bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma NT1‐tau and Aβ42 correlate with age and cognitive function in two large Down syndrome cohorts
Authors: Stern Andrew M. , Van Pelt Kathryn L. , Liu Lei , Anderson Amirah K. , Ostaszewski Beth , Mapstone Mark , O'Bryant Sid , Petersen Melissa E. , Christian Bradley T. , Handen Benjamin L. , Selkoe Dennis J. , Schmitt Frederick , Head Elizabeth ,   the Alzheimer's Biomarker Consortium–Down Syndrome (ABC‐DS) investigators
Published: July 2023

INTRODUCTION

People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N‐terminal fragment (NT1‐tau) and Aβ isoforms predict cognitive impairment.

METHODS

Plasma NT1‐tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross‐sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort.

RESULTS

Discovery cohort linear mixed models for NT1‐tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross‐sectional models, NT1‐tau increased and Aβ42 decreased with age. NT1‐tau predicted cognitive and functional scores. The discovery cohort linear model for NT1‐tau predicted levels in the validation cohort.

DISCUSSION

NT1‐tau correlates with age and worse cognition in DS. Further validation of NT1‐tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.
Advances in Intracellular and On‐Surface Polymerization in Living Cells: Implications for Nanobiomedicines
Authors: Laskar Partha , Varghese Oommen P. , Shastri V. Prasad
Published: July 2023

The cellular environment offers some unique features to carry out polymerizations under controlled conditions. Polymerization of monomers in cellular compartments and on the surface of living organisms holds much promise in the engineering of biofunctional synthetic polymers for sensing and probing cell behavior and of late has received significant interest. This effort lies at the interface of synthetic biology and polymer chemistry and can pave the way for innovative solutions to many existing challenges in healthcare, environment, energy, and the study of the “origin of life”. Herein, recent advances in controlled polymerization strategies for intracellular and surface of living cells are presented with a particular emphasis on nanobiomedicines. Furthermore, polymerization strategies, cytocompatible monomer structures, compatible cell lines and microorganisms, nature of stimulus, catalysts, along with specific polymerization conditions to produce non‐natural biofunctional polymers that can undergo polymerization‐induced self‐assembly within and onto the living cells are presented in detail. Furthermore, the review offers a window into the future of such novel emerging synthetic bionano systems in biomedical sciences.
Evaluation of the contents and ratios of five fractionated proteins to elucidate the protein composition in soybean seeds
Authors: Sugiyama Masahiro , Samoto Masahiko , Ichinose Takashi , Nakamura Akihiro , Matsumiya Kentaro , Matsumura Yasuki
Published: July 2023

Selecting suitable soybean cultivars is important for food processing and exploring their endowment with desirable physiological functions. We applied the fractionation method previously established to compare soy protein composition among cultivars to promote such a selection. More than 95% of the proteins in soybean cotyledons were extracted from 13 soybean cultivars using a high‐concentration salt solution. The extracted proteins were fractionated into five fractions, namely oil body‐associated protein (OBAP), polar lipid‐associated protein (PLAP), globulins (11S and 7S), and whey by centrifugation after tuning the solubility behavior of the proteins with various solutions. Protein species in each fraction were analyzed by SDS‐PAGE. Protein content in the total extract and five fractions was quantified to characterize the protein composition of soybean cultivars. The correlation between the protein content of each fraction and the total protein in cotyledon was investigated. A strong positive correlation was found only for the 11S fraction (r = 0.82), followed by a positive correlation in the 7S fraction (r = 0.65). Thus, we surmised that the increased protein content in soybean was due to increased globulin content. Furthermore, the calculation of the average ratio of protein content in each fraction indicated the globulin fraction (7S and 11S) to be 52%, the lipophilic protein fraction (OBAP and PLAP) to be 33%, and the whey fraction to be 13%. The preparation method employed in this study is a promising tool for efficiently comparing the protein composition of soybean cultivars to evaluate the potential use of cultivars for food production.
Topological Dirac Spin‐Gapless Materials ‐ a New Horizon for Topological Spintronics Without Spin‐Orbit Interaction
Authors: Nadeem Muhammad , Wang Xiaolin
Published: July 2023

The existence of chiral edge states (CES), corresponding to nontrivial bulk‐band topology characterized by a non‐vanishing topological invariant, and the manipulation of topological transport via CES promise topological electronic/spintronic device applications. This study predicts the existence, practical realization, topological protection, and topological switching of spin‐gapless valley‐filtered chiral edge states (SG‐VF‐CES), representing a novel topological Dirac spin‐gapless/half‐metal phase in antiferromagnetic honeycomb structures terminated on zigzag edges. It demonstrates that this phenomenon is realizable if a perpendicular (transverse) electric field is applied in zigzag nanoribbons with an antiferromagnetic ordering on the boundary (in the bulk), and the Weber‐Fechner type nonlinear behavior is optimizable by a transverse (perpendicular) electric field. The existence of SG‐VF‐CES, their correspondence with nontrivial topological character in the bulk, and electric‐field‐driven switching of their spin‐polarization that is accompanied by switching of bulk‐band topology promise a new strategy for topological spintronics without spin‐orbit interaction (SOI).
The medicinal panorama of benzimidazoles and their scaffolds as anticancer and antithrombotic agents: A review
Authors: Chalkappa Prasanth Kumar Babu , Aralihalli Sudhakara , Sudileti Murali , Aithal Shubhra Jyotsna , Praveen Beekanahalli Mokshanatha , Birjadar Kedarnath
Published: July 2023

