bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol: an improved method for inducing sporophyte generation in the model moss Physcomitrium patens under nitrogen starvation
Authors: Yoro Emiko , Koshimizu Shizuka , Murata Takashi , Sakakibara Keiko
Published: September 2023

Background

Land plants exhibit a haplodiplontic life cycle, whereby multicellular bodies develop in both the haploid and diploid generations. The early-diverging land plants, known as bryophytes, have a haploid-dominant life cycle, in which a short-lived multicellular body in the diploid generation, known as the sporophyte, develops on the maternal haploid gametophyte tissues. The moss Physcomitrium (Physcomitrella) patens has become one of the most powerful model systems in evolutionary plant developmental studies. To induce diploid sporophytes of P. patens, several protocols are implemented. One of the conventional approaches is to grow approximately one-month-old gametophores for another month on Jiffy-7 pellets made from the peat moss that is difficult to fully sterilize. A more efficient method to obtain all tissues throughout the life cycle should accelerate studies of P. patens.

Results

Here, we investigated the effect of nitrogen conditions on the growth and development of P. patens. We provide an improved protocol for the sporophyte induction of P. patens using a BCD-based solid culture medium without Jiffy-7 pellets, based on the finding that the formation of gametangia and subsequent sporophytes is promoted by nitrogen-free growth conditions. The protocol consists of two steps; first, culture the protonemata and gametophores on nitrogen-rich medium under continuous light at 25 °C, and then transfer the gametophores onto nitrogen-free medium under short-day and at 15 °C for sporophyte induction. The protocol enables to shorten the induction period and reduce the culture space.

Conclusions

Our more efficient and shortened protocol for inducing the formation of sporophytes will contribute to future studies into the fertilization or the diploid sporophyte generation of P. patens.
Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance
Authors: Caminati Marco , Maule Matteo , Benoni Roberto , Micheletto Claudio , Tecchio Cristina , Vaia Rachele , De Franceschi Lucia , Guarnieri Gabriella , Vianello Andrea , Senna Gianenrico
Published: September 2023

Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. According to the available real-life evidence mepolizumab 300 mg and 100 mg, licensed for severe eosinophilic asthma, are comparable in terms of drug efficacy. However, the clinical rationale for selecting one dose or the other has not been explored. We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3–6–12 months follow-up. Overall, 11 patients were enrolled (females 4–36%) with a median age of 62 years (IQR 55.0–72.0). At 3-month visit both prednisone daily dose and BEC significantly decreased from baseline, whilst a substantial improvement of Brief fatigue inventory score (BFI) was not recorded before the 6 months assessment. More than 70% of patients completely stopped prednisone at 12-months follow-up, without any flare in terms of BEC and BFI. No adverse event was registered. Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.
Evaluation of intervertebral disc degeneration in young adult asymptomatic Dachshunds with magnetic resonance imaging and radiography
Authors: Reunanen Vilma Liisa Jerosa , Jokinen Tarja Susanna , Hytönen Marjo Kristiina , Junnila Jouni Juho Tapio , Lappalainen Anu Katriina
Published: September 2023

Background

Dachshunds have a high prevalence of intervertebral disc disease (IVDD) to which they are predisposed due to early intervertebral disc (IVD) degeneration and calcification. Moreover, the recently found 12-FGF4 retrogene (RG) is associated with calcified discs visible on radiographs (CDVR) and IVDD. Earlier studies suggest that all IVDs of one-year-old Dachshunds show signs of degeneration. This prospective, analytical, blinded study aimed to investigate the extent and distribution of IVD degeneration in young adult (24–31 months) asymptomatic Dachshunds (n = 21) hypothesizing that not all IVDs of two-year-old Dachshunds are degenerated. Another aim was to explore the correlations between IVD degeneration evaluated with magnetic resonance imaging (MRI), the number of CDVR, and the dog’s 12-FGF4RG status. The study protocol included grading the CDVR on spinal radiographs, grading the IVD degeneration on T2-weighted sagittal and transverse high-field MR images of all IVDs (n = 546), and 12-FGF4RG variant genotyping.

Results

Of all IVDs evaluated, 2% (n = 11) were normal based on MRI grading. Despite the study population having moderately degenerated IVDs (median MRI grade 3), there was also variation in the degree of IVD degeneration between individuals and in the distribution of IVD degeneration between different vertebral regions. The number of CDVR correlated significantly with the magnitude of IVD degeneration based on MRI evaluation and with the 12-FGF4RG genotype. The odds for being 12-FGF4RG homozygous were higher for Dachshunds with CDVR. However, the 12-FGF4RG variant did not alone explain the phenotypic variation in IVD degeneration.

