bluuebunny/crossref_metadata_2025 huggingface dataset:
Microalgae—Sustainable Source for Alternative Proteins and Functional Ingredients Promoting Gut and Liver Health
Authors: Eilam Yahav , Khattib Hamdan , Pintel Noam , Avni Dorit
Published: April 2023

Dietary proteins derived from animal sources, although containing well‐balanced profiles of essential amino acids, have considerable environmental and adverse health effects associated with the intake of some animal protein‐based products. Consuming foods based on animal proteins carries a higher risk of developing non‐communicable diseases such as cancer, heart disease, non‐alcoholic fatty liver disease (NAFLD), and inflammatory bowel disease (IBD). Moreover, dietary protein consumption is increasing due to population growth, posing a supply challenge. There is, therefore, growing interest in discovering novel alternative protein sources. In this context, microalgae have been recognized as strategic crops that can provide a sustainable source of protein. Compared to conventional high‐protein crops, using microalgal biomass for protein production presents several advantages in food and feed in terms of productivity, sustainability, and nutritional value. Moreover, microalgae positively impact the environment by not exploiting land or causing water pollution. Many studies have revealed the potential of microalgae as an alternative protein source with the added value of positive effects on human health due to their anti‐inflammatory, antioxidant, and anti‐cancer properties. The main emphasis of this review is on the potential health‐promoting applications of microalgae‐based proteins, peptides, and bioactive substances for IBD and NAFLD.
Prediction of potential habitat suitability of snow leopard (Panthera uncia) and blue sheep (Pseudois nayaur) and niche overlap in the parts of western Himalayan region
Authors: Islam Mohd , Sahana Mehebub , Areendran Gopala , Jamir Chubamenla , Raj Krishna , Sajjad Haroon
Published: April 2023

The snow leopard (Panthera uncia) and blue sheep (Pseudois nayaur) are the inhabitants of remote areas at higher altitudes with extreme geographic and climatic conditions. The habitats of these least‐studied species are crucial for sustaining the Himalayan ecosystem. We employed the Maximum Entropy (MaxEnt) species distribution model to predict the potential habitat suitability of snow leopards and blue sheep and extracted common overlapped niches. For this, we utilised presence location, bio‐climatic and environmental variables, and correlation analysis was applied to reduce the negative impact of multicollinearity. A total of 134 presence locations of snow leopards and 64 for blue sheep were selected from the Global Biodiversity Information Facility (GBIF). The annual mean temperature (Bio1) was found to be the most useful and highly influential factor to predict the potential habitat suitability of snow leopards. Annual mean temperature, annual precipitation and isothermality were the major influencing factors for blue sheep habitat suitability. Highly influential bio‐climatic, topographic and environmental variables were integrated to construct the model for predicting habitat suitability. The area under the curve (AUC) values for snow leopard (0.87) and blue sheep (0.82) showed that the models are under good representation. Of the total area investigated, 47% was suitable for the blue sheep and 38% for the snow leopards. Spatial habitat assessment revealed that nearly 11% area from the predicted suitable habitat class of both species was spatially matched (overlapped), 48.6% area was unsuitable under niche overlap and 40.5% area was spatially mismatched niche. The presence of snow leopards and blue sheep in some highly suitable areas was not observed, yet such areas have the potential to sustain these elusive species. The other geographical regions interested in exploring habitat suitability may find the methodological framework adopted in this study useful for formulating an effective conservation policy and management strategy.
Identifying moisture transport pathways for north‐west India
Authors: Joshi Suneel Kumar , Kumar Sudhir , Sinha Rajiv , Rai Shive Prakash , Khobragade Suhas , Rao M. Someshwar
Published: April 2023

The isotopic composition (δ18O and δ2H) of precipitation is widely used as a moisture source tracer. In north‐west India, the δ18O, δ2H and D‐excess values of precipitation correlate mainly with air temperature; however, the moisture sources of water vapour are unclear. Therefore, we collected daily precipitation isotope data (n = 425) from 13 rain gauge stations in northwest India in 2013. We established a regional meteoric water line (MWL) for northwest India and local MWLs for all 13 rain gauge stations separately. We observed an altitudinal gradient of about 0.11‰/100 m in slope and about 1.22‰/100 m in intercept from the western to the northeast part of the study area. The isotopic composition of precipitation shows spatial and temporal variability across the study area. We found higher Deuterium excess values during winter (December–February) and lower during the monsoon season (July–September), which may be associated with the different moisture sources, namely, the Bay of Bengal, Arabian Sea and Westerly disturbances. Our results suggest local moisture recycling may also occur during the study period. The present study can enhance the knowledge of the isotopic evolution of precipitation and moisture sources in northwest India.
Trends in elder abuse and age discrimination during the COVID‐19 pandemic in Hong Kong: Findings from a two‐wave representative telephone survey study
Authors: Yan Elsie , To Louis , Ng Haze K. L. , Lai Daniel W. L. , Bai Xue , Lee Vincent W. P
Published: April 2023

Objectives

Empirical evidence about the heightened risks of elder abuse and age discrimination during the COVID‐19 pandemic is scarce. This study aimed to track the changes in rates of both, and investigated their associated factors in the community‐dwelling older population in Hong Kong.

