bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal exposure to low-dose bisphenol A disrupts hippocampal DNA methylation and demethylation in male rat offspring
Authors: Wang Yuxin , Guo Yi , Ren Jiajia , Liu Qiling , Wang Chong
Published: May 2024

Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400 μg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3 weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.
A novel approach of stability and topography prediction in five-axis ball-end milling process through workpiece-edge-coupling
Authors: Wu Shuiyuan , Chen Dongju , Pan Ri , Fan Jinwei , Tang Yuhang
Published: May 2024

By studying the workpiece-edge-coupling (WEC) in five-axis ball-end milling, the contact characteristics between the workpiece and edge curve are analyzed, and the chip model is extracted and simplified. The edge curve involved in the cutting process of each edge are calculated at each time and a new instantaneous numerical chip thickness model is established. Then the milling forces and stability lobe diagram (SLD) are calculated in following cut process with lead and tilt angle. The milling forces and SLD of lead angle at 15° and tilt angle at −15° are verified by comparing with Otzurk model as references, and it is found the SLD of WEC model can reflect the unstable points more properly than that of Otzurk model. Also the vibration in [Formula: see text] and [Formula: see text] directions show a divergence trend, which proves the high precision for the new algorithm adapted to the stability prediction of five-axis ball-end milling process. In addition, the surface topography is acquired considering lead and tilt angle as well as forced vibration, and the result is consistent with the experiment in the existing literature. It is found that the milling forces, SLD and surface topography show the same variation trend with the increase of lead and tilt angle. Besides, the stability region significantly expands and the surface topography improves by applying positive tilt angle other than the negative. Then, under the conditions of positive lead and tilt angle, increasing lead angle and decreasing tilt angle reduces the milling force, expands the stability region of SLD and improve the surface topography. The optimized tool posture is acquired by the coincident analysis of milling force, SLD and surface topography under different lead and tilt angle.
Enhanced MRI Radiomics Based Model for Predicting Recurrence or Metastasis of Nasopharyngeal Cancer (NC) Undergoing Concurrent Chemoradiotherapy: A Retrospective Study
Authors: Song Lina , Liu Junjie , Shang Yu , Hu Yan , Zhang Junyan , Ye Yingjian , Ji Xianqun , An Peng
Published: May 2024

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.
Spatiotemporal Distribution, Time to Treatment Outcome Clustering and Determinants of Esophageal Cancer in Ethiopia, a Scoping Study
Authors: Beyen Teresa Kisi , Seife Edom , Gurara Abenet M. , McCormack Valerie , Taye Girma , Addissie Adamu
Published: May 2024

Introduction

Esophageal cancer was the eighth and sixth leading cause of morbidity of all cancers in the world, and the 15th and 12th in Ethiopia, respectively. There is a lack of comprehensive data regarding Ethiopia’s esophageal cancer hotspot, treatment outcome clustering, and other factors.

Objective

This scoping review was designed to understand the extent and type of existing evidence regarding spatiotemporal distribution, time to treatment outcome clustering, and determinants of esophageal cancer in Ethiopia up to March 28, 2023.

Methods

Three-step search strategies were employed for the scoping review from March 15 to 28, 2023. Targeted databases included PubMed/Medline, PubMed Central (PMC), Google Scholar, Hinari, and Cochrane for published studies and different websites for unpublished studies for evidence synthesis. Data were extracted using the Joanna Briggs Institute (JBI) manual format.

Results

Our final analysis comprised 17 (16 quantitative a nd 1 qualitative) studies. Three studies attempted to depict the country’s temporal distribution, whereas 12 studies showed the spatial distribution of esophageal cancer by proportion. The regional state of Oromia recorded a high percentage of cases. Numerous risk factors linked to the tumor have been identified in 8 investigations. Similarly, 5 studies went into detail regarding the likelihood of survival and the factors that contribute to malignancy, while 2 studies covered the results of disease-related treatments.

