstances, hybrid nanofluid plays a prominent role than nanofluid.
Optimal control for Hilfer fractional neutral integrodifferential evolution equations with infinite delay
Authors: Kavitha Krishnan , Vijayakumar Velusamy
Published: September 2022

The optimal control solutions for Hilfer fractional neutral integrodifferential evolution equations with infinite delay in Banach space are investigated in this study. To begin, we use fractional computations, Holder inequality, and Banach fixed point approaches to examine conclusions for fractional integrodifferential evolution equations. Following that, we created the fractional integrodifferential evolution system's continuous dependency. We also looked at optimal controls for the Lagrange problem. Finally, an application is given to extract the primary theory.
Crystal structure and reaction mechanism of a bacterial Mg‐dechelatase homolog from the Chloroflexi Anaerolineae
Authors: Dey Debayan , Nishijima Masayoshi , Tanaka Ryouichi , Kurisu Genji , Tanaka Hideaki , Ito Hisashi
Published: September 2022

Chlorophyll degradation plays a myriad of physiological roles in photosynthetic organisms, including acclimation to light environment and nutrient remobilization during senescence. Mg extraction from chlorophyll a is the first and committed step of the chlorophyll degradation pathway. This reaction is catalyzed by the Mg‐dechelatase enzyme encoded by Stay‐Green (SGR). The reaction mechanism of SGR protein remains elusive since metal ion extraction from organic molecules is not a common enzymatic reaction. Additionally, experimentally derived structural information about SGR or its homologs has not yet been reported. In this study, the crystal structure of the SGR homolog from Anaerolineae bacterium was determined using the molecular replacement method at 1.85 Å resolution. Our previous study showed that three residues—H32, D34, and D62 are essential for the catalytic activity of the enzyme. Biochemical analysis involving mutants of D34 residue further strengthened its importance in the functioning of the dechelatase. Docking simulation also revealed the interaction between the D34 side chain and central Mg ion of chlorophyll a. Structural analysis showed the arrangement of D34/H32/D62 in the form of a catalytic triad that is generally found in hydrolases. The probable reaction mechanism suggests that deprotonated D34 side chain coordinates and destabilizes Mg, resulting in Mg extraction. Besides, H32 possibly acts as a general base catalyst and D62 facilitates H32 to be a better proton acceptor. Taken together, the reaction mechanism of SGR partially mirrors the one observed in hydrolases.
Structural basis for the interaction between the first SURP domain of the SF3A1 subunit in U2 snRNP and the human splicing factor SF1
Authors: Nameki Nobukazu , Takizawa Masayuki , Suzuki Takayuki , Tani Shoko , Kobayashi Naohiro , Sakamoto Taiichi , Muto Yutaka , Kuwasako Kanako
Published: September 2022

SURP domains are exclusively found in splicing‐related proteins in all eukaryotes. SF3A1, a component of the U2 snRNP, has two tandem SURP domains, SURP1, and SURP2. SURP2 is permanently associated with a specific short region of SF3A3 within the SF3A protein complex whereas, SURP1 binds to the splicing factor SF1 for recruitment of U2 snRNP to the early spliceosomal complex, from which SF1 is dissociated during complex conversion. Here, we determined the solution structure of the complex of SURP1 and the human SF1 fragment using nuclear magnetic resonance (NMR) methods. SURP1 adopts the canonical topology of α1–α2–310–α3, in which α1 and α2 are connected by a single glycine residue in a particular backbone conformation, allowing the two α‐helices to be fixed at an acute angle. A hydrophobic patch, which is part of the characteristic surface formed by α1 and α2, specifically contacts a hydrophobic cluster on a 16‐residue α‐helix of the SF1 fragment. Furthermore, whereas only hydrophobic interactions occurred between SURP2 and the SF3A3 fragment, several salt bridges and hydrogen bonds were found between the residues of SURP1 and the SF1 fragment. This finding was confirmed through mutational studies using bio‐layer interferometry. The study also revealed that the dissociation constant between SURP1 and the SF1 fragment peptide was approximately 20 μM, indicating a weak or transient interaction. Collectively, these results indicate that the interplay between U2 snRNP and SF1 involves a transient interaction of SURP1, and this transient interaction appears to be common to most SURP domains, except for SURP2.
Population pharmacokinetic‐pharmacodynamic analyses of amyloid positron emission tomography and plasma biomarkers for lecanemab in subjects with early Alzheimer's disease
Authors: Hayato Seiichi , Takenaka Osamu , Sreerama Reddy Sree Harsha , Landry Ishani , Reyderman Larisa , Koyama Akihiko , Swanson Chad , Yasuda Sanae , Hussein Ziad
Published: September 2022