Methods

In this two‐wave, cross‐sectional telephone survey, we interviewed a population‐based sample of individuals (≥55 years), and captured the situation of elder abuse and age discrimination before the COVID‐19 outbreak (n = 1209, Wave 1: October–December 2019) and during the pandemic (n = 891, Wave 2: December 2020–January 2021). Participants reported their experiences of different types of abuse and discrimination, financial health, subjective well‐being, satisfaction with environment, health and social services, and resilience.

Results

Abuse was reported by 20.2% of the sample before the outbreak and 17.8% during the pandemic; while discrimination was reported by 24.6% and 29.8% at the two time points, respectively. A drop in physical abuse was observed, but it was accompanied by a rise in discrimination in the form of harassment or refusal of services. Findings of logistic regression analysis show that abuse during the pandemic was associated with younger age, poorer subjective well‐being, and lower resilience; while discrimination was associated with female gender, being married, and poorer subjective well‐being.

Conclusions

Elder abuse and discrimination were prevalent across time points. The pandemic has highlighted the marginalization of older persons in our communities. There is an urgent need for development of effective interventions to end abuse and discrimination.
Processes and factors controlling the groundwater flow in a complex landslide: A case study in the northern Italy
Authors: Petrella Emma , Raimondo Melinda , Chelli Alessandro , Valentino Roberto , Severini Edoardo , Diena Michela , Celico Fulvio
Published: April 2023

The present work provides new insights on some factors controlling the groundwater flow in low‐permeability media affected by deep Apennine landslide, involving several million cubic meters of soil and rock. Rainfall and groundwater circulation are among the major triggers of landslides. However, if the first factor is well studied, only few research deal with the hydrogeological processes in the landslide. Thus, in this study, combined hydrogeological, geochemical and isotopic investigation were performed in order to: (1) characterize infiltration and flow processes and (2) understand the role of sliding surface on groundwater circulation in a complex landslide that mainly involves sandstones and clay materials. Results indicate that at least two circuits coexist: a faster one, where rainfall preferentially infiltrates and flows in a well‐connected network of macropores, cracks and soil pipes, which mainly feeds the springs; a slower and a deeper one that flows in the soil matrix and fractures of the landslide body. Moreover, the investigated slip zones show an aquiclude characteristic in terms of groundwater circulation, where the flow is very slow and precipitation influence is negligible. These results could be helpful in an accurate slope stability considerations and to improve the reliability of landslide risk assessment.
The significance of fluorinated compound chain length, treatment technology, and influent composition on per- and polyfluoroalkyl substances removal in worldwide wastewater treatment plants
Authors: Ilieva Zanina , Hamza Rania A. , Suehring Roxana
Published: April 2023

Wastewater treatment plants (WWTPs) are deemed major conveyors and point sources of per- and polyfluoroalkyl substances (PFAS) to the environment. This statistical meta-analysis of existing literature from the past 15 years focused on the significance of treatment type for PFAS removal efficiencies and the influence of PFAS sources (domestic vs. industrial) on their removal. Different sampling events, WWTPs across the world, different treatment technologies, configurations, and processes, as well as different PFAS classes and compounds were considered. This study evaluated 13 PFAS analyzed predominantly in 161 WWTPs across the world. The statistical test results revealed that these 13 frequently detected and reported PFAS can be divided into four groups based on their behavior during wastewater treatment, namely (1) C6–10 perfluorocarboxylic acids (PFCAs), (2) C4,5,11,12 PFCAs, (3) C4,6,8 perfluoroalkane sulfonic acids (PFSAs), and (4) C10 PFSA. In this study, biological treatments such as (1) membrane bioreactors, (2) combination of two or more biological treatments, and (3) biofilm processes revealed the highest PFAS removals, although the addition of a tertiary treatment actually had a nonbeneficial effect on PFAS removal. Moreover, a strong statistical correlation was observed between industrial wastewater sources and the presence of high influent PFAS concentrations in the receiving WWTPs. This indicates that industrial sources were the main contributors of the PFAS load in the analyzed WWTPs. Integr Environ Assess Manag 2024;20:59–69. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Nanoparticle drug delivery to target breast cancer brain metastasis: Current and future trends
Authors: Kannan Siddarth , Cheng Vinton W. T.
Published: April 2023

Breast cancer brain metastasis (BCBM) is rapidly becoming an impediment to continuing survival gains seen in breast cancer patients. Drug delivery across the blood‐brain barrier is the main issue hindering systemic therapy against BCBM. This review details recent advances in nanoparticle (NP) drug delivery systems to target BCBM. Their primary benefits are: enhanced circulating and intra‐BCBM drug biodistribution, BCBM targeting through NP functionalization, opportunities for gene manipulation and their theragnostic applications. Multiple NPs have been synthesized to deliver therapeutic HER2 blockade, which is particularly important given HER2‐positive breast cancer's tendency to form BCBM. Finally, we review the clinical context in which NP‐based therapeutics have been investigated in BCBM patients. While a breakthrough in improving patient outcomes remain awaited, these clinical trials represent positive steps in the changing attitude towards BCBM as a treatable illness. Although multiple challenges remain in the clinical translation of BCBM‐directed NP therapies, ongoing research in the field offers promising avenues for novel targeting of this devastating disease.
Saturated fatty acid intake, genetic risk and colorectal cancer incidence: A large‐scale prospective cohort study
Authors: Fan Linyun , Cai Yimin , Wang Haoxue , Zhang Heng , Chen Can , Zhang Ming , Lu Zequn , Li Yanmin , Zhang Fuwei , Ning Caibo , Wang Wenzhuo , Liu Yizhuo , Li Hanting , Li Gaoyuan , Peng Jingyi , Hu Kexin , Li Bin , Huang Chaoqun , Yang Xiaojun , Wei Yongchang , Zhu Ying , Jin Meng , Miao Xiaoping , Tian Jianbo
Published: April 2023