Conclusions

The number of CDVR is a valid indicator of overall IVD degeneration, as it correlates with MRI-based IVD grading. Also, as the extent and distribution of IVD degeneration varies between individual Dachshunds, selective breeding against IVDD using radiographic screening and 12-FGF4RG variant genotyping is possible.
A study protocol for Project I-Test: a cluster randomized controlled trial of a practice coaching intervention to increase HIV testing in substance use treatment programs
Authors: Frimpong Jemima A. , Parish Carrigan L. , Feaster Daniel J. , Gooden Lauren K. , Nelson Mindy C. , Matheson Tim , Siegel Karolynn , Haynes Louise , Linas Benjamin P. , Assoumou Sabrina A. , Tross Susan , Kyle Tiffany , Liguori Terri K. , Toussaint Oliene , Annane Debra , Metsch Lisa R.
Published: September 2023

Background

People with substance use disorders are vulnerable to acquiring HIV. Testing is fundamental to diagnosis, treatment, and prevention; however, in the past decade, there has been a decline in the number of substance use disorder (SUD) treatment programs offering on-site HIV testing. Fewer than half of SUDs in the USA offer on-site HIV testing. In addition, nearly a quarter of newly diagnosed cases have AIDS at the time of diagnosis. Lack of testing is one of the main reasons that annual HIV incidences have remained constant over time. Integration of HIV testing with testing for HCV, an infection prevalent among persons vulnerable to HIV infection, and in settings where they receive health services, including opioid treatment programs (OTPs), is of great public health importance.

Methods/design

In this 3-arm cluster-RCT of opioid use disorders treatment programs, we test the effect of two evidence-based “practice coaching” (PC) interventions on the provision and sustained implementation of on-site HIV testing, on-site HIV/HCV testing, and linkage to care. Using the National Survey of Substance Abuse Treatment Services data available from SAMHSA, 51 sites are randomly assigned to one of the three conditions: practice coach facilitated structured conversations around implementing change, with provision of resources and documents to support the implementation of (1) HIV testing only, or (2) HIV/HCV testing, and (3) a control condition that provides a package with information only. We collect quantitative (e.g., HIV and HCV testing at 6-month-long intervals) and qualitative site data near the time of randomization, and again approximately 7–12 months after randomization.

Discussion

Innovative and comprehensive approaches that facilitate and promote the adoption and sustainability of HIV and HCV testing in opioid treatment programs are important for addressing and reducing HIV and HCV infection rates. This study is one of the first to test organizational approaches (practice coaching) to increase HIV and HIV/HCV testing and linkage to care among individuals receiving treatment for opioid use disorder. The study may provide valuable insight and knowledge on the multiple levels of intervention that, if integrated, may better position OTPs to improve and sustain testing practices and improve population health.

Trial registration

ClinicalTrials.gov NCT03135886. Registered on 2 May 2017.
Cross-cultural adaptation of the Parental Perceptions of Children’s Exposure to Tobacco Smoke instrument to the Brazilian context
Authors: Tavares Maria Alice Santos , Myers Vicki , Nogueira Leandro Alberto Calazans , Lopes Agnaldo José
Published: September 2023

Objective

To perform a cross-cultural adaptation of the Parental Perceptions of Children’s Exposure to Tobacco Smoke (PPE) instrument to the Brazilian context.

Results

The cross-cultural adaptation process was performed in 10 stages. Four translators, eight specialists, and 35 primary care users participated in the study. Both translations were similar. The synthesis version that was back-translated was equivalent to the original. The committee of experts scored all items in the content validity index as 3 or 4, suggesting only small changes such as changing “photo” to “image” and “service balcony” to “service area”. After the completion of the first sequence of pretests, some adjustments were required by the committee of experts for the second round. The form of application of the self-administered questionnaire for the interview was changed, the Likert scale was reduced from 7 to 5 points, and the option “I don’t know” was added to questions 18, 19, and 20. After these adjustments, the instrument was well accepted by the study population and presented good internal consistency (Cronbach’s α score = 0.82). The PPE instrument, which assesses the perception of parents about their children’s exposure to cigarette smoke, was satisfactorily translated and adapted to the Brazilian context.
Hematological entities with plasmacytic differentiation: a case report
Authors: Inamdar Arati , Bhattacharyya Siddharth
Published: September 2023

Introduction

Plasmacytoma, a localized tumor of monoclonal plasma cells without any clinical, radiological or physical evidence of plasma cell neoplasm (PCN), is a rare entity that accounts for 1% of PCN. Immunoglobulin M (IgM) extramedullary plasmacytoma of mediastinal region has never been reported and is a diagnostic challenge considering other differential diagnoses.

Case presentation

We present the case of a 51-year-old African-American female with progressively increasing cough, dyspnea, and dysphagia for 6 months with a computed tomography (CT) scan revealing a subcarinal mass. The histopathological analysis of the mass reveals a diagnosis of lymphoma with plasma cell differentiation, with a differential of lymphoplasmacytic lymphoma and plasma cell neoplasm. The lymphoma panel via next-generation sequencing (NGS) and a myeloma-targeted fluorescent in situ hybridization (FISH) panel confirmed the diagnosis of IgM extramedullary plasmacytoma, an entity of rare occurrence. Treatment with radiation led to complete regression of the plasmacytoma with normal blood work-up.

