bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Personality and Motivation on Students’ Academic Engagement and Metacognitive-Cognitive Strategies
Authors: Ramirez-Arellano Aldo
Published: November 2024

Several investigations have focused on the relationship between personality and learning performance. However, the relationships among personality traits, motivation, emotional and behavioral engagement, and metacognitive-cognitive strategies remain unexplored. This research introduces a model based on a personality system set comprising metacognition, cognition, motivation, emotional and behavioral engagement. Five core education theories support this model. Three hundred seventy-four Mexican university students who were enrolled in a Biology and Industrial Management bachelor’s degree program participated. Personality traits mainly affect academic engagement but not motivation. Additionally, academic engagement mediates the relationship between personality traits and metacognitive-cognitive strategies. The findings show that agreeableness and neuroticism traits influence emotional engagement and disaffection. Consciousness and extraversion affect behavioral disaffection and engagement, respectively. Meanwhile, motivation affects emotional engagement, disaffection and metacognitive-cognitive strategies. Finally, openness does not affect any of the constructs. Hence, personality traits directly influence academic engagement and disaffection but not motivation and cognitive strategies.
Fear of Missing Out and Consumption-Sharing Behavior on Social Media: The Moderating Role of Self-Presentation Desire and Social Network Type
Authors: Dinh Thi Cam Tu , Lee Yoonjae
Published: November 2024

While sharing positive content about a brand’s products can bring huge benefits, when and what motivates consumers to post on social media is still an underexplored area, especially in a conspicuous consumption context. Therefore, this study tries to explain customers’ journey when engaging in conspicuous consumption and consumption-sharing behavior on social media by applying fear of missing out (FOMO), self-presentation, and social network types. This research was conducted with 400 respondents in the US, and the data were analyzed using PROCESS models. Results reveal that FOMO positively affects conspicuous consumption and consumption-sharing behavior. Moreover, conspicuous consumption and consumption-sharing behavior differ under the influence of self-presentation desire and the type of social network they have. The study contributes to the current literature by investigating the factors encouraging customers to share their conspicuous consumption on social media. It also offers significant insights and recommendations for marketers to increase brand awareness.
Understanding the Experience of Workplace Violence in Hospitals as Documented by Nursing Staff: Using the READ Approach
Authors: Brunero Scott , Tetik Emine , Donnelly Nikita , Lamont, PhD Scott
Published: November 2024

Background: Workplace violence has a significant impact on patients, families, and staff safety. Workplace violence can produce traumatic results for those involved; the importance of preventive measures needs to be paramount in health service policy and process. Health care staff are required to document their experiences of violent incidents after every occasion, usually via an incident reporting system, which allows for a free text description of the event. There is a lack of understanding of how health care staff document reports of violence and how they explain the events. Methods: This study aims to determine the circumstances surrounding workplace violent events as documented by health care staff. The four-step Review, Extract, Analyze, and Document (READ) approach to document analysis was used to examine workplace violence incident reports over 12 months (September 2021–September 2022) in a tertiary referral hospital. Findings: Six categories of workplace violence were found: (a) “Escalation Dynamics”—patterns and progression of how violence incidents intensify; (b) “Warning Behaviors”—verbal or non-verbal signals that may foreshadow physical violence if not addressed; (c) “Authoritative Institutional Interventions”—how aggression correlates to protocols involving security personnel or law enforcement; (d) “Care Delivery Methods”—how certain treatment procedures and approaches might inadvertently elicit violence; (e) “Situational Stressors”—external circumstances or changes that act as triggers for violence; and (f) “Unprovoked triggers”—sudden and seemingly unprovoked violent outbursts. Conclusions and application to practice: Workplace violence in health care is a multifaceted interplay of events with the nurse involved in all aspects of the process. These findings can be used by occupational health nurses in education and policy development. The findings can be used to focus education on how violent incidents may escalate and provide more opportunities for de-escalation by health care staff.
In Whose Best Interests? Comparing Children’s Treatment in Immigration Court and in Child Protection Hearings in Minnesota: Similar Issues Without the Relevant Tools or Best Interests Standard
Authors: Schmidt Susan
Published: November 2024

Executive Summary

Federal immigration courts and state child welfare courts make decisions regarding certain similarly situated children in need of protection, but how does immigration court compare in its procedures for dealing with them? This article uses a comparative court observation approach to consider that question, by analyzing six months of observational data from the Fort Snelling Immigration Court juvenile docket, along with observations in Minnesota juvenile court child protection proceedings. Findings include the prioritization of federal government interests over children’s best interests, apparent in the US Government ensuring that an attorney represent its own interests before the immigration judge, while children must represent themselves if unable to find or afford an attorney. Furthermore, unrepresented children must navigate complex multi-agency procedures in order to seek the two most common forms of legal protection (Special Immigrant Juvenile Status, and asylum). Finally, the federal government fails to provide appropriate tools for responding to indicators of child welfare matters mentioned in immigration court, despite holding states to account for their handling of child maltreatment.
Need for Structured Pain Management Curriculum and Competency-Based Evaluation in GME: An Observational Study in One Internal Medicine Residency Program
Authors: Thangarasu Sudhagar , Renganathan Gowri , Soskin Barney , Ruck Lela , Prakash Vishakh , Unnikrishnan Sumedha , Goranti Jyothsna , Cobos Everardo
Published: November 2024

OBJECTIVES

One of the major contributing factors to the opioid crisis, marked by a surge in opioid prescriptions, includes inadequate adherence to guideline-based pain management practices, highlighting the need for a comprehensive curriculum during residency training. In this study, we aim to assess opioid exposure prevalence among hospitalized patients and examine potential associations between disease conditions, patient demographics, and opioid prescriptions during their hospital stay.