Previous investigations mainly focused on the associations of dietary fatty acids with colorectal cancer (CRC) risk, which ignored gene‐environment interaction and mechanisms interpretation. We conducted a case‐control study (751 cases and 3058 controls) and a prospective cohort study (125 021 participants) to explore the associations between dietary fatty acids, genetic risks, and CRC. Results showed that high intake of saturated fatty acid (SFA) was associated with a higher risk of CRC than low SFA intake (HR =1.22, 95% CI:1.02‐1.46). Participants at high genetic risk had a greater risk of CRC with the HR of 2.48 (2.11‐2.91) than those at low genetic risk. A multiplicative interaction of genetic risk and SFA intake with incident CRC risk was found (PInteraction = 7.59 × 10−20), demonstrating that participants with high genetic risk and high SFA intake had a 3.75‐fold greater risk of CRC than those with low genetic risk and low SFA intake. Furthermore, incorporating PRS and SFA into traditional clinical risk factors improved the discriminatory accuracy for CRC risk stratification (AUC from 0.706 to 0.731). Multi‐omics data showed that exposure to SFA‐rich high‐fat dietary (HFD) can responsively induce epigenome reprogramming of some oncogenes and pathological activation of fatty acid metabolism pathway, which may contribute to CRC development through changes in gut microbiomes, metabolites, and tumor‐infiltrating immune cells. These findings suggest that individuals with high genetic risk of CRC may benefit from reducing SFA intake. The incorporation of SFA intake and PRS into traditional clinical risk factors will help improve high‐risk sub‐populations in individualized CRC prevention.
Bond Energies of UO+ and UC+: Guided Ion Beam and Quantum Chemical Studies of the Reactions of Uranium Cation with O2 and CO
Authors: Zhang Wenjing , Hunt Ashley R. E. , Kim Jung Soo , Demireva Maria , Peterson Kirk A. , Armentrout P. B.
Published: April 2023

Guided ion beam tandem mass spectrometry was used to examine the kinetic energy dependent reactions of U+ with O2 and CO. In the reaction of U+ with O2, the UO+ product is formed in a barrierless and exothermic process with a reaction efficiency at low energies of k/kcol=1.1±0.2, but increases at higher collision energies. Formation of both UO+ and UC+ in the reaction of U+ with CO is endothermic. 0 K bond dissociation energies (BDEs) of D0(U+‐O)=7.88±0.09 eV and D0(U+‐C)=4.03±0.13 eV were determined by analyzing the kinetic energy dependent cross sections in the latter endothermic reactions. These values are within experimental uncertainty of previously reported experimental values. Additionally, the electronic states of UO+ and UC+ and the potential energy surfaces for the reactions were explored by quantum chemical calculations. The former include a full Feller‐Peterson‐Dixon composite approach with correlation contributions up to CCSDT(Q) for UO and UO+, yielding D0(U‐O)=7.82 eV and D0(U+‐O)=7.99 eV, as well as more approximate CCSD(T) calculations where a semi‐empirical model was used to estimate spin‐orbit energy contributions, which are generally found to improve the agreement with experiment. Both experimental BDEs are observed to be close to those of their transition metal congeners, ScL+, YL+, and GdL+ (L=O and C).
Structural dynamics and mechanistic action guided engineering of lipolytic enzymes
Authors: Kumar Rajender
Published: April 2023

Lipases have been established as important biocatalysts in several industrial applications, owing to their diverse substrate specificity. The availability of data on three‐dimensional crystal structures for various lipases offers an opportunity for modulating their structural and functional aspects to design and engineer better versions of lipases. With the aim of investigating the structural components governing the extremophilic behavior of lipases, structural analysis of microbial lipases was performed using advanced bioinformatics and molecular dynamics simulation approaches. In sequences and functionally distinct alkaliphilic and thermophilic lipases were investigated for their functional properties to understand the distinguishing features of their structures. The alkaliphilic lipase from Bacillus subtilis (LipA) showed conformational changes in the loop region Ala132–Met137, subsequently, the active site residue His156 shows two conformations, toward the active site nucleophilic residues Ser77 and away from the Ser77. Interestingly, the active site of LipA is more solvent‐exposed and can be correlated with the adoption of an open conformation which might extend and expose the active site region to solvents during the catalysis process. Furthermore, the MD simulation of thermophilic lipase from marine Streptomyces (MAS1) revealed the role of N‐ and C‐terminal regions with disulfide bridges and identified a metal ion binding site that facilitates the enzyme stability. The novel thermo‐alkaliphilic lipase can be designed to integrate the stability features of MAS1 into the alkaliphilic LipA. These structural‐level intrinsic characteristics can be used for lipase engineering to amend the lipase activity and stability as per the requirements of the industrial processes.
Spectra and excitation properties of (AlP)8: Effect of external electric fields
Authors: Aizezi Nuerbiye , Xiang Mei , Abulimiti Bumaliya , Liu Qifan
Published: April 2023