Nitrogen‐containing heterocyclic scaffolds have become a prospective pharmacophore with therapeutic importance due to their biological similarities with natural and synthetic drugs. Among all nitrogen heterocyclic compounds, benzimidazoles and their derivatives are privileged molecules structurally akin to naturally available nucleotides, enabling them to intercommunicate with numerous biopolymers in biological systems. This reason enlightens modern researchers worldwide to assess their potential significance in the context of synthetic and biological chemistry. Therefore, it is crucial to merge the latest data with the prior documentation to apprehend the ongoing situation of the benzimidazole moiety in various therapeutic zones of research. The current work displays that the benzimidazole center is a versatile nucleus that offers the necessary data of synthetic alterations for pre‐existing compounds to provide new scaffolds to resist numerous therapeutic sectors, including those associated with anticancer and antithrombosis. Due to the potential significance of benzimidazoles, this review aims to emphasize the latest innovations in synthesizing several other notable benzimidazole substrates and their significant pharmacological prospects for the future, including anticancer and antithrombosis.
Future of land surface water availability over the Mediterranean basin and North Africa: Analysis and synthesis from the CMIP6 exercise
Authors: Arjdal Khadija , Driouech Fatima , Vignon Étienne , Chéruy Frédérique , Manzanas Rodrigo , Drobinski Philippe , Chehbouni Abdelghani , Idelkadi Abderrahmane
Published: July 2023

The Mediterranean basin and Northern Africa are projected to be among the most vulnerable areas to climate change. This research documents, analyzes, and synthesizes the projected changes in precipitation P, evapotranspiration E, net water supply from the atmosphere to the surface P–E, and surface soil moisture over these regions as simulated by 17 global climate models from the sixth exercise of the Coupled Model Intercomparison Project (CMIP6) under two Shared Socioeconomic Pathways, SSP2‐4.5, and SSP5‐8.5. It also explores the sensitivity of the results to the chosen climate scenario and model resolution and assesses how the projections have evolved from the fifth exercise (CMIP5). Models project a statistically robust drying over the entire Mediterranean and coastal North Africa. Over the Northern Mediterranean sector, a significant precipitation decrease reaching −0.4 ∓ 0.1 mm  is projected during the 21st century under the SSP5‐8.5 scenario. Conversely, a significant increase in precipitation of +0.05 to 0.3 ∓ 0.1 mm day−1 is projected over South‐Eastern Sahara under the same scenario. Evapotranspiration and soil moisture exhibit decreasing trends over the Mediterranean basin and an increase over the Sahara for both SSPs, with a notable acceleration from the 2020s. As a result, P‐E is projected to decrease at a rate of about −0.3 mm day−1 under the high‐end scenario SSP5‐8.5 over the Mediterranean whilst no significant changes are expected over the Sahara due to evapotranspiration compensation effects. CMIP6 and CMIP5 models project qualitatively similar patterns of changes but CMIP6 models exhibit more intense changes over the Mediterranean basin and South‐Eastern Sahara, especially during winter.
Associations between health insurance status, neighborhood deprivation, and treatment delays in women with breast cancer living in Georgia
Authors: Awan Sofia , Saini Geetanjali , Gogineni Keerthi , Luningham Justin M. , Collin Lindsay J. , Bhattarai Shristi , Aneja Ritu , Williams Courtney P.
Published: July 2023

Background

Little is known regarding the association between insurance status and treatment delays in women with breast cancer and whether this association varies by neighborhood socioeconomic deprivation status.

Methods

In this cohort study, we used medical record data of women diagnosed with breast cancer between 2004 and 2022 at two Georgia‐based healthcare systems. Treatment delay was defined as >90 days to surgery or >120 days to systemic treatment. Insurance coverage was categorized as private, Medicaid, Medicare, other public, or uninsured. Area deprivation index (ADI) was used as a proxy for neighborhood‐level socioeconomic status. Associations between delayed treatment and insurance status were analyzed using logistic regression, with an interaction term assessing effect modification by ADI.