Conclusions

This report describes the challenges of diagnosing IgM extramedullary plasmactyoma. Our case report highlights the importance of cytogenetics and NGS in establishing a correct diagnosis that indeed has prognostic and therapeutic implications.
Autoimmune bullous disorder flares following severe acute respiratory syndrome coronavirus 2 vaccination: a case series
Authors: Rasner Cody J. , Schultz Brittney , Bohjanen Kimberly , Pearson David R.
Published: September 2023

Background

Autoimmune bullous disorders develop due to autoantibodies targeting intercellular adhesion proteins of hemidesmosomes and desmosomes and may be triggered by viral infections and vaccines. Recent reports suggest that the coronavirus disease 2019 vaccination may trigger flares or exacerbations of preexisting autoimmune diseases, including new onset autoimmune bullous disorders. There are less data on whether vaccination against severe acute respiratory syndrome coronavirus 2 may also exacerbate preexisting autoimmune bullous disorders.

Case presentation

Here we present three cases, two white males (ages 69 years and 88 years) with bullous pemphigoid and one white 50-year-old female with pemphigus foliaceus, wherein all individuals developed minor, tractable flares of their preexisting autoimmune bullous disorders after receiving the coronavirus disease 2019 vaccination, which were readily treatable with topical or low-dose systemic corticosteroids.

Conclusions

Dermatologists managing patients with autoimmune bullous disorders should be cognizant of the uncommon potential for flares of the disorder following vaccination for severe acute respiratory syndrome coronavirus 2. Flares of bullous pemphigoid and pemphigus foliaceus following vaccination for severe acute respiratory syndrome coronavirus 2 in these cases were mild and tractable.
Modeling and analysis for group delay mismatch effect on wideband adaptive spatial interference cancellation
Authors: Zhang Yunshuo , He Fangmin , Liu Hongbo , Li Yaxing , Yang Zhong , Wang Ze , Meng Jin
Published: September 2023

The adaptive interference cancellation technique has been widely utilized in radar, GPS, data link, etc., systems to address challenges from external interference, such as co-site and hostile interference. Since the anti-jamming performance of the adaptive interference cancellation technique is sensitive to group delay mismatch between channels, the group delay mismatch becomes one of the main factors that limit the system’s anti-jamming capability. However, the traditional adaptive interference cancellation system’s mathematical model cannot quantitatively characterize the group delay mismatch effect on the wideband interference cancellation performance. In this paper, the mathematical model of the wideband adaptive spatial interference cancellation (ASIC) system is established, which considers the group delay mismatch, to quantitatively analyze the impact of group delay mismatch on the hostile interference cancellation. The mathematical model utilizes the weighted multi-tone signals to fit the wideband interference, and then, delay differences are attached to each tone signal to simulate the group delay mismatch. Then, the analytic expressions of weight and interference cancellation ratio are derived, which consider the interference bandwidth and group delay mismatch, to quantitatively analyze the group delay mismatch effect on the anti-jamming performance of the wideband ASIC system. Simulation results indicate that the theoretical analysis based on the mathematical model of wideband ASIC system are accurate, which can achieve the quantitative analysis of the group delay mismatch effect on the WIC performance.
Hermite-Hadamard type inequalities for multiplicatively p-convex functions
Authors: Özcan Serap
Published: September 2023

In this paper, we introduced the concept of multiplicatively p-convex functions and established Hermite-Hadamard type integral inequalities in the setting of multiplicative calculus for this newly created class of functions. We also gave integral inequalities of Hermite-Hadamard type for product and quotient of multiplicatively p-convex functions. Furthermore, we obtained novel multiplicative integral-based inequalities for the product and quotient of convex and multiplicatively p-convex functions. Additionally, we derived certain upper limits for this new class of functions. The findings we proved are generalizations of the results in the literature. The results obtained in this study may inspire further research in various scientific areas.
Wheat seedling extract and its constituents attenuate RANKL-induced differentiation and fusion of osteoclasts and bone resorption
Authors: Lee HanGyeol , Yang Ji-Yeong , Kim Shin-Hye , Lim So-An , Kim Jae Kwang , Kang Chon-Sik , Kim Kyeong-Hoon , Choi Sik-Won , Seo Woo Duck
Published: September 2023