METHODS

In this retrospective cohort study at a southern California county teaching hospital, we analyzed the medical records of 2272 patients admitted to the IM resident inpatient teaching service for 1 year, from September 2017 through September 2018.

RESULTS

The study found that 44% of patients received opioid prescriptions during their hospital admission, with 23% receiving prescriptions at discharge and 45% having prior opioid exposure. Patients with prehospital opioid exposure had a 2-fold increased risk at discharge (Relative Risk: 2.51; P < .0001). The hypothesis that factors such as gender, certain medical conditions, and previous opioid use influenced opioid prescriptions during hospitalization is disproved. Instead, hospital admission itself was the significant contributing factor to receiving opioids during acute care and at discharge, irrespective of the source of pain.

CONCLUSION

In conclusion, our study revealed that the primary determinant for opioid exposure during hospitalization is the inpatient admission itself rather than specific patient-related factors. The lack of a structured curriculum in residency training contributes to the default use of opioids for all pain types, highlighting the need for curricular reforms to focus on multimodal pain management principles.
Norse gods on Instagram - Developing critical literacy through multimodal text production
Authors: Undrum Linda V. M. , Burgess Marthe Øidvin , Veum Aslaug
Published: November 2024

This article explores how critical literacy can be developed through multimodal text production. The study was conducted with lower secondary school students in Norway, who in a school task were asked to reconstruct the identities of gods from Old Norse mythology in fictitious Instagram posts. The purpose of this task was to improve the students’ critical literacy especially concerning social media, and to increase their understanding of how all representations are constructed. The students' texts were analysed for traces of how they have remade and transformed meaning through reproduction of Instagram’s technical functions and literacy practices, and how they have built on knowledge from both Old Norse mythology and present-day culture. The findings suggest that reproducing social media texts challenged the students to be critical producers of text and to demonstrate linguistic, visual and technological awareness, without using digital technologies.
Life between Stations: A visualization of non-metro trips and associated station pairs in Hong Kong
Authors: Miao Yunting , Zhou Jiangping
Published: November 2024

Trip chains, consisting of multiple interconnected trips serving different functions and/or purposes, occur commonly among urban residents. Non-metro trips (NMTs) between a pair of metro stations as parts of trip chains predominantly carried by metro systems have received little attention in the existing scholarship and practice. They contribute, however, to “Life between Stations” (LbS)—various activities engaged in by metro riders and other urban residents around or between stations. LbS affects residents’ level of satisfaction for trip chains, sense of belonging, and even overall quality of life. But for a given city, where do those NMTs occur more frequently and how long are the durations? Using the 12-weekend metro smartcard swipe records in 2019 in Hong Kong, we defined, quantified, and visualized NMTs and associated metro station pairs in a real-world setting. We found that (a) the NMTs and LbS occurred between as many as 179 metro station pairs, involving 84 out of the 95 local metro stations, (b) the NMTs and LbS varied across the station pairs and/or metro lines, and (c) commercial and densely populated areas saw more than elsewhere. These findings shed light on efforts undertaken to better understand and improve LbS of metro riders.
Exploring the Landscape of Digital Nudging: A Comprehensive Bibliometric Analysis Using VOSviewer
Authors: Thomas Merliyn Anna , T. Jyothis
Published: November 2024

In recent years, digital nudging, which is based on human-computer interaction and behavioural economics, has received much attention as a means to influence users' behaviour in digital environments. There has been a notable proliferation of scholarly investigations within diverse academic disciplines related to the concept of digital nudge and its implementation in real-life contexts. However, there remains a significant gap in the comprehensive understanding of the current state of research on digital nudging and its future directions. This article offers an extensive bibliometric analysis of the digital nudging literature by examining 1,713 publications sourced from the Scopus database, covering the period from 2008 to mid-2023. This study outlines trends in digital nudging publications, identifies the most pertinent sources and highlights frequently used keywords. A bibliometric analysis using VOSviewer was subsequently performed to uncover thematic clusters. The co-authorship network analysis of authors and countries, the co-occurrence of specific keywords and author-level co-citation analysis reveal notable patterns and themes within the field of digital nudging. This study serves as a valuable resource for gaining a comprehensive understanding of recent research developments in digital nudging.
Rundqvistite-(Ce), Na3(Sr3Ce)(Zn2Si8O24), a new mineral from the Darai-Pioz alkaline massif, Tien-Shan Mountains, Tajikistan: mineral description and crystal structure
Authors: Agakhanov Atali A. , Day Maxwell C. , Sokolova Elena , Karpenko Vladimir Yu. , Hawthorne Frank C. , Pautov Leonid A. , Kasatkin Anatoly V. , Pekov Igor V. , Agakhanova Vitaliya A.
Published: November 2024

