bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian analysis of Generalized Modified Weibull Distribution Under Censored Data and Presence of Covariates
Authors: Antonio Moala Fernando , Augusto Niiyama Clóvis , Minoru Oikawa Sérgio , Santos Aguilar Guilherme Aparecido
Published: February 2025

The generalized modified Weibull (GMW) distribution extends the modified Weibull distribution by offering a hazard function with various shapes, including constant, increasing, decreasing, unimodal, and bathtub. This paper aims to estimate the four unknown parameters of the GMW distribution using a Bayesian approach, assuming a lack of prior information represented by noninformative priors such as Jeffreys, Uniform, and Gamma priors. The Bayesian analysis considers both censored data and the presence of covariates. The results of the Bayesian inference are compared with those of the maximum likelihood approach. The Markov Chain Monte Carlo (MCMC) algorithm is employed to compute the Bayesian estimators and construct credible intervals. A simulation study evaluates the performance of these estimators, with comparisons made based on bias, mean square error, and coverage probability. Real data sets are analyzed for illustrative purposes.
The climate movement and the meaning of sustainability in the Anthropocene
Authors: Lara de la Fuente Daniel
Published: February 2025

The climate movement has been gaining prominence in global climate politics since 2019. Research has been growing on the main features of its public speech along with its sociological and organizational characteristics. Yet we lack systematic analyses of the normative implications of this public speech to provide a thorough explanation of this political phenomenon. Applying discourse analysis, I identify and rationally reconstruct a set of categories and metaphors that activists use to make sense of the climate crisis. When it comes to advancing the politics of sustainability, I argue that although the climate movement promotes ecologically grounded, far-sighted, and integrated sustainability, it still embraces closed and static understandings of this concept. The paper advances the discussion on the contribution of global activism to deliberative climate politics and governance beyond national borders.
Artificial intelligence in drug development: reshaping the therapeutic landscape
Authors: Niazi Sarfaraz K. , Mariam Zamara
Published: February 2025

Artificial intelligence (AI) is transforming medication research and development, giving clinicians new treatment options. Over the past 30 years, machine learning, deep learning, and neural networks have revolutionized drug design, target identification, and clinical trial predictions. AI has boosted pharmaceutical R&D (research and development) by identifying new therapeutic targets, improving chemical designs, and predicting complicated protein structures. Furthermore, generative AI is accelerating the development and re-engineering of medicinal molecules to cater to both common and rare diseases. Although, to date, no AI-generated medicinal drug has been FDA-approved, HLX-0201 for fragile X syndrome and new molecules for idiopathic pulmonary fibrosis have entered clinical trials. However, AI models are generally considered “black boxes,” making their conclusions challenging to understand and limiting the potential due to a lack of model transparency and algorithmic bias. Despite these obstacles, AI-driven drug discovery has substantially reduced development times and costs, expediting the process and financial risks of bringing new medicines to market. In the future, AI is expected to continue to impact pharmaceutical innovation positively, making life-saving drug discoveries faster, more efficient, and more widespread.
‘I want to know that it’s worth me attending’: A qualitative analysis of consumers’ decisions not to attend their chronic pain group education session
Authors: Searle Amelia K , Wall Cindy L , Tan Celia , Herriot Peter
Published: February 2025

Background: Many pain clinics encourage/mandate attendance at introductory group pain education sessions. Despite high non-attendance rates, no studies have examined consumer-reported reasons for non-attendance.

Purpose: The aim of this study was to better understand why consumers fail to attend their pain education session.

Research Design and Study Sample: We attempted to contact all non-attendees of our South Australian tertiary pain unit’s group pain education sessions from February–August 2020. Of the 23 we could reach, 10 completed semi-structured telephone interviews.

Data Analysis: Audio-recordings were transcribed verbatim and subject to thematic content analysis.

Results: ‘Attendance barriers’ themes highlighted the complex lives of non-attendees. Pain prevented them from leaving their house, deterred them from travel to, and sitting through, the entire session. Competing responsibilities including other medical appointments and comorbidities were commonly mentioned. Most explicitly stated their dislike for the group format. Other factors included fear of the unknown nature of the session, not wanting education, and wanting a doctor’s appointment. Several participants expressed a distrust of medical professionals, and perceived the benefits of attending as not exceeding the perceived time, money and pain associated.

Conclusions: Pain management may not be individuals’ main priority and attendance may only occur when other personal issues are addressed. Significant non-attendance rates may be unavoidable. Providing additional session detail may reduce misconceptions and allay concerns. Educating referring GPs may assist consumers to make an informed decision regarding attending. Online sessions may address various barriers and prove a more cost-effective alternative.

