bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiretroviral drug exposure in lymph nodes is heterogeneous and drug dependent
Authors: Rosen Elias P. , Deleage Claire , White Nicole , Sykes Craig , Brands Catherine , Adamson Lourdes , Luciw Paul , Estes Jacob D. , Kashuba Angela D. M.
Published: April 2022

Introduction

HIV reservoirs and infected cells may persist in tissues with low concentrations of antiretrovirals (ARVs). Traditional pharmacology methods cannot assess variability in ARV concentrations within morphologically complex tissues, such as lymph nodes (LNs). We evaluated the distribution of six ARVs into LNs and the proximity of these ARVs to CD4+ T cells and cell‐associated RT‐SHIV viral RNA.

Methods

Between December 2014 and April 2017, RT‐SHIV infected (SHIV+; N = 6) and healthy (SHIV–; N = 6) male rhesus macaques received two selected four‐drug combinations of six ARVs over 10 days to attain steady‐state conditions. Serial cryosections of axillary LN were analysed by a multimodal imaging approach that combined mass spectrometry imaging (MSI) for ARV disposition, RNAscope in situ hybridization for viral RNA (vRNA) and immunohistochemistry for CD4+ T cell and collagen expression. Spatial relationships across these four imaging domains were investigated by nearest neighbour search on co‐registered images using MATLAB.

Results

Through MSI, ARV‐dependent, heterogeneous concentrations were observed in different morphological LN regions, such as the follicles and medullary sinuses. After 5–6 weeks of infection, more limited ARV penetration into LN tissue relative to the blood marker heme was found in SHIV+ animals (SHIV+: 0.7 [0.2–1.4] mm; SHIV–: 1.3 [0.5–1.7] mm), suggesting alterations in the microcirculation. However, we found no detectable increase in collagen deposition. Regimen‐wide maps of composite ARV distribution indicated that up to 27% of SHIV+ LN tissue area was not exposed to detectable ARVs. Regions associated with B cell follicles had median 1.15 [0.94–2.69] ‐fold reduction in areas with measurable drug, though differences were only statistically significant for tenofovir (p = 0.03). Median co‐localization of drug with CD4+ target cells and vRNA varied widely by ARV (5.1–100%), but nearest neighbour analysis indicated that up to 10% of target cells and cell‐associated vRNA were not directly contiguous to at least one drug at concentrations greater than the IC50 value.

Conclusions

Our investigation of the spatial distributions of drug, virus and target cells underscores the influence of location and microenvironment within LN, where a small population of T cells may remain vulnerable to infection and low‐level viral replication during suppressive ART.
Identification of illicit street drugs with swept‐source Raman spectroscopy
Authors: Kay Kemberly X. E. , Atabaki Amir H. , Ng Wei Bo , Li Zheng , Singh Gajendra P. , Tan Stella W. L. , Ram Rajeev J.
Published: April 2022

The identification of the illicit substances in low‐purity seized drugs with Raman spectroscopy is an outstanding problem. The low concentration of the target molecule demands high sensitivity and the presence of impurities produces a strong fluorescence background that makes identification challenging. Although Raman analyzers with 785 and 830 nm excitation wavelengths provide high sensitivity, the longer 1064 nm wavelength produces lower fluorescence. In this work, we demonstrate a Raman spectrometer that simultaneously achieves both high sensitivity and low background fluorescence. We utilize swept‐source Raman spectroscopy in which the spectrometer is replaced by a single high‐collection spectral channel, and the Raman spectrum is swept using a tunable laser. By eliminating the spectrometer and its slit, the optical throughput and sensitivity are improved. Moreover, our swept‐source system requires a single uncooled silicon photodiode that provides higher quantum efficiency at longer wavelengths compared with CCDs. This allowed us to use excitation wavelengths in the 900 nm range to reduce background fluorescence without sacrificing sensitivity. We have demonstrated 6x background fluorescence reduction in colored seized drugs compared with 830 nm excitation. With lower background fluorescence and high sensitivity, we could identify heroin with only 1% purity in a seized sample. Besides forensics and security, the demonstrated swept‐source Raman spectroscopy approach can be a powerful technique in biomedical applications where strong background fluorescence limits detection capabilities.
Peanut skin procyanidins ameliorate insulin resistance via modulation of gut microbiota and gut barrier in type 2 diabetic mice
Authors: Liu Min , Huang Bijun , Wang Li , Lu Qun , Liu Rui
Published: April 2022

BACKGROUND

Peanut skin procyanidins (PSP) have been shown to possess antidiabetic activities. However, the mechanism remains poorly understood due to its low bioavailability. This study aims to investigate the preventive effect of PSP on type 2 diabetes (T2D) in mice through regulating gut microbiota and gut barrier in mice with streptozotocin (STZ)‐induced T2D. During the 30 consecutive days of the study, T2D mice were administered PSP intragastrically at 75, 150 and 300 mg kg−1 body weight d−1.

RESULTS

PSP treatment obviously alleviated glucolipid metabolism disorders, decreased the levels of lipopolysaccharide (LPS), interleukin (IL)‐6 and myeloperoxidase(MPO), and increased that of IL‐10. PSP treatment enhanced the abundance of Lachnospiraceae_NK4A136_group, Alloprevotella, Akkermansia and Faecalibaculum, and reduced that of Muribaculaceae. Some of these were associated with the production of short‐chain fatty acids and anti‐inflammatory effect, suggesting their important roles in T2D mice. More importantly, PSP improved the gut barrier integrality by restoring gut morphology and enhancing tight junction protein expression including ZO1, claudin1 and occludin in colon. Subsequently, PSP ameliorated insulin resistance by decreasing the LPS/Toll‐like receptor 4/c‐Jun N‐terminal kinase inflammatory response, and enhancing insulin receptor substrate 1/ phosphatidylinositol‐3‐kinase/protein kinase B insulin signaling pathways in the liver.

