bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA nanomedicine: Design and recent applications
Authors: Kubiatowicz Luke J. , Mohapatra Animesh , Krishnan Nishta , Fang Ronnie H. , Zhang Liangfang 
Published: September 2022

AbstractThe rational design and application of mRNA‐based medicine have recently yielded some key successes in the clinical management of human diseases. mRNA technology allows for the facile and direct production of proteins in vivo, thus circumventing the need for lengthy drug development cycles and complex production workflows. As such, mRNA formulations can significantly improve upon the biological therapies that have become commonplace in modern medicine. Despite its many advantages, mRNA is inherently fragile and has specific delivery requirements. Leveraging the engineering flexibility of nanobiotechnology, mRNA payloads can be incorporated into nanoformulations such that they do not invoke unwanted immune responses, are targeted to tissues of interest, and can be delivered to the cytosol, resulting in improved safety while enhancing bioactivity. With the rapidly evolving landscape of nanomedicine, novel technologies that are under development have the potential to further improve the clinical utility of mRNA medicine. This review covers the design principles relevant to engineering mRNA‐based nanomedicine platforms. It also details the current research on mRNA nanoformulations for addressing viral infections, cancers, and genetic diseases. Given the trends in the field, future mRNA‐based nanomedicines have the potential to change how many types of diseases are managed in the clinic.
Long‐term use of probiotics for the management of office and ambulatory blood pressure: A systematic review and meta‐analysis of randomized, controlled trials
Authors: Zhao Tian‐Xue , Zhang Li , Zhou Ning , Sun Dong‐Sheng , Xie Jian‐Hong , Xu Shao‐Kun 
Published: September 2022

AbstractPrevious studies showed a controversial result on the relationship between probiotics treatment duration and blood pressure (BP). The present meta‐analysis is performed to summarize the effects of long‐term (≥8 weeks) use of probiotics on office and ambulatory BP using combined evidence from randomized, controlled trials. We searched PubMed, Embase, Cochrane library, and the ClinicalTrials.gov till January, 2021 to identify eligible articles. Primary outcomes were changes in office BP. In the presence of heterogeneity, a random‐effects model was used to calculate the combined treatment effect. Begg's funnel plots and Egger's regression test were used to assess the publication bias. Meta‐analysis of 26 trials in 1624 participants demonstrated that probiotic consumption significantly decreased office systolic BP by 2.18 mmHg (95% confidence interval [CI], −3.41 to −0.94 mmHg) and diastolic BP by 1.07 mmHg (95% CI, −1.72 to −0.41 mmHg). The analysis on ambulatory BP from three trials showed a similar reduction by −2.35/−1.61 mmHg (p ≤ .052). Subgroup analysis in hypertensive and diabetic patients showed a significant reduction in systolic and diastolic BP (p ≤ .02). The reductions in diabetic and hypertensive patients were comparatively larger than nondiabetic and normotensive patients (p ≥ .052). With the increase of age, baseline body mass index (BMI), treatment duration, and systolic BP, the effects of probiotics on BP did not increase significantly (ptrend ≥ .18). The present meta‐analysis suggests a beneficial effect of probiotics on BP by a modest degree, especially in the diabetes mellitus and hypertension. Prolonging the treatment duration could not improve the antihypertensive effect.
Decision‐making for early major amputation in selected diabetic foot ulcer patients with peripheral vascular disease
Authors: Gorden Lim York Tee , Ariel Ying Fangting , Pei Ho , Meng Lingyan , Yi Zhen N. G. , Graves Nicholas 
Published: September 2022