Rundqvistite-(Ce), ideally Na3(Sr3Ce)(Zn2Si8O24), is a new mineral from the Darai-Pioz alkaline massif, Tien-Shan Mountains, Tajikistan. The mineral occurs as elongated grains up to 0.1 mm long and up to 0.03 mm thick embedded in quartz–pectolite aggregate in a silexite-like peralkaline pegmatite. Associated minerals are quartz, fluorite, pectolite, baratovite, aegirine, leucosphenite, neptunite, reedmergnerite, orlovite, sokolovaite, mendeleevite-(Ce), odigitriaite, pekovite, zeravshanite, kirchhoffite and garmite. The mineral is colourless with a vitreous lustre and a white streak, brittle, Dmeas. is 3.70(2) and Dcalc. is 3.709 g/cm3. Rundqvistite-(Ce) is monoclinic, space group P21/c, a = 5.1934(16), b = 7.8934(16), c = 26.011(5) Å, β = 90.02(3)° and V = 1066.3(4) Å3. The chemical composition of rundqvistite-(Ce) is SiO2 40.17, La2O3 2.64, Ce2O3 7.55, Pr2O3 0.80, Nd2O3 2.43, Sm2O3 0.33, Eu2O3 0.09, Gd2O3 0.24, Tb2O3 0.18, Dy2O3 0.21, PbO 1.03, SrO 19.83, FeO 0.37, ZnO 13.08, CaO 2.55, Na2O 8.04, total 99.54 wt.%. The empirical formula calculated on 24 O apfu (atoms per formula unit) is Na3.10Sr2.29Ca0.54Pb0.06(Ce0.55La0.19Nd0.17Pr0.06Sm0.02Gd0.02Eu0.01Tb0.01Dy0.01)Σ1.04Zn1.92Fe0.06 Si8.00O24Z = 2. The structural formula based on refined site-occupancies is (Na2.94Sr0.06)Σ3.00 [(Sr2.23Ca0.54Pb0.06Na0.13)Σ2.96Ln3+1.04]Σ4.00[(Zn1.92Fe2+0.06)Σ1.98Si8O24], where Ln3+1.04 = (Ce0.55La0.19Nd0.17Pr0.06Sm0.02Gd0.02Eu0.01Tb0.01Dy0.01)Σ1.04. The crystal structure of rundqvistite-(Ce) was refined to R1 = 2.76% on the basis of 3184 unique reflections [F > 4σ|F|]. In rundqvistite-(Ce), the main structural unit is a (Zn2Si8O24)12– sheet parallel to (100). In the sheet, the Si and Zn tetrahedra form four-, five- and eight-membered rings. The interstitial cations at the Na and M(1–3) sites sum to [Na3(Sr3Ce)]12– apfu. The Na and M(1–3) polyhedra share common edges to form a layer. Rundqvistite-(Ce) is a structural analogue of vladykinite, ideally Na3Sr4(Fe2+Fe3+)Si8O24. Rundqvistite-(Ce) and vladykinite are related by the following substitution: [8]Ce3+ + [4](Zn2+)2 ↔ [8]Sr2+ + [4](Fe2+Fe3+). The mineral is named after Dmitry Vasilievich Rundqvist (1930–2022), a prominent Russian geologist and an expert on the geology of ore deposits, metallogeny and mineralogy of Precambrian rocks.
Approaching a therapeutic inflection point for FLT3-mutated AML
Authors: Perl Alexander E.
Published: November 2024

Combining FLT3 inhibitors with intensive chemotherapy and transplant has substantially improved AML outcomes, prompting a recent re-evaluation of FLT3-ITD's historically negative prognostic effect. Treatment approaches may soon undergo major changes as emerging data suggest maximal intensity does not benefit all patients and MRD potentially can guide several treatment choices. Finally, recent data also suggest FLT3 inhibitors could transform outcomes in patients unsuitable for intensive therapy. If confirmed, this has important implications for fit patients and could revolutionize the treatment paradigm.
Building the future management of follicular lymphoma with T-cell–redirecting strategies
Authors: Iacoboni Gloria , Morschhauser Franck
Published: November 2024

Follicular lymphoma (FL) usually requires multiple lines of therapy, and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell–redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.
Association between life’s essential 8 and cognitive impairment in older patients: results from NHANES 2011–2014
Authors: Wang Hui , Wu Sensen , Pan Dikang , Ning Yachan , Wang Cong , Guo Jianming , Gu Yongquan
Published: November 2024

Background

This study aimed to examine the association between the American Heart Association’s (AHA) newly revised Life’s Essential 8 (LE8) algorithm, designed for assessing cardiovascular health (CVH), and cognitive impairment among older adults in the United States.

Methods

This study employed a cross-sectional design, utilizing data from the 2011–2014 National Health and Nutrition Examination Survey to explore the relationship between CVH and cognitive impairment in older adults. CVH scores are assessed based on the AHA definition of the LE8, categorized into three tiers: low (0–49), medium (50–79), and high (80–100). Cognitive impairment is evaluated using three distinct scoring systems: the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The lowest quartile as the cut-off point; below or equal to the lower quartile was considered as low cognitive population, and above the lower quartile was normal population. To analyze the association, multivariable logistic regression and restricted cubic spline (RCS) models were employed.

