bluuebunny/crossref_metadata_2025 huggingface dataset:
Cure Kinetics of Epoxy Resin with Styrene Maleic Anhydride Copolymer by Differential Scanning Calorimetry Technique
Authors: Vora Rasikial A. , Trivedi Harikrishna C. , Patel Chandrakant P. , Kazlauciunas Algy , Guthrie J.T. , Trivedi Mukundray C.
Published: March 2023

The curing reactions of an epoxy resin with a styrene-maleic anhydride copolymer were investigated using differential scanning calorimetry at various scan rates (5, 10, 20 and 50°C/min) in a nitrogen atmosphere. The values of certain kinetic parameters, namely activation energy (E), pre-exponential factor (Z), rate constant (k) and half-life (T1/2) were evaluated for various mixtures of a commercial epoxy resin and a styrene maleic anhydride copolymer on the basis of the Ozawa as well as Kissinger methods, which were found to be in reasonably good agreement with each other.
Lapinus Fibre Reinforced Phenolic Composites: Flexural and Friction Properties
Authors: Dong Feng , Blum Frank D. , Dharani L.R.
Published: March 2023

The flexural and frictional properties of Lapinus fibre-reinforced phenolic friction materials at different fibre loadings have been studied via three point bend tests and SAE J661a friction tests, respectively. A positive correlation was observed between flexural moduli and fibre volume fraction for these materials. The empirical constant in the Halpin-Tsai model is about 0.22 for this material compared with 0.375 for some other fibre reinforced structural composites with randomly distributed fibres in a plane. The coefficient of friction of the composites fell in the range of 0.1 to 0.5 and the minimum friction was found in materials with volume fraction of 0.024 to 0.05 fibre loading. These two fibre loadings also showed a more stable coefficient of friction than the other fibre loadings did over the wide range of temperatures in the second fade test. A minimum volumetric wear was found in the material with 0.05 fibre loading during the wear test. The wear mechanisms at different fibre loadings have also been discussed.
NDT of Composite Materials - Problems and Solutions 1. NDT as a Source of Information
Authors: Matiss I.
Published: March 2023

This introductory paper is devoted to highlighting distinctive features of the non-destructive testing (NDT) techniques used in the study of polymers and composite materials. More than 30 years experience at the Institute of Polymer Mechanics has shown that success in the application of NDT to advanced materials depends crucially on the optimal choice of the technique and on the skill of the operator. The reason for a special approach to testing of these materials is that a number of specific features characterise composite structures. Analysis of these features, recommendations to increase the reliability and the accuracy of the NDT methods and a search for new testing techniques are the major areas of research carried out in the Institute. The following topics will be covered:

1. Non-destructive testing as a source of information.

2. Relaxation spectrometry for the structural study of polymers and polymer composites.

3. Modelling of dielectric relaxation phenomena.
In-Situ Composite Manufacture Using an Electrostatic Powder Spray Process and Filament Winding
Authors: Duvall Mark , Ramani Karthik , Bays Mark , Caillat Frederic
Published: March 2023

This paper details the development of a composite manufacturing process that uses an electrostatic powder spray technique to impregnate a continuous fibre tow with a thermoplastic polymer. The resulting towpreg undergoes intermediate forming to induce further wetout of the fibres by the polymer matrix. An on-line filament winding apparatus then consolidates the towpreg into a finished cylinder. Experimental results detail the effects of key spray coating parameters such as electrostatic corona voltage, powder velocity, and powder mass flowrate. The process demonstrates its effectiveness in coating and consolidating a variety of materials, including E-glass, S-glass, and carbon fibres.
Fatigue Damage Nucleation and Growth in a Unidirectional Glass-Epoxy Composite Subjected to Hygrothermal Ageing
Authors: Vauthier E. , Oiateauminois A. , Bailliez T.
Published: March 2023

The effects of hygrothermal ageing on the fatigue properties of a unidirectional glass/epoxy composite have been investigated. Damage nucleation was monitored in terms of fibre breakage by in-situ microscopic observation of the tensile face of the specimens during flexural tests. From the mapping of individual fibre breaks during monotonic and fatigue loading, the overall losses of properties were linked to the drop in the glass fibres’ load-bearing properties. The endurance properties of the composite declined after water ageing. A drop in the in-situ statistical distribution of fibre strengths could account for such an observation. Furthermore, this fibre weakening was associated with an increase in the pH of the ageing media. During water sorption, the water gradually becomes alkaline due to leaching and the hydrolysis of the matrix's unreacted hardener.
Effect of Styrene Content and ZnO-Stearic Acid on the Dynamic Mechanical Properties of Electron Beam Vulcanised Styrene-Co-Butadiene Rubber
Authors: Abdel-Aziz M.M. , Youssef H.A. , Miligy A.A. El , Yoshii F. , Makuuchi K.
Published: March 2023

The dynamic mechanical properties of electron beam vulcanized Styrene-Co-butadiene rubber (SBR) in presence of different additives over a wide temperature range were investigated. Also, the effect of HAF carbon black, the ZnO-Stearic acid system, and styrene content on the other mechanical properties was studied. It was found that, the more pronounced contribution from by ZnO was in SBR (23.5% styrene) where the storage modulus and damping as well as tensile strength, elongation, tear strength, hardness and abrasion resistance were remarkably improved.