CONCLUSION

Peanut skin procyanidins may alleviate the symptoms of T2D by mitigating inflammatory response, modulating gut microbiota and improving intestinal integrity. © 2022 Society of Chemical Industry.
A Systematic Review of Eustachian Tube Procedures for Baro‐challenge Eustachian Tube Dysfunction
Authors: Raymond Mallory J. , Shih Michael C. , Elvis Phillip Ryan , Nguyen Shaun A. , Brennan Emily , Meyer Ted A. , Lambert Paul R.
Published: April 2022

Objective

To examine the effectiveness of Eustachian tube procedures for the treatment of baro‐challenge Eustachian tube dysfunction.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, databases, including PubMed (National Library of Medicine, National Institutes of Health), Scopus (Elsevier), and CINAHL (EBSCO), were searched for articles examining the effectiveness of Eustachian tube procedures for baro‐challenge Eustachian tube dysfunction. Outcome measures included symptom resolution, ability to return to work, equalization problems (EP) scores, Eustachian Tube Dysfunction Questionnaire (ETDQ‐7) scores, and pressure chamber testing parameters. Pooled meta‐analysis was performed for dichotomous measures and ETDQ‐7 scores.

Results

Eleven articles with 81 patients were included. Seventy‐two patients from 10 articles underwent balloon Eustachian tube dilation; nine patients in 1 study underwent laser Eustachian tuboplasty (LET). All 81 patients were preoperatively symptomatic with barometric pressure change, and 26/30 (86.7%) were unable to work due to symptoms. On meta‐analysis, after balloon dilation Eustachian tuboplasty (BDET), 82.5% (n = 30 [95% confidence interval: 42%–100%]) had improvement in ability to valsalva, 79.1% (n = 16 [57.9%–94.1%]) in ability to return to work, and 84.3% (n = 69 [69.8%–94.7%]) in any symptom. Of 25 patients with individual ETDQ‐7 scores, 79.1% [51.4, 96.9] had improvements after BDET. For four case series with 36 patients, ETDQ‐7 scores decreased by 1.2 [0.7, 1.7] (p < 0.00001). Of 20 patients with preoperative ETDQ‐7 scores >2.0, there was a mean decrease of 2.1 [1.3, 2.8] (p < 0.00001).

Conclusion

From the available evidence, Eustachian tube procedures appear to be effective at improving symptoms of baro‐challenge Eustachian tube dysfunction. However, higher quality evidence is needed to support making definite recommendations for the use of balloon Eustachian tube dilation or LET for these patients. Laryngoscope, 132:2473–2483, 2022
The Birth of Fluorescence from Thermally Polymerized Glycine
Authors: Cossu Franca Lucia , Poddighe Matteo , Stagi Luigi , Anedda Roberto , Innocenzi Plinio
Published: April 2022

Thermal polymerization of glycine, the simplest amino acid bearing only one alfa carbon atom, is not an efficient process in mild conditions. Hydrothermal processing of glycine produces only small peptides, up to four units on average, with only a fraction of glycine that reacts. In the present work, boric acid is used as a catalyst to promote the formation of glycine polypeptides. The final product is characterized by an extended polymeric structure and an intense blue fluorescence characterizes the final product. A comparison with glycine reacted in hydrothermal conditions without the catalyst shows that boric acid plays a primary role in promoting the amidation reactions. The structure of the glycine polymers has been investigated by nuclear magnetic resonance, Fourier transform infrared and Raman spectroscopies, and the optical properties by UV–vis and fluorescence spectroscopies. The full reaction of glycine promoted by boric acid catalysis produces a disordered structure with loss of molecular conformations and blue emission.
Assessment of tissue toxicity risk in breast radiotherapy using Bayesian networks
Authors: Ciunkiewicz Philip , Roumeliotis Michael , Stenhouse Kailyn , McGeachy Philip , Quirk Sarah , Grendarova Petra , Yanushkevich Svetlana
Published: April 2022

Purpose

The purpose of this analysis is to predict worsening post‐treatment normal tissue toxicity in patients undergoing accelerated partial breast irradiation (APBI) therapy and to quantitatively identify which diagnostic, anatomical, and dosimetric features are contributing to these outcomes.

Methods

A retrospective study of APBI treatments was performed using 32 features pertaining to various stages of the patient's treatment journey. These features were used to inform and construct a Bayesian network (BN) based on both statistical analysis of feature distributions and relative clinical importance. The target feature for prediction was defined as a measurable worsening of telangiectasia, subcutaneous tissue induration, or fibrosis when compared against the observed baseline. Parameter learning for the network was performed using data from the 299 patients included in the ACCEL trial and predictive performance was measured. Feature importance for the BN was quantified using a novel information‐theoretic approach.

Results

Cross‐validated performance of the BN for predicting toxicity was consistently higher when compared against conventional machine learning (ML) techniques. The measured BN receiver operating characteristic area under the curve was 0.9600.013 against the best ML result of 0.9420.021 using five‐fold cross‐validation with separate test data across 100 trials. The volume of the clinical target volume, gross target volume, and baseline toxicity measurements were found to have the highest feature importance and mutual dependence with normal tissue toxicity in the network, representing the strongest contribution to patient outcomes.