Results

Of the 14,195 women with breast cancer, 54% were non‐Hispanic Black and 52% were privately insured. Compared with privately insured patients, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 79%, 75%, and 27% higher odds of delayed treatment, respectively (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.32–2.43; OR: 1.75, 95% CI: 1.43–2.13; OR: 1.27, 95% CI: 1.06–1.51). Among patients living in low–deprivation areas, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 100%, 84%, and 26% higher odds of delayed treatment than privately insured patients (OR: 2.00, 95% CI: 1.44–2.78; OR: 1.84, 95% CI: 1.48–2.30; OR: 1.26, 95% CI: 1.05–1.53). No differences in the odds of delayed treatment by insurance status were observed in patients living in high‐deprivation areas.

Discussion/Conclusion

Insurance status was associated with treatment delays for women living in low‐deprivation neighborhoods. However, for women living in neighborhoods with high deprivation, treatment delays were observed regardless of insurance status.
P2X7‐Receptor Pathway Involvement in the Anti‐Inflammatory Activity of Medicinal Plants
Authors: Ortiz Sergio , Šavikin Katarina , Massicot France , Olivier Elodie , Dutot Melody , Rat Patrice , Deguin Brigitte , Gođevac Dejan , Menković Nebojša , Živković Jelena , Zdunić Gordana , Boutefnouchet Sabrina
Published: July 2023

Medicinal plants used in European folk medicine attached to Lamiales, Gentianales or Asterales orders are used to treat inflammatory disorders. Many targets have been identified but to date, implication of purinergic receptor P2X7 activation has not yet been investigated. We managed to evaluate the protective effect on P2X7 activation by plant extracts used as anti‐inflammatory in European folk medicine by the YO‐PRO‐1 uptake dye in vitro bioassay. Results revealed that among our selected plants, species from Scrophularia and Plantago genus were able to decrease significantly P2X7 activation (>50 % at 0.1 and 1 μg/mL). UPLC/MS, dereplication and metabolomic analysis of Scrophularia extracts, allowed us to identify the cinnamoyl‐iridoid harpagoside as putative inhibitor of P2X7 activation. These results open a new research field regarding the anti‐inflammatory mechanism of cinnamoyl‐iridoids bearing plants, which may involve the P2X7 receptor.
Facile Synthesis of Hybrid Nanoflowers Using Glycine and Phenylalanine and Investigation of Their Catalytic Activity
Authors: Demirbas Ayse , Karsli Baris , Ocsoy Ismail
Published: July 2023

In the context of the proposed work, two different amino acids (Glycine, Phenylalanine) have interacted with copper ions in a phosphate buffer (PBS) in place of enzymes. This interaction resulted in the nucleation of copper phosphate crystals and the formation of flower‐shaped amino acid‐copper hybrid nanostructures (AA‐hNFs), which grew through self‐assembly. While Cu (II) ions in the structure of AA‐hNFs were used as Fenton's agent for the catalytic activity. SEM, energy dispersive X‐ray spectroscopy, X‐ray diffraction, and Fourier transform infrared spectroscopy measurements were used to define the AA‐hNFs′ characterisation. The peroxidase‐like activities of AA‐hNFs were investigated by UV/VIS spectrophotometer. Metal nanoparticles have peroxidase‐like activity. A class of enzymes known as peroxidases is able to catalyze the conversion of hydrogen peroxide into hydroxyl radicals. These radicals also take part in electron transfers with substrates, which results in color during oxidation. When cupric oxide nanoparticles are added to the peroxidase substrate while H2O2is present, a blue color product with a maximum absorbance at=652 nm can result, demonstrating the catalytic activity of a peroxidase. The morphology and composition of AA‐hNFs were carefully characterized and the synthesized parameters were optimized systematically. Results showed that the nanoparticles were dispersed with an average diameter of 7–9 μm and indicated a uniform flower shape. The results of the investigation are anticipated to significantly advance a number of technical and scientific sectors.
Should CINAHL be used as one of the main databases for evidence synthesis of health services intervention?
Authors: Dhippayom Teerapon , Rattanachaisit Natnicha , Wateemongkollert Apinya , Napim Rawiwan , Chaiyakunapruk Nathorn
Published: July 2023

Introduction

CINAHL is not listed as one of the minimum databases for systematic review (SR) of interventions in the Methodological Expectations of the Cochrane Intervention Review.

Objective

To determine additional studies uniquely identified from the CINAHL search in SR of health services interventions (HSI).

Methods

We searched PubMed from inception to October 1, 2022 to identify SRs of HSI that determined clinical or humanistic outcomes of HSI and used CINAHL. Out of 5655 Systematic reviews identified, we randomly selected 374 SRs and extracted all primary studies included. We then explored the bibliographic databases in which the journals of those studies were indexed. The outcome of interest was the number of studies uniquely available in CINHAL. We also performed a subgroup analysis based on the type of HSI. We performed descriptive statistics to report the study outcomes using Excel (Microsoft 365).