Lecanemab is a humanized immunoglobulin G1 monoclonal antibody that selectively binds to soluble Aβ aggregate species, while demonstrating low affinity for Aβ monomer. This article describes the population pharmacokinetic (PK) and PK/pharmacodynamic (PD) analyses for amyloid plaques, as measured using positron emission tomography (PET), and biomarkers of amyloid pathology as evidenced by Aβ42/40 ratio and plasma p‐tau181 following i.v. administration of lecanemab in subjects with early Alzheimer's disease. Lecanemab PKs were well‐characterized with a two‐compartment model with first‐order elimination. Final PK model contained covariate effects of anti‐drug antibody positive status, sex, body weight, and albumin on clearance. The time course of amyloid PET standard uptake ratio (SUVr), plasma Aβ42/40 ratio, and p‐tau181 were described using indirect response models with lecanemab exposure as a maximum effect function stimulating the reduction of SUVr, and as a linear function increasing Aβ42/40 ratio and decreasing p‐tau181 formation rates. PK/PD simulations show that 10 mg/kg biweekly dosing results in larger and faster decrease in SUVr and p‐tau181 and increase in Aβ42/40 ratio as compared to 10 mg/kg monthly dose. Furthermore, the PK/PD simulations showed that after treatment discontinuation the brain amyloid re‐accumulation to baseline levels is slow with a recovery half‐life of ~4 years, whereas plasma Aβ42/40 ratio and p‐tau181 return to baseline levels faster than amyloid. Given the relationship between changes in amyloid PET SUVr and soluble biomarkers, the developed PK/PD models can be used to inform lecanemab dose regimens in future clinical studies.
Hydrophilic, dual amino acid–functionalized zinc sulfide quantum dot for specific identification of N‐glycopeptides from biological samples
Authors: Feng Quanshou , Xie Zehu , Liang Hongze , Zhang Zhenbin , Yan Yinghua , Ding Chuan‐Fan
Published: September 2022

Rationale

Glycosylation of proteins is one of the most significant and complex post‐translational modifications, and N‐glycosylation plays a crucial role in life activities. Mass spectrometry (MS) has been a powerful technique in the analysis of protein glycosylation. However, the direct detection of glycoproteins in biological samples based on MS still suffers from huge challenges. Therefore, enrichment and purification of samples before MS analysis is an essential prerequisite.

Methods

Hydrophilic interaction liquid chromatography (HILIC) has significantly developed for selective enrichment of glycopeptides due to its simple operation process and unbiased enrichment. Herein, hydrophilic, dual amino acid–functionalized zinc sulfide quantum dots (ZnS QDs) were prepared to enrich glycopeptides using an easy procedure. The enriched glycopeptides were detected using matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS).

Results

The obtained material exhibited high selectivity (1:2000), low detection limit (0.1 fmol/μl), good repeatability (10 times), and excellent recovery (89.8%) in glycopeptide enrichment. In the actual application in biological samples, 71 N‐glycopeptides and 161 N‐glycopeptides were detected from human saliva and serum, respectively.

Conclusions

ZnS‐Au‐GC was successfully prepared using an easy method. The results showed that the obtained material exhibited excellent performance in glycopeptide enrichment. Furthermore, it had showed great potential for glycopeptide enrichment in complex biological samples.
When it starts in the skin and goes to the lungs, where does it stop?
Authors: Catarino Ferro Ana Rita , Ferreira Campos Ana Margarida
Published: September 2022