Conclusions

The BN outperformed conventional ML techniques in predicting tissue toxicity outcomes and provided deeper insight into which features are contributing to these outcomes.
Determination of the ion collection efficiency of the Razor Nano Chamber for ultra‐high dose‐rate electron beams
Authors: Cavallone Marco , Gonçalves Jorge Patrik , Moeckli Raphaël , Bailat Claude , Flacco Alessandro , Prezado Yolanda , Delorme Rachel
Published: April 2022

Background

Ultra‐high dose‐rate (UHDR) irradiations (>40 Gy/s) have recently garnered interest in radiotherapy (RT) as they can trigger the so‐called “FLASH” effect, namely a higher tolerance of normal tissues in comparison with conventional dose rates when a sufficiently high dose is delivered to the tissue. To transfer this to clinical RT treatments, adapted methods and practical tools for online dosimetry need to be developed. Ionization chambers remain the gold standards in RT but the charge recombination effects may be very significant at such high dose rates, limiting the use of some of these dosimeters. The reduction of the sensitive volume size can be an interesting characteristic to reduce such effects.

Purpose

In that context, we have investigated the charge collection behavior of the recent IBA Razor™ Nano Chamber (RNC) in UHDR pulses to evaluate its potential interest for FLASH RT.

Methods

In order to quantify the RNC ion collection efficiency (ICE), simultaneous dose measurements were performed under UHDR electron beams with dose‐rate‐independent Gafchromic™ EBT3 films that were used as the dose reference. A dose‐per‐pulse range from 0.01 to 30 Gy was investigated, varying the source‐to‐surface distance, the pulse duration (1 and 3 μs investigated) and the LINAC gun grid tension as irradiation parameters. In addition, the RNC measurements were corrected from the inherent beam shot‐to‐shot variations using an independent current transformer. An empirical logistic model was used to fit the RNC collection efficiency measurements and the results were compared with the Advanced Markus plane parallel ion chamber.

Results

The RNC ICE was found to decrease as the dose‐per‐pulse increases, starting from doses above 0.2 Gy/pulse and down to 40% of efficiency at 30 Gy/pulse. The RNC resulted in a higher ICE for a given dose‐per‐pulse in comparison with the Markus chamber, with a measured efficiency found higher than 85 and 55% for 1 and 10 Gy/pulse, respectively, whereas the Markus ICE was of 60 and 25% for the same doses. However, the RNC shows a higher sensitivity to the pulse duration than the Advanced Markus chamber, with a lower efficiency found at 1 μs than at 3 μs, suggesting that this chamber could be more sensitive to the dose rate within the pulse.

Conclusions

The results confirmed that the small sensitive volume of the RNC ensures higher ICE compared with larger chambers. The RNC was thus found to be a promising online dosimetry tool for FLASH RT and we proposed an ion recombination model to correct its response up to extreme dose‐per‐pulses of 30 Gy.
A comparative investigation between the beam spring method and the modified routine method in special‐section shield tunnels: A case study for quasi‐rectangular tunnels
Authors: Zhang Weixi , De Corte Wouter , Liu Xian , Taerwe Luc
Published: April 2022

The modified routine modelling (MRM) and the beam spring modelling (BSM) are two of the classical design methods for circular shield tunnels, but a comparison between their applications in special‐section shield tunnels (SSSTs) has not yet been conducted. In this study, these two methods are investigated and compared specifically for the case of quasi‐rectangular shield tunnels (QRSTs). While the MRM gives acceptable results for axial force values, some critical bending moments in joint sections and segment sections can be overestimated or underestimated, not giving accurate values for design. It is demonstrated that the MRM cannot precisely predict the degree of bending moment transfer and convergence deformations of the studied SSST, and should only be used in preliminary design. On the other hand, deeper insights into the mechanical behaviour of the QRST lining structure can be gained through the analysis of the BSM. The staggered assembly pattern results in a bending moment transfer between rings and the relatively stiff area sustains the transferred moment from its neighbouring less stiff areas. For most of the longitudinal joints, 20% to 40% of bending moment is redistributed to its neighbouring segments. The transfer increases the non‐symmetric distribution of bending moments in the two halves of a QRST lining ring. This characteristic does not exist in a traditional circular shield tunnel but needs due attention to the types of shield tunnels with two compartments in one tube. Finally, the influences of different parameters related to the assumed pressures and soil reactions are discussed.
MXenes: An emergent materials for packaging platforms and looking beyond
Authors: Zhou Xing , Hao Yaya , Li Yaxin , Peng Jiahe , Wang Guosheng , Ong Wee‐Jun , Li Neng
Published: April 2022