On the basis of density functional theory (DFT), the geometry and infrared spectrum of the (AlP)8 cluster have been calculated under external electric fields (EEFs). In addition, on the basis of time‐dependent DFT, the ultraviolet–visible absorption spectra, oscillator strengths, wavelengths, and hole–electron orbits of the first 20 excited states have been calculated. Under EEFs, the energy of (AlP)8 gradually decreases, the dipole moment increases, and the molecular configuration significantly changes. In the infrared spectrum, the vibration frequency corresponding to the stretching vibration of the Al–P bond decreases, and a red shift occurs. With increasing EEF, the infrared spectrum splits and shows an obvious Stark effect; the ultraviolet absorption intensity is enhanced, and the molecular excitation energy decreases. Additionally, the excitation wavelength increases with increasing EEF. It is conclusively shown that the (AlP)8 cluster is easily excited under an EEF. Separation of the holes and electrons of the (AlP)8 cluster is obvious. Theoretical investigation of the spectra and excitation properties of (AlP)8 is an important step toward a comprehensive understanding of the effects of EEFs on the molecular structure, stability, and dynamics.
Importance of the neutrophil–lymphocyte ratio and systemic immune‐inflammation index in predicting colorectal pathologies in fecal occult blood‐positive patients
Authors: Hasirci Ismail , Şahin Alpaslan
Published: April 2023

Background

The fecal occult blood (FOB) test is one of the primary screening methods for colorectal cancer (CRC). In this study, we aimed to investigate the effect of the neutrophil/lymphocyte ratio (NLR) and systemic immune‐inflammation index (SII) in predicting CRC and other colorectal pathologies in patients with a positive FOB test.

Methods

This retrospective study included patients with a positive FOB test who underwent colonoscopy for the investigation of the etiology. The optimal cutoff levels of NLR and SII for predicting colorectal pathologies were determined using the receiver operating characteristic analysis.

Results

Of the 157 FOB+ patients, 35% were male and 65% were female, with a median age of 59 years. There were 96 patients in Group 1 and 61 patients in Group 2. The mean age of the patients in Group 2 was significantly higher (p < 0.001). The rate of male patients was significantly higher in Group 2. NLR and SII were significantly higher in Group 2 than in Group 1 (p < 0.001). The area under the curve values of NLR and SII in predicting colorectal pathologies in FOB+ patients were 0.817 and 0.825, respectively. At the cutoff values of 0.689 and 0.795, NLR and SII had a sensitivity of 60.66% and 95.83%, respectively, and a specificity of 95.83% and 100%, respectively.

Conclusion

Neutrophil/lymphocyte ratio and SII can be used as important biomarkers in the early diagnosis of CRC and other colorectal lesions in patients with a positive FOB test.
A new isolation method for bacterial extracellular vesicles providing greater purity and improved proteomic detection of vesicle proteins
Authors: Le Lena Hoang My , Steele Joel R. , Ying Le , Schittenhelm Ralf B. , Ferrero Richard L.
Published: April 2023

Contaminants within cell culture media often co‐isolate with eukaryotic extracellular vesicles (EVs) thus affecting their biological properties. It has yet to be investigated if this is also true for bacterial EVs (BEVs), especially for organisms grown in complex culture media containing animal‐derived products. To address this question, we isolated BEVs from the fastidious bacterium Helicobacter pylori grown in either standard Brain Heart Infusion (BHI) medium or BHI depleted of animal‐derived products (D‐BHI). We show that BEVs prepared from bacteria grown in D‐BHI medium have similar morphologies, size ranges and yields to those prepared from standard medium. Similarly, no differences were found in the ability of H. pylori BEVs to induce IL‐8 responses in epithelial cells. However, H. pylori BEVs prepared from D‐BHI medium were of higher purity than those prepared from standard medium. Importantly, proteomic analyses detected 3.4‐fold more H. pylori proteins and 10‐fold fewer bovine‐derived proteins in BEV samples prepared from D‐BHI rather than the standard method. Fifty‐seven H. pylori proteins were uniquely detected in BEV samples prepared from D‐BHI. In conclusion, we have described an improved method for BEV isolation. Furthermore, we demonstrate how animal‐derived products in bacteriological culture media may adversely affect proteomic analyses of BEVs.
Molecular evolution of patristacin genes in teleosts based on the genome survey
Authors: Nakano Yuko , Nagasawa Tatsuki , Okazawa Yohei , Mashiko Naoya , Yasumasu Shigeki , Kawaguchi Mari
Published: April 2023