The occurrence of osteoporosis gradually increases within the aging population. As the side effects of therapeutic agents currently used for osteoporosis are increasing, the development of preventive and therapeutic agents derived from natural products without any long-term side effects is important. Here, we investigated the effect of wheat seedling extract (WSE) on the RANKL-mediated differentiation, fusion, and function of osteoclasts. WSE inhibited the differentiation of RANKL-induced bone marrow macrophages and phosphorylation of AKT and ERK. Moreover, the protein and mRNA expression levels of c-Fos and NFATc1 as well as RANKL-induced transcription of TRAP and OSCAR were suppressed by WSE treatment. DC-STAMP and cathepsin K, which are essential for cell fusion and bone degradation, were also inhibited by WSE. Furthermore, eight components constituting WSE were confirmed to decrease the osteoclast TRAP activity. Taken together, WSE may have potential implications as a useful therapeutic or preventive agent for inhibition of bone loss.
Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration
Authors: Teranishi Yu , Miyawaki Satoru , Nakatochi Masahiro , Okano Atsushi , Ohara Kenta , Hongo Hiroki , Ishigami Daiichiro , Sakai Yu , Shimada Daisuke , Takayanagi Shunsaku , Ikemura Masako , Komura Daisuke , Katoh Hiroto , Mitsui Jun , Morishita Shinichi , Ushiku Tetsuo , Ishikawa Shumpei , Nakatomi Hirofumi , Saito Nobuhito
Published: September 2023

Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages.
The synergic impacts of salt mixture and frost damage on rock decay: implications for the deterioration of rock-hewn heritages
Authors: Wang Yinghong , Zhang Hui
Published: September 2023

Soluble salt and freeze–thaw are two significant weathering factors that contribute to the deterioration of rock-hewn heritages. Previous research has predominantly focused on the separate influences of salt weathering and freeze–thaw. However, in a realistic scenario, these two processes can occur simultaneously in nature, leading to a more complex decay process for such heritage. The aim of this study was to assess the combined impact of salt weathering and freeze–thaw on the severity of deterioration in rock-hewn heritage through evaluation of the variation of stone samples’ appearance and physical–mechanical properties, such as deterioration patterns, pore structure, surface hardness and splitting tensile strength. A laboratory ageing test was conducted using materials and climatic conditions representative of the West Lake Cultural Landscape of Hangzhou (WLCL), a UNESCO World Heritage Site located in Southeast China. Five different types of stones were collected from the WLCL area and its vicinity and subjected to 25 ageing cycles, each consisting of three phases: salt impregnation, freezing-thaw, and evaporation. The mixture of

$${{Na}_{2}SO}_{4}{-MgSO}_{4}$$

Na

2

S
O

4

-
M
g
S
O

4

was used as the contaminant substance. Results show that stones with moderate porosity (~ 5%) and a higher proportion of micropores, like flint, were susceptible to the combined effects of salt weathering and freeze–thaw, exhibiting significant surface deformation and strength decline. The porous tuff was primarily impacted by the development of a hard and thick crust on its surface, along with noticeable pore fill. The compact carbonate rock exhibited limited dimensional expansion with no discernible signs of deterioration patterns. Most rock specimens, except tuff, experienced a shift in their pore size distribution towards larger magnitudes, resulting in an increased average pore radius. This suggests that the inherent properties of rock-hewn heritages play a significant role in determining their vulnerability to various weathering agents. Consequently, these properties should serve as the foundation for developing future preventive conservation measures.

Graphical Abstract
A guide to creating an effective big data management framework
Authors: Arundel S. T. , McKeehan K. G. , Campbell B. B. , Bulen A. N. , Thiem P. T.
Published: September 2023

Many agencies and organizations, such as the U.S. Geological Survey, handle massive geospatial datasets and their auxiliary data and are thus faced with challenges in storing data and ingesting it, transferring it between internal programs, and egressing it to external entities. As a result, these agencies and organizations may inadvertently devote unnecessary time and money to convey data without existing or outdated standards. This research aims to evaluate the components of data conveyance systems, such as transfer methods, tracking, and automation, to guide their improved performance. Specifically, organizations face the challenges of slow dispatch time and manual intervention when conveying data into, within, and from their systems. Conveyance often requires skilled workers when the system depends on physical media such as hard drives, particularly when terabyte transfers are required. In addition, incomplete or inconsistent metadata may necessitate manual intervention, process changes, or both. A proposed solution is organization-wide guidance for efficient data conveyance. That guidance involves systems analysis to outline a data management framework, which may include understanding the minimum requirements of data manifests, specification of transport mechanisms, and improving automation capabilities.
Cystitis: significant associations between pathology, histology, and quantitative bacteriology in sows, a cross-sectional study
Authors: Tolstrup Lola Kathe , Leifsson Páll Skúli , Guardabassi Luca , Nielsen Jens Peter , Pedersen Ken Steen
Published: September 2023

Background

The importance of cystitis in pig production is controversial and sparse information is available on its frequency and etiology in sows. The aim of this study was to determine the prevalence of bacteriuria, macroscopical and histological lesions of the urinary bladder in culled sows. Urinary bladders and urine samples were obtained from 176 culled sows at slaughter. The urine samples collected by cystocentesis were analyzed to determine bacterial content and pathological findings, macroscopic as well as microscopic, of the bladder were recorded for each sow.