MXenes have been employed as two‐dimensional (2D) nanostructured fillers in polymers matrix to design composites, which have tailored multi‐functional properties with great potential applications in catalysis, sensor, energy storage, membrane and biomedicine areas. Analogous to 2D materials such as graphene and hexagonal boron nitrides, MXenes serve as robust support to expand a significant pathway to prepare composites. This paper outlines an overview of the recent development of MXenes and MXenes‐based composites decorated by functional properties that potentially hold a promise on the packaging applications. A particular emphasis is to illustrate the essential properties of MXenes/polymer membrane intended food packaging such as barrier and antibacterial properties, biocompatibility and thermal stability. Furthermore, the progress and emergent values are presented in the perspective of instrumentation packaging that broadens prospects for antistatic, electromagnetic shielding and invisibility purposes. As a whole, this review promotes an emerging field to formulate the good ingredient of food packaging and safety to produce green and versatile membranes with high barrier performance. Finally, challenges and insightful perspectives for the application of MXenes in the packaging area are elucidated.
Molecular dynamics inferred transfer learning models for finite‐strain hyperelasticity of monoclinic crystals: Sobolev training and validations against physical constraints
Authors: Vlassis Nikolaos N. , Zhao Puhan , Ma Ran , Sewell Tommy , Sun WaiChing
Published: April 2022

We present a machine learning framework to train and validate neural networks to predict the anisotropic elastic response of a monoclinic organic molecular crystal known as ‐HMX in the geometrical nonlinear regime. A filtered molecular dynamic (MD) simulations database is used to train neural networks with a Sobolev norm that uses the stress measure and a reference configuration to deduce the elastic stored free energy functional. To improve the accuracy of the elasticity tangent predictions originating from the learned stored free energy, a transfer learning technique is used to introduce additional tangential constraints from the data while necessary conditions (e.g., strong ellipticity, crystallographic symmetry) for the correctness of the model are either introduced as additional physical constraints or incorporated in the validation tests. Assessment of the neural networks is based on (1) the accuracy with which they reproduce the bottom‐line constitutive responses predicted by MD, (2) the robustness of the models measured by detailed examination of their stability and uniqueness, and (3) the admissibility of the predicted responses with respect to mechanics principles in the finite‐deformation regime. We compare the training efficiency of the neural networks under different Sobolev constraints and assess the accuracy and robustness of the models against MD benchmarks for ‐HMX.
Long‐term results from the multicentric European randomized phase 3 trial CWS/RMS‐96 for localized high‐risk soft tissue sarcoma in children, adolescents, and young adults
Authors: Sparber‐Sauer Monika , Ferrari Andrea , Kosztyla Daniel , Ladenstein Ruth , Cecchetto Giovanni , Kazanowska Bernarda , Scarzello Giovanni , Ljungman Gustaf , Milano Giuseppe Maria , Niggli Felix , Alaggio Rita , Vokuhl Christian , Casanova Michela , Klingebiel Thomas , Zin Angelica , Koscielniak Ewa , Bisogno Gianni
Published: April 2022

Background: CWS/RMS‐96 was an international multicenter trial with randomization between two therapy arms of the standard four‐drug therapy (vincristine, ifosfamide, adriamycin, dactinomycin [VAIA]) versus an intensified six‐drug regimen (carboplatin, epirubicin, vincristine, dactinomycin, ifosfamide, and etoposide [CEVAIE]) for high‐risk rhabdomyosarcoma (RMS), extraskeletal Ewing sarcoma (EES), and undifferentiated sarcoma (UDS) in children, adolescents, and young adults aiming to improve their survival. Intensified chemotherapy with CEVAIE did not improve outcome.

Methods: Patients younger than 21 years with a previously untreated localized HR‐RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 × 21 days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32–44.8 Gy) was added at week 9–12 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event‐free (EFS) and overall survival (OS).

Results: Five hundred fifty‐seven patients (HR‐RMS:n = 416, EES and UDS:n = 141) underwent randomization: VAIA (n = 273) or CEVAIE (n = 284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5‐year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% (p = .89), and 74.2% and 68.3% (p = .16), respectively. No differences in response, toxicity, or second malignancies emerged in the two groups.

Conclusion: The use of an intensified regimen failed to show a significant improvement in tumor response and outcome of patients with localized HR‐RMS, EES, and UDS.
Expression of neuroblastoma‐related genes in bone marrow at end of high‐risk neuroblastoma therapy
Authors: Asgharzadeh Shahab , Marachelian Araz , Villablanca Judith G. , Liu Wei Yao , Kennedy Rebekah , Sposto Richard , Naranjo Arlene , Tenney Sheena , Yu Alice L. , Ozkaynak M. Fevzi , Sondel Paul M. , Park Julie R. , Seeger Robert C.
Published: April 2022

Background

Minimal disease quantification may predict event‐free survival (EFS) and overall survival (OS).

Methods

We evaluated mRNA expression of five neuroblastoma‐associated genes (NB5 assay) in bone marrows (BM) of patients with newly diagnosed high‐risk neuroblastoma who received consistent immunotherapy. mRNA expression of CHGA, DCX, DDC, PHOX2B, and TH genes in BM of 479 patients enrolled on the immunotherapy arm of Children's Oncology Group trials ANBL0032 and ANBL0931 was evaluated using real‐time polymerase chain reaction (PCR)‐based TaqMan low‐density array. Results from end‐consolidation and end‐therapy were analyzed for association with five‐year EFS/OS and patient and tumor characteristics. Tests of statistical significance were two‐sided.

Results

NB5 assay detected neuroblastoma‐related mRNA in 222 of 286 (77.6%) of BMs obtained at end‐consolidation and 188 of 304 (61.8%) at end‐therapy. Any mRNA level detected in end‐therapy BM correlated with significantly worse EFS (57% [49.6%‐63.7%] vs 73.0% [63.5%‐80.4%]; P = 0.005), but not OS. Analysis limited to patients in complete response at end‐therapy still found a significant difference in EFS with detectable versus not detectable NB5 assay results (58.9% [49.5%‐67.1%] vs 76.6% [66.1%‐84.2%]; P = 0.01). End‐consolidation results did not correlate with EFS or OS. Multivariable analysis determined end‐therapy NB5 assay BM results (P = 0.02), age at diagnosis (P = 0.002), and preconsolidation response (P = 0.02) were significantly associated with EFS independent of other clinical and biological parameters evaluated, including end‐therapy response.