The high efficiency of ZnO toward SBR (23.5% styrene) compared with SBR (46% styrene) may be attributed to the enhancement of the crosslinking density as a result of there being more butadiene units in the former.
Impact Performance of a Woven Fabric CFRP Laminate
Authors: Kim J.K. , Leung L.M. , Lee S.W.R. , Hirai Y.
Published: March 2023

Low velocity instrumented impact, ultrasonic C-scan and compression-after-impact tests have been employed to assess the damage resistance and damage tolerance of carbon fibre-epoxy matrix composites (CFRPs). The potential advantages of using woven fabrics, compared to cross ply unidirectional fibres, in impact performance of carbon fibre composites were examined. The laminates had two distinct fibre configurations and similar static in-plane mechanical properties in the undamaged state. The characteristic impact loads and the corresponding absorbed energies were used to evaluate the initial damage resistance of the laminates. The residual strengths, measured from the compression-after-impact tests, were analysed to predict the threshold energy and the threshold damage area, which are a measure of the damage tolerance of the laminates.
Tensile Properties of Short Glass Fibre Reinforced Polycarbonate
Authors: Ho Kye-Chyn , Hwang Jiun-Ren , Doong Ji-Liang
Published: March 2023

The present study analyses the tensile properties of polycarbonate and of polycarbonate reinforced with 20 and 30 wt.% short glass fibre. The specimens were prepared under various injection moulding conditions, such as filling time, melting temperature and mould temperature. The fracture mechanism was examined by scanning electron microscopy. The results indicated that the polycarbonate reinforced with 30 wt.% short glass fibre shows the highest strength, together with the highest Young's modulus and yield strength. The ultimate strength of the 30 wt.% reinforced-material is approximately 20% higher than that of the 20 wt.% reinforced equivalent and about twice as high as that of unreinforced polycarbonate. Also, the ultimate strength measured in the direction of injection flow was about 10% higher than that measured normal to it. The optimum injection moulding conditions for ultimate strength are: filling time 5 s, melting temperature 290°C and mould temperature 80°C. The ranking of the ultimate strength is strongly related to the layer thickness in which the fibres align with the tensile direction. The higher the fibre content, the higher the strength. The striations, cleavage and tearing fracture mechanisms dominate in unreinforced polycarbonate when the tensile stress was parallel with the flow direction, while splits and secondary cracks were found when the tensile direction was perpendicular to the flow direction. The fibre pull-out, fibre breakage and striations are the major fracture mechanisms in short glass fibre reinforced polycarbonate.
Characterization of Oral Microbiota Following Chemotherapy in Patients With Hematopoietic Malignancies
Authors: Omori Michi , Kato-Kogoe Nahoko , Sakaguchi Shoichi , Komori Eri , Inoue Kazuya , Yamamoto Kayoko , Hamada Wataru , Hayase Tomoyoshi , Tano Tomoyuki , Nakamura Shota , Nakano Takashi , Une Hidenori , Ueno Takaaki
Published: March 2023

Oral microbiota may be associated with serious local or systemic medical conditions resulting from chemotherapy. This study was conducted to evaluate the changes in the oral microbiota following the initiation of chemotherapy in patients with hematopoietic malignancies and to identify the characteristics of the oral microbiota associated with oral mucositis. Oral samples were collected from 57 patients with hematopoietic malignancies at 2 time points: before the start of chemotherapy and 8 to 20 days after the start of chemotherapy, when chemotherapy-induced oral mucositis often occurs, and 16S rRNA metagenomic analyses were performed. Comparative and linear discriminant analysis effect size (LEfSe) analyses were used to determine the characteristic bacterial groups before and after the initiation of chemotherapy and in those who developed oral mucositis. The alpha and beta diversities of oral microbiota before and after the initiation of chemotherapy differed significantly (operational taxonomic unit index, P < .001; Shannon’s index, P < .001; unweighted UniFrac distances, P = .001; and weighted UniFrac distances, P = .001). The LEfSe analysis revealed a group of bacteria whose abundance differed significantly before and after the initiation of chemotherapy. In the group of patients who developed oral mucositis, a characteristic group of bacteria was identified before the start of chemotherapy. In conclusion, we characterized the oral microbiota associated with the initiation of chemotherapy in patients with hematopoietic malignancies. In addition, our findings suggest that oral microbiota composition before the start of chemotherapy may be associated with oral mucositis. The results of this study emphasize the importance of oral management focusing on the oral microbiota during chemotherapy in patients with hematologic malignancies.
Readmission After COVID-19 for Late Acute Venous Thrombosis; CASE SERIES and Systematic Review of the Literature
Authors: Gómez Gutiérrez Oliver Antonio , McQuary Gabriel Salinas , Gonzalez-Urquijo Mauricio , Lozano Balderas Gerardo , Fabiani Mario Alejandro
Published: March 2023

Objective

Assess heterogeneity within patients with resolved COVID-19 to broaden the vision about post-discharge thrombotic cases and postulate possible related mechanisms in search of better anticoagulation guidelines. This study details patients’ characteristics, medical history, treatment, and outcomes of readmitted patients with late acute thrombosis through a systematic review of the literature and patients from our academic center database.