Results

A total of 7550 primary studies were identified from the 374 Systematic reviews that met the inclusion criteria. Of these studies, 7380 were journal publications that have been indexed in MEDLINE/PubMed (75.1%), Scopus (74.5%), Sciences Citation Index, SCI (54.7%), Embase (48.1%), and CINAHL (34.9%). Only 83 out of 7380 (1.1%) studies were published in journals that were uniquely indexed in CINAHL. The percentage of studies that were only available in other databases was 9.7% (Scopus), 4.3% (MEDLINE/PubMed), 1.6% (SCI), and 0.3% (Embase). The number of studies that were unique to CINAHL in specific types of HSI were: 24/1570 (1.5%) for community health services, 20/1520 (1.3%) for preventive health services, 45/3624 (1.2%) for patient care, 8/1173 (0.7%) for mental health services, and 18/2804 (0.6%) for rehabilitation.

Conclusion

The gain of CINAHL to identify unique primary studies for SR of HSI appears minimal. The impact of missing studies uniquely available in CINAHL on SR summary or magnitude of effect estimates from meta‐analysis requires further investigation.
Current Status of Weekly Insulin Analogs and Their Pharmacokinetic/Pharmacodynamic Evaluation by the Euglycemic Clamp Technique
Authors: An Na , Wang Xuhong , He Anshun , Chen Wei
Published: July 2023

Diabetes mellitus represents a significant global health threat characterized by hyperglycemia caused by inadequate insulin secretion and/or insulin resistance. Exogenous insulin supplements had been recognized as a crucial treatment for achieving successful glycemic control in patients with Type 1 and most patients with Type 2 diabetes. Over the past century, substantial progress has been made in the development of novel insulin formulations, including the super‐fast‐acting and long‐acting basal insulin analogs, of which the latter is indispensable for the management of nocturnal fasting and intraprandial blood glucose within the normal physiological range. Recently, combining chemical and genetic engineering with drug optimization have resulted in a formidable evolution in ultra‐long‐acting weekly insulin. Here, the current state of once‐weekly insulin analogs and the euglycemic clamp technique used in the early clinical development to elucidate the pharmacokinetics and pharmacodynamics of this type of novel weekly insulin analogs were systematically overviewed.
Isolation of Adult Mouse Cardiac Fibroblasts
Authors: Almazloum Abir , Khalil Hadi
Published: July 2023

Fibroblasts are dynamic cells of mesenchymal origin that regulate tissue homeostasis, extracellular matrix production, and acute wound healing. Fibroblasts respond to tissue injury and inflammation by differentiating into myofibroblasts and secreting extracellular matrix proteins. Fibroblasts are the principal mediators of the fibrotic response in all tissues and organs. Adult primary fibroblasts represent an essential tool for in vitro studies. Although they lack surface markers, fibroblasts are relatively easy to obtain and culture; primary fibroblasts are sensitive heterogeneous cell subpopulations with limited expansion potential and increased differentiation capacity. Adult primary fibroblasts fail to maintain an undifferentiated state ex vivo for long periods and quickly differentiate into myofibroblasts in culture, which necessitates the utilization of these cells either directly after isolation or after a few passages. Herein, we describe a detailed protocol for enzymatic isolation of primary cardiac fibroblasts from adult mouse hearts and their culture and expansion in a serum‐containing culture medium. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol: Preparation of primary adult cardiac fibroblasts for culture and single‐cell analysis
Psychophysiological disorders and the skin
Authors: Carniciu Simona , Jafferany Mohammad
Published: July 2023

The interaction between the mind, skin, and body is well studied lately and many studies focus on the multiple mechanisms between them that affects skin health. From psychology, psychoneuroimmunology, and immunology, to psychophysiological and inflammation, there are many issues to consider for the brain–skin cross‐interaction. Altered balance or activation of the neuroendocrine‐immune system triggers a cascade of events that allow the so‐called fight–flight reaction that influences several skin diseases, as a risk factor for developing a dermatological disease or disease flares. Psychosocial stressors change the responses of neuroactive substances that regulates the immune system. Research focuses on study of several influencers like neuroendocrine mediators (corticotrophin‐releasing factor, substance P, adrenocorticotrophic hormone, glucocorticoids, and catecholamines), pro‐inflammatory cytokines (IFN‐g, IL‐2, IL‐4, IL‐5, IL‐10, IL‐13), the activity of mast cells, NK cells or dendritic cells in the skin. The conditions exacerbated by psychological factors and stress are seborrheic dermatitis, psoriasis, acne, rosacea, atopic dermatitis, urticaria, zona zoster, herpes simplex, neurodermatitis, hyperhidrosis, allodynia.
Urban habitat fragmentation and floral resources shape the occurrence of gut parasites in two bumblebee species
Authors: Tommasi Nicola , Colombo Beatrice , Pioltelli Emiliano , Biella Paolo , Casiraghi Maurizio , Galimberti Andrea
Published: July 2023