AbstractObjectiveTo estimate the costs from delaying major amputation in patients with concurrent diabetic foot ulcer and peripheral vascular disease. We seek to model economic benefits from saved costs from promoting timely major amputations among these patients.MethodsRetrospective modeling using data from National University Hospital, Singapore. We identified patients who might have delayed major amputations by applying a hierarchical clustering algorithm. We then modeled the transitions of all patients over time with a Markov process using a number of relevant health states to enable estimation of cost outcomes. We next summarized the expected changes to the bed days used and cost outcomes arising from reassigning some patients who may have had a delayed amputation to timely amputation. The findings from the sample were scaled to reflect national incidence rates for this disease for the years 2014–2019 in Singapore.Results and ConclusionsNine of the 137 patients (6.57%) would be suitable for a major amputation at 3 months, yet in reality, their amputation was delayed. Based on this, and assuming a timely amputation is done for the entire population of patients in Singapore we expect annual savings of 264,791 bed days and $211 million in costs. These findings are preliminary and uncertain. The value of this paper is to show a method for estimating outcomes, report the findings from a small sample, and stimulate future research. New cohort studies might be designed to capture a wider range of outcomes and recruit a larger sample of individuals.
Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives
Authors: Aswathy Maniyamma , Vijayan Ajesh , Daimary Uzini D. , Girisa Sosmitha , Radhakrishnan Kokkuvayil V. , Kunnumakkara Ajaikumar B. 
Published: September 2022

AbstractNatural products serve as the single most productive source for the discovery of drugs and pharmaceutical leads. Among the various chemicals derived from microbes, plants, and animals, phytochemicals have emerged as potential candidates for the development of anticancer drugs due to their structural diversities, complexities, and pleiotropic effects. Herein, we discuss betulinic acid (BA), a ubiquitously distributed lupane structured pentacyclic triterpenoid, scrutinized as a promising natural agent for the prevention, suppression, and management of various human malignancies. Ease of availability, common occurrences, cell‐specific cytotoxicity, and astonishing selectivity are the important factors that contribute to the development of BA as an anticancer agent. The current review delineates the mechanistic framework of BA‐mediated cancer suppression through the modulation of multiple signaling pathways and also summarizes the key outcomes of BA in preclinical investigations.
Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles
Authors: Visan Kekoolani S. , Lobb Richard J. , Ham Sunyoung , Lima Luize G. , Palma Carlos , Edna Chai Pei Zhi , Wu Li‐Ying , Gowda Harsha , Datta Keshava K. , Hartel Gunter , Salomon Carlos , Möller Andreas 
Published: September 2022

AbstractSmall extracellular vesicles (sEVs) provide major promise for advances in cancer diagnostics, prognostics, and therapeutics, ascribed to their distinctive cargo reflective of pathophysiological status, active involvement in intercellular communication, as well as their ubiquity and stability in bodily fluids. As a result, the field of sEV research has expanded exponentially. Nevertheless, there is a lack of standardisation in methods for sEV isolation from cells grown in serum‐containing media. The majority of researchers use serum‐containing media for sEV harvest and employ ultracentrifugation as the primary isolation method. Ultracentrifugation is inefficient as it is devoid of the capacity to isolate high sEV yields without contamination of non‐sEV materials or disruption of sEV integrity. We comprehensively evaluated a protocol using tangential flow filtration and size exclusion chromatography to isolate sEVs from a variety of human and murine cancer cell lines, including HeLa, MDA‐MB‐231, EO771 and B16F10. We directly compared the performance of traditional ultracentrifugation and tangential flow filtration methods, that had undergone further purification by size exclusion chromatography, in their capacity to separate sEVs, and rigorously characterised sEV properties using multiple quantification devices, protein analyses and both image and nano‐flow cytometry. Ultracentrifugation and tangential flow filtration both enrich consistent sEV populations, with similar size distributions of particles ranging up to 200 nm. However, tangential flow filtration exceeds ultracentrifugation in isolating significantly higher yields of sEVs, making it more suitable for large‐scale research applications. Our results demonstrate that tangential flow filtration is a reliable and robust sEV isolation approach that surpasses ultracentrifugation in yield, reproducibility, time, costs and scalability. These advantages allow for implementation in comprehensive research applications and downstream investigations.
Galectin-3 as a biomarker in breast neoplasms: Mechanisms and applications in patient care
Authors: Niang Doudou Georges Massar , Gaba Folly Mawulolo , Diouf Adame , Hendricks Jacobus , Diallo Rokhaya Ndiaye , Niang Maguette Deme Sylla , Mbengue Babacar , Dieye Alioune 
Published: September 2022