During the evolution of astacin metalloprotease family genes, gene duplication occurred, especially in the lineage of teleosts, in which several types of astacins containing six conserved cysteines (c6ast) emerged. One of them is patristacin, originally found in syngnathid fishes, such as pipefishes and seahorses. Patristacin is expressed in the brood pouch and is present on the same chromosome as other c6ast (pactacin and nephrosin) genes. We first surveyed all the genes from 33 teleost species using a genome database, and characterized the genes by phylogenetic analysis. Pactacin and nephrosin gene homologs were found from all the examined species with only few exceptions, while patristacin gene homologs were found from only several lineages. The patristacin gene homologs were found as multicopy genes in most species of Percomorpha, one of the diverged groups in teleosts. Further diversification of the gene occurred during the evolution of Atherinomorphae, one of the groups in Percomorpha. Fishes of Atherinomorphae possess two types of patristacin, belonging to subclades 1 and 2. Among the Atherinomorpha, we chose the southern platyfish to examine the patristacin gene expression. Platyfish possess eight patristacin gene homologs, called XmPastn1, 2, 3, 4, 5, 7, 10, and 11. Of these genes, only XmPastn2 belongs to subclade 1, while the other seven belong to subclade 2. Only XmPastn2 showed strong expression in several organs of adult platyfish, as observed in reverse‐transcription polymerase chain reaction of RNA extracts. Cells expressing XmPastn2 were predominantly mucus‐secreting cells found in epidermis around the jaw, as revealed by in‐situ hybridization. This result suggests that XmPastn2 is secreted and may contribute to mucus formation or secretion.
Entrustment decision‐making in genetic counseling supervision: Exploring supervisor and student perspectives to enhance training practices
Authors: Lenhart Kelsey , Yashar Beverly M. , Sandhu Gurjit , Marvin Monica
Published: April 2023

Entrustment decisions are an essential part of genetic counseling supervision and have the potential to influence a student's progression toward autonomy. However, there is often uncertainty among supervisors regarding how and when to make these decisions and very few studies have examined the impact of these decisions on students. This study utilized a mixed methods approach including surveys of genetic counseling supervisors (n = 76) and students (n = 86) as well as qualitative interviews with genetic counseling supervisors (n = 20) and students (n = 20) that explored factors that influence the entrustment decisions of genetic counseling supervisors and their effect on genetic counseling students. Genetic counseling supervisors and students were recruited from various organizations across the United States and Canada and represented a range of geographic regions, hospital systems, and genetic counseling programs. A hybrid process of deductive and inductive coding and thematic analysis was used to evaluate and interpret transcripts from the supervisor and student interviews. All participants identified advantages of increased autonomy during training. However, many supervisors reported low entrustment, seldom allowing students to complete unsupervised sessions or supervised cases without interruption. Entrustment decisions were heavily influenced by student ability and confidence, as well as patient feedback. Students emphasized the negative impact of decreased entrustment on their confidence and described clear benefits to increased autonomy before, during, and after the genetic counseling appointment. Supervisors identified various barriers to entrustment pertaining to the student, clinical setting, and the patient, whereas students more often emphasized barriers pertaining to themselves. Our results highlight a tension between the clear advantages of increased entrustment and autonomy and various barriers to the provision of these opportunities. Additionally, our data suggest several ways to enhance the supervisor–student relationship and promote additional learning opportunities to support student‐centered supervision.
Relating the independence number and the dissociation number
Authors: Bock Felix , Pardey Johannes , Penso Lucia D. , Rautenbach Dieter
Published: April 2023

The independence number and the dissociation number of a graph are the largest orders of induced subgraphs of of maximum degree at most 0 and at most 1, respectively. We consider possible improvements of the obvious inequality . For connected cubic graphs distinct from , we show , and describe the rich and interesting structure of the extremal graphs in detail. For bipartite graphs, and, more generally, triangle‐free graphs, we also obtain improvements. For subcubic graphs though, the inequality cannot be improved in general, and we characterize all extremal subcubic graphs.
The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection
Authors: Qudus Muhammad Suhaib , Tian Mingfu , Sirajuddin Summan , Liu Siyu , Afaq Uzair , Wali Muneeba , Liu Jinbiao , Pan Pan , Luo Zhen , Zhang Qiwei , Yang Ge , Wan Pin , Li Yongkui , Wu Jianguo
Published: April 2023

In patients with severe COVID‐19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive and uncontrolled release of pro‐inflammatory cytokines. High levels of numerous crucial pro‐inflammatory cytokines, such as interleukin‐1 (IL‐1), IL‐2, IL‐6, tumor necrosis factor‐α, interferon (IFN)‐γ, IFN‐induced protein 10 kDa, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1, and IL‐10 and so on, have been found in severe COVID‐19. They participate in cascade amplification pathways of pro‐inflammatory responses through complex inflammatory networks. Here, we review the involvements of these critical inflammatory cytokines in SARS‐CoV‐2 infection and discuss their potential roles in triggering or regulating cytokine storm, which can help to understand the pathogenesis of severe COVID‐19. So far, there is rarely effective therapeutic strategy for patients with cytokine storm besides using glucocorticoids, which is proved to result in fatal side effects. Clarifying the roles of key involved cytokines in the complex inflammatory network of cytokine storm will help to develop an ideal therapeutic intervention, such as neutralizing antibody of certain cytokine or inhibitor of some inflammatory signal pathways.
The effects of NF‐κB suppression on the early healing response following intrasynovial tendon repair in a canine model
Authors: Lane Ryan A. , Migotsky Nicole , Havlioglu Necat , Iannucci Leanne E. , Shen Hua , Lake Spencer , Sakiyama‐Elbert Shelly E. , Thomopoulos Stavros , Gelberman Richard H.
Published: April 2023