Results

A significant negative correlation exists between the LE8 and cognitive impairment. After adjusting for multiple variables, the odds ratios (OR) for cognitive impairment, as measured by the CERAD, AFT, and DSST, were compared between patients with high and low CVH. The results indicated OR values of 0.60 (95% CI: 0.36–0.98), 0.72 (95% CI: 0.52–0.97), and 0.29 (95% CI: 0.16–0.53) for the CERAD, AFT, and DSST, respectively. Additionally, the RCS curve demonstrated a significant linear relationship between lifestyle factors encapsulated by the LE8 and cognitive impairment.

Conclusions

The findings indicate higher adherence to LE8 was associated with lower odds of cognitive impairment. Furthermore, maintaining optimal CVH is crucial in preventing cognitive impairment.
Displacement of maxillary dental implants: a case series on various scenarios
Authors: Bär Anne-Kathrin , Werkmeister Richard , Becker Philipp , Lindwedel Kim , Al-Nawas Bilal
Published: November 2024

Background

Oral rehabilitation with dental implants is a common procedure in modern dentistry due to its high success rates. However, complications such as implant displacement can occur, particularly in the maxillary region due to factors like atrophied maxilla, thin alveolar bone, and low bone density. This case series explores scenarios of maxillary dental implant displacement, emphasizing the impact of immediate preoperative imaging on patient outcomes.

Case presentation

Three cases of maxillary implant displacement are presented, each illustrating a different scenario. Complications resulting from the displacement of implants into adjacent structures such as the maxillary sinus and nasal cavity are described. All cases involved implants that were displaced during second-stage surgery, occurring four to six months post-implantation. Removal attempts used transnasal endoscopic, intraoral, or combined approaches, with only one implant successfully retrieved. Delays in surgery ranged up to 72 h, leading to one implant being swallowed and another unlocated. Outcomes varied, with some patients requiring hospitalization for up to five days.

Conclusion

This series highlights the crucial role of immediate preoperative 3D imaging in precisely locating displaced implants to ensure their safe and efficient removal. While implant displacement may not always be preventable, optimizing the timeframe between diagnostic imaging and surgical intervention can significantly enhance management. Accurately locating the implant minimizes treatment invasiveness and patient discomfort, thereby improving clinical outcomes.
Exploring the dynamics of ultrasound training in medical education: current trends, debates, and approaches to didactics and hands-on learning
Authors: Recker Florian , Neubauer Ricarda , Dong Yi , Gschmack Anna Maria , Jenssen Christian , Möller Kathleen , Blaivas Michael , Ignacio Prats Michael , Lucius Claudia , Ruppert Johannes , Sänger Sophie-Luise , Sirli Roxana , Weimer Johannes , Westerway Susan Campbell , Zervides Constantinos , Dietrich Christoph Frank
Published: November 2024

Introduction

Medical education, especially in ultrasound training, is undergoing significant changes. This study examines practical issues in ultrasound medical education, emphasizing state-of-the-art teaching methods, their effectiveness, and implementation challenges.

Methods

The study analyzed advancements in ultrasound education, including randomized controlled trials comparing peer-to-peer teaching with traditional faculty-led instruction. It evaluated the effectiveness of collaborative small-group training and group size impact in simulation-based training. The study also assessed practical training components outlined in the WFUMB Position Paper Part II.

Results

Findings indicate that peer-to-peer and collaborative small-group training are effective and cost-efficient. Group size did not significantly affect training outcomes. Key practical training elements, including early hands-on sessions and exposure to various equipment, substantially improved learning outcomes. Simulation tools like virtual reality (VR), augmented reality (AR), and phantoms were crucial for teaching standardized procedures and rare pathologies. Challenges identified include developing robust image acquisition skills, scarcity of qualified student tutors, and the need for reliable ultrasound skill assessment methods.

Conclusion

Integrating peer-to-peer teaching and advanced simulation technologies significantly advances ultrasound medical education. These methods enhance cognitive and psychomotor skills but also present challenges such as ensuring quality education and developing effective assessment methods. Future research should compare different simulation tools and establish objective ultrasound proficiency assessment criteria. Continual method evaluation and improvement are essential for effective and standardized ultrasound training, ultimately enhancing patient care and clinical outcomes.
The next generation of physician-researchers: undergraduate medical students’ and residents’ attitudes, challenges, and approaches towards addressing them
Authors: Mokhtari Behnaz , Badalzadeh Reza , Ghaffarifar Saeideh
Published: November 2024

Background

Undergraduate medical education and residency training are critical periods for conducting research. Medical diagnoses and therapies are direct results of successful research efforts that have advanced several scientific fields. This review highlights the importance of incorporating scientific research training into the curricula of undergraduate medical education and residency programs.

Methods

We utilized key databases such as PubMed, Web of Science, and Google Scholar to conduct a narrative review of English-language articles published between 2002 and 2024. Ultimately, we selected 49 studies that examined the attitudes of undergraduate medical students and residents toward research, the common challenges they encounter while participating in research activities, and the strategies that support and encourage their involvement, all in alignment with our study objectives and keywords. In addition, we identified several relevant themes, including the value of research experience in shaping well-rounded medical professionals; the integrity of research practices in residency selection, which addresses concerns such as the arms race and misrepresentation, as well as the balance between quality and quantity; striking a balance between research and clinical training while promoting equity and inclusion; and effective programs and mentorship strategies to enhance research engagement.