Conclusions

The substantial body of data that underpins this finding supports the fact that esophageal cancer has several risk factors and that its prevalence varies greatly across the country and among regions. Surgery, radiotherapy, or chemotherapy helped the patient live longer. However, no research has investigated which treatment is best for boosting patient survival and survival clustering. Therefore, research with robust models for regional distribution, clustering of time to treatment outcomes, and drivers of esophageal cancer will be needed.
Association of suPAR, ST2, and galectin-3 with eGFR decline and mortality in patients with advanced heart failure with reduced ejection fraction
Authors: Roehm Bethany , McAdams Meredith , Gordon Jonathan , Zhang Song , Xu Pin , Grodin Justin L , Hedayati S Susan
Published: May 2024

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m2, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = −0.36 √(ml/min/1.73 m2), 95% confidence interval (−0.48 to −0.24), p < 0.001), standardized galectin-3 (−0.14 √(ml/min/1.73 m2) (−0.27 to −0.02), p = 0.02), and log NT-proBNP (−0.23 √(ml/min/1.73 m2) (−0.31 to −0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.
Development of a defined mixed starter culture for the improvement of Tej, Ethiopian honey wine
Authors: Girma Blen , Desalegn Asnake , Birri Dagim Jirata , Ashenafi Mogessie , Tigu Fitsum
Published: May 2024

Ethiopian honey wine, Tej, is the most popular traditionally fermented alcoholic beverage in Ethiopia. Owing to the spontaneous fermentation process, the final product is neither predictable nor consistent in quality. Attempts have not been made before to solve this problem. Thus, the aim of this study was to develop a potential mixed starter culture of yeast and lactic acid bacteria isolated from Tej samples for the production of Tej with consistent quality. One hundred seventy-seven lactic acid bacteria and 194 yeasts were isolated from 30 Tej samples collected from southwest Ethiopia. After sequentially testing the isolates towards physiological stress tolerance and desired metabolic products, 10 lactic acid bacteria and 10 yeast isolates were screened. Later, four lactic acid bacteria and four yeast isolates were found to be compatible in co-culture tests. Finally, the combination of lactic acid bacteria and yeast isolates was formulated using the design of expert version 7.0.0 software, and six formulates (F #1–6) were designed. Controlled Tej fermentation was performed under laboratory conditions using six lactic acid bacteria–yeast starter culture formulations. The sensory attributes, in terms of color, flavor, odor, turbidity, and overall acceptance analysis scored 4.8/5.0 (F #2) and 4.7/5.0 (F #6), with mean significant variations ( p < 0.05) among the other formulates. These two formulates were considered the best-mixed starter cultures compared to the control and other formulates. Matrix-assisted laser desorption ionization-time of flight analysis revealed that the lactic acid bacteria starters (AAUL7 and AAUL10) belonged to Lactobacillus paracasei. While the yeast starters (AAUY2 and AAUY8) belonged to Saccharomyces cerevisiae. These mixed lactic acid bacteria–yeast starter cultures could be used as the best starter culture for the fermentation of Ethiopian honey wine, Tej, with consistent quality.
Commentary: Customer-Perceived Innovation: Considerations for Financial Performance and Methodological Approaches
Authors: Gustafsson Anders , Ghanbarpour Tohid
Published: May 2024