The highly variable clinical outcomes noted after intrasynovial tendon repair have been associated with an early inflammatory response leading to the development of fibrovascular adhesions. Prior efforts to broadly suppress this inflammatory response have been largely unsuccessful. Recent studies have shown that selective inhibition of IkappaB kinase beta (IKK‐β), an upstream activator of nuclear factor kappa‐light chain enhancer of activated B cells (NF‐κB) signaling, mitigates the early inflammatory response and leads to improved tendon healing outcomes. In the current study, we test the hypothesis that oral treatment with the IKK‐β inhibitor ACHP (2‐amino‐6‐[2‐(cyclopropylmethoxy)‐6‐hydroxyphenyl]‐4‐piperidin‐4‐yl nicotinenitrile an inhibitor) will modulate the postoperative inflammatory response and improve intrasynovial flexor tendon healing. To test this hypothesis, the flexor digitorum profundus tendon of 21 canines was transected and repaired within the intrasynovial region and assessed after 3 and 14 days. Histomorphometry, gene expression analyses, immunohistochemistry, and quantitative polarized light imaging were used to examine ACHP‐mediated changes. ACHP led to reduction in phosphorylated p‐65, indicating that NF‐κB activity was suppressed. ACHP enhanced expression of inflammation‐related genes at 3 days and suppressed expression of these genes at 14 days. Histomorphometry revealed enhanced cellular proliferation and neovascularization in ACHP‐treated tendons compared with time‐matched controls. These findings demonstrate that ACHP effectively suppressed NF‐κB signaling and modulated early inflammation, leading to increased cellular proliferation and neovascularization without stimulating the formation of fibrovascular adhesions. Together, these data suggest that ACHP treatment accelerated the inflammatory and proliferative phases of tendon healing following intrasynovial flexor tendon repair. Clinical Significance: Using a clinically relevant large‐animal model, this study revealed that targeted inhibition of nuclear factor kappa‐light chain enhancer of activated B cells signaling with ACHP provides a new therapeutic strategy for enhancing the repair of sutured intrasynovial tendons.
Biologically‐coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue‐bone healing
Authors: Kremen Thomas J. , Shi Brendan Y. , Wu Shannon Y. , Sundberg Oskar , Sriram Varun , Kim Won , Sheyn Dmitriy , Lyons Karen M. , Wang Weiguang , McKenna Charles E. , Nishimura Ichiro
Published: April 2023

Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel‐3 that is composed of a bone‐targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K‐sensitive peptide sequence. Using a murine Achilles tendon‐to‐bone repair model, BP‐based and/or Ctsk‐coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon‐bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p < 0.001), with signal peaking at 7–10 days after surgery. Our findings demonstrate the feasibility of using a novel BP‐based targeting and Ctsk‐activated delivery of molecules to the site of tendon‐to‐bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.
Hyaluronic acid sheet transplantation attenuates infrapatellar fat pad fibrosis and pain in a rat arthritis model
Authors: Qu Zhen , Koga Hideyuki , Tsuji Kunikazu , Tang Guo , Yang Yang , Yoshihara Aritoshi , Katakura Mai , Katagiri Hiroki , Miyatake Kazumasa , Nakamura Tomomasa , Sekiya Ichiro , Nakagawa Yusuke
Published: April 2023

Fibrosis of the infrapatellar fat pad (IFP) occurs after knee joint surgery or during knee osteoarthritis (KOA) and causes persistent pain and limited mobility. Previous studies demonstrated that treating IFP fibrosis alleviated pain in animal models. In this study, we examined the effects of hyaluronic acid (HA) sheet transplantation on IFP fibrosis and articular cartilage degeneration in a monoiodoacetic acid (MIA) rat arthritis model (95 male rats). Rats received bilateral intra‐articular MIA injections (1.0 mg/30 μL) and underwent surgery 4 days later. HA sheets were transplanted on the right knee of each rat (HA group), with the left knee receiving sham surgery (sham group). Incapacitance tests were performed at multiple time points up to 28 days after MIA injection. Macroscopic, histological, and immunohistochemical analyzes were performed 14 and 28 days after injection. The concentrations of HA and interleukin‐1β (IL‐1β) in the synovial fluid were measured using ELISA. Transplantation of HA sheets could alleviate persistent pain 10–28 days after injection. The HA sheets inhibited articular cartilage degeneration at 14 days. Fibrosis and the invasion of calcitonin gene‐related peptide‐positive nerve fiber endings in the IFP were inhibited at both 14 and 28 days. Moreover, the HA sheets remained histologically until 10 days after transplantation. The concentration of HA reached its peak on Day 10 after transplantation; the concentration of IL‐1β in the sham group was significantly higher than that in the HA group on Day 7. Therefore, HA sheets could be a promising option to treat IFP fibrosis occurring in KOA and after knee joint surgery.
Reliable low‐power high‐performance low‐temperature polycrystalline thin‐film transistor technologies in bottom gate‐controlled device architectures for AMOLED displays
Authors: Kim Keunwoo , Sung Bummo , Kim Doona , Kim Sangsub , Kim Hanbit , Shin Jiyeong , Kwak Hyena , Lee Dokyeong , Seol Chanyoub , Choi Sanggun , Lim Jun Hyung , Kang Taewook , Lee Changhee
Published: April 2023