Results

Translating the positive attitudes of undergraduate medical students and residents into improved knowledge and practice necessitates the development of structured mentoring programs and advanced training systems. Institutions must provide the necessary tools, guidance, and support to overcome research barriers. This will help establish an environment in undergraduate medical education and residency training that values research, facilitates access to it, and integrates it into the curriculum.

Conclusions

To address the critical shortage of physician-researchers and improve evidence-based medical practice, it is crucial for medical schools to focus on research education and create avenues for student involvement. By tackling research challenges and implementing supportive strategies, these efforts empower the next generation of physician-researchers to embrace research, contribute to medical progress, and uphold the highest standards of patient care.
Contemporary comparative surgical outcomes of type A aortic dissection in US and China: an analysis of the national inpatient sample database and a Chinese multi-institutional registry
Authors: Jiang Feng , Wang Xiaodi , Carmichael Michael , Chen Yanfei , Huang Ruijian , Xiao Yue , Zhou Jifang , Su Cunhua
Published: November 2024

Background

To investigate the contemporary comparative inpatient prognosis among US and Chinese patients with type A aortic dissection (TAAD).

Methods

Data from Chinese multi-institutional TAAD registry and the US National Inpatient Sample databases were analyzed. We used multivariable logistic regression models to compare in-hospital mortality and perioperative complication rates between the US and China. Length of stay and overall costs were fitted with quantile regression models. Independent prognostic factors associated with post-operative survival were assessed via Cox proportional hazards models.

Results

Among 3,121 eligible TAAD patients, 1,073 were from China (25.0% female; mean ± SD age, 53.9 ± 12.4) and 2,048 were from the US (31.2% female; mean ± SE age, 59.8 ± 0.3). During the study period, the in-hospital mortality rates in China and the US were 15.5% and 13.3%, yet the difference was insignificant after adjustment (aOR, 1.16; 95% CI, 0.69–1.97). While there was no significant difference in overall perioperative complications (aOR, 1.07; 95% CI, 0.52–2.18), the patterns of complications differed between two cohorts. While Chinese TAAD patients experienced significantly longer duration of hospitalization (median difference, + 10.4 days; 95% CI, 9.2–11.5), the US TAAD cohort had significantly greater overall hospitalization costs (49.9; 95% CI, 55.4–44.5, in 1000 USD).

Conclusions

Notwithstanding significant differences in demographic and clinical characteristics, TAAD patients from China and the US demonstrated comparable in-hospital mortality and overall perioperative complication rates. Future initiatives should focus on expanding surgical eligibility to the elderly Chinese TAAD patients and optimizing the duration of hospitalization without undermining meaningful clinical outcomes.

Trial registration

KY20220425-05, April 5th 25 2022.
An integrated approach for studying exposure, metabolism, and disposition of traditional Chinese medicine using PATBS and MDRB tools: a case study of semen Armeniacae Amarum
Authors: Zhang Dandan , Zhang Junyu , Chen Simian , Zhang Hairong , Yang Yuexin , Jiang Shan , Hong Yun , Zhu Mingshe , Xie Qiang , Wu Caisheng
Published: November 2024

Background

Deciphering the in vivo processes of traditional Chinese medicine (TCM) is crucial for identifying new pharmacodynamic substances and new drugs. Due to the complexity and diversity of components, investigating the exposure, metabolism, and disposition remains a major challenge in TCM research. In recent years, a number of non-targeted smart mass-spectrometry (MS) techniques, such as precise-and-thorough background-subtraction (PATBS) and metabolomics, have realized the intelligent identification of in vivo components of TCM. However, the metabolites characterization still largely relies on manual identification in combination with online databases.

Results

We developed a scoring approach based on the structural similarity and minimal mass defect variations between metabolites and prototypes. The current method integrates three dimensions of mass spectral data including m/z, mass defect of MS1 and MS2, and the similarity of MS2 fragments, which was sequentially analyzed by a R-based mass dataset relevance bridging (MDRB) data post-processing technique. The MDRB technology constructed a component relationship network for TCM, significantly improving metabolite identification efficiency and facilitating the mapping of translational metabolic pathways. By combining MDRB with PATBS through this non-targeted identification technology, we developed a comprehensive strategy for identification, characterization and bridging analysis of TCM metabolite in vivo. As a proof of concept, we adopted the proposed strategy to investigate the process of exposure, metabolism, and disposition of Semen Armeniacae Amarum (CKXR) in mice.

Significance

The currently proposed analytical approach is universally applicable and demonstrates its effectiveness in analyzing complex components of TCMs in vitro and in vivo. Furthermore, it enables the correlation of in vitro and in vivo data, providing insights into the metabolic transformations among components sharing the same parent nucleus structure. Finally, the developed MDRB platform is publicly available for (https://github.com/933ZhangDD/MDRB) for accelerating TCM research for the scientific community.