Urbanization and the expansion of human activities foster radical ecosystem changes with cascading effects also involving host‐pathogen interactions. Urban pollinator insects face several stressors related to landscape and local scale features such as green habitat loss, fragmentation and availability reduction of floral resources with unpredictable effects on parasite transmission. Furthermore, beekeeping may contribute to the spread of parasites to wild pollinators by increasing the number of parasite hosts. Here we used DNA‐based diagnostics tools to evaluate how the occurrence of parasites, namely microsporidians (Nosema spp.), trypanosomatids (Crithidia spp.) and neogregarines (Apicystis bombi), is shaped by the above‐mentioned stressors in two bumblebee species (i.e. Bombus terrestris and Bombus pascuorum). Infection rates of the two species were different and generally higher in B. terrestris. Moreover, they showed different responses towards the same ecological variables, possibly due to differences in body size and foraging habits supposed to affect their susceptibility to parasite infection. The probability of infection was found to be reduced in B. pascuorum by green habitat fragmentation, while increased along with floral resource availability. Unexpectedly, B. terrestris had a lower parasite richness nearby apiaries maybe due to the fact that parasites are prone to be transmitted among the most abundant species. Our finding supports the need to design proper conservation measures based on species‐specific knowledge, as suggested by the variation in the parasite occurrence of the two species. Moreover, conservation policies aiming at safeguarding pollinators through flower planting should consider the indirect effects of these measures for parasite transmission together with pollinator biodiversity issues.
Tend‐and‐befriend and rally around the flag effects during the COVID‐19 pandemic: Differential longitudinal change patterns in multiple aspects of social cohesion
Authors: Silveira Sarita , Hecht Martin , Voelkle Manuel C. , Singer Tania
Published: July 2023

The COVID‐19 pandemic and its lockdowns have uniquely challenged our social lives. The current study seeks to explore changes in social cohesion on various psychological dimensions (trust, belonging, social interaction, social engagement) and social system levels (family, friends, neighbours, institutions, nations), assessed in 3522 Berlin residents before, during, and after the first lockdown, and four times during the second lockdown. The first lockdown had a consistently negative impact on psychological dimensions of social cohesion. However, the picture was more nuanced regarding social systems: micro‐level cohesion with family members and neighbours, and macro‐level processes of institutional trust and national and international belonging increased, particularly in women. This suggests tend‐and‐befriend tendencies of affiliation, and affirmation of political and national identities. However, social cohesion collapsed during the second lockdown, indicating pandemic fatigue effects. Findings suggest a multidimensional approach to social cohesion and highlight the relevance of stressor duration in times of collective crisis.
Templated insertions—DNA repair gets acrobatic
Authors: Stroik Susanna , Luthman Adam J. , Ramsden Dale A.
Published: July 2023

Deletions associated with the repair of DNA double‐strand breaks is a source of genetic alternation and a recognized source of disease‐causing mutagenesis. Theta‐mediated end joining is a DNA repair mechanism, which guarantees deletions by its employment of microhomology (MH) alignment to facilitate end joining. A lesser‐characterized templated insertion ability of this pathway, on the other hand, is associated with both deletion and insertion. This mechanism is characterized by at least one round of polymerase θ‐mediated synthesis, which does not result in successful repair, followed by a subsequent round of polymerase engagement and synthesis that does lead to repair. Here we focus on the mechanisms by which polymerase θ introduces these insertions—direct, inverse, and a new class which we have termed strand switching. We observe this new class of templated insertions at multiple loci and across multiple species, often at a comparable frequency to those previously characterized. Templated insertion mutations are often enriched in cancer genomes and repeat expansion disorders. This repair mechanism thus contributes to disease‐associated mutagenesis, and may plausibly even promote disease. Characterization of the types of polymerase θ‐dependent insertions can provide new insight into these diseases and clinical promise for treatment.
Modeling the Partitioning of Anionic Carboxylic and Perfluoroalkyl Carboxylic and Sulfonic Acids to Octanol and Membrane Lipid
Authors: Torralba-Sanchez Tifany L. , Di Toro Dominic M. , Dmitrenko Olga , Murillo-Gelvez Jimmy , Tratnyek Paul G.
Published: July 2023

Perfluoroalkyl carboxylic and sulfonic acids (PFCAs and PFSAs, respectively) have low acid dissociation constant values and are, therefore, deprotonated under most experimental and environmental conditions. Hence, the anionic species dominate their partitioning between water and organic phases, including octanol and phospholipid bilayers which are often used as model systems for environmental and biological matrices. However, data for solvent–water (SW) and membrane–water partition coefficients of the anion species are only available for a few per- and polyfluoroalkyl substances (PFAS). In the present study, an equation is derived using a Born-Haber cycle that relates the partition coefficients of the anions to those of the corresponding neutral species. It is shown via a thermodynamic analysis that for carboxylic acids (CAs), PFCAs, and PFSAs, the log of the solvent–water partition coefficient of the anion, log KSW(A−), is linearly related to the log of the solvent–water partition coefficient of the neutral acid, log KSW(HA), with a unity slope and a solvent-dependent but solute-independent intercept within a PFAS (or CA) family. This finding provides a method for estimating the partition coefficients of PFCAs and PFSAs anions using the partition coefficients of the neutral species, which can be reliably predicted using quantum chemical methods. In addition, we have found that the neutral octanol–water partition coefficient, log KOW, is linearly correlated to the neutral membrane–water partition coefficient, log KMW; therefore, log KOW, being a much easier property to estimate and/or measure, can be used to predict the neutral log KMW. Application of this approach to KOW and KMW for PFCAs and PFSAs demonstrates the utility of this methodology for evaluating reported experimental data and extending anion property data for chain lengths that are unavailable. Environ Toxicol Chem 2023;42:2317–2328. © 2023 SETAC
Bioinspired gradient scaffolds for osteochondral tissue engineering
Authors: Peng Yachen , Zhuang Yaling , Liu Yang , Le Hanxiang , Li Di , Zhang Mingran , Liu Kai , Zhang Yanbo , Zuo Jianlin , Ding Jianxun
Published: July 2023