As firms increasingly uncover their activities to key stakeholders through various media, the perception of these activities is becoming more important for firm performance. Traditionally, access to industry-wide databases provides important metrics on customer perceptions of performance, such as customer satisfaction and brand equity. In addition, numerous studies have highlighted firms' innovation-related actions (e.g., R&D spending and patent counts) as critical metrics linked to their financial performance. Perceived Firm Innovation (PFI) emerges as a relatively new and under-studied metric with the potential to impact a firm's financial success. Keiningham et al. are among the pioneers in this area. This commentary views their article as a vital initial step in understanding PFI’s impact. Considering that the service sector accounts for over 70 percent of the GDP in any developed country, service innovation is a broad phenomenon. Given the breadth of the area, we point to the challenge of capturing this phenomenon with a single metric like PFI. We also discuss crucial methodological considerations for future research, including estimation methods, sample size, and financial metrics.
Flighty like the pīwakawaka!: personal reflections on mid-life ADHD diagnosis and the beginnings of a framework for conceptualising the condition from a Māori perspective
Authors: Rangiwai (Ngāi Tūhoe, Ngāti Porou, Ngāti Manawa, Ngāti Whare Byron
Published: May 2024

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder characterised by persistent inattention, hyperactivity, impulsivity, and executive dysfunction. While commonly associated with childhood, attention-deficit hyperactivity disorder often persists into adulthood and poses significant challenges in various aspects of life, leading to negative self-perceptions, decreased quality of life, and increased risk of comorbid mental health conditions. There is a desperate need for more research about attention-deficit hyperactivity disorder from a Māori (Indigenous peoples of New Zealand) perspective. Considering the limited research, this article introduces the metaphor of the pīwakawaka (New Zealand Fantail) as a culturally grounded way of conceptualising attention-deficit hyperactivity disorder from a Māori perspective. The pīwakawaka’s characteristics, including its quick movements, curiosity, and ability to adapt to changing environments, mirror certain aspects of attention-deficit hyperactivity disorder.
“People don’t have the answers”: A qualitative exploration of the experiences of young people with Long COVID
Authors: Newlands Fiona , Lewis Celine , d’Oelsnitz Anais , Pinto Pereira Snehal M , Stephenson Terence , Chalder Trudie , Coughtrey Anna , Dalrymple Emma , Heyman Isobel , Harnden Anthony , Ford Tamsin , Ladhani Shamez N , Powell Claire , McOwat Kelsey , Bhopal Rowan , Dudley Jake , Kolasinska Paige , Muhid Mohammed Z , Nugawela Manjula , Rojas Natalia K , Shittu Angel , Simmons Ruth , Shafran Roz
Published: May 2024

Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted ( n = 17); 11 young people (aged 13–19) and six parents were recruited from the Children and Young People with Long COVID (CLoCk) study ( n = 12) or its patient and public involvement and engagement (PPIE) group ( n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID’s Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID.
Imagine art: The status of works generated by artificial intelligence
Authors: Jerrentrup Maja
Published: May 2024

Artificial intelligence (AI) can create works deceptively resembling paintings, graphics, or photographs. This article examines how to treat these works, and under what circumstances, if any, they should be understood as art. The focus is placed on the work itself in the l’art-pour-l’art-tradition, on the reception, on the skills involved in the creation, and on the authors themselves. Besides looking at literary sources touching on the aforementioned aspects, the evaluation considers the perspective of people with an affinity for art through in-depth interviews. Most interviewees revised their initial reaction after learning that the works were AI generated, being more skeptical about their status as art. It then becomes obvious that the role of the artist is undergoing change. The confrontation with the artificial brings the human creator into the foreground and makes them inseparable from the work. The new technical-cultural situation leads to a new, more contextual evaluation of art.
Implementing a Safe Sleep Shelter and Baby Bundle Kit Distribution Program
Authors: Salm Ward Trina C. , Miller Terri J.
Published: May 2024