Results

The prevalence of bacteriuria, defined by bacterial concentrations ≥ 103 colony forming units per mL of urine, was 34%. Escherichia coli was isolated from 69% of the samples with bacteriuria. Redness of the mucosa was the most frequently observed macroscopic change of the bladder. Intense redness and presence of pus was considered significant pathological changes and occurred in 27% of the urinary bladders. The histopathological examination showed that mononuclear cells were the predominant type of cell infiltration in the bladder mucosa, while neutrophils occurred in very few samples. The criteria for cystitis determined by histopathology were met in 46% of the samples. The criteria were based on presence of hyperemia, edema, and inflammatory cell reaction defined as 40 or more neutrophils or mononuclear cells per high power field. All three indicators of cystitis were significantly associated with each other (p < 0.05) at sow level.

Conclusion

This study shows that signs of cystitis are common in culled sows. The prevalence of cystitis was 34% based on bacteriological examination, 27% based on macroscopic examination and 46% based on histological examination. Significant associations were found between the three indicators of cystitis: bacteriuria, pathological and histological lesions of the bladder. Based on macroscopic changes and histopathology of the bladder, the cut-off of ≥ 103 colony forming units per mL of urine seems to be appropriate for assessing urine cultures obtained by cystocentesis.
The “home-based exercise for breast and prostate cancer patients during treatment—a feasibility trial” (BENEFIT CA trial): rationale and methodological protocol
Authors: da Silva Larissa Xavier Neves , Leite Jayne Santos , Ignacio Andresa Conrado , Massierer Fernanda Dias , Pfeifer Lucinéia Orsolin , dos Santos Cardoso Linda Ariene , Alano Tainá Silveira , Umpierre Daniel
Published: September 2023

Background

Physical activity has been shown to benefit patients undergoing adjuvant cancer therapy. Although exercise interventions may be applied in several settings, most trials have focused on specialized facilities for their interventions. While these approaches benefit the access for individuals living near exercise centers, it hampers the assessment of real-world effectiveness. Therefore, evaluating the feasibility and implementation of home-based models of exercise training, especially in low-to-middle-income settings, may inform future physical activity trials and programs. In this article, we present the protocol for the BENEFIT CA trial, which aims to assess the implementation of a remote exercise intervention for patients with breast cancer or prostate cancer, primarily quantifying adherence to an exercise program.

Methods

This is a 12-week study, utilizing a non-randomized, single-arm design to assess the feasibility of a home-based exercise training. The intervention is remotely guided, and participants also receive an educational component about cancer and exercise. The study aims to recruit 40 patients diagnosed with breast cancer and 40 patients diagnosed with prostate cancer, all of whom undergoing active hormonal treatment. The primary outcome is the level of adherence, indicated as the proportion of performed exercise episodes. Secondary outcomes include recruitment rates, fatigue, quality of life, and functional capacity. Adverse events will be monitored throughout the study. Because this is a feasibility trial, the statistical analysis plan is based on descriptive statistics, which encompasses an intention-to-treat analysis and a plan for handling missing data.

Discussion

This is a low-cost feasibility study to orient the design of a wide-range, pragmatic phase 3 trial based on remote exercise intervention. With this study, we aim to better understand the adherence and implementation strategies regarding home-based exercise for the proposed population and, in the near future, move forward to a randomized clinical trial. In addition, this trial may contribute to engage patients with cancer in exercise programs throughout their treatment and beyond.

Trial registration

This trial has been approved by the Hospital de Clínicas de Porto Alegre Ethics Committee/IRB (48,869,621.9.0000.5327), and it is registered at Clinicaltrials.gov (NCT05258526), registered on February 25, 2022, prior to the beginning of the study.
Awe and anxiety for cancer cells: connecting scientists and patients in a holistic approach of metastasis research
Authors: Bronkhorst Hildert , van Weerden Wytske M. , Bunnik Eline M. , Zwart Hub
Published: September 2023

Background

Metastatic cancer is often experienced by patients as a death sentence. At the same time, translational scientists approach metastasis also as an interesting phenomenon that they try to understand and prevent. These two sides of the same coin do not mask the considerable gap that exists between the laboratory world of scientists and the life world of patients. Funding agencies nowadays increasingly demand researchers to be responsive to the values and priorities of patients and public. One approach to bridge this gap and to increase the impact of science is patient and public involvement (PPI). A concise literature review of PPI research and practice in this paper revealed that although PPI is often deployed in translational health care research, its methodology is not settled, it is not sufficiently emancipatory, and its implementation in basic and translational science is lagging behind. Here, we illustrate the practical implementation of PPI in basic and translational science, namely in the context of HOUDINI, a multidisciplinary network with the ultimate goal to improve the management of metastatic disease.