AbstractGalectin-3 is a member of the lectin family encoded by the LGALS3 gene on chromosome 14. It is secreted by a wide range of immune cells and mammary tumor cells. Through its activity on the tumor microenvironment, in particular on tumor-infiltrating leukocytes, galectin-3 improves the proliferation, survival, and colonizing ability of mammary neoplastic cells. Consequently, galectin-3 expression in the tumor microenvironment could worsen therapeutic outcomes of breast neoplasms and become a biomarker and a therapeutic target in combined immunotherapy in breast neoplasms. There is a limited amount of information that is available on galectin-3 in breast cancer in Africa. In this review, we analyze how galectin-3 influences the tumor microenvironment and its potential as a biomarker and therapeutic target in breast neoplasms. We aim to emphasize the significance of investigating galectin-3 in breast neoplasms in Africa based on the results of studies conducted elsewhere.
Tree species affect the vertical distribution of soil organic carbon and total nitrogen
Authors: Steffens Christina , Beer Christian , Schelfhout Stephanie , Vesterdal Lars 
Published: September 2022

AbstractBackgroundForest soils are considered sinks for atmospheric C. Many studies revealed that tree species and their mycorrhizal association affect forest floor and topsoil organic C (OC) and total N, while the knowledge of their effect on subsoil OC and N is still scarce.AimsWe aimed to identify (1) tree species and mycorrhizal association effects on forest floor, topsoil (0–30 cm) and subsoil (30–80 cm) OC and N stocks and vertical distribution and (2) drivers for soil OC and N distribution.MethodsWe sampled forest floor, topsoil and subsoil under Fagus sylvatica L., Quercus robur L., Acer pseudoplatanus L. and Fraxinus excelsior L. in four Danish common garden experiments along a gradient in soil texture and determined OC and N stocks.ResultsTotal N (forest floor + soil) was higher under oak than beech, while total OC was unaffected by species. Forest floor C and N were higher under oak and beech, both ectomycorrhizal species (ECM), compared to under maple and ash, which are both arbuscular mycorrhizal species (AM). Relatively more OC and N were transferred to the topsoil under AM than ECM species, and this could be explained by greater endogeic earthworm biomass in AM species. In contrast, a higher proportion of OC was stored under ECM than AM species in the subsoil, and here OC correlated negatively with anecic earthworms. Subsoil N was highest under oak.ConclusionsTree species and in particular their mycorrhizal association affected the vertical distribution of soil OC and N. Tree species differences in topsoil OC and N were not mirrored in the subsoil, and this highlights the need to address the subsoil in future studies on AM‐ versus ECM‐mediated soil OC and N stocks.
Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea
Authors: Hwang Se Hwan , Kim Sun Won , Kim Do Hyun 
Published: September 2022

ObjectiveTo assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea.Data SourcesThe PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar databases were searched up to December 2021.Review MethodsDiagnostic accuracy was compared among seven radiological methods: computed tomography (CT), CT cisternography (CTC), magnetic resonance imaging (MRI), magnetic resonance cisternography (MRC), CT + MRI, radionuclide cisternography, and intrathecal gadolinium (Gd)‐MRC. Sensitivity, specificity, and accuracy were used as outcomes of the analysis. Both a traditional pairwise meta‐analysis and a network meta‐analysis were performed.ResultsTwenty‐three trials were included in the analysis. The results of a network meta‐analysis performed on a network consisting of seven diagnostic methods showed that all imaging modalities had greater diagnostic accuracy than CT, with the exception of CTC, which had lower sensitivity. Only intrathecal Gd‐MRC was significantly superior to other imaging methods with regard to sensitivity and accuracy. Gd‐MRC also showed the greatest surface under the cumulative ranking curve values for all of the outcomes (sensitivity: 0.9200; specificity: 0.8364; accuracy: 0.8920).ConclusionThis network meta‐analysis demonstrates that intrathecal Gd‐MRC is the most useful diagnostic method to detect CSF rhinorrhea. Laryngoscope, 133:1281–1287, 2023
A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate
Authors: Bevis Nicholas , Effertz Thomas , Beutner Dirk 
Published: September 2022