The Georgia Department of Public Health developed the Safe Sleep Shelter Program to expand Georgia Safe to Sleep campaign efforts. The program focused on engaging with housing support agencies, homeless shelters, and domestic violence shelters. The program offered a menu of resources that agencies could choose from, including portable cribs for agency use and distribution to families, safe sleep education for staff, assistance with creating/updating agency safe sleep policies, and Baby Bundle Safe Sleep kits with education and resources for families. The program showed promising results: 44 agencies across the state applied, serving an estimated 20,950 individuals annually. Agencies expressed strong interest in expanding safe sleep education and resources for the families they served. Most agencies reported that the program filled gaps in services, including having enough cribs to meet demand and limited safe sleep education and resources. Agencies reported that parents appreciated the cribs and Baby Bundle Safe Sleep kits as most did not have money to purchase an infant sleep surface. Agencies reported that the resources provided new information to infant parents, facilitated discussion, and reinforced safe sleep messaging. Evaluation challenges included difficulties collecting distribution data and a low response rate for parent surveys. Implications are discussed for others interested in implementing such a program, including to develop processes for communicating updated recommendations, leverage existing relationships to engage additional agencies, evaluate efforts to refine program components, and consider strategies to increase parent survey response rates.
Developing an IoT-enabled probabilistic model for quick identification of hidden radioactive materials in maritime port operations to strengthen global supply chain security
Authors: Jakovlev Sergej , Eglynas Tomas , Jusis Mindaugas , Voznak Miroslav
Published: May 2024

Uncovering hidden radioactive materials continues to be a major hurdle in worldwide supply chains. Recent research has not adequately investigated practical Internet of Things (IoT)-based approaches for improving and implementing efficient data fusion techniques. Current systems often misuse resources, leading to security vulnerabilities in typical settings. Our research delves into the fundamental principles of detection using both single and multiple sensor configurations, adopting a probabilistic method for merging data. We introduce a model aimed at accelerating the detection of radiation emissions in actual port operations. The results highlight the model’s effectiveness in rapid identification and determine the best conditions for its application in scenarios involving stacked containers, whether they are on ships or positioned in storage areas.
Tribuloside: Mechanisms and Efficacy in Treating Acute Lung Injury Revealed by Network Pharmacology and Experimental Validation
Authors: Yang Zheng , Hao Tiantian , Ma Junbing , Yang Dan , Qiu Min , Wang Rui
Published: May 2024

Background

Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo.

Objective

This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation.

Methods

We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the “drug or disease-target” network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside’s therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1β in the lungs through many pathways and targets.

Conclusion

This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.
Intensive care nurses’ compassion and patience levels and their attitude towards elderly people
Authors: Turen Sevda , Efil Sevda , Turkoglu Meryem , Issever Merve
Published: May 2024

Backgrounds:

Intensive care nurses’ attitudes towards the elderly and their emotional readiness before giving care can have an impact on the quality of care.

Aims:

The objective of this study was to investigate intensive care nurses’ compassion and patience levels and their attitude towards elderly people.

Methods:

‘Data Gathering Form’, the ‘Compassion Competence Scale’, the ‘Patience Scale and the University of California at Los Angeles Geriatrics Attitude (UCLA-GA) were used.

Results:

A total of 212 intensive care nurses participated in the study. It was found that nurses whose time working in the intensive care unit and total professional experience were 6 years or more and those who were married and had children had higher levels of both compassion and patience. In addition, patience levels were significantly higher in nurses aged 29 or more. It was found that the nurses’ sociodemographic and professional characteristics did not affect their UCLA-Geriatrics Attitudes total score.

Conclusion:

It was found in the study that there was a significant positive correlation between the nurses’ compassion and patience levels and their attitudes toward elderly people.
SDGs and public health policies: implementing the S2D grid in the city of Lausanne, Switzerland
Authors: Forbat Julien , Roué Le Gall Anne , Porcherie Marion , Gosset Christiane , Bantuelle Martine , Marchandise Charlotte , Thébault Pascal , Latrèche Souhail , Bédat Alexandre , Simos Jean
Published: May 2024