Graphical Abstract
Theoretically-informed vs standard cover letter to improve participant response to mailed questionnaire: results of an embedded randomised retention trial
Authors: Everett Colin C. , Brown Sarah T. , Dennett Joanna L. , Collier Howard , Davies Claire L. , Game Frances , Nelson E Andrea
Published: November 2024

Background

Participant non-response is a source of bias in all research, especially in randomised controlled trials. Participants followed up remotely can have high non-response rates. Four such trials have been conducted of a cover letter with content informed by behaviour change theory to overcome hypothesised barriers to responding to a mailed questionnaire. Pooled results to date have suggested further research to be worthwhile. We conducted an embedded randomised study within a trial of such cover letters in the hope that we would improve response rates to our postal quality of life questionnaires.

Methods

One hundred forty-eight participants in the CODIFI2 diabetic foot ulcer sampling trial were randomised 1:1 to receive one of two different cover letters at follow-up timepoints: either a standard cover letter accompanying their postal follow-up questionnaires or to an ‘enhanced’ (theory-informed) cover letter. Questionnaires were mailed at 39, 52 and (for some participants) 104 weeks post randomisation. Outcome measures were response to mailing at each timepoint. Analysis was restricted to those for whom a questionnaire and letter was issued. Owing to limited recruitment, a reduced analysis plan, comprising solely observed response rates and 95% confidence intervals for difference in response rates was followed. Post hoc, we added our week 52 results to an already-published meta-analysis.

Results

Sixty-seven out of 74 enhanced cover letter group (Enhanced) and 67/74 standard cover letter group (Standard) participants who had not already died or withdrawn were sent their first mailing at 39 weeks. The 39-week response rates were 47/67 (70.1%) and 39/67 (58.2%) for Enhanced and Standard participants, respectively. At week 52, the response rates were 45/64 (70.3%) and 35/63 (55.6%) for Enhanced and Standard participants, respectively. At week 104, the response rates were 24/33 (72.7%) and 19/33 (57.6%) for the Enhanced and Standard participants, respectively. Adding our week 52 results to a published meta-analysis increased the pooled estimate of differences in response rates to 0.04 (− 0.01 to 0.09) favouring enhanced letters.

Conclusion

While this embedded randomised controlled trial observed greater response rates at all times among those randomised to the enhanced letter, the reduced sample size meant that these results are imprecise.

Trial registration

ISRCTN registry ISRCTN74929588. Registered on 5 March 2019.
Supporting diversity in clinical trials: the equitable breakthroughs in medicine site maturity model
Authors: Harris Tesheia , Nunez-Smith Marcella , Suttiratana Sakinah C. , Fretz Samantha L. , Leonard Savannah , Linnander Erika , Curry Leslie A. ,   and the EQBMED Network Partners
Published: November 2024

Background

Among the most powerful barriers to broader inclusion of diverse participants in clinical trials are social determinants of health, trustworthiness of health care providers and research institutions, and competing pressures on potential participants. Nevertheless, current tools to assess organizational capabilities for clinical trial diversity focus primarily on trial infrastructure, rely solely on quantitative self-reported data, and lack meaningful assessment of capabilities related to community engagement.

Methods

The Equitable Breakthroughs in Medicine (EQBMED) initiative developed a holistic, collaborative, site-driven formative model and accompanying assessment to catalog sites’ current capabilities and identify opportunities for growth in both conducting industry-sponsored clinical trials and enriching diversity of those trials. The model builds upon prior work and reflects unification of two historically distinct components—research operations and community engagement—since sustainable clinical trial diversity efforts must overcome these silos. Here we present the methodology we used to develop the model and accompanying assessment, describe how findings can support clinical trial diversity efforts, and report findings from early field testing at three U.S. sites.

Results

The first three sites were diverse in size (e.g., < 250–1 K beds), with varying levels of clinical trial capabilities and community engagement. The maturity assessment laid the foundation for sites to identify and prioritize key areas to advance clinical trial diversity capabilities, and each has made tangible progress. In parallel to completing the assessment with these early sites to understand their maturity and set actionable goals, we also collected their feedback on content validity (e.g., clarity, comprehensiveness, terminology) and feasibility (e.g., ability to collect needed information and data, time required). We describe refinements made to improve the assessment and streamline the process. The EQBMED program will deploy the assessment across various site types (e.g., FQHCs, safety net hospitals) and make further refinements as warranted.

Conclusions

Strategic investment in clinical trial diversity requires structured assessment of site maturity as a starting point for collaborative action. We propose the EQBMED maturity model as a first step toward informing efforts to increase representation of diverse populations in clinical research.
Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway
Authors: Cheng Ya-Wen , Yang Ling-Yu , Chen Yi-Tzu , Chou Sheng-Che , Chen Kuo-Wei , Chen Yi-Hsing , Deng Chuan-Rou , Chen I-Chin , Chou Wan-Ju , Chang Chen-Chih , Chen Yong-Ren , Hwa Hsiao-Lin , Wang Kuo-Chuan , Kuo Meng-Fai
Published: November 2024

Background

Chronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the cerebral or carotid arteries. CCI may lead to progressive cognitive impairment that is considered as a prelude to neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair in ischemic cerebrovascular diseases, primarily by differentiating into endothelial cells (ECs) or through paracrine effects. However, the clinical transplantation of stem cell therapies remains limited. In this study, we investigated the effects of EPC-derived conditioned medium (EPC-CM) on the impaired vasculature and neurological function in a rodent model of CCI and the mechanism involved.