This paper presents a recent process for bottom gate‐controlled low‐temperature polysilicon (LTPS) TFT technologies for reliable low‐power high‐performance AMOLED displays. The experimental and physics‐based analysis leads to the pragmatic device design concept for LTPS TFT performance enhancement. The process integration of bottom (second) gate and top (first) gate metals, controlled by optimal two gates‐based device structures, is explored in conjunction with improved poly crystallization and poly‐Si/gate‐oxide interface by reducing defect density‐of‐state (DOS), especially in the grain boundaries of the channel region. We obtain optimal device performance, such as optimal sub‐threshold slope, high driver current (Ion), and low leakage current (Ioff), in addition to enhanced device reliability characteristics. Numerical device simulations, supplemented by physics‐based analysis, are performed to corroborate experimental results in fabricated TFTs and gain more physical insight into the bottom‐gate LTPS device configuration to enable reliable low‐power high‐performance AMOLED display applications.
Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer
Authors: Behrens Shay , Sutton Thomas L. , Patel Ranish , Schwantes Issac R. , O'Grady Jack , Johnson Alicia , Grossberg Aaron , Lopez Charles , Gilbert Erin , Mayo Skye , Sheppard Brett C.
Published: April 2023

Background

Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection.

Methods

A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis.

Results

Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC‐alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5‐fluorouracil versus gemcitabine‐based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism‐specific changes or antibiotic resistance patterns.

Conclusions

Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.
Understanding the sense‐making process of visitor experience in the integrated resort setting: Investigating the role of experience‐centric attributes
Authors: Li Kefang , Ji Chunli , He Qiuyue , Rastegar Raymond
Published: April 2023

Almost all existing customer experience research has been based on the stimulus‐organism‐response (S‐O‐R) paradigm or the interaction‐based perspective, and very few on the sensemaking theoretical perspective. This study aims to address this gap by developing and testing an integrated conceptual model of customer experience creation based on the sensemaking theory. Focusing on the case of six luxury integrated resorts in Macao, the findings indicate that experience‐centric attributes significantly affect self‐image congruity and sense of place respectively, which in turn are positively and significantly related to subjective well‐being. In addition, both self‐image congruity and sense of place play a mediating role between customer‐centric experience and subjective well‐being.
Ultrafast Laser Microlaryngeal Surgery for In Vivo Subepithelial Void Creation in Canine Vocal Folds
Authors: Andrus Liam , Camli Berk , Mau Ted , Ben‐Yakar Adela
Published: April 2023

Background/Objectives

Tightly‐focused ultrafast laser pulses (pulse widths of 100 fs–10 ps) provide high peak intensities to produce a spatially confined tissue ablation effect. The creation of sub‐epithelial voids within scarred vocal folds (VFs) via ultrafast laser ablation may help to localize injectable biomaterials to treat VF scarring. Here, we demonstrate the feasibility of this technique in an animal model using a custom‐designed endolaryngeal laser surgery probe.

Methods

Unilateral VF mucosal injuries were created in two canines. Four months later, ultrashort laser pulses (5 ps pulses at 500 kHz) were delivered via the custom laser probe to create sub‐epithelial voids of ~3 × 3‐mm2 in both healthy and scarred VFs. PEG‐rhodamine was injected into these voids. Ex vivo optical imaging and histology were used to assess void morphology and biomaterial localization.

Results

Large sub‐epithelial voids were observed in both healthy and scarred VFs immediately following in vivo laser treatment. Two‐photon imaging and histology confirmed ~3‐mm wide subsurface voids in healthy and scarred VFs of canine #2. Biomaterial localization within a void created in the scarred VF of canine #2 was confirmed with fluorescence imaging but was not visualized during follow‐up two‐photon imaging. As an alternative, the biomaterial was injected into the excised VF and could be observed to localize within the void.

Conclusions

We demonstrated sub‐epithelial void formation and the ability to inject biomaterials into voids in a chronic VF scarring model. This proof‐of‐concept study provides preliminary evidence towards the clinical feasibility of such an approach to treating VF scarring using injectable biomaterials.