Methods

This paper reports on a societal workshop that was organized to launch the holistic PPI approach of HOUDINI. During this workshop, societal partners, patients, and physicians discussed societal issues regarding cancer metastasis, and contributed to prioritization of research objectives for HOUDINI. In a later stage, the workshop results were discussed with scientists from the network to critically review its research strategy and objectives.

Results

Workshop participants chose the development of metastasis prediction tools, effective therapies which preserve good quality of life, and non-invasive tissue sampling methods as most important research objectives for HOUDINI. Importantly, during the discussions, mutual understanding about issues like economic feasibility of novel therapies, patient anxiety for metastases, and clear communication between stakeholders was further increased.

Conclusions

In conclusion, the PPI workshop delivered valuable early-stage input and connections for HOUDINI, and may serve as example for similar basic and translational research projects.
Corporate social responsibility communication in the ICT sector: digital issues, greenwashing, and materiality
Authors: Famularo Jordan
Published: September 2023

Digitalization brings with it new social and governance issues and heightened responsibility, particularly for corporations. In recent years, society has demanded more transparency from companies about digital technology practices, oversight, and impacts. One sector that sharpens the view on these dynamics is information and communication technology (ICT). This study introduces for the first time an examination of corporate social responsibility (CSR) discourse on digital issues among large ICT firms by using signaling theory to analyze a broad set of media (sustainability, ESG, CSR, integrated, impact, purpose, consolidated management, and annual reports as well as issue briefs and webpages). It clarifies how ICT firms present materiality—a reporting concept associated with fair representation and relevance of information—in their CSR reporting on digital topics. It then discusses implications for greenwashing and makes recommendations for improving disclosure credibility.

Graphical Abstract
[225Ac]Ac- and [111In]In-DOTA-trastuzumab theranostic pair: cellular dosimetry and cytotoxicity in vitro and tumour and normal tissue uptake in vivo in NRG mice with HER2-positive human breast cancer xenografts
Authors: Kondo Misaki , Cai Zhongli , Chan Conrad , Forkan Nubaira , Reilly Raymond M.
Published: September 2023

Background

Trastuzumab (Herceptin) has improved the outcome for patients with HER2-positive breast cancer (BC) but brain metastases (BM) remain a challenge due to poor uptake of trastuzumab into the brain. Radioimmunotherapy (RIT) with trastuzumab labeled with α-particle emitting, 225Ac may overcome this challenge by increasing the cytotoxic potency on HER2-positive BC cells. Our first aim was to synthesize and characterize [111In]In-DOTA-trastuzumab and [225Ac]Ac-DOTA-trastuzumab as a theranostic pair for imaging and RIT of HER2-positive BC, respectively. A second aim was to estimate the cellular dosimetry of [225Ac]Ac-DOTA-trastuzumab and determine its cytotoxicity in vitro on HER2-positive BC cells. A third aim was to study the tumour and normal tissue uptake of [225Ac]Ac-DOTA-trastuzumab using [111In]In-DOTA-trastuzumab as a radiotracer in vivo in NRG mice with s.c. 164/8-1B/H2N.luc+ human BC tumours that metastasize to the brain.

Results

Trastuzumab was conjugated to 12.7 ± 1.2 DOTA chelators and labeled with 111In or 225Ac. [111In]In-DOTA-trastuzumab exhibited high affinity specific binding to HER2-positive SK-BR-3 human BC cells (KD = 1.2 ± 0.3 × 10–8 mol/L). Treatment with [225Ac]Ac-DOTA-trastuzumab decreased the surviving fraction (SF) of SK-BR-3 cells dependent on the specific activity (SA) with SF < 0.001 at SA = 0.74 kBq/µg. No surviving colonies were noted at SA = 1.10 kBq/µg or 1.665 kBq/µg. Multiple DNA double-strand breaks (DSBs) were detected in SK-BR-3 cells exposed to [225Ac]Ac-DOTA-trastuzumab by γ-H2AX immunofluorescence microscopy. The time-integrated activity of [111In]In-DOTA-trastuzumab in SK-BR-3 cells was measured and used to estimate the absorbed doses from [225Ac]Ac-DOTA-trastuzumab by Monte Carlo N-Particle simulation for correlation with the SF. The dose required to decrease the SF of SK-BR-3 cells to 0.10 (D10) was 1.10 Gy. Based on the D10 reported for γ-irradiation of SK-BR-3 cells, we estimate that the relative biological effectiveness of the α-particles emitted by 225Ac is 4.4. Biodistribution studies in NRG mice with s.c. 164/8-1B/H2N.luc+ human BC tumours at 48 h post-coinjection of [111In]In-DOTA-trastuzumab and [225Ac]Ac-DOTA-trastuzumab revealed HER2-specific tumour uptake (10.6 ± 0.6% ID/g) but spleen uptake was high (28.9 ± 7.4% ID/g). Tumours were well-visualized by SPECT/CT imaging using [111In]In-DOTA-trastuzumab.