Methods

We extracted the records of patients readmitted for venous thrombosis complications after discharge from the database of the first 2000 patients admitted with COVID-19 in our academic center; we also performed a systematic review of the literature using the Medical Subject Headings terms “late thrombosis,” “COVID-19,” + “venous thrombosis” in PubMed and Google Scholar according to PRISMA guideline.

Results

The literature review found 20 patients suitable for review matching the inclusion criteria. These patients were added to those in our database, summing up a total of 26 patients. The median age was 50 years old, 76.9% were male, and most were overweight or had grade 1 obesity (n = 11, 42.3%). None had a previous thrombotic history, but 50% had an underlying comorbidity. Thrombotic events presented on a median of 20 days (range: 4-150 days) from discharge. Pulmonary embolisms occurred in 23 patients (88.46%), deep vein thrombosis in 4, mesenteric thrombosis, and cerebral venous thrombosis in 1, respectively.

Conclusion

This study found that most patients readmitted for thrombotic events after COVID-19 discharge were middle-aged men with Venous Thrombo Embolism events.
A Safer Work Environment for Stabilization of Moldy Collections
Authors: Tarnowski Amber L.
Published: March 2023

The National Museum of African American History and Culture (NMAAHC) is an actively collecting museum, and collections stewardship preservation activities include treatment of objects affected by mold. Mold adversely impacts the physical stability and esthetic qualities of collection objects and creates unsafe conditions; providing a safe treatment environment is part of an overall risk-reduction strategy. Federal standards for working with moldy museum objects do not exist therefore disaster recovery-type practices are utilized, but it is unknown if basic isolation tents provide the safest environment for protecting those treating the objects. Prolonged use of a disaster-type isolation tent at NMAAHC proved unsatisfactory and unsafe; defining the optimal specifications and identifying applicable standards were key to designing a safer solution. Input from the museum industry and engineers, along with an examination of standards for similar hazards, impacted the overall design of an improved enclosure. Comparisons between the disaster-recovery isolation type enclosure and the new negative-pressure enclosure are compared for appropriate applications, context, and scale of different situations.
“You’ve Been Living Here For as Long as You Can Remember”: Trauma in OMORI's Environmental Design
Authors: Younis Aya , Fedtke Jana
Published: March 2023

Developed by Omocat and released in December 2020, OMORI is a surreal psychological horror role-playing game. The game follows the titular protagonist Omori as it examines such sensitive topics as suicide, grief, death, and depression. Such traumatic events are triggered in several planes of existence—White Space, Headspace, and Black Space—leading to anxiety, regression, and resurfacing trauma. In our article, we examine such representations of trauma with particular attention to the role of environmental design. The planes represent different approaches to memory, trauma, and repression, which Omori and the player navigate in non-linear, recursive paths. We analyze how each space seeks to illuminate and explore aspects of trauma in its respective atmosphere. Through environmental design, OMORI provides players with three distinct experiences with escapism and trauma that are representative of the experiences of trauma victims, ultimately elucidating the psychological phenomenon on a larger scale to de-stigmatize trauma.
Effect of cooling and lubrication conditions on cutting performance and surface integrity of Inconel 718 superalloy in end face milling
Authors: Lei Xuelin , Wei Xiangzheng , He Yun
Published: March 2023

Inconel 718 nickel-based superalloy has superior thermal and mechanical properties. Nevertheless, it is a hard-to-machine material, and the heat generated by processing is excessive. Reasonable cooling and lubrication (CL) methods have essential effects on its cutting performance and surface integrity. In this study, Dry cutting (DC), flood cutting (FC), cryogenic cutting (CC), and cryogenic minimum quantity lubrication cutting (CMQLC), are used to cutting Inconel 718 under the same parameters. Cutting forces, temperature, tool wear, chip, Ra, microstructure, and residual stress (RS) are measured. It is concluded that the combination of CL is beneficial for processing. The average temperature obtained by CMQLC is 55.47% lower than that of DC. And the workpiece obtained by CMQLC is measured compared with FC, the area of tool chipping is reduced by 25%, and the surface Ra is decreased by 32.05%, the lowest among the four methods. As for RS, although TRS increased by 7.9%, the MCRS and influence depth of the subsurface increased by 3.9% and 10.2% respectively. Furthermore, the machining condition with a high mechanical thermal ratio can obtain a more favorable RS state. Generally speaking, the CMQLC shows the advantages of mild environmental pollution, preferred cutting performance, and superior workpiece surface integrity.
Between remembrance and commerce: Writing a painting treatise in nineteenth-century Shanghai
Authors: Klasing Chen Monica
Published: March 2023

This study takes a socio-historical approach to analyze a case of how practical painting knowledge was historicized during nineteenth-century China. After the Taiping War (1850–1864), a civil war that left urban centers in the cultural heartland of China in ruins, scholars sought to recover and commemorate the past. The professional painter Dai Yiheng publicly engaged his traumatic war experience to cater to a new audience of foreign students in Shanghai. The tension between the commercial environment of Shanghai and his personal experience becomes visible in both his paintings and writings. Through a practice of temporal layering in his work, Dai managed to combine the demands of his profession and his personal trauma.
Direct GDP-KRASG12C inhibitors and mechanisms of resistance: the tip of the iceberg
Authors: Rosen Joshua C. , Sacher Adrian , Tsao Ming-Sound
Published: March 2023