Repairing articular osteochondral defects present considerable challenges in self‐repair due to the complex tissue structure and low proliferation of chondrocytes. Conventional clinical therapies have not shown significant efficacy, including microfracture, autologous/allograft osteochondral transplantation, and cell‐based techniques. Therefore, tissue engineering has been widely explored in repairing osteochondral defects by leveraging the natural regenerative potential of biomaterials to control cell functions. However, osteochondral tissue is a gradient structure with a smooth transition from the cartilage to subchondral bone, involving changes in chondrocyte morphologies and phenotypes, extracellular matrix components, collagen type and orientation, and cytokines. Bioinspired scaffolds have been developed by simulating gradient characteristics in heterogeneous tissues, such as the pores, components, and osteochondrogenesis‐inducing factors, to satisfy the anisotropic features of osteochondral matrices. Bioinspired gradient scaffolds repair osteochondral defects by altering the microenvironments of cell growth to induce osteochondrogenesis and promote the formation of osteochondral interfaces compared with homogeneous scaffolds. This review outlines the meaningful strategies for repairing osteochondral defects by tissue engineering based on gradient scaffolds and predicts the pros and cons of prospective translation into clinical practice.
Karyotype diversity in four Terminalia L. species and its taxonomic implications
Authors: Akter Suma , Dash Chandan Kumar , Sultana Syeda Sharmeen
Published: July 2023

Four Terminalia L. species namely, T. arjuna (Roxb.) Wight and Arn., T. bellirica (Gaertn.) Roxb., T. chebula Retz. and T. catappa L. were studied to evaluate the chromosomal relationship corresponding with their taxonomic characters. Analysis of mitotic metaphases showed that the somatic chromosome numbers and the centromeric formulas of these species were 2n = 24 (16m + 8sm) for T. arjuna, 2n = 48 (36m + 12sm) for T. bellirica, 2n = 48 (46m + 2sm) for T. chebula and 2n = 24 (24m) for T. catappa. Two pairs of satellites were found in T. bellirica and T. catappa. Based on different karyological data, T. chebula was positioned in 1A, T. arjuna and T. catappa in 1B and T. bellirica in 2B. Based on comparative karyomorphological data, T. bellirica and T. arjuna presented more advanced features in comparison with T. chebula and T. catappa, which also correlated with the taxonomic characters in respect of the evolutionary point of view. Therefore, the present investigation effectively evaluated chromosomal relationships with morphological implications that conferred upon evolutionary changes among these four Terminalia species.
Surgery‐ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region gain clinical benefit from definitive weekly hypofractionated radiotherapy
Authors: De Felice Francesca , Serpone Maria , Cattaneo Carlo Guglielmo , Di Giammarco Federico , Fallico Alberto , Delle Donne Alessia , Lanzilao Maura , Vitti Elisa , Marampon Francesco , Musio Daniela , Tombolini Vincenzo , Minniti Giuseppe
Published: July 2023

Background

To evaluate the role of definitive weekly hypofractionated radiotherapy (RT) for the treatment of surgery‐ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region (cHNSCC).

Methods

Eligible elderly patients (aged ≥75 years) with cHNSCC were included. Patients received definitive weekly hypofractionated RT, using megavoltage electrons, to a total dose of 56–64 Gy (8 Gy per fraction). Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression‐free survival (PFS), overall survival (OS), pain response, tolerability, and safety.

Results

A total of 19 patients with 27 lesions were included and treated with definitive weekly hypofractionated RT. All patients received the prescribed total dose. ORR was 92.6%, including 70.4% of lesions with a CR and 22.2% with a PR. Median DOR was 12 months. No severe toxicity occurred.