Conclusions

If further validated in additional patient cohorts, the NB5 assay's ability to independently predict EFS from end‐therapy could improve patient stratification for novel maintenance therapy trials after current end‐therapy to improve outcome.
Dasatinib‐therapy induced sustained remission in a child with refractory TCF7‐SPI1 T‐cell acute lymphoblastic leukemia
Authors: He Yingyi , Zhang Jingliao , Zhang Yingchi , Hu Zhengbin , Wang Pengfei , Gan Wenting , Xie Shao , Qian Maoxiang , Pui Ching‐Hon , Jiang Hua , Zhu Xiaofan , Zhang Hui , Zhang Weina
Published: April 2022

The prognosis of patients with T‐cell acute lymphoblastic leukemia (T‐ALL) has been largely lacked behind than that of patients with B‐cell ALL, especially in refractory or relapsed cases. Here, we describe a 4.7‐year‐old male child with TCF‐SPI1‐postitve T‐ALL who developed refractoriness disease after a seven drugs‐conventional therapy. Several studies have suggested the therapeutic potential of dasatinib in refractory T‐ALL. Actually, dasatinib‐included therapy dramatically reduces the leukemic burden and re‐induces this patient into complete remission without systemic adverse events. Although this is a single exceptional case, the translational potential evidence of dasatinib in specific T‐ALL subtype should not be under‐estimated.
Influence of stacking sequence on flax/kevlar hybrid epoxy composites: Mechanical and morphological studies
Authors: Kangokar Mukesh Sathvik , Bettagowda Nuthan , Praveenkumara Jagadeesh , Thyavihalli Girijappa Yashas Gowda , Puttegowda Madhu , Mavinkere Rangappa Sanjay , Siengchin Suchart , Gorbatyuk Sergey
Published: April 2022

In this research work, the natural fiber reinforced hybrid epoxy composites were fabricated using the hand lay‐up method. The flax and kevlar are used as a reinforcement and epoxy as a binding material. This study aims to analyze the influence of stacking sequence and hybridization on the mechanical, water absorption, and morphological properties of polymer composites. The results reveal that the neat kevlar reinforced composite achieved a maximum tensile strength, modulus, and impact strength of 189.94 MPa, 2345.35 MPa and 37.16 kJ/m2 respectively with less water absorption behavior. Whereas, the hybrid composite with kevlar as an outer layers and flax as core layers was exhibited a maximum flexural strength, modulus, and inter laminar shear strength of 360.76, 37124.2, and 213.51 MPa, respectively. The water absorption percentage was more in neat natural flax reinforced epoxy composite due to its more hydrophilic nature. The scanning electron microscope analysis reveals the proper bonding and adhesion of both kevlar and flax fabrics with the epoxy matrix.
Preventing species extinctions: A global conservation consortium for Erica
Authors: Pirie Michael D. , Blackhall‐Miles Robbie , Bourke Greg , Crowley Dan , Ebrahim Ismail , Forest Félix , Knaack Michael , Koopman Rupert , Lansdowne Alex , Nürk Nicolai M. , Osborne Jo , Pearce Timothy R. , Rohrauer Daniel , Smit Martin , Wilman Victoria
Published: April 2022

Societal Impact Statement

Human‐caused habitat destruction and transformation is resulting in a cascade of impacts to biological diversity, of which arguably the most fundamental is species extinctions. The Global Conservation Consortia (GCC) are a means to pool efforts and expertise across national boundaries and between disciplines in the attempt to prevent such losses in focal plant groups. GCC Erica coordinates an international response to extinction threats in one such group, the heaths, or heathers, of which hundreds of species are found only in South Africa's spectacularly diverse Cape Floristic Region.

Effectively combating the biodiversity crisis requires coordinated conservation efforts. Botanic Gardens Conservation International (BGCI) and numerous partners have established Global Conservation Consortia (GCC) to collaboratively develop and implement comprehensive conservation strategies for priority threatened plant groups. Through these networks, institutions with specialised collections and staff can leverage ongoing work to optimise impact for threatened plant species. The genus Erica poses a challenge similar in scale to that of the largest other GCC group, Rhododendron, but almost 700 of the around 800 known species of Erica are concentrated in a single biodiversity hotspot, the Cape Floristic Region (CFR) of South Africa. Many species are known to be threatened, suffering the immediate impacts of habitat destruction, invasive species, changes in natural fire regimes and climate change. Efforts to counter these threats face general challenges: disproportionate burden of in situ conservation falling on a minority of the community, limited knowledge of species‐rich groups, shortfalls in assessing and monitoring threat, lack of resources for in situ and limitations of knowledge for ex situ conservation efforts and in communicating the value of biological diversity to a public who may never encounter it in the wild. GCC Erica brings together the world's Erica experts, conservationists and the botanical community, including botanic gardens, seed banks and organisations in Africa, Madagascar, Europe, the United States, Australia and beyond. We are collaboratively pooling our unique sets of skills and resources to address these challenges in working groups for conservation prioritisation, conservation in situ, horticulture, seed banking, systematic research and outreach.
IGF‐dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2
Authors: Jaipuria Garima , Shet Divya , Malik Shahid , Swain Monalisa , Atreya Hanudatta S. , Galea Charles A. , Slomiany Mark G. , Rosenzweig Steven A. , Forbes Briony E. , Norton Raymond S. , Mondal Somnath
Published: April 2022