Conclusion

We conclude that [225Ac]Ac-DOTA-trastuzumab exhibited potent and HER2-specific cytotoxicity on SK-BR-3 cells in vitro and HER2-specific uptake in s.c. 164/8-1B/H2N.luc+ human BC tumours in NRG mice, and these tumours were imaged by SPECT/CT with [111In]In-DOTA-trastuzumab. These results are promising for combining [111In]In-DOTA-trastuzumab and [225Ac]Ac-DOTA-trastuzumab as a theranostic pair for imaging and RIT of HER2-positive BC.
Understanding the patient experience of Classic Galactosemia in pediatric and adult patients: increased disease burden, challenges with daily living, and how they evolve over time
Authors: Randall Jason A. , Sutter Carolyn , Raither Lydia , Wang Stella , Bailey Evan , Perfetti Riccardo , Shendelman Shoshana , Burbridge Claire
Published: September 2023

Background

Classic Galactosemia (CG) is a rare, autosomal recessive condition. Newborn screening and a timely galactose-restricted diet can resolve acute symptoms and decrease fatalities, but significant chronic, progressive morbidities remain and significantly impact daily life. The objective of this study was to better understand the burden of disease in children and adults with CGs and describe how morbidities evolve over time.

Methods

A total of 49 individuals with CG from the United States (US) were included in the qualitative surveys (13 adults [9 self-reported] and 36 pediatric patients). Fifteen follow-up interviews were conducted with 5 adults and 10 caregivers, discussing 17 individuals with CG overall (2 caregivers each discussed 2 children).

Results

Qualitative survey and interview data demonstrated the substantial burden of CG. Difficulties in a wide range of functions were experienced, which included: speech articulation; language and communication; cognition, memory and learning; emotions; and social interactions. Most difficulties appeared in childhood and persisted or worsened with age. Most adults did not live independently. Others lived semi-independently and experienced many daily challenges and required support. Caregivers also described the burden of caring for someone with CG and spoke about the impact this has on their day-to-day life, work, and relationships.

Conclusions

These findings demonstrate the pronounced and persistent burden of disease encountered by individuals with CG, and that the condition has a significant impact on the quality of life of caregivers.
White cord syndrome—an unforeseen complication and diagnosis of exclusion: a case report and review of management
Authors: Kumar Vishal , Rai Ankit , Dhatt Sarvdeep Singh
Published: September 2023

Background

White cord syndrome is an unexpected and dreaded complication of decompression surgery in cervical myelopathy with an unforeseeable prognosis. Ischemic reperfusion injury has been advocated as an underlying pathophysiology. Not only must the surgeon be acquainted with this complication, but the patient should also be counseled before surgery regarding the expected outcome and worsening of neurological status after surgery in severe chronic compressive myelopathy.

Case presentation

A 48-year-old female presented with difficulty walking and numbness in all four limbs. The clinical and radiological assessment was suggestive of multilevel cervical cord compression. Posterior cervical decompression with C3–C7 lateral mass screw was performed. The patient developed a worsening neurological status in the immediate postoperative period. The patient was shifted to the intensive care unit and managed with high-dose dexamethasone along with monitoring and maintaining mean arterial pressure above 85 mm Hg. A partial improvement in neurology was noted during the in-hospital stay. The patient was attached to the local rehabilitation clinic. At the one-year follow-up, the patient was ambulatory with some residual numbness and weakness in the upper limbs.

Conclusions

White cord syndrome following spinal decompression in chronic cervical myelopathy is a rare, unfortunate complication and a diagnosis of exclusion with variable outcomes. An increase in signal hyper-intensity on T2-weighted MRI imaging in this entity is the most consistent finding. This report reviewed our current knowledge on the management of white cord syndrome based on our present experience.
Investigating the correlation between morphological features of microplastics (5–500 µm) and their analytical recovery
Authors: Hagelskjær O. , Crézé A. , Le Roux G. , Sonke J. E.
Published: September 2023