ObjectiveIn passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre‐tension in the annular ligament resulting in unsatisfactory hearing results.MethodsIn collaboration with MED‐EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser‐Doppler‐Vibrometry, we measured the sound‐induced velocity of the stapes footplate relative to a given acoustic stimulus.ResultsThe new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane.ConclusionThis development is a further step toward a physiological reconstruction of the ossicular chain.Level of EvidenceNA Laryngoscope, 133:1717–1721, 2023
A comparative study on corrosion failure analysis of hearing aid devices from different markets
Authors: Yadav Abhijeet , Ambat Rajan 
Published: September 2022

AbstractThe vulnerability of hearing aid devices to corrosion is critical due to their exposure to various kinds of ionic contaminants from the human body, such as sweat, sebum, and so forth, and harsh climatic conditions such as high temperature, humidity, and atmospheric pollutants. The device failure rate will vary depending upon the type of geographical location at which the device is used and root cause failure analysis is a crucial tool to understand the effect of geographical location on corrosion failures. In this study, field failed hearing aid devices from Europe, the United States, and Japan markets were investigated using a scanning electron microscope and elemental dispersive spectroscopy to locate failure mechanisms and causes. Information from the analysis was used for statistical analysis to compare the performance of the devices in the three markets based on failure percentage and failure probability for different parts and components. Solder terminals, battery contacts, light‐emitting diodes, and wireless‐link coil showed consistent and high failure probability across all three markets, whereas a higher failure rate for microphones was found in Europe and the United States market as compared to the Japanese market. The majority of the components corrosion failures occurred in the presence of high chloride ions from human sweat and the atmospheric conditions, whereas potassium hydroxide from the leakage of Zn–air battery was found as the additional cause for microphone failure.
Tannic Acid Crosslinked Self‐Healing and Reprocessable Silicone Elastomers with Improved Antibacterial and Flame Retardant Properties
Authors: Jiao Yizhi , Rong Zhihao , Gao Chuanhui , Wu Yumin , Liu Yuetao 
Published: September 2022

AbstractSilicone elastomers are widely used in aviation, electronics, automotive, and medical device fields, and their overuse inevitably causes recycled problems. In addition, the elastomers are subject to attack by bacteria and fire during use in some application scenarios, which is a safety hazard. Therefore, there is a great need to prepare silicone elastomers with improved antibacterial, flame retardant, self‐healing, and recyclable functions. A new strategy is proposed to prepare silicone elastomers with bio‐based tannic acid as cross‐linkers to solve this problem by using polydimethylsiloxane as a soft chain segment and 2,2‐bis(hydroxymethyl)propionic acid as an intermediate chain extender. Based on the phenol carbamate bonding and hydrogen bonding interactions, the elastomer has efficient self‐healing ability and can achieve dynamic dissociation at 120 °C for complete recovery. In addition, due to the unique spatial structure and polyphenolic hydroxyl groups of tannic acid, the mechanical properties of the elastomer are greatly improved with an antimicrobial efficiency of over 90% and a final oxygen index of 25.5%. The multifunctional silicone elastomer has great potential applications in recyclable refractory materials and antimicrobial materials.
Two types of detrusor underactivity in men with nonneurogenic lower urinary tract symptoms
Authors: Matsukawa Yoshihisa , Naito Yushi , Ishida Shohei , Matsuo Kazuna , Majima Tsuyoshi , Gotoh Momokazu 
Published: September 2022