Methods

EPC-CM was analyzed by cytokine array to identify key factors involved in angiogenesis and cellular senescence. The effects and mechanism of the candidate factors in the EPC-CM were validated in vitro using oxygen–glucose deprivation (OGD)-injured ECs and EPCs. The therapeutic effects of EPC-CM and the identified key factor were further examined in a rat model of CCI, which was induced by bilateral internal carotid artery ligation (BICAL). EPC-CM was administered via intracisternal injection one week post BICAL. The cerebral microvasculature and neurobehavior of the rats were examined three weeks after BICAL.

Results

Macrophage migration inhibitory factor (MIF) was identified as a key factor in the EPC-CM. Recombinant MIF protein promoted angiogenesis and prevented senescence in the injured EPCs and ECs. The effect was similar to that of the EPC-CM. These therapeutic effects were diminished when the EPC-CM was co-treated with MIF-specific antibody (Ab). Additionally, the vascular, motor, and cognitive improvements observed in the BICAL rats treated with EPC-CM were abolished by co-treated with MIF Ab. Furthermore, we found MIF promoted angiogenesis and anti-senescence via activating the AKT pathway. Inhibition of the AKT pathway diminished the protective effects of MIF in the in vitro study.

Conclusions

We demonstrated that EPC-CM protected the brain from chronic ischemic injury and promoted functional recovery through MIF-mediated AKT pathway. These findings suggest EPC-CM holds potential as a novel cell-free therapeutic approach for treating CCI through the actions of MIF.
B2M or CIITA knockdown decreased the alloimmune response of dental pulp stem cells: an in vitro study
Authors: Hu Mingxin , Zhang Yuchen , Liu Junqing , Chen Yihan , Kang Jun , Zhong Jialin , Lin Shulan , Liang Ye , Cen Rong , Zhu Xiaofei , Zhang Chengfei
Published: November 2024

Background

Dental pulp stem cells (DPSCs) have acquired noteworthy attention for their application in treating ischemic diseases and facilitating tissue regeneration. However, the host’s immune response following allogenic DPSC transplantation often handicaps the long-term survival of transplanted cells, thereby limiting the application of DPSCs in cell therapy. This study aims to investigate whether genetic modification can alleviate the immunogenicity of DPSCs.

Methods

Beta 2-microglobulin (B2M) and the class II histocompatibility complex transactivator (CIITA) were individually knocked down in DPSCs by lentiviral particles encoding short hairpin (sh) RNAs. The self-renewal capacity and pluripotency of DPSCs-shB2M (B2M silenced DPSCs) and DPSCs-shCIITA (CIITA silenced DPSCs) were evaluated by CCK8 and differentiation assays including osteogenesis, adipogenesis, and neurogenesis. The expression of HLA-I and HLA-II in DPSCs-shB2M and DPSCs-shCIITA after IFN-γ treatment were analyzed by western blotting, immunofluorescence, and flow cytometry. The function of genetically modified cells was assessed by leukocyte-mediated cytotoxicity and T-cell proliferation assays.

Results

Western blotting, immunofluorescence, and flow cytometry revealed that DPSCs-shB2M and DPSCs-shCIITA exhibited impaired IFN-γ inducible HLA-I and HLA-II expression. There were no significant differences in the self-renewal capacity and pluripotency among DPSCs-shB2M, DPSCs-shCIITA, and control groups (p > 0.05). Lower leukocyte-mediated cytotoxicity and higher cell survival rates were found in DPSCs-shB2M and DPSCs-shCIITA groups compared to the control (p < 0.05). T cell proliferation was significantly inhibited in both DPSCs-shB2M and DPSCs-shCIITA groups (p < 0.05).

Conclusion

Genetic knockdown of B2M or CIITA in DPSCs substantially reduced their immunogenicity without compromising their stemness, thereby broadening the clinical application of DPSCs in cell therapy and tissue regeneration.
Ancestral retrovirus envelope protein ERVWE1 upregulates circ_0001810, a potential biomarker for schizophrenia, and induces neuronal mitochondrial dysfunction via activating AK2
Authors: Li Wenshi , Xue Xing , Li Xuhang , Wu Xiulin , Zhou Ping , Xia Yaru , Zhang Jiahang , Zhang Mengqi , Zhu Fan
Published: November 2024

Background

Increasingly studies highlight the crucial role of the ancestral retrovirus envelope protein ERVWE1 in the pathogenic mechanisms of schizophrenia, a severe psychiatric disorder affecting approximately 1% of the global population. Recent studies also underscore the significance of circular RNAs (circRNAs), crucial for neurogenesis and synaptogenesis, in maintaining neuronal functions. However, the precise relationship between ERVWE1 and circRNAs in the etiology of schizophrenia remains elusive.