Kirsten rat sarcoma viral oncogene homolog mutations are observed in 25% of lung adenocarcinoma and 40% of these are G12C mutations. Historically, no approved targeted agents were available for patients with any KRAS mutation, and response rates to standard-of-care therapies were suboptimal. Newly developed inhibitors directed toward KRASG12C have been successful in clinical trials with overall response rates ranging between 32% and 46%, and two FDA approvals were granted in May 2021 and December 2022 as second-line or later monotherapies. However, rapid tumor resistance complicates their use as a monotherapy. With the rapid development of this novel class of inhibitors, it is important to discern the different types of tumor resistance that may arise and how each can differently contribute to tumor growth and survival. G12C inhibitor resistance is under investigation and combinations of therapies with G12C inhibitors have been proposed. Much of this insight is gleaned from preclinical investigations, as our knowledge of clinical resistance is in its infancy. In this review, we summarize the preclinical development of KRASG12C inhibitors, their clinical evaluations, different types of resistance mechanisms to these compounds, and ways of overcoming them. Finally, we underscore the importance of basic and translational investigations of these molecules in a landscape where their clinical evaluations garner the most attention, and we set the stage for what is to come.
Incidence of barotrauma in patients with COVID-19 (alpha- and beta-predominant period) requiring mechanical ventilation: Single-center retrospective study
Authors: Donohue Kristina-Noel , Sivanushanthan Shankarapryan , Etling Emily , Hockstein Michael , Yohannes Seife , Clark Paul
Published: March 2023

Objective:

We sought to determine predictors, incidence, and interventions required for patients who developed barotrauma. Pneumothorax, subcutaneous emphysema, and pneumomediastinum have all been reported as complications related to COVID-19-positive patients requiring invasive mechanical ventilation.

Methods:

In this retrospective study, clinical and imaging data from COVID-19 patients were collected and reviewed by two independent intensivists between January 4, 2020 and January 10, 2020. Data were used to identify COVID-19-positive patients requiring invasive mechanical ventilation and the incidence of barotrauma. Two separate cohorts were created as non-injured (no barotrauma) and injured (barotrauma present). We then sought to identify the risk factors for barotrauma in the non-injured cohort on Days 0, 7, 10, and 14 after intubation and day of injury in the injured cohort.

Results:

Of the 264 patients with COVID-19, 55.8% were African American. The non-injured group was older (60 ± 15 versus 49 ± 16, p  = 0.006), with male predominance in the injured group versus non-injured group (75% versus 55%). A total of 16 (6.5%) patients developed one or more complications of barotrauma, defined as subcutaneous emphysema, pneumothorax, or pneumomediastinum. Length of stay was longer for the injured group versus non-injured group (47 versus 25 days). Plateau pressure ( p  = 0.024), fraction of inspired oxygen ( p < 0.001), and driving pressure ( p = 0.001) were statistically significant in injured cohort. Mortality rate in non-injured versus injured was 49.4% versus 69%. Using random effect model, fraction of inspired oxygen ( p = 0.003) and mean airway pressure ( p  = 0.010) were significant at the time of injury. When comparing alive versus deceased in the injured cohort, thoracostomy placement in alive versus deceased was 80% versus 54.5%.

Conclusion:

COVID acute respiratory distress syndrome patients requiring invasive mechanical ventilation had a higher rate of barotrauma and were younger than those who did not develop barotrauma. Possible interventions to be considered to decrease barotrauma are decreased driving pressure goal and universal use of esophageal balloon manometry.
Photographs and COVID-19: The therapeutic quality of shared narratives and collective memory
Authors: Kwesell Allison , Wu Yufei , Lama Dechen , Lin Shuyang
Published: March 2023

Mainstream media photographically documented intimate and difficult moments of COVID-19 while also publishing hopeful images. These spanned from intubation, death, and facial bruising from personal protective equipment to Italians harmonizing in song and nightly balcony cheers for US health workers. At the same time, people were documenting and sharing their own experiences across social media. Past research suggests impactful photographs elicit stimuli that can slow people’s psychological recovery or offer a therapeutic quality that incites post-traumatic growth. Despite a large body of research that examines visual framing with media photographs, few studies examine the ways in which viewing photographs of disaster influences disaster survivors, and to our knowledge, no studies examine this during an unfolding trauma in a world in which the survivors themselves digitally archive the event through images. The present panel longitudinal study seeks to investigate this gap by better understanding the impact of COVID-19 photographs through employing a visual self-narrative approach and photo-elicitation interviews. Fifty-seven participants were recruited in May 2020 and 35 repeat participants were recruited in May 2021. The research examines (1) reasons people vulnerable to the pandemic may find viewing and sharing photographs important, (2) responses to shared images, and (3) changes people experience in their relationship to photographs over time. Findings suggest that participants have a drive to share their experiences and learn about others, while pandemic photographs in themselves hold more of a negative impact for the viewer as they are experiencing the pandemic, which, over time, lessens and trends toward more positive nostalgia.
Resilience and (Dis)empowerment: Use of Social Media Among Female Mainland Low-Skilled Workers in Macao During the COVID-19 Pandemic
Authors: Ju Bei , Dai Hai Min , Sandel Todd L.
Published: March 2023