Key message

This clinical case reports a rare disease—Birt‐Hogg‐Dubé Syndrome—characterized by skin lesions and multiple lung cysts. Because of its rarity, BHDS is likely undiagnosed and mistaken for primary spontaneous pneumothorax or emphysema. An early diagnosis is important to set up screening for renal cancer in patients and affected relatives.
A flexible‐hazards cure model with application to patients with soft tissue sarcoma
Authors: Xie Can , Huang Xuelin , Li Ruosha , Pisters Peter W. T.
Published: September 2022

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow‐up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan‐Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the current literature, most regression models for estimating cure rates assume proportional hazards (PH) between different subgroups. It turns out that the estimation of cure rates for subgroups is highly sensitive to this assumption, so more flexible models are needed, especially when this PH assumption is clearly violated. We propose a new cure model to simultaneously incorporate both PH and non‐PH scenarios for different covariates. We develop a stable and easily implementable iterative procedure for parameter estimation through maximization of the nonparametric likelihood function. The covariance matrix is estimated by adding perturbation weights to the estimation procedure. In simulation studies, the proposed method provides unbiased estimation for the regression coefficients, survival curves, and cure rates given covariates, while existing models are biased. Our model is applied to a study of stage III soft tissue sarcoma and provides trustworthy estimation of cure rates for different treatment and demographic groups.
The effectiveness of self‐distanced versus self‐immersed reflections among adults: Systematic review and meta‐analysis of experimental studies
Authors: Murdoch Elizabeth M. , Chapman Michael T. , Crane Monique , Gucciardi Daniel F.
Published: September 2022

Stressor events can be highly emotional and disruptive to our functioning, yet they also present opportunities for learning and growth via self‐reflections. Self‐distanced reflections in which one reasons about target events in ways that maximise their removal of the current self from the experiential reality are said to facilitate this reflective process. We tested the expectation that self‐distanced reflections offer an advantage over self‐immersed vistas via a pre‐registered systematic review of seven electronic databases (Scopus, Medline, Web of Science, PsycInfo, CINAHL Plus, Embase, and ProQuest Dissertations and Theses Global) to identify experimental tests with adults aged 18–65 years where the focus of the reflection was a stressor or adverse event that participants had already experienced. A three‐level, random effects meta‐analysis of 25 experiments (N = 2,397, 68 effects) revealed a small‐to‐moderate advantage of self‐distanced reflections (g = 0.19, SE = 0.07, 95% CI [0.05, 0.33]) and were most effective when they targeted a stressor experience that emphasised one's emotional state or lifetime. Nevertheless, our assessment of the overall quality of evidence including risk of bias suggested uncertainty regarding the benefit of this pragmatic self‐regulatory tactic and therefore the need for future high‐powered, high‐quality experiments.
Strategy of Enhancing Built‐in Field to Promote the Application of C‐TiO2/SnO2 Bilayer Electron Transport Layer in High‐Efficiency Perovskite Solar Cells (24.3%)
Authors: Shu Hui , Peng Changtao , Chen Qian , Huang Zhangfeng , Deng Chen , Luo Wenjie , Li Haijin , Zhang Wenfeng , Zhang Wenhua , Huang Yuelong
Published: September 2022

Combining two kinds of electron transport layer (ETL) which have complementary advantages into a bilayer structure to form a bilayer ETL is an effective way to transcend inherent limitations of single‐layer ETL, which is very helpful in the development of perovskite solar cells (PSCs). In this work, a strategy is proposed to break constraints on the application of the staggered bilayer ETL in high‐efficiency PSC, namely utilizing a built‐in field to overcome the dilemma in ECBM making it possible to improve VOC and FF simultaneously by tuning the Fermi level of ETLs properly. According to the strategy, a bilayer ETL structure comprised of C‐TiO2 and SnO2 layer and corresponding Li‐doping process are developed, and the characterization results confirm the effectiveness of the strategy, making the potentials of the C‐TiO2(Li)/SnO2 bilayer ETL fully released for its application in high‐efficiency PSCs: a VOC of 1.201 V for an ordinary triple‐cation‐perovskite‐based PSC and a photoelectric conversion efficiency of 24.3% for a low‐bandgap‐perovskite‐based PSC with high haze FTO superstrate are successfully achieved, indicating that the C‐TiO2(Li)/SnO2 bilayer ETL is a successful application paradigm of the proposed strategy and very promising in the application of high‐efficiency PSCs.