As a direct result of laboratory sample manipulation required to identify microplastics (MPs) within a given matrix, some MPs are inevitably lost. The extent of this loss can be quite significant and varies greatly depending on the sample matrix, choice of protocol and target MPs in question. Defining analytical MP recovery is therefore a critical component in ensuring the quality of MP protocols. The potential relationship between particle size and recovery rate has been widely discussed but remains uncertain. To determine whether MP loss correlated with particle size, three aliquots of polyethylene fragments in the 5–50 µm size range and three aliquots of polypropylene fragments in the 50–500 µm size range, were consecutively transferred back and forth from filter to liquid. After each individual transfer the analytical recovery within specified size groups, was evaluated by applying high-resolution darkfield microscopy. Average recovery across the entire size range was estimated at 80% with a standard deviation (std. dev.) of 26%. Notably, particle coverage on filters (A%) showed a more significant impact on recovery than particle size. Maintaining A% below 5% on filters for microscopic analysis is advised to prevent excessive loss due to particle agglomeration. To determine whether the use of red polyethylene fragments in the 5–50 µm size range in combination with darkfield microscopy could potentially improve MP recovery evaluation in environmental samples, three aliquots of 0.5 g of dry brown trout muscle tissue were spiked and treated according to a relevant protocol. This size-discriminating approach accurately determined average recovery at 52% with a std. dev. of 4% and demonstrated the potential for correction of the concentration enhancement of smaller MPs resulting from particle breakup during sample pre-treatment, which would otherwise lead to overestimation of smaller size fractions.
Missed connections: Exploring features of undergraduate biology students’ knowledge networks relating gene regulation, cell–cell communication, and phenotypic expression
Authors: Flowers Sharleen , Holder Kal H. , Rump Gabrielle K. , Gardner Stephanie M.
Published: September 2023

Think-aloud interviews with undergraduate biology majors were conducted to characterize the definitions of gene regulation, cell-cell communication, and phenotypic expression as well as the features of the student knowledge networks connecting them. Implications for developing students’ systems thinking are discussed.
Relevance of Science, Conceptualization of Scientists, and Contextualized “Failure” as Mediators in the Development of Student Science Identity
Authors: Ambrosino Christine M. , Rivera Malia Ana J.
Published: September 2023

Data collected during the Research Experiences in Marine Science (REMS) program suggest place-based elements and an authentic research experience may shift students’ conceptualization of scientists to a “humanized” construct. A course-based undergraduate research experience (CURE) that emphasizes culturally relevant science may contribute to historically marginalized students better recognizing themselves as scientists.
“I don’t Know what I Would do Without it” How Life Science Graduate Students Describe Resource Value
Authors: Weatherton Maryrose , Von der Mehden Bailey M. , Schussler Elisabeth E.
Published: September 2023

Utilizing expectancy-value theory for help sources, this national, qualitative study explored life science graduate students’ choice of their highest-value resources, their explanations about why they chose those resources, and how students’ perceptions of value differed among resources and across demographic characteristics.
Intersecting Identities: A Look at How Ethnic Identity Interacts With Science Identity in Native Hawaiian and Pacific Islander Students
Authors: Greenall Rebeka F. , de Alba Jose Gaspar , Nichols Samara , Allen G. E. Kawika , Bailey Elizabeth G.
Published: September 2023

This study investigates differences between Native Hawaiian and Other Pacific Islander (NHPI) and non-NHPI undergraduate Biology students in terms of Science identity, self-efficacy, alignment with science values, belonging, and environmental concern. NHPI experiences involving the influence of their ethnic-racial identities on their Science identities are discussed.
Healthcare costs for young people transitioning the boundary between child/adolescent and adult mental health services in seven European countries: results from the MILESTONE study
Authors: Canaway Alastair , Appleton Rebecca , van Bodegom Larissa , Dieleman Gwen , Franić Tomislav , Gerritsen Suzanne , de Girolamo Giovanni , Maras Athanasios , McNicholas Fiona , Overbeek Mathilde , Paul Moli , Purper-Ouakil Diane , Santosh Paramala , Schulze Ulrike , Singh Swaran P. , Street Cathy , Tah Priya , Tremmery Bie , Tuomainen Helena , Verhulst Frank C. , Wolke Dieter , Madan Jason ,   for the MILESTONE Consortium
Published: September 2023

Background

The boundary between services for children and adolescents and adults has been identified as problematic for young people with mental health problems.

Aims

To examine the use and cost of healthcare for young people engaged in mental healthcare before and after the child/adolescent and adult service boundary.

Method

Data from 772 young people in seven European countries participating in the MILESTONE trial were analysed. We analysed and costed healthcare resources used in the 6-month period before and after the service boundary.

Results

The proportion of young people engaging with healthcare services fell substantially after crossing the service boundary (associated costs €7761 pre-boundaryv.€3376 post-boundary). Pre-boundary, the main cost driver was in-patient care (approximately 50%), whereas post-boundary costs were more evenly spread between services; cost reductions were correlated with pre-boundary in-patient care. Severity was associated with substantially higher costs pre- and post-boundary, and those who were engaged specifically with mental health services after the service boundary accrued the greatest healthcare costs post-service boundary.

Conclusions

Costs of healthcare are large in this population, but fall considerably after transition, particularly for those who were most severely ill. In part, this is likely to reflect improvement in the mental health of young people. However, qualitative evidence from the MILESTONE study suggests that lack of capacity in adult services and young people's disengagement with formal mental health services post-transition are contributing factors. Long-term data are needed to assess the adverse long-term effects on costs and health of this unmet need and disengagement.