Functional regulation via conformational dynamics is well known in structured proteins but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy, we have identified a dynamic regulatory mechanism in the human insulin‐like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF‐binding protein‐2 (hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF‐binding proteins. In the case of hIGFBP2, the linker domain (L‐hIGFBP2) retains its intrinsic disorder upon binding IGF‐1, but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF‐1 binding may explain the IGF‐dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF‐dependent tumors.
Prediction of the potential distribution pattern of the great gerbil (Rhombomys opimus) under climate change based on ensemble modelling
Authors: Wen Xuanye , Zhao Guanghua , Cheng Xiaotian , Chang Guobin , Dong Xiaobo , Lin Xiao
Published: April 2022

BACKGROUND

Rodent infestation is a global biological problem. Rodents are widely distributed worldwide, cause harm to agriculture, forestry, and animal husbandry production and spread a variety of natural focal diseases. In this study, 10 ecological niche models were combined into an ensemble model to assess the distribution of suitable habitats for Rhombomys opimus and to predict the impact of future climate change on the distribution of R. opimus under low, medium and high socioeconomic pathway scenarios of CMIP6.

RESULTS

In general, with the exception of extreme climates (2090‐SSP585), the current and potential future ranges of R. opimus habitat are maintained at approximately 220 × 104 km2. In combination with human footprint data, the potential distribution area of R. opimus was found to coincide with areas with a moderate human footprint. In addition, this distribution area will gradually shift to higher‐latitude regions, and the suitable habitat area of R. opimus will gradually shrink in China, Iran, Afghanistan, and Turkmenistan while increasing in Mongolia and Kazakhstan.

CONCLUSIONS

These results help identify the impact of climate change on the potential distribution of R. opimus and provide supportive information for the development of management strategies to protect against future ecological and human health risks. © 2022 Society of Chemical Industry.
Fabrication of Ferroelectric Gate Thin‐Film Transistors with a Lanthanum‐Doped HZO Gate Insulator and Indium‐Tin‐Oxide Channel via a Solution Process
Authors: Mohit  , Murakami Tatsuya , Tokumitsu Eisuke
Published: April 2022

In recent years, lanthanum‐doped hafnium–zirconium dioxide (La‐HZO) has garnered attention as a material for application in ferroelectric devices; moreover, atomic layer deposition has been applied to prepare La‐HZO films with metal–ferroelectric–metal structures. This article describes the fabrication of ferroelectric La‐HZO thin films on Pt/Ti/SiO2/Si substrates via a solution process. The dependence of the electrical properties on the La concentration of La‐HZO films annealed at 800 °C in vacuum is also discussed. The film with a La concentration of 8 at% exhibits the highest remanent polarization, whereas undoped HZO exhibits paraelectric behavior. Additionally, the leakage current of La‐HZO specimens tends to be significantly lower than that of undoped HZO. Furthermore, a higher annealing temperature corresponds to better ferroelectric properties and a lower leakage current. The characterization of fabricated ferroelectric gate thin‐film transistors (FGTs) with an 8 at% La‐HZO gate insulator and indium‐tin‐oxide channel is shown to confirm typical n‐channel transistor operation, i.e., a counterclockwise hysteresis loop in the transfer curve; this is attributable to the ferroelectric nature of the La‐HZO gate insulator. The results demonstrate that the proposed FGT design offers a low subthreshold voltage swing, high on/off drain current ratio of 106, large on‐current, and large memory window.
Effects of almond on cardiometabolic outcomes in patients with type 2 diabetes: A systematic review and meta‐analysis of randomized controlled trials
Authors: Moosavian Seyedeh Parisa , Rahimlou Mehran , Rezaei Kelishadi Mahnaz , Moradi Sajjad , Jalili Cyrus
Published: April 2022

An enhanced risk for cardiovascular disease (CVD) still exists even when T2DM patients have tight control on blood sugar. Thus, identification of treatment approaches that address CVD risk factors may be useful for patients beyond the blood sugar management. Although emerging evidence suggests that nuts consumption have beneficial effects on cardiometabolic health, the effects of almond intake in patients with type 2 diabetes are still controversial. Therefore, our objective was to investigate the effect of almond on cardiometabolic outcomes in patients with T2DM through a systematic review and meta‐analysis of available randomized controlled trials (RCTs). A systematic search was conducted in PubMed, Web of Science, Scopus, Embase, and Google Scholar to identify relevant RCTs up to March 2021. There was no language and time limitation. Weighted mean difference (WMD) was pooled using a random effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. Nine RCTs were included in the final analysis. Almond intake resulted in significant reduction in low‐density lipoprotein cholesterol (LDL‐C) (WMD: −5.28 mg/dL; 95% CI, −9.92, −0.64; p = .026) compared with the control group. This lowering effect of LDL‐C was robust in subgroups with almond consumption >50 g/day, and baseline LDL‐C level <130 mg/dL. However, the effect of almond on total cholesterol, triglycerides, high‐density lipoprotein cholesterol, fasting plasma glucose, insulin, hemoglobin A1c, body mass index, weight, body fat, systolic and diastolic blood pressure, and CRP was not significant compared with the control group. In summary, the current meta‐analysis indicated that almond consumption decreased LDL‐C, and had no favorable effect on other cardiometabolic outcomes in patients with T2DM. However, further high‐quality studies are needed to firmly establish the clinical efficacy of the almond.
Echocardiographic characteristics of patients with antisynthetase syndrome
Authors: Bryan Jaimie L. , Matar Ralph , Raviprasad Abheek , Kuteyeva Veronica , Milla Eduardo , Betageri Omkar , Patel Divya , Manjarres Diana G. , Kalra Saminder S. , Robinson Jeffrey , Khan Akram , Reddy Raju
Published: April 2022