Conclusions

Our study confirmed the satisfying efficacy and acceptable toxicity of definitive weekly hypofractionated RT for cHNSCC in elderly patients. Our results establish weekly hypofractionated scheduleas a promising treatment option for elderly patients with cHNSCC.
Sparse wavelengths data in mid‐infrared spectroscopy: Modelling approaches and channel sampling
Authors: Aledda Miriam , Kohler Achim , Zimmermann Boris , Patel Nageshvar , Shapaval Volha , Tafintseva Valeria
Published: July 2023

Infrared instruments with smaller and cost‐effective components such as bandpass filters, single channel detectors, and laser‐based light sources are being developed to provide cheaper and faster analysis of biological samples. Such instruments often provide measurements in form of sparse data, which include a collection of single‐frequency channels or a collection of channels covering very narrow spectral ranges, called here multi‐frequency channels. To keep costs low, the number of channels needs to be kept at a minimum. However, modelling and preprocessing of sparse data needs enough channels to perform the task. The aim of this study therefore was to understand the effect of channels sampling on data modelling results and find optimal modelling algorithm for different type of sparse data. The sparse data was simulated using Fourier Transform Infrared spectra of milk and fungi. Regression models were established to predict fatty acid composition by partial least squares regression (PLSR), multiple linear regression (MLR) and random forest (RF) methods. We observe that PLSR algorithm is very well suited for sparse data such as multi‐frequency channels: excellent calibration models were obtained with only three channels comprising three wavenumbers each. The results were comparable to results obtained with full spectra. MLR and RF in turn provided similarly good results using data with single‐frequency channels requiring nine channels in total.
Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease
Authors: Chatrenet Antoine , Piccoli Giorgina , Audebrand Jean Michel , Torreggiani Massimo , Barbieux Julien , Vaillant Charly , Morel Baptiste , Durand Sylvain , Beaune Bruno
Published: July 2023

Background

Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients.

Methods

Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m2, age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50, RFD75, RFD100, RFD150 and RFD200, respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time‐to‐peak RFD (t‐RFDpeak) and the relative force at RFDpeak (MVF‐RFDpeak). A statistical parametric mapping approach was performed on the force, impulse and RFD–time curves. The integrated sEMG with time at 0–30, 0–50, 0–100 and 0–200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex.

Results

The cohort of 159 individuals had a median age of 69 (9IQR) years and body mass index was 27.6 (6.2IQR) kg/m2. Propensity‐score‐matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2p = 0.034) and RFD75 and RFD100 (for both P < 0.001; η2p = 0.068 and 0.064). The one‐dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0–100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0–200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 0.421) time windows. Controls showed greater decrease of sEMG than CKD patients in the 0–30 ms (P = 0.020, Cohen's d = 0.533) and 0–50 ms (P = 0.010, Cohen's d = 0.640) time windows. As opposite to females, males showed almost the same differences between groups.

Conclusions

Our study is the first to show that CKD patients have higher fatigability than controls, which may be associated with an impaired motor‐unit recruitment, highlighting a neural drive disturbance with CKD. Further studies are needed to confirm these findings.
Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38‐MAPK/FoxO3 pathway in cancer cachexia
Authors: Zhang Ruiqin , Shen Qiang , Wang Yueping , Deng Xue , Fan Jialing , Gu Xiaofan , Fan Meng , Wei Kun , Cheng Chun‐Ru , Zhang Wei‐Dong , Zhang Xiong‐wen , Liu Xuan
Published: July 2023

Background

Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone‐induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms.

Methods

C26 tumour‐bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF‐α‐induced C2C12 myotubes or ad‐mRFP‐GFP‐LC3B‐transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy‐lysosome system. The possible direct targets of CYA were searched using the biotin‐streptavidin pull‐down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay.

Results

The administration of CYA prevented body weight loss and muscle wasting in C26 tumour‐bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P < 0.05. The values of gastrocnemius muscle weight/body weight of mice treated with 15 or 30 mg/kg CYA (0.53 ± 0.02% and 0.54 ± 0.01%, respectively) were both significantly higher than that of the C26 model group (0.45 ± 0.01%) with P < 0.01. CYA decreased both UPS‐mediated protein degradation and autophagy in muscle tissues of C26 tumour‐bearing mice as well as in C2C12 myotubes treated with TNF‐α. The thousand‐and‐one amino acid kinase 1 (TAOK1) was found to be the direct binding target of CYA. CYA inhibited the activation of TAOK1 and its downstream p38‐MAPK pathway thus decreased the level and nuclear location of FoxO3. siRNA knockdown of TAOK1 or regulation of the p38‐MAPK pathway using activator or inhibitor could affect the ameliorating effects of CYA on myotube atrophy.