Level of Evidences

N/A Laryngoscope, 133:3042–3048, 2023
Response of phytoplankton to coastal upwelling: The importance of temporal and spatial scales
Authors: Favareto Luciane , Brotas Vanda , Rudorff Natalia , Zacarias Nuno , Tracana Andreia , Lamas Luisa , Nascimento Ângela , Ferreira Afonso , Gomes Mara , Borges Carlos , Palma Carla , Brito Ana C.
Published: April 2023

The Western Iberian Coast (WIC) is characterized by a dynamic coastal upwelling system with interactions between oceanographic features and continental river run‐off. The present study investigates the spatio‐temporal variability in the concentrations of Chlorophyll a (Chl a) and turbidity, and their relationships with physical and other biogeochemical properties along the entire coast of Portugal, as well as the response of phytoplankton to coastal upwelling pulses. In situ data were obtained during four oceanographic campaigns conducted in spring (April–May 2019), autumn (October 2018 and 2019), and early spring (February–March 2020). Upwelling conditions were evaluated through an upwelling index and auxiliary data such as sea surface temperature and height. In the WIC, the in situ surface temperature and salinity have a clear spatial pattern, both increasing from North to South. In autumn 2018 the highest temperatures coincided with the weakening of spring–summer upwelling conditions. Overall, high Chl a was associated with lower temperatures and higher dissolved oxygen concentrations (e.g., spring 2019). During spring 2019, an increase in Chl a, especially in the northern area, was associated with previous upwelling conditions. In early spring 2020, ongoing upwelling conditions in the northern area were associated with high turbidity and nutrients close to the shoreline with no immediate biological responses. An increase in Chl a was visible in satellite imagery a few days later. These results highlight the importance of understanding the complexity of coastal processes in the WIC.
Efficacy of non‐ablative 1927‐nm fractional thulium fiber laser for the treatment of Becker's nevus: Intra‐ and interobserver agreement study
Authors: Alajlan Abdulmajeed , Alsuwaidan Sami
Published: April 2023

Objective

To assess the efficacy and safety of a 1927‐nm fractional thulium fiber laser treatment for Becker's nevus.

Methods

A retrospective analysis of patients with Becker's nevus who were treated with a 1927‐nm fractional thulium fiber laser was conducted. Grading for lightening was set quarterly by physician global assessment of the pre‐ and postphotographs (I: <25%; II: 25%–50%; III: 51%–75%; and IV: >75% for marked lightening). Grading validation was exercised using intra‐ and interobserver agreement analysis among 10 dermatologists to determine the percent of agreement and the intraclass correlation coefficient. Grades I and II were classified as treatment failure.

Results

A total of 21 patients were recruited for analysis. The average number of treatment sessions was 2.1 per patient. A total of 13 patients achieved successful outcomes (grades III and IV) while 8 patients experienced treatment failure (grades I and II). Partial recurrence and transient hypopigmentation on adjacent skin were the main adverse effects. Only one patient reported worsening of the nevus. Overall agreement among the raters for the outcomes was graded from “very good” to “excellent,” and the intraclass correlation coefficient, kappa, was 0.8.

Conclusion

A 1927‐nm fractional thulium fiber laser may be effective to ameliorate the pigment of Becker's nevus and achieve acceptable cosmetic outcomes. However, further studies are required in this area to improve and optimize the results.
Bioinspired Multi‐Layer Biopolymer‐Based Dental Implant Coating for Enhanced Osseointegration
Authors: Uzulmez Betul , Demirsoy Zeynep , Can Ozge , Gulseren Gulcihan
Published: April 2023

The major drawbacks of metal‐based implants are weak osseointegration and post‐operational infections. These limitations restrict the long‐term use of implants that may cause severe tissue damage and replacement of the implant. Recent strategies to enhance the osseointegration process require an elaborate fabrication process and suffer from post‐operative complications. To address the current challenges taking inspiration from the extracellular matrix (ECM), the current study is designed to establish enhanced osseointegration with lowered risk of infection. Natural biopolymer pectin, peptide amphiphiles, and enzyme‐mimicking fullerene moieties are governed to present an ECM‐like environment around the implant surfaces. This multifunctional approach promotes osseointegration via inducing biomineralization and osteoblast differentiation. Application of the biopolymer‐based composite to the metal surfaces significantly enhances cellular attachment, supports the mineral deposition, and upregulates osteoblast‐specific gene expression. In addition to the osteoinductive properties of the constructed layers, the inherent antimicrobial properties of multilayer coating are also used to prevent infection possibility. The reported biopolymer‐artificial enzyme composite demonstrates antimicrobial activity against Escherichia coli and Bacillus subtilis as a multifunctional surface coating.
Natural and archaeological analogues for corrosion prediction in nuclear waste systems
Authors: King Fraser , Behazin Mehran , Keech Peter
Published: April 2023

Natural and archaeological analogues can be a powerful means to build confidence in the long‐term prediction of corrosion in nuclear waste systems. Analogues are meaningful to both experts and lay audiences. Useful analogues exist to support the long‐term behaviour for both copper and steel used fuel containers (UFC) and examples are given for the corrosion processes that are, and are not, expected to occur under repository conditions for both materials. The concept of kinetic versus thermodynamic stability is used to explain the persistence of such analogues. The use of analogues to support the prediction of the long‐term corrosion performance of the UFC in the safety case is also discussed. While there have been a wide range of analogue studies in the past, it is suggested that future studies should be focussed on addressing specific aspects of the treatment of corrosion issues in the safety case.