Sustainable development goals (SDGs) and public health are often considered as separate policy fields, whereas there is a considerable potential in better coordinating their objectives and measures. Using an analytical grid (S2D grid) linking SDGs and public health objectives and comprising 6 thematic issues and 56 categories, the research team conducted an assessment of health promotion programs in the city of Lausanne, Switzerland. Their objective was to determine whether SDGs and public health concerns can translate into complementary policy objectives, and what was the level of achievement of Lausanne in terms of implementation, intersectoral collaboration and avoidance of redundancy, regarding the vast array of measures potentially dealing with SDGs and health promotion. Results show that measures implemented by Lausanne deal with 80% of categories included in the S2D grid, with a high level of intersectorality and a low level of redundancy. These results also emphasize the fact that linkages between SDGs and health promotion go well beyond the SDG 3 dedicated to ‘good health and well-being’, and that the S2D grid could be used as a tool in favor of organizational change, promoting the collaboration between stakeholders often reluctant to engage in public health policies.
Environmental measures to improve pedestrian safety in low- and middle-income countries: a scoping review
Authors: Sabi Boun Saidou , Janvier Ronaldo , Jean Marc Rose Eveyoung , Paul Peterline , Senat Rachel , Demes Joseph Adrien Emmanuel , Burigusa Guillaume , Chaput Sarah , Maurice Pierre , Druetz Thomas
Published: May 2024

Objectives:

This scoping study aims to identify environmental road safety measures implemented in low- and middle-income countries (LMICs) to reduce pedestrian injuries from collisions with motor vehicles.

Methods:

This review followed Arksey and O’Malley’s approach and reported results using the PRISMA-SCR 2018 checklist. A literature review was conducted in Medline, Google Scholar, and the Transport Research International Documentation database using keyword-derived medical subject heading terms. A total of 14 articles met the pre-established inclusion criteria and were analyzed using a data extraction matrix. The findings were categorized methodically into three prominent themes: (1) methods for reducing pedestrian exposure, (2) traffic calming strategies, and (3) measures for enhancing pedestrian visibility.

Results:

Traffic calming strategies, including vehicular speed reduction, roadway contraction, and vertical and horizontal diversionary tactics, emerged as the most effective interventions for reducing pedestrian injuries within LMICs. Conversely, interventions geared towards minimizing pedestrian exposure, such as zebra crossings, crosswalks controlled by traffic signals, underpasses, or overpasses, often produced minimal effects, and occasionally exacerbated the risk of pedestrian accidents. Lack of pedestrian visibility due to density of street vendors and parked vehicles was associated with a higher risk of injuries, while billboards impaired drivers’ attention and increased the likelihood of collisions with pedestrians.

Discussion:

In LMICs, the effectiveness of environmental measures in reducing vehicle–pedestrian crashes varies widely. In the face of resource constraints, implementing interventions for pedestrian safety in LMICs necessitates careful prioritization and consideration of the local context.
Extremely Loud and Incredibly Close: Creating Connection in Divisive Times
Authors: Childers Trenita B.
Published: May 2024

Sometimes divisions make more noise than connections. In this Presidential Address for the 2023 Annual Meeting of the Association of Applied and Clinical Sociology, Dr. Childers invites sociologists to lean into our strengths when finding ways to cut through the noise of divisions to amplify connections. Intentionality, using our tools and resources, and leading with understanding are strategies that build bridges as we seek new ways to apply sociology in our worlds.
Perceived depth reversals of images on a concave screen
Authors: Gu Xiayi , Yu Han , Ito Hiroyuki , Kanematsu Tama
Published: May 2024

Reverspectives and hollow masks cause a reversal of perceived depth when observed from a position beyond certain critical distances, even if viewed binocularly. Their 3D structures or images invariably contain a linear perspective, shading, or familiarity cue to depth. Using a concave screen, we demonstrate a novel type of perceived depth reversal in binocular viewing with a variety of depth cues.
Clinical outcomes after use of checkpoint inhibitor immunotherapies in people with multiple sclerosis
Authors: Nylander Alyssa N , Rowles William , Poole Shane , Bove Riley
Published: May 2024

Background

Immune checkpoint inhibitors (ICIs) represent a novel class of agents approved for the treatment of several cancers and progressive multifocal leukoencephalopathy (PML). However, due to the risk of autoimmune side effects, their use in people with autoimmune diseases such as multiple sclerosis (MS) has been limited.