Perspective

This article examines consumers’ reasons for non-attendance at pre-clinic group education programs. Findings could be used by Pain Units to shape patient and GP communications regarding such programs, as well as program content and format, to improve patient acceptance and program attendance, and potentially engagement with self-management.
The fact-checking dilemma: Fact-checking increases the reputation of the fact-checker but creates perceptions of ideological bias
Authors: Aruguete Natalia , Calvo Ernesto , Ventura Tiago
Published: February 2025

This study examines how exposure to counter- and pro-attitudinal fact-checking messages impacts the fact-checker’s perceived quality and ideological leaning. In a well-powered and pre-registered survey experiment conducted during the 2021 mid-term election in Argentina, when COVID-19 was a polarizing issue, we exposed 5757 respondents to real tweets reporting the number of COVID-19 cases, followed by fact-checking adjudications that appropriately confirmed or refuted the original publication. Results show that pro-attitudinal messages increased the quality rating of the fact-checker, Chequeado, and made respondents perceive the organization ideologically closer to their views. Counter- attitudinal fact-checking also increases the perceived quality but has no significant effect on the perceived ideology of the fact-checker. Fact-checks are reputation-improving and do not seem to backfire. However, the intervention affects how voters perceive the ideological leaning of fact-checking organizations.
Data governance and open sharing in the fields of life sciences and medicine: A bibliometric analysis
Authors: Qiu Yanrui , Hu Zhimin
Published: February 2025

Objective

This study aims to conduct a bibliometric analysis of literature related to data governance and open sharing in the fields of life sciences and medicine, so as to clarify the characteristics of publications and explore research hotspots and trends.

Methods

A total of 2529 valid documents published in the Web of Science Core Collection database from 2000 to 2024 were included in this study. VOSviewer was used for co-occurrence analysis, while CiteSpace was employed for clustering, burst detection, and thematic evolution analysis.

Results

Between 2000 and 2024, the number of studies on data governance and open sharing in the fields of life sciences and medicine has increased annually, indicating the growing importance of research in this area. The USA led as the country with the most research output in this field. The University of Oxford was the institution with the highest publication volume, Amy L. McGuire was the most active author, and the Journal of Medical Internet Research and the Journal of the American Medical Informatics Association were the most frequent publication outlets. The most cited reference was ‘Comment: The FAIR Guiding Principles for Scientific Data Management and Stewardship’.

Conclusions

Topics such as the FAIR principles, ethical issues, public attitudes toward data sharing, data quality, databases, and big data analysis techniques are hotspots in this field. Potential research frontiers include the FAIR principles, data quality, public trust and attitudes toward data sharing, the application of artificial intelligence technology in data governance and sharing, governance and sharing of epidemiological and public health data, governance and sharing of data on chronic diseases such as diabetes, and the construction of data governance models.
Peer bullying according to the opinions of school counselors: Türkiye–France example
Authors: Aşantuğrul Nuray , Kara İlyas
Published: February 2025

School counselors play an important role in detecting and resolving peer bullying, which is commonly seen in schools. Many characteristics of school counselors, such as their perspective on peer bullying, the communication they provide with students, their observation skills, and their position in the school, are effective factors on these challenging experiences of students. This research aimed to examine the views of school counselors working in Türkiye and France regarding peer bullying. The research is a qualitative study and its participants consist of a total of 24 school counselors, 12 counselors working in Türkiye and 12 counselors working in France. Research participants were determined by purposeful sampling method. The data was obtained from the participants through a semi-structured interview form and the data obtained was subjected to content analysis with the MAXQDA 2020 program. According to the research results, participants defined peer bullying as interpersonal power imbalance, violence, and aggression. Participants as reasons for peer bullying; they stated several factors such as digital content creating a negative example, lack of empathy, poor communication skills, individual differences, and psychological problems. Finally, the participants aimed at solving peer bullying. They made suggestions such as providing individual counseling to students, increasing cooperation between school and family, and training all stakeholders against bullying. As a result, the problem of peer bullying in schools negatively affects students physically, socially, and psychologically, and there is a need for collaborative work by all stakeholders to solve this problem in order to raise healthy generations.
Vibing the Young Consumer to Wellness: Exploring Lo-Fi Music Consumption Through the Positive Design Lens
Authors: Dsouza Melanie Pius , Shetty Ankitha , D’Souza Sara Ellen , Buthello Elisha , Gudi Nachiket
Published: February 2025