Right ventricular (RV) dysfunction and pulmonary hypertension (PH) occurs in approximately one‐third of patients with interstitial lung disease (ILD) and is associated with reduced 6‐minute walk distance (6MWD), and increased hospitalizations and mortality. Although the impact of RV dysfunction and PH has been well described in several types of ILD, data is scarce on antisynthetase syndrome. Therefore, we sought to examine the presence of RV dysfunction and PH in patients with antisynthetase syndrome and the impact on clinical outcomes. We conducted a retrospective study of patients with antisynthetase syndrome. Seventy‐five subjects were identified. Fifty‐one (68%) subjects had echocardiographic data. Patients were grouped into those with normal fractional area change (FAC) ≥ 35% and reduced FAC < 35%. Clinical, echocardiographic, and right heart catheterization data were compared between the two groups. Subjects with FAC < 35% had lower diffusion capacity of the lung for carbon monoxide (29% vs. 47%, p = 0.004), fibrotic features on computed tomography of the chest (79% vs. 33%, p = 0.005), larger RV diameter (5.4 vs. 3.9 cm, p < 0.001), higher right atrial pressures (8 vs. 5 mmHg, p = 0.02), and required supplemental oxygen more frequently (100% vs. 44%, p < 0.001) compared to those with FAC ≥ 35%. We found no difference in 6MWD and hospitalizations between the two groups. The presence of RV dysfunction in antisynthetase syndrome may identify patients at risk of poor outcomes.
DNA damage in human sperm: The sperm chromosome assay
Authors: Watanabe Seiji
Published: April 2022

Background

Sperm DNA damage is a major cause of pre‐ and post‐implantation embryonic loss in humans. However, the factors that control how and when such DNA damage occurs in human sperm are poorly understood.

Methods

Here, I review information relating to sperm DNA damage that can be obtained from the sperm chromosome assays described in the existing literature.

Main findings

The sperm chromosome assays, which consist of interspecific in vitro fertilization or intracytoplasmic sperm injection using murine oocytes and subsequent chromosome analysis, indicate that the proportion of sperm showing DNA damage is initially low and there are larger numbers of sperm with potential membrane and DNA damage that are induced after ejaculation and separation from the seminal plasma. Other assays that directly detect sperm DNA (e.g., TUNEL assays, Comet assays, and acridine orange test) are not able to distinguish and detect the initial and potential DNA damage. Furthermore, the positive values in these direct assays are influenced by the frequency of immotile sperm and amorphous sperm populations.

Conclusion

The findings in the sperm chromosome assays show that further improvements in sperm preparation protocols may result in the reduction of sperm DNA damage, followed by more successful outcomes in infertility treatment.
Hepatitis B virus core‐related antigen (HBcrAg) as a prognostic marker for the development of hepatocellular carcinoma: A mini systematic review of the literature
Authors: Afifi Ahmed M. , Elgenidy Anas , Hashim Mahmoud , Awad Ahmed K. , Jalal Prasun K.
Published: April 2022

Chronic hepatitis B (CHB) infection is a risk factor for hepatocellular carcinoma (HCC). Previous studies showed that elevated levels of Hepatitis B Virus (HBV) DNA and HBsAg are associated with increased HCC risk in patients with chronic HBV infection. Multiple studies showed that high levels of HBV DNA and Hepatitis B Surface Antigen (HBsAg) are associated with higher HCC risk in CHB patients. Patients treated with antiviral therapy may have undetectable or low levels of HBV DNA and HBsAg loss. However, HCC may develop in some patients with low‐level HBV DNA and HBsAg seroconversion. In this study, we evaluated the role of HBcrAg in predicting HBV related HCC development. We searched PubMed, Scopus, and Web of Science databases using keywords (hepatitis B core‐related antigen, hepatocellular carcinoma, liver neoplasm, hepatocellular and hepatic cancer, to identify studies assessing serum level of HBcrAg in patients with CHB and HCC. The search resulted in 184 studies. Seven studies were included: Four of which were retrospective cohort studies, and the rest were prospective cohort, case controls. Six of them reported a higher HBcrAg positivity rate in the HCC group when compared with the HBV DNA assay, yet with similar hazard ratio (HR) in predicting the incidence of HCC. However, four studies found that HBcrAg positivity was an independent risk factor for HCC development with a HR ranging from 3.27 to 7.05. HBV‐related HCC has many proposed biomarkers in its prediction, yet our findings revealed HBcrAg to may have superiority over other biomarkers. High quality studies with bigger sample size research is needed to understand the potential role of HBcrAg in CHB induced HCC.
Back to the future: Exploring riverine macroinvertebrate communities' invasibility
Authors: Guareschi Simone , Wood Paul J. , England Judy , Barrett Jon , Laini Alex
Published: April 2022