The role of social media in a resilient process is associated with the co-constitution of structural forces and users’ agency. During COVID-19, how women—particularly low-skilled labor migrants—used social media for empowerment is underexplored. By taking a socio-techno approach, this study qualitatively examines mobile phone-based social media usage among female mainland low-skilled workers in Macao when coping with the pandemic. The enabling yet constraining role of social media has been identified through semi-structured interviews. Social media use is a double-edged sword: on the one hand, social media is appropriated to relieve stress and anxiety, open access to updated COVID-19 related information, and manage contagious risks; on the other hand, it reinforces existing constraints and thus hinders resilience, due to female migrant workers’ high risk of addictive social media use and limited information literacy. Moving beyond the Information and Communication Technology empowerment, a more inclusive approach is recommended in the long term to cope with the risks and uncertainties posed by the pandemic.
“What is Wrong With You People That You are Happy Someone has Covid” Impoliteness in the Coronavirus Pandemic Era
Authors: Tsoumou Jean Mathieu
Published: March 2023

Whilst the coronavirus pandemic keeps threatening the world at large, little is yet known about the impoliteness implications of user-generated- Covid-related contents on social media such as Facebook. The aim of this study is to examine the comments made in response to Giuliani’s Covid- 19 diagnosis, from an impoliteness perspective. A merely qualitative analysis of a dataset of 3,000 comments evenly collected from three different news outlets (i.e., BBC, CNN, Fox News), the findings reveal that the reactions to Giuliani’s diagnosis are more focused on him being a politician, than him being a human being affected by the virus. The reactions attack his actions and the actions of others within his political party, which suggests that impoliteness has a strong dependence on previous actions and political engagement. Giuliani is seen by some users to be undeserving of compassion or empathy not just on the grounds of his active involvement in attempting to overturn the presidential election results, but also for his disregard toward mask wearing in public spheres. Not all the users, however, appreciate the attacks against Giuliani. Through metadiscursive comments, some users not just feel the need to treat Giuliani as a human being, but more importantly remind fellow users that Covid-19 should be a concern for all. What is particularly critical about these metacomments is that while the users advocate for civil interactions, they mostly do not condone Giuliani’s actions. This so because these users understand what should be obligatory, permissible, or forbidden on the human level under the circumstances.
Invega Hafyera (Paliperidone Palmitate): Extended-Release Injectable Suspension for Patients With Schizophrenia
Authors: Peters Lindsey , Dyer Megan , Schroeder Emily , D’Souza Manoranjan S.
Published: March 2023

Objective: The objective of this study was to describe the safety, efficacy, and potential role in therapy of once in 6 months paliperidone palmitate formulation (PP6M; Invega Hafyera). PP6M is a long-acting injectable antipsychotic recently approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. Data Sources: A PubMed literature search was conducted using the following terms: paliperidone palmitate and long-acting antipsychotic injections (January 1, 2017, to November 1, 2022). FDA product labeling was also reviewed for pertinent data. Study Selection and Data Extraction: All relevant English-language articles focused on the efficacy and safety of PP6M were considered for inclusion. Data Synthesis: A multicenter, randomized, active controlled relapse prevention noninferiority study showed that PP6M is comparable to paliperidone palmitate once in 3 months formulation (PP3M) in terms of efficacy and safety in clinically stable schizophrenia patients. Place in Therapy: PP6M is indicated in the treatment of adult patients with schizophrenia, who need treatment over a prolonged period. It improves adherence and decreases the rate of relapse and hospitalizations among patients with schizophrenia. It is useful for patients who may have difficulty accessing health care or would prefer the convenience of less frequent injections. Conclusion: PP6M with its long duration of action and lowered frequency of administration (once every 6 months) expands the therapeutic choices available to patients with schizophrenia. More studies in patients with schizophrenia with PP6M, and perhaps other mental illnesses (eg, schizoaffective disorder), are required to fully elucidate the therapeutic potential of PP6M.
Efficacy of platelet-inspired hemostatic nanoparticles on bleeding in Von Willebrand disease murine models
Authors: Roullet Stéphanie , Luc Norman , Rayes Julie , Solarz Jean , Disharoon Dante , Ditto Andrew J , Gahagan Emily , Pawlowski Christa , Sefiane Thibaud , Adam Frédéric , Casari Caterina , Christophe Olivier D. , Bruckman Michael A , Lenting Peter J , Sen Gupta Anirban , Denis Cecile V
Published: March 2023

The lack of innovation in Von Willebrand disease (VWD) originates from many factors including the complexity and heterogeneity of the disease but also from a lack of recognition of the impact of the bleeding symptoms experienced by VWD patients. Recently, a few research initiatives aiming to move past replacement therapies using plasma-derived or recombinant Von Willebrand factor (VWF) concentrates have started to emerge. Here we report an original approach using synthetic platelet (SP) nanoparticles for treatment of VWD type 2B (VWD-2B) and severe VWD (type 3 VWD). SP are liposomal nanoparticles decorated with peptides enabling them to concomitantly bind to collagen, VWF and activated platelets. In vitro, using various microfluidic assays, we show the efficacy of SP to improve thrombus formation in VWF-deficient condition (with human platelets) or using blood from VWD-2B mice and VWF-deficient mice (VWF-KO, i.e., type 3 VWD). In vivo, using a tail clip assay, SP treatment reduced blood loss by 35% in VWD-2B mice and 68% in VWF-KO mice. Additional studies using nanoparticles decorated with various combinations of peptides demonstrated that the collagen binding peptide, although not sufficient by itself, was absolutely crucial for SP efficacy in VWD-2B while all three peptides appeared necessary for VWF-KO mice. Clot imaging by immunofluorescence and scanning electron microscopy revealed that SP treatment of VWF-KO mice led to a strong clot, similar to those obtained in wild-type mice. Altogether, our results show that SP could represent an attractive therapeutic alternative for VWD, especially considering their long half-life and stability.
IMiD Resistance in Multiple Myeloma: Current Understanding of the Underpinning Biology and Clinical Impact
Authors: Bird Sarah Anne , Pawlyn Charlotte
Published: March 2023