The consumption of lo-fi music as a wellness and productivity-inducing product has become increasingly popular among young consumers in recent years. This pioneering article explores emerging evidence on lo-fi music consumption for young consumer wellness, using the positive design framework as a lens, and envisions an extensive future research agenda. Following a systematic approach to reviewing the literature, modeled on scoping review methodology, a thematic analysis of the literature is conducted, and theories from multiple disciplines support arguments. Key research gaps and current trends are identified, and a curated definition of the “lofi product” is provided. The study enhances the positive design framework of Desmet and Pohlmeyer with significant contributions from the themes generated, providing product strategists with a framework to design products that optimize young consumers’ wellness. The findings reveal that consumption of the “lofi product” may intensify positive affect, accelerate goal attainment, and improve health and performance while fostering the development of character strengths in young consumers. Intentionally designing products for young consumers using the proposed framework may also result in similar wellness outcomes. This study would empower marketers to leverage the lofi product effectively in their marketing strategies. Consultation with industry experts informs the future research directions proposed. This study calls out a pressing need for robust scientific investigation and academic discussion.
Analyses of the Barriers and Drivers of Ghana’s COVID-19 Vaccination Program Using the 5A Taxonomy: A Scoping Review
Authors: Agboh Herman Nuake Kofi , Yarney Lily
Published: February 2025

The review explored topical vaccination themes in literature to describe the barriers and drivers of effective COVID-19 vaccination in Ghana. We searched Scopus, Medline, Cinahl, and Google Scholar, covering papers published exclusively in Ghana between December 2019 and January 2023. Using predefined inclusion and exclusion criteria, 27 papers were included in the review. We adopted the 5As taxonomy to organize the papers into five dimensions, namely, Access, Affordability, Awareness, Acceptance, and Activation. Our analysis shows that Acceptance was the most frequently research theme ( n = 23, 85.1%), followed by Awareness ( n = 19, 70.4%), Activation ( n = 14, 52%), Access ( n = 7, 25.7%), and Affordability ( n = 6, 22.2%). Further, we found awareness campaign messages to be largely concentrated in Accra, Kumasi and other hotspots. Further studies on vaccine financing, access and inclusion of individuals and families in information dissemination campaigns is highly recommended.
Evaluating Elastographic Tendon Stiffness as a Predictor of Return to Work and Sports After Primary Rotator Cuff Repair
Authors: Maloof Alexander G. , Hackett Lisa , Bilbrough James , Hayek Christyon , Murrell George A.C.
Published: February 2025

Background:

Despite many patients not returning to their preoperative levels of work and sports after primary rotator cuff repair, few studies have investigated the association between findings on postoperative imaging and patients returning to work and sports. Shear wave elastography ultrasound (SWEUS) is a recent technology that quantifies the stiffness of healing repaired cuff tendons.

Hypothesis:

Stiffer repaired cuff tendons that reflect improved healing would be associated with improved return to work and sports.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

This was a prospective cohort study of 50 patients undergoing primary arthroscopic rotator cuff repair. Preoperatively, all patients completed a questionnaire ranking their level of sports and work activity on a 4-point Likert scale. At 8 days, 6 weeks, 12 weeks, 6 months, and 1 year postoperatively, patients reported their current levels of sports and work on the same scale and had SWEUS stiffness measurements taken at 3 points along their repaired tendons.

Results:

The elastographic stiffness of supraspinatus tendons at their repaired insertion sites increased by a mean of 22% over 12 months ( P = .0001). Elevated supraspinatus tendon stiffness at 6 weeks and 12 weeks was associated with return to sports at 12 months ( r = 0.46; P = .003 and r = 0.39; P = .01), and tendon stiffness at 12 weeks and 6 months was associated with return to work at 12 months ( r = 0.49; P = .001 and r = 0.46; P = .003). Patients returning to sports ( r = 0.46; P = .003) and work ( r = 0.49; P = .001) were most strongly associated with SWEUS stiffness 12 weeks after cuff repair.

Conclusion:

The elastographic stiffness of a healing repaired supraspinatus tendon is moderately associated with improved return to work and sports 12 months after rotator cuff repair. Tendon stiffness at 12 weeks postrepair was the most critical timepoint in predicting both return to work and sports at 12 months postrepair.
Children of women prisoners in Kashmir: Consequences of structural and social invisibility
Authors: Nisa Roonaq un , Eriksson Anna
Published: February 2025