Riverine communities have been subject to numerous biological invasion events, with crustaceans among the most successful group of invasive animals worldwide. Understanding what makes a river system prone to invasion is of considerable interest to environmental regulators, resource managers, scientists and wider society globally. The Ponto‐Caspian amphipod, Dikerogammarus haemobaphes (Crustacea: Gammaridae), is a hyper‐successful invasive species that was first recorded in the UK in 2012. The use of contemporary distribution data for D. haemobaphes (2009–2020) from England provided a unique opportunity to study faunal community patterns and differences between sites that experienced invasion compared to those that have not. Macroinvertebrate community taxonomic, functional and phylogenetic features, as well as the presence of co‐occurrent invaders and abiotic features of the river systems, were examined from sites before the invasion and compared to control sites that were not invaded during the study period. Sites that would later experience invasion by D. haemobaphes were characterized by higher abundances of other invaders (e.g., especially Ponto Caspian taxa), lower abundances of crustaceans and typically had greater channel width and water depth. These basic characteristics may help identify sites at risk of future invasion by D. haemobaphes. Most biomonitoring tools examined displayed no difference between control and pre‐invaded samples, while both taxonomic and functional richness displayed higher values at sites that were subsequently invaded, questioning classic biological invasion hypotheses. Recognizing specific community characteristics that may be a precondition for subsequent invasion is essential for understanding and better predicting their future trajectories of change.
A configurational analysis of firms' environmental innovation: Evidence from China's key pollutant‐discharge listed companies
Authors: Liao Zhongju , Zhu Xiang
Published: April 2022

A firm's environmental innovation behavior results from the interdependence and interaction of multiple factors, and the antecedent conditions are multiple and concurrent. From the perspective of configuration, this study integrates institution theory, stakeholder theory, and strategic management theory, and uses a fuzzy set qualitative comparative analysis (fsQCA) to investigate the combinations of paths that drive firms' environmental innovation. The results revealed that the basic resource capacity of a firm was the basis for environmental innovation, and the role of institution‐ and market‐level factors in driving a firm's environmental innovation requires the support of the firm's resources. The different factors at these three levels—firm, market, and institution—do not contribute equally to a firm's environmental innovation under all conditions; based on a firm's individual resources, the models that drive a firm's environmental innovation can be categorized as market‐driven, institution‐driven, and dual‐stressed.
Sustainable Fabrication of Copper Nanoparticles: A Potent and Affordable Candidate for Water Treatment, Water Disinfection, Antioxidant Activity and Theranostic Agent
Authors: Sinha Tanur , Adhikari Partha Pradip , Bhandari Vinay M
Published: April 2022

This study reports a simple, green, and large–scale biosynthetic fabrication of spherical copper nanoparticles (Cu NPs), approximate 28 nm, using the aqueous extracts of Diaplazium esulentum (Retz.) Sw. fern. Characterization was carried out for morphology, size, elemental analysis, crystallinity and for identification of functionalities responsible for reduction and stabilization. Extraordinary remediation efficiency was obtained for the developed Cu NPs for the elimination of two industrially important pollutants; Methyl Violet 6B and Methylene Blue (greater than 92 % within 150 mins). A mechanism was postulated for the process using the data on the identification of NPs and also spent NPs apart from degraded products.

Furthermore, the Cu NPs revealed excellent antibacterial activity against gram positive bacteria: Staphylococcus aureus, Streptococcus pneumonia and Bacillus subtilis, as well as gram negative bacteria: Pseudomonas aeruginosa, Escherichia coli and potential action against fungal strains; Aspergillus niger and Candida albicans.

Additionally, the assay depicted that Cu NPs has fairly decent radical scavenging activity with IC50 value 2.11 mM.

Moreover, the Cu NPs were found to exhibit profound anticancerous activity against two human cancer line cells.

The present research work has implications for exploitation of DE fern extract for the development of Cu NPs and their numerous applications ranging from pollutants removal to antibacterial, antifungal, antioxidant and anticancerous agents.
Comparative Investigation on the Crystal Structures, Hirshfeld Surface Analysis, Antitubercular Assays, and Molecular Docking of Regioisomeric 1,2,3‐Triazoles
Authors: Anand Ashish , Sindogi Kishorkumar , Dixit Sheshagiri R. , Shetty Richa P. , Pujar Gurubasavaraj V. , Kulkarni Manohar V. , Guru Row Tayur N.
Published: April 2022

1,2,3‐triazole system is readily obtained by the click reaction in a facile and regioselective way. Regioselectivity is introduced under Copper(CuAAC), and Ruthenium(RuAAC) catalysed azide‐alkyne cycloaddition reaction furnishing 1,4 and 1,5‐disubstituted triazoles, respectively. These two regioisomeric systems offer discrete physicochemical and medicinal properties based on crucial binding interactions and biocompatibility with the biological targets. In this regard, a comparative investigation on the coumarin‐linked regioisomeric 1,2,3‐triazoles via its crystal structure, Hirshfeld surface analysis, and antitubercular assays and molecular docking are reported. It sheds light on the variation of in vitro antitubercular efficacy against Mycobacterium tuberculosis H37Rv followed by molecular docking studies that justify the prominent interactions at the binding site. Further, solid‐state and Hirshfeld surface analysis provided significant crystallographic insights on the critical intermolecular interactions that dictate the crystal packing in these systems. Thus structure‐property correlation for these regioisomeric systems can open new avenues in drug design and discovery.