Immunomodulatory agents (IMiDs) are a cornerstone of treatment for patients with multiple myeloma. IMiDs are used in therapeutic combinations at all stages of disease and are approved as a single agent maintenance treatment after autologous stem cell transplantation. However patients will become resistant to ongoing therapy over time and inevitably relapse. It is only in the last decade that the mechanism of IMiD action has been elucidated; through binding to the cereblon component of the CRL4CRBN E3 ubiquitin ligase a set of neosubstrates is designated for degradation by the proteosome. In myeloma cells this includes the zinc-finger B cell transcription factors Ikaros and Aiolos which in turn leads to decreased levels of IFR4 and c-MYC and cell death. As our knowledge of IMiD mechanism of action has advanced, the ability to study resistance mechanisms has also developed. This review will explore the existing work on IMiD resistance and propose areas of future research that may advance our understanding and management of this common clinical condition.
Precision Medicine Intervention in Severe Asthma (PRISM) study: molecular phenotyping of patients with severe asthma and response to biologics
Authors: Lee Ji-Hyang , Dixey Piers , Bhavsar Pank , Raby Katie , Kermani Nazanin , Chadeau-Hyam Marc , Adcock Ian M. , Song Woo-Jung , Kwon Hyouk-Soo , Lee Sei-Won , Sook Cho You , Fan Chung Kian , Kim Tae-Bum
Published: March 2023

Severe asthma represents an important clinical unmet need despite the introduction of biologic agents. Although advanced omics technologies have aided researchers in identifying clinically relevant molecular pathways, there is a lack of an integrated omics approach in severe asthma particularly in terms of its evolution over time. The collaborative Korea–UK research project Precision Medicine Intervention in Severe Asthma (PRISM) was launched in 2020 with the aim of identifying molecular phenotypes of severe asthma by analysing multi-omics data encompassing genomics, epigenomics, transcriptomics, proteomics, metagenomics and metabolomics. PRISM is a prospective, observational, multicentre study involving patients with severe asthma attending severe asthma clinics in Korea and the UK. Data including patient demographics, inflammatory phenotype, medication, lung function and control status of asthma will be collected along with biological samples (blood, sputum, urine, nasal epithelial cells and exhaled breath condensate) for omics analyses. Follow-up evaluations will be performed at baseline, 1 month, 4–6 months and 10–12 months to assess the stability of phenotype and treatment responses for those patients who have newly begun biologic therapy. Standalone and integrated omics data will be generated from the patient samples at each visit, paired with clinical information. By analysing these data, we will identify the molecular pathways that drive lung function, asthma control status, acute exacerbations and the requirement for daily oral corticosteroids, and that are involved in the therapeutic response to biological therapy. PRISM will establish a large multi-omics dataset of severe asthma to identify potential key pathophysiological pathways of severe asthma.
Comparison of the incidence of fetal prolonged deceleration after induction of labor analgesia between dural puncture epidural and combined spinal epidural technique: a pilot study
Authors: Okahara Shoko , Inoue Rie , Katakura Yumi , Nagao Hitomi , Yamamoto Saori , Nojiri Shuko , Takeda Jun , Itakura Atsuo , Sumikura Hiroyuki
Published: March 2023

Background

Abnormal cardiotocogram (CTG) tracing may appear after induction of neuraxial labor analgesia. Non-reassuring fetal status (NRFS) indicated by severely abnormal tracings, such as prolonged deceleration (PD) or bradycardia, can necessitate immediate operative delivery. Combined spinal epidural analgesia (CSEA) is known to result in more frequent abnormal tracings than epidural analgesia (EA); however, the corresponding data related to dural puncture epidural (DPE) are unclear. We aimed to evaluate the rates of incidence of severe abnormal CTG after induction of DPE and CSEA.

Methods

In this study of nulliparous women with full-term pregnancy, data for the DPE intervention group were prospectively collected, while those for the CSEA control group were obtained from medical records. Neuraxial analgesia was performed with cervical dilation ≤ 5 cm, administering initial epidural dosing of 15 mL of 0.125% levobupivacaine with fentanyl 2.5µg/mL for DPE, and intrathecal 0.5% bupivacaine 2.5 mg (0.5ml), fentanyl 10 µg (0.2ml), and 1.3 mL of saline for CSEA. The primary outcome was the incidence of PD, defined as a fetal heart rate reduction ≥ 15 bpm below the baseline and with a lowest value < 80 bpm, and lasting for ≥ 2 min but < 10 min (fetal heart rate < 80 bpm does not have to last for ≥ 2 min), within 90 min after induction of neuraxial labor analgesia.