This article draws on in-depth interviews conducted with children and caregivers of children left behind due to maternal imprisonment in Kashmir. The narratives illuminate the challenging circumstances faced by these children, including experiences with alternative caregiving, the consequential impact on educational attainment, and the pervasive stigma associated with maternal imprisonment. These challenges are all given heightened significance within the pre-existing context of vulnerability that surrounds children in Kashmir in Kashmir, a region marked by long-term political disturbance. The intricate interplay of these issues is further complicated by the unique cultural dynamics shaping the societal position of women in the region. This article presents a scholarly exploration of the multifaceted challenges embedded within the specific socio-cultural milieu of Kashmir. In doing so, it makes a substantial contribution to the evolving discourse on children of prisoners by elucidating the social and structural invisibilities experienced as a result of maternal imprisonment. The recognition of the social and structural context also enriches our understanding of the “symbiotic harms” experienced by children and families of incarcerated women as part of the complexities of punishment in a non-Western society.
Stokes-Adams syndrome, a rarely reported disease
Authors: Rincón Romero Camilo Andrés , Amézquita Sebastián Forero , Velasco Castro Julio César , Agudelo Lorena García
Published: February 2025

Stokes-Adams syndrome is defined as a transient loss of consciousness with spontaneous recovery after a decrease in cardiac output that leads to a state of cerebral hypoxia and may cause seizures. It is a rare and poorly documented condition. High-degree atrioventricular block, paroxysmal ventricular arrest, and pulseless ventricular tachycardia have been described as causes, and depending on the case, temporary or permanent pacemaker implantation or cardiac defibrillation may be necessary. We present the case of a 78-year-old male patient with Stokes-Adams syndrome secondary to 2:1 atrioventricular block requiring definitive pacemaker implantation without recurrence of syncopal or convulsive episodes. It is important to consider Stokes-Adams syndrome as a possible cause of syncope or seizures and that the recognition of this disease through an adequate clinical history and interpretation of paraclinical tests can save lives due to the risk of sudden death. There is not much information about this syndrome, since there are few cases reported in the literature.
Commentary on Minna Ruckenstein's ‘breathing spaces’
Authors: Marres Noortje
Published: February 2025

This commentary is based on a review of the reflection paper by Minna Ruckenstein's on breathing spaces.
Cross-cultural Adaptation, Reliability and Validity Tests of Screen for Child Anxiety and Related Emotional Disorders (SCARED) Child Version and SCARED-5-items in Indonesian Adolescents
Authors: Kaligis Fransiska , Cassandra Inez , Diatri Hervita , Wiguna Tjhin , Suarthana Eva
Published: February 2025

Anxiety disorders are prevalent among adolescents and significantly impair social and academic functioning. It should be identified early to avoid detrimental effects. This study aimed to validate and assess the reliability of the Indonesian SCARED Child Version for detecting anxiety disorders in Indonesian adolescents. The SCARED Child Version was translated into an Indonesian version according to the standard cross-cultural adaptation method. Reliability was tested with internal consistency test on 123 adolescents aged 12 to 18 years old in Jakarta, which obtained Cronbach’s alpha value for SCARED-41 items of .927, and .741 for SCARED-5 items. The content validity test was carried out through a qualitative relevance assessment involving 9 experts and the results showed an average Content-Validity-Index for items of 0.94, Content-Validity-Ratio of 0.88, and Validity-Index for scales of 0.94. The Indonesian version of the SCARED Child Version has good reliability and validity for the early detection of anxiety disorders among Indonesian adolescent.
STING activation improves T-cell-engaging immunotherapy for acute myeloid leukemia
Authors: Linder Andreas , Nixdorf Daniel , Kuhl Niklas , Piseddu Ignazio , Xu Teng Teng , Holtermann Anne Verena , Kuut Gunnar , Endres Rebekka Elena , Philipp Nora , Bücklein Veit L. , de Graaff Johann , Carell Thomas , Kobold Sebastian , Kischel Roman , Hornung Veit , Subklewe Marion
Published: February 2025

T-cell recruiting bispecific antibodies (BsAbs) are in clinical development for relapsed/refractory acute myeloid leukemia (AML). Despite promising results, early clinical trials have failed to demonstrate durable responses. We investigated whether activation of the innate immune system through stimulator of interferon genes (STING) can enhance target-cell killing by a BsAb targeting CD33 (CD33 BiTE® molecule, AMG 330). Indeed, we show that cytotoxicity against AML mediated by AMG 330 can be greatly enhanced when combined with the STING agonist 2',3'-cyclic GMP-AMP (cGAMP), or diABZI. We used in vitro cytotoxicity assays, immunoblotting, transcriptomic analyses, and extensive CRISPR-Cas9 knockout experiments to investigate the enhancing effect of a STING agonist on the cytotoxicity of AMG 330 against AML. Importantly, we validated our findings with primary AML cells, and in a xenograft AML model. Mechanistically, in addition to direct cytotoxic effects of STING activation on AML cells, activated T cells render AML cells more susceptible to STING activation through their effector cytokines interferon-