Results

This study observed elevated levels of hsa_circ_0001810 (circ_0001810) in the blood samples of schizophrenia patients, displaying a significant positive correlation with ERVWE1 expression. Interestingly, in vivo studies demonstrated that ERVWE1 upregulated circ_0001810 in neuronal cells. Circ_0001810, acting as a competing endogenous RNA (ceRNA), bound to miR-1197 and facilitated the release of adenylate kinase 2 (AK2). The bioinformatics analysis of the schizophrenia datasets revealed increased levels of AK2 and enrichment of mitochondrial dynamics. Notably, miR-1197 was reduced in schizophrenia patients, while AK2 levels were increased. Additionally, AK2 showed positive correlations with ERVWE1 and circ_0001810. Further studies demonstrated that AK2 led to mitochondrial dysfunction, characterized by loss of intracellular ATP, mitochondrial depolarization, and disruption of mitochondrial dynamics. Our comprehensive investigation suggested that ERVWE1 influenced ATP levels, promoted mitochondrial depolarization, and disrupted mitochondrial dynamics through the circ_0001810/AK2 pathway.

Conclusions

Circ_0001810 and AK2 were increased in schizophrenia and positively correlated with ERVWE1. Importantly, ERVWE1 triggered mitochondrial dysfunction through circ_0001810/miR-1197/AK2 pathway. Recent focus on the impact of mitochondrial dynamics on schizophrenia development had led to our discovery of a novel mechanism by which ERVWE1 contributed to the etiology of schizophrenia, particularly through mitochondrial dynamics. Moreover, these findings collectively proposed that circ_0001810 might serve as a potential blood-based biomarker for schizophrenia. Consistent with our previous theories, ERVWE1 is increasingly recognized as a promising therapeutic target for schizophrenia.
Incorporating Limestone Powder and Ground Granulated Blast Furnace Slag in Ultra-high Performance Concrete to Enhance Sustainability
Authors: Sharma Yashovardhan , Yeluri Meghana , Allena Srinivas , Owusu-Danquah Josiah
Published: November 2024

While ultra-high performance concrete (UHPC) offers numerous advantages, it also presents specific challenges, primarily due to its high cost and excessive cement content, which can pose sustainability concerns. To address this challenge, this study aims to develop cost-effective and sustainable UHPC mixtures by incorporating ground granulated blast furnace slag (GGBFS) and limestone powder (LP) as partial replacements for portland cement. Eight fiber-reinforced UHPC mixtures were investigated, with a water-to-cementitious materials (w/cm) ratio of 0.15. In four of the UHPC mixtures, 25% of the cement was replaced with GGBFS, and further, LP was added as a mineral filler, partially substituting up to 20% of the cement. In the remaining four mixtures, cement was replaced with only LP up to 20% (without GGBFS). The 28-day compressive strength of the UHPC mixture with 25% GGBFS and 20% LP was 149 MPa, 3.50% lower than the mixture without GGBFS. Its 28-day flexural strength decreased by 30%. Increasing LP replacement reduced drying and autogenous shrinkage, with a 29% shrinkage reduction at 20% LP replacement. Moreover, UHPC mixtures with GGBFS exhibited lower shrinkage compared to those without GGBFS for all LP replacements up to 20%. For evaluating the sustainability of UHPC mixtures, the cement composition index (CCI) and clinker to cement ratio (CCR) were determined. For 20% LP replacement with 25% GGBFS, CCI was 3.6 and the CCR was 0.5, 38% decrease from the global clinker to cement ratio. Overall, 20% LP replacement UHPC mixtures with and without GGBFS can produce UHPC class performance and reduce the environmental impact.
Effectiveness of cold atmospheric plasma in decontaminating enterococcus faecalis colonized collagen and PTFE membranes used in guided bone regeneration: a comparative in vitro investigation
Authors: Weitkamp Jan-Tobias , Hogreve Adrian , Spille Johannes , Veziroglu Salih , Aktas Oral Cenk , Flörke Christian , Liedtke Kim Rouven , Wiltfang Jörg , Gülses Aydin
Published: November 2024

Purpose

Wound healing disorders caused by bacterial infections in dental surgery, especially where membranes are used, are a common issue in oral surgery. Cold atmospheric plasma (CAP) offers a non-invasive solution for surface decontamination, including dental implants. The aim of this study was to evaluate the antibacterial effectiveness of CAP on various clinically applied membranes made of collagen and polytetrafluoroethylene (PTFE).

Materials and methods

To assess the antibacterial properties of CAP, enterococcus faecalis were seeded on different membranes: Memlock (collagen), Memlock Pliable (collagen), Agronaut (collagen), and PermaPro (PTFE); n = 4. After in vitro cultivation for 6 days, CAP using a kINPen® MED with an output of 5 W was applied 5 min and 10 min. Bacterial colony-forming units (CFU) were quantified to detect decontamination effectiveness. In addition, live and dead staining as well as scanning electron microscopy (SEM) of membranes was performed for validation and surface texture analysis.

Results

Bacterial colonization was highest on collagen-based membranes (CFU Memlock: 14.38 ± 8.91). The results showed that CAP significantly reduced bacterial colonization on all membrane types after 10 min application of CAP; Memlock (CFU after 10 min 0.22 ± 0.16^106; p = 0.0256), Argonaut (CFU after 10 min 0.02 ± 0.01^106; p = 0.0129) and PermaPro (complete bacterial decontamination; p = 0.0058). This was paralleled by fluorescence and scanning electron microscopy. CAP was most effective on smooth membrane surfaces as SEM revealed.

Conclusion

CAP thus offers a non-invasive, cost-effective method to reduce bacterial infections in guided bone regeneration using membranes.

Graphical Abstract