Results

A total of 302 patients were analyzed, with 151 in each group. The incidence of PD after DPE induction was significantly lower than that after CSEA induction (4.0% vs. 14.6%, P = 0.0015, odds ratio = 0.243, 95% confidence interval = 0.095–0.617).

Conclusion

DPE appears to be a safer method compared to CSEA for neuraxial labor analgesia in the early stages of labor for nulliparous women.

Trial registration

UMIN-CTR: UMIN000035153. Date registered: 01/01/2019.
Exploring the antenatal care challenges faced during the COVID-19 pandemic in rural areas of Indonesia: a qualitative study
Authors: Anggraeni Mekar Dwi , Setiyani Rahmi , Triyanto Endang , Iskandar Asep , Nani Desiyani , Fatoni Amin
Published: March 2023

Introduction

The COVID-19 pandemic affected almost all healthcare services in Indonesia, including antenatal care (ANC). Pregnant women were a vulnerable group during the pandemic since the Indonesian government’s policies at the time influenced the delivery of ANC services, particularly in rural areas. Investigating the ANC challenges faced during the pandemic from the perspectives of pregnant women and healthcare providers is important for our understanding of ANC provision. This study, therefore explores barriers to ANC appointments faced during the COVID-19 pandemic in rural areas of Indonesia from the perspectives of pregnant women and health care providers.

Methods

This was a qualitative exploratory descriptive study involving 31 participants, consisting of 25 pregnant women and six healthcare providers who were selected via a purposive sampling method. Thadeus and Maine’s Three Delays Model was used as the theoretical framework. Data were collected between March and August 2021, through two focus group discussions (FGDs), ten in-depth interviews, and field notes. Data were analyzed using a thematic analysis method.

Results

Three themes describing barriers to ANC during the COVID-19 pandemic in rural areas of Indonesia emerged from this study. Those themes were: (1) The fear of being infected with COVID-19, related to anxiety, perceived vulnerability, and the desire to protect oneself and loved ones; (2) The stay-at-home policy, related to transport barriers and restricted social activity; and (3) Re-designed ANC services, related to ANC adjustments, high-risk pregnancies, insufficient information, and adherence to COVID-19 preventive behaviors.

Conclusion

Based on the Three Delays Model, several challenges to carrying out ANC during the COVID-19 pandemic in rural areas of Indonesia were identified. These findings demonstrate the need to formulate and implement ANC packages to facilitate pregnant women’s access to health care services.
Activated FGFR3 suppresses bone regeneration and bone mineralization in an ovariectomized mouse model
Authors: Kawashima Itaru , Matsushita Masaki , Mishima Kenichi , Kamiya Yasunari , Osawa Yusuke , Ohkawara Bisei , Ohno Kinji , Kitoh Hiroshi , Imagama Shiro
Published: March 2023

Background

Postmenopausal osteoporosis is a widespread health concern due to its prevalence among older adults and an associated high risk of fracture. The downregulation of bone regeneration delays fracture healing. Activated fibroblast growth factor receptor 3 (FGFR3) accelerates bone regeneration at juvenile age and downregulates bone mineralization at all ages. However, the impact of FGFR3 signaling on bone regeneration and bone mineralization post-menopause is still unknown. This study aimed to evaluate the impact of FGFR3 signaling on bone regeneration and bone mineralization during menopause by developing a distraction osteogenesis (DO) mouse model after ovariectomy (OVX) using transgenic mice with activated FGFR3 driven by Col2a1 promoter (Fgfr3 mice).

Methods

The OVX or sham operations were performed in 8-week-old female Fgfr3 and wild-type mice. After 8 weeks of OVX surgery, DO surgery in the lower limb was performed. The 5-day-latency period followed by performing distraction for 9 days. Bone mineral density (BMD) and bone regeneration was assessed by micro-computed tomography (micro-CT) scan and soft X-ray. Bone volume in the distraction area was also evaluated by histological analysis after 7 days at the end of distraction. Osteogenic differentiation and mineralization of bone marrow-derived mesenchymal stem cells (BMSCs) derived from each mouse after 8 weeks of the OVX or sham operations were also evaluated with and without an inhibitor for FGFR3 signaling (meclozine).

Results

BMD decreased after OVX in both groups, and it further deteriorated in Fgfr3 mice. Poor callus formation after DO was also observed in both groups with OVX, and the amount of regenerated bone was further decreased in Fgfr3 mice. Similarly, histological analysis revealed that Fgfr3 OVX mice showed lower bone volume. Osteogenic differentiation and mineralization of BMSCs were also deteriorated in Fgfr3 OVX mice. An inhibitor for FGFR3 signaling dramatically reversed the inhibitory effect of OVX and FGFR3 signaling on BMSC mineralization.

Conclusion

Upregulated FGFR3 decreased newly regenerated bone after DO and BMD in OVX mice. FGFR3 signaling can be a potential therapeutic target in patients with postmenopausal osteoporosis.
Nursing students’ simulated home-visit learning experiences with dementia -a qualitative research
Authors: Um Youn-Joo
Published: March 2023

Background

In response to the growing demand for community nursing, practical and dynamic changes in educational methods are essential to nurturing competent nurses. The aim of this study was to explore the learning experiences of nursing students’ simulation-based community visits and understand these experiences in detail.

Methods

This study followed Colizzi’s phenomenological research method. Nineteen participants were divided into three teams and participated in focus group interviews. The research question was: “How was your experience with the simulated nursing home visit?”