Objective

To characterize outcomes in a cohort of adults with MS who received ICIs.

Methods

A single-center retrospective review of medical record data was performed for people with MS treated with ICIs.

Results

Seven people with MS were identified, with a mean (SD) age at ICI use of 55.4 (13.7) years and a mean MS duration of 18.2 (12.2) years. Six were treated for cancer; 1 was treated for PML. After mean (SD) follow-up of 1.76 (2.15) years after ICI, outcomes are: no evidence of disease (2), residual metastatic disease (1), death due to cancer (1), death due to PML (1), and lost to follow-up (2). Notably, 0 out of 7 patients experienced an MS relapse; two out of six had new asymptomatic demyelinating magnetic resonance imaging lesions. In the three patients with expanded disability status scale (EDSS) scores at baseline and follow-up, EDSS remained stable (mean delta 0.13).

Conclusion

In this cohort, no people with MS experienced clinical relapses and one-third experienced asymptomatic radiological activity following ICI treatment.
ICT and Economic Growth Nexus in Saudi Arabia, Controlling Human Capital in the COVID-19 Era: A NARDL Exercise
Authors: Islam Md. Saiful , Rehman Anis ur , Khan Imran , Abdelrasuol Ibrahim
Published: May 2024

ICT use has significantly increased over the years across the world, including Saudi Arabia. This study links ICT with economic growth (EG) in Saudi Arabia, controlling human capital (HC) and COVID-19. We employ time-series annual data from 1990 to 2021, a nonlinear Autoregressive Distributed Lag (NARDL) approach, and a cointegrating regression analysis to look at the asymmetric effects of ICT diffusion on EG. The NARDL assessment establishes a cointegrating relationship among variables; the effect of ICT negative shocks on EG is favorable and relatively larger. In contrast, the positive shocks of ICT generate a negative and somewhat less impact on EG with an overall positive impact. The findings imply that the ICT, during its expansion stage, cannot contribute positively to EG, perhaps because of a lack of required skilled human capital to administer and utilize the ICT instruments. The positive and insignificant coefficient of HC supports this conclusion. Despite Saudi Arabia’s generous efforts, physical and human capital have no significant impact on EG. COVID-19 has hindered the usual economic activities in the Kingdom and impaired EG. The cointegrating regressions authenticate the robustness of the NARDL findings. The outcomes suggest policymakers should appraise the existing ICT infrastructure and initiate raising the capability of HC through practical training and education to benefit from ICT diffusion and positively impact EG.
More Than a Flesh Wound: Trisomy 21 Patients Undergoing Posterior Spinal Fusion for Scoliosis Have High Odds of Wound Complications
Authors: Benvenuti Michael , Ang Bryan , Kannan Kiertana , Dunham Alexandra , Bosco Alexa , Cook Danielle , Hresko M. Timothy , Birch Craig , Hedequist Daniel , Hogue Grant
Published: May 2024

Study Design

Retrospective cohort study.

Objectives

Patients with trisomy 21 (T21) often have soft tissue differences that lead to greater risk of postoperative wound complications. Our aim was to use a matched cohort of adolescent idiopathic scoliosis (AIS) patients with >2 year outcomes to determine odds of specific wound complications when comparing T21 and AIS patients.

Methods

14 T21 and 544 AIS patients were available for matching. Propensity score matching was conducted using logistic regression models and yielded a 1:5 match of 14 T21 patients and 70 AIS patients. Bivariate analyses were conducted across both patient groups. The proportion of wound complications was estimated along with a 95% confidence interval. Multivariable logistic regression analysis was utilized to determine if there was a significant association between T21 patients and wound outcomes.