Conclusions

CYA ameliorates cancer cachexia muscle atrophy by decreasing both UPS degradation and autophagy. The ameliorating effects of CYA on muscle atrophy might be based on its binding with TAOK1 and inhibiting the TAOK1/p38‐MAPK/FoxO3 pathway.
Nipple properties affect sensorimotor integration during bottle feeding in an infant pig model
Authors: Johnson Maxwell L. , Steer Kendall E. , Edmonds Chloe E. , Adjerid Khaled , German Rebecca Z. , Mayerl Christopher J.
Published: July 2023

Infant feeding is a critical neurological milestone in development defined by the coordination of muscles, peripheral nerves, and brainstem nuclei. In infants, milk flow rate is often limited to improve feeding performance without treating the underlying deficiencies in the sucking and swallowing processes. Modification of the neuromotor response via sensory information from the nipple during bottle feeding is an unexplored avenue for physiology‐based interventions. In this study, we assessed how differences in nipple hole size and nipple stiffness affect sucking muscle activation and subsequent movement. We fabricated four bottle nipples of varying hole size and stiffness to determine how variation in nipple properties affects the sucking behavior of infant pigs. Our results demonstrate that sensory information from the nipple affects sucking motor output. Nipple hole sizes and stiffnesses with a larger milk flow rate resulted in greater muscle activity and kinematic movement. Additionally, our results suggest that sensorimotor interventions are better directed toward modulating tongue function rather than the mandible movements due to a greater response to sensory information. Understanding how sensory information influences infant feeding is instrumental in promoting effective infant feeding.
Securing accelerated access to long‐acting injectable cabotegravir for HIV prevention in low‐ and middle‐income countries
Authors: Jenkins Sarah Y. , Resar Danielle , Panos Zachary , Staple Alan , Watkins Melynda , Ripin David , Amole Carolyn
Published: July 2023

Introduction

Reductions in HIV acquisition have slowed, and the global community is significantly off track from global goals. Oral pre‐exposure prophylaxis (PrEP) alone cannot address the diverse needs of the millions of people at risk of HIV acquisition. Long‐acting injectable cabotegravir (CAB‐LA) received United States Food and Drug Administration approval for HIV prevention in December 2021. When studied, CAB‐LA demonstrated high effectiveness, provides months of protection versus daily use, is preferred by some users and has the potential to achieve commodity cost reduction. These factors position CAB‐LA to catalyse transformation in HIV prevention. Significant work must be undertaken to ensure at‐scale uptake in low‐ and middle‐income countries. Leveraging decades of product introduction experience, Clinton Health Access Initiative (CHAI) has developed an innovative roadmap to support equitable CAB‐LA introduction, comprising tightly executed market‐shaping, product development, regulatory, and programmatic and implementation action.

Discussion

Proven models exist (e.g. long‐acting reversible contraceptives, paediatric tuberculosis treatment and antiretrovirals (ARVs), such as paediatric dolutegravir and tenofovir disoproxil fumarate, lamivudine, and dolutegravir) for partnership‐driven, accelerated, impactful product introduction. Based on learnings from these models and needs in the prevention space, CHAI developed a roadmap to maximize the near‐term impact of CAB‐LA and accelerate the development of, access to and impact of quality‐assured, low‐cost generic CAB‐LA. This roadmap is intended to inform introduction planning and investment decision‐making across a range of stakeholders, including donors, governments, manufacturers and other partners working in the HIV prevention space. Elements include (1) ensuring coordination and alignment across partners, and avoiding redundancy experienced during oral PrEP introduction; (2) preparing national programmes and providing support to maximize impact, including the development of national policies, guidelines and introduction plans; system strengthening; quantification and procurement; and addressing evidence needs, among other areas; (3) supporting community engagement, ensuring that demand generation and delivery approaches are person‐centred and community‐led; (4) incentivizing generic product development through, for example, milestone‐based commercialization incentives and product development cost‐sharing; and (5) expediting regulatory reviews.

Conclusions

Accelerating access to affordable, generic CAB‐LA can transform progress towards HIV epidemic control. This vision of impact at scale in prevention is achievable, if informed by results‐backed approaches to introduction.
Comparative studies on physicochemical properties of three potato varieties different in RS2 and RS3 contents
Authors: Zhang Siyan , Cheng Linrun , Gong Wanxin , Huang Jie , Peng Zhangchi , Meng Kaiwei , Zhang Liang , Shu Xiaoli , Wu Dianxing
Published: July 2023

BACKGROUND

At present, increasing importance has been attracted to healthy food enriched in resistant starch (RS), which has great benefits in health‐promoting. Raw potato has rich RS2, whereas most RS2 may become digestible after gelatinization, resulting in few RS being left in processed potato. Breeding potatoes with high RS2 or RS3 or both can meet the demand for various healthy potato products.

RESULTS

There were apparent discrepancies among three potatoes with contrast RS2 and RS3 content in thermal properties, viscosity and digestibility. ZS‐5 had the highest RS2 with 50.17% but the lowest RS3 with 3.31%. Meanwhile, ZS‐5 had the largest starch granule, the highest proportion of B3, viscosity and hardness, and the highest digestibility. DN303 with the highest content of RS3 (5.08%) had the lowest hardness and fracturability. MG56‐42 with both higher RS2 and RS3 content showed the highest resistance to digestion and moderate hardness and fracturability.

CONCLUSION

The present study enriches the potential resources and provides a reliable scientific basis for high RS potatoes breeding. The various features of different potatoes make it possible to screen potatoes according to different demands. © 2023 Society of Chemical Industry.