Results

Four essential themes were identified: “burden of community nursing simulation-based learning,” “solving the problems faced by patients with dementia through teamwork,” “home-visiting nursing skills learned through physical practice,” and “community nursing competency growth.”

Conclusion

The study results provide a basis for developing a community nursing curriculum with effective evaluation and management of community nursing home-visit education using simulation.
Proteome of airway surface liquid and mucus in newborn wildtype and cystic fibrosis piglets
Authors: Rodriguez-Piñeiro Ana M. , Jaudas Florian , Klymiuk Nikolai , Bähr Andrea , Hansson Gunnar C. , Ermund Anna
Published: March 2023

Background

The respiratory tract is protected from inhaled particles and microbes by mucociliary clearance, mediated by the mucus and the cilia creating a flow to move the mucus cephalad. Submucosal glands secrete linear MUC5B mucin polymers and because they pass through the gland duct before reaching the airway surface, bundled strands of 1000–5000 parallel molecules exit the glands. In contrast, the surface goblet cells secrete both MUC5AC and MUC5B.

Methods

We used mass-spectrometry based proteomic analysis of unstimulated and carbachol stimulated newborn wild-type (WT) and cystic fibrosis transmembrane conductance regulator (CFTR) null (CF) piglet airways to study proteins in the airway surface liquid and mucus, to investigate if levels of MUC5AC and MUC5B were affected by carbachol stimulation and whether the proteins clustered according to function.

Results

Proteins in the first four extracted fractions clustered together and the fifth fraction contained the mucus cluster, mucins and other proteins known to associate with mucins, whereas the traditional airway surface liquid proteins clustered to fraction 1–4 and were absent from the mucus fraction. Carbachol stimulation resulted in increased MUC5AC and MUC5B.

Conclusions

These results indicate a distinct separation between proteins in the washable surface liquid and the mucus fraction. In fractions 1–4 from newborn CF piglets an additional cluster containing acute phase proteins was observed, suggesting an early inflammatory response in CF piglets. Alternatively, increased levels of these proteins could indicate altered lung development in the CF piglets. This observation suggests that CF airway disease is present at birth and thus, treatment should commence directly after diagnosis.
Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis
Authors: Liu Xijuan , Yuan Jinghong , Wu Zhiwen , Zhang Junqiu , Shen Yunfeng , Jia Jingyu
Published: March 2023

Background

Currently, the etiology of idiopathic short stature (ISS) is still unclear. The poor understanding of the molecular mechanisms of ISS has largely restricted this strategy towards safe and effective clinical therapies.

Methods

The plasma exosomes of ISS children were co-cultured with normal human chondrocytes. The differential expression of exosome miRNA between ISS and normal children was identified via high-throughput microRNA sequencing and bioinformatics analysis. Immunohistochemistry, In situ hybridization, RT-qPCR, western blotting, luciferase expression, and gene overexpression and knockdown were performed to reveal the key signaling pathways that exosome miRNA of aberrant expression in ISS children impairs longitudinal bone growth.

Results

Chondrocytes proliferation and endochondral ossification were suppressed after coculture of ISS plasma exosomes with human normal chondrocytes. High-throughput microRNA sequencing and RT-qPCR confirmed that plasma exosome miR-26b-3p was upregulated in ISS children. Meanwhile, exosome miRNA-26b-3p showed a high specificity and sensitivity in discriminating ISS from normal children. The rescue experiment showed that downregulation of miR-26b-3p obviously improved the repression of chondrocyte proliferation and endochondral ossification caused by ISS exosomes. Subsequently, miR-26b-3p overexpression inhibited chondrocyte proliferation and endochondral ossification once again. In situ hybridization confirmed the colocalization of miR-26b-3p with AKAP2 in chondrocytes. In vitro and in vivo assay revealed exosome miRNA-26b-3p impairs longitudinal bone growth via the AKAP2 /ERK1/2 axis.

Conclusions

This study is the first to confirm that miR-26b-3p overexpression in ISS plasma exosomes leads to disorders in proliferation and endochondral ossification of growth plate cartilage via inhibition of AKAP2/ERK1/2 axis, thereby inducing ISS. This study provides a new research direction for the etiology and pathology of ISS and a new idea for the biological treatment of ISS.

Graphical Abstract
HIV-1 infection of renal epithelial cells: 30 years of evidence from transgenic animal models, human studies and in vitro experiments
Authors: Blasi Maria , Klotman Mary
Published: March 2023

Although antiretroviral therapy (ART) has increased life expectancy in people with HIV-1 (PWH), acute and chronic kidney disease remain common in this population and are associated with poor outcomes. A broad spectrum of kidney disorders can be observed in PWH, some of which are directly related to intrarenal HIV infection and gene expression. HIV-associated nephropathy (HIVAN) was the most common kidney disease in PWH before ART became available. Animal models and human biopsy studies established the causal relationships between direct HIV-1 infection of renal epithelial cells and HIVAN, expression of viral genes in renal epithelial cells, and dysregulation of host genes involved in cell differentiation and cell cycle. In this review, we provide a summary of the body of work demonstrating HIV-1 infection of epithelial cells in the kidney and recent advancements in the understanding of viral entry mechanisms and consequences of HIV-1 gene expression in those cells.

Graphical Abstract