Results

64% of T21 patients experienced a wound complication (9/14; 95% CI = 35.63-86.02) while only 3% of the AIS patients experienced a wound complication (2/70; 95% CI = .50-10.86). Patients with T21 had 56.6 times the odds of having a wound complication compared to matched AIS patients (OR = 56.57; 95% CI = 8.12-394.35; P < .001), controlling for age at surgery, BMI percentile, and propensity score. T21 patients had 10.4 times the odds of reoperation compared to AIS patients (OR = 10.36; 95% CI = 1.62-66.02; P = .01).

Conclusion

T21 patients have 10.4× the odds of reoperation and 56.6× the odds of overall wound complication when compared to AIS patients in a 1:5 matched cohort with appropriate controls. This is important for surgical planning, surgeon awareness, and communication with families preoperatively.
Does Intraoperative Extracochlear Electrocochleography Correlate With Postoperative Audiometric Hearing Thresholds in Cochlear Implant Surgery? A Retrospective Analysis of Cochlear Monitoring
Authors: Haumann Sabine , Mynarek (née Bradler) Marlene , Maier Hannes , Helmstaedter Victor , Büchner Andreas , Lenarz Thomas , Teschner Magnus J.
Published: May 2024

In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group.

During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed.

The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies—although no significant relationships—were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions.

Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients?
Opportunities and Challenges: Process Raman for the Real-Time Release Testing (RTRT) of Extended-Release Formulations
Authors: Webster Gregory K. , Mankani Bharat , Mozharov Sergey , Marquardt Brian
Published: May 2024

The use of a process analytical technology has been demonstrated using near-infrared spectroscopy for continuous manufacturing of pharmaceutical formulations and is within the scope of the U.S. Food and Drug Administration's real-time release testing initiative. While effective for simple formulations, this preliminary study investigates whether such a spectroscopic surrogate application can replace pharmaceutical dissolution testing for extended-release formulations. In this study, we will assess the use of process Raman spectroscopy for real-time dissolution testing. Extended-release tablet formulations often accomplish the release rate delay through the addition of gelling agents. In this work, hydroxypropyl methylcellulose (HPMC) polymers were used to formulate extended-release niacin tablets. Process Raman spectroscopy was evaluated as a tool to effectively model dissolution profiles to determine if the optical technique has the ability to differentiate HPMC polymers from the background and be selective for the polymer type employed. Our preliminary work indicates that while Raman can effectively detect and monitor the niacin response of the tablet formulations, there are not enough unique spectral features between the different HPMC polymers to selectively resolve their responses. Additional measurements and chemometric analysis might suggest otherwise. Thus, for extended-release tablet applications with continuous manufacturing, further dissolution surrogate development is needed.
An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections
Authors: Gomez Esteban A. , De Matteis Roberta , Udomjarumanee Palita , Munroe Patricia B. , Dalli Jesmond
Published: May 2024

The leucine-rich repeat-containing G-protein–coupled receptor 6 (LGR6) was recently identified as the cognate receptor for the proresolving mediator maresin 1 (MaR1). To address the biological role of LGR6 in humans, we investigated the functional impact of a genetic variant in the gene encoding for LGR6, which is predicted to lead to a frameshift mutation in one of the receptor isoforms, on both receptor expression and immune cell responses. In neutrophils, monocytes, and natural killer (NK) cells from volunteers homozygous for this variant, we found a significant downregulation in the expression of LGR6 when compared with controls without the variant; whereas the LGR6 expression was essentially similar in monocyte-derived macrophages and CD8+ T cells. Functionally, loss of LGR6 expression was linked with a decreased ability of neutrophils and monocytes to phagocytose bacteria. We observed an increase in neutrophil chemotaxis and leukotriene B4 production and increased expression of activation markers, including markers for platelet-leukocyte phagocyte heterotypic aggregates, such as CD41, in neutrophils and monocytes from the variant group. Using data from the UK Biobank, we found that at a population level the rs4266947 variant, which is in high linkage disequilibrium with rs74355478, was associated with a higher incidence of viral infections. Intriguingly, neutrophils, NK cells, and CD8+ T cells from volunteers with the LGR6 variant displayed altered viral responses when stimulated with Toll-like receptor 3 (TLR3), TLR7/TLR8, and TLR9 agonists. Together, these findings shed new light on the cell type–specific regulation of LGR6 expression and the role of this receptor in directing host immune responses.
Mediastinitis and septic shock complicating spontaneous esophageal rupture “Boerhaave’s syndrome”: a case report
Authors: Kortli Said , Andrianjafy Hery
Published: May 2024