AbstractAimsTo clarify the clinical features of men with nonneurogenic detrusor underactivity (DU) by focusing on storage dysfunction (SD).MethodsWe retrospectively reviewed the clinical and urodynamic data of men with nonneurogenic DU. Patients were divided into two groups according to the presence or absence of SD, such as detrusor overactivity (DO) and reduced bladder compliance (BC). Patient characteristics, lower urinary tract symptoms (LUTS), and urodynamic parameters were compared. DU was defined as bladder contractility index (BCI) ≤ 100 and bladder outlet obstruction index (BOOI) ≤ 40.ResultsOf 212 men with DU, 123 (58.0%) had concomitant SD (SD + DU group), and 89 (42.0%) had only DU (DU‐only group). Age, prostate volume, and severity of storage symptoms were significantly higher in the SD + DU group. Particularly, >80% of men in the SD + DU group met the diagnostic criteria for overactive bladder in Japan, which was significantly higher than the 26% of men in the DU‐only group. The frequency of urinary urgency incontinence (UUI) was also significantly higher in the SD + DU group (65% vs. 12% in DU‐only group). In contrast, voiding symptoms, including straining, were more severe in the DU‐only group. Regarding the urodynamic parameters, compared to the DU‐only group, bladder capacity was significantly smaller and BOOI and BCI were significantly higher in the SD + DU group. However, there was no significant difference in the maximum flow rate and bladder voiding efficiency.ConclusionsApproximately 60% of men with DU had SD, such as DO and/or reduced BC, whereas the remaining 40% had increased bladder capacity without an increase in detrusor pressure during the storage phase. There were significant differences in the storage and voiding symptoms between the groups. It is important to divide patients with DU based on SD to accurately clarify the clinical picture of DU.
A qualitative descriptive study of effective leadership and leadership development strategies used by nurse leaders in European island countries
Authors: Hughes Victoria , Wright Rebecca , Taylor Janice , Petchler Claire , Ling Catherine 
Published: September 2022

AbstractAimNurse leaders influence workplace culture; however, little is known about ethnic cultural influences on nurse leader development. This research aims to identify personal strategies promoting effective leadership by nurse leaders from European small island countries.DesignDescriptive qualitative study.MethodsIn 2017, nineteen semi‐structured interviews with nurse leaders from England, Greece, Republic of Ireland and Malta explored leadership journeys, strategies employed to support their growth and development, and how cultural identity played a role. Transcripts were analysed using reflexive thematic analysis.ResultsFour main themes and 12 subthemes captured the strategies and approaches of the nurse leaders: (1) Influences, (2) Communication, (3) Process and (4) Relationships. These findings reflect and validate the five transformational leadership practices of the Exemplary Leadership Model. While cultural island identity was discussed, there was a shared cultural identity within the role of “nurse leader” that spanned all islands.Patient or Public ContributionsNineteen nurse leaders contributed to this study.
Early evidence of extra‐masticatory dental wear in a Neolithic community at Bestansur, Iraqi Kurdistan
Authors: Walsh Sam 
Published: September 2022

AbstractThis paper presents the first evidence of extra‐masticatory dental wear from Neolithic Bestansur, Iraqi Kurdistan (7700–7200 BC). Bestansur is a rare, recently excavated burial site of this period in the Zagros region, of Iraqi Kurdistan. A total of 585 teeth from 38 individuals were analyzed for features indicative of activities including oblique wear planes, notches, grooves, and chipping. Indications of extra‐masticatory wear were found in 27 of 38 individuals, and 277 of 585 teeth (47%) available for study. The most frequent features were chipping and notches suggesting activities such as processing fibers by using the teeth as a “third hand.” Evidence for these wear features was present in both males, females, and in children aged five and older. These aspects of childhood life‐course and dentition are rarely investigated. The presence of dental wear features in the deciduous dentition can indicate an age range at which activities began in different groups and highlights the importance of including juvenile remains in such studies. The variety of forms of dental wear may relate to the mixed diet and activities of these people. This study adds to our understanding of human behaviors and socio‐cultural aspects of life during this transitional period.