Boerhaave’s syndrome, also known as spontaneous esophageal rupture, is a rare but life-threatening condition characterized by a tear in the esophagus. It is most commonly caused by a sudden increase in intraesophageal pressure, often due to severe vomiting or retching.

Early diagnosis of Boerhaave’s syndrome is crucial for improving patient outcomes. The classic triad of symptoms includes severe chest pain, vomiting, and subcutaneous emphysema (air under the skin). However, not all patients present with this triad, and the diagnosis can be challenging, especially in patients without the typical symptoms.

In this case report, we present the clinical details of a 52-year-old male patient who presented to the emergency department (ED) with severe abdominal pain and vomiting for several days. The patient had a history of chronic alcohol abuse and a recent episode of vigorous vomiting.
Integrated approach to generate artificial samples with low tumor fraction for somatic variant calling benchmarking
Authors: Sergi Aldo , Beltrame Luca , Marchini Sergio , Masseroli Marco
Published: May 2024

Background

High-throughput sequencing (HTS) has become the gold standard approach for variant analysis in cancer research. However, somatic variants may occur at low fractions due to contamination from normal cells or tumor heterogeneity; this poses a significant challenge for standard HTS analysis pipelines. The problem is exacerbated in scenarios with minimal tumor DNA, such as circulating tumor DNA in plasma. Assessing sensitivity and detection of HTS approaches in such cases is paramount, but time-consuming and expensive: specialized experimental protocols and a sufficient quantity of samples are required for processing and analysis. To overcome these limitations, we propose a new computational approach specifically designed for the generation of artificial datasets suitable for this task, simulating ultra-deep targeted sequencing data with low-fraction variants and demonstrating their effectiveness in benchmarking low-fraction variant calling.

Results

Our approach enables the generation of artificial raw reads that mimic real data without relying on pre-existing data by using NEAT, a fine-grained read simulator that generates artificial datasets using models learned from multiple different datasets. Then, it incorporates low-fraction variants to simulate somatic mutations in samples with minimal tumor DNA content. To prove the suitability of the created artificial datasets for low-fraction variant calling benchmarking, we used them as ground truth to evaluate the performance of widely-used variant calling algorithms: they allowed us to define tuned parameter values of major variant callers, considerably improving their detection of very low-fraction variants.

Conclusions

Our findings highlight both the pivotal role of our approach in creating adequate artificial datasets with low tumor fraction, facilitating rapid prototyping and benchmarking of algorithms for such dataset type, as well as the important need of advancing low-fraction variant calling techniques.
Response mechanisms of different Saccharomyces cerevisiae strains to succinic acid
Authors: Xie Cai-Yun , Su Ran-Ran , Wu Bo , Sun Zhao-Yong , Tang Yue-Qin
Published: May 2024

Background

The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it’s necessary to clearly understand how S. cerevisiae cells respond to SA.

Results

In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA.

Conclusions

The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains’ potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.
Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center
Authors: Wang Yi , Wu Yajing , Zheng Chen , Li Qihui , Jiao Wenpeng , Wang Jianing , Xiao Linlin , Pang Qingsong , Zhang Wencheng , Wang Jun
Published: May 2024

Background

Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC.

Methods

Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC.

Results

The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC.

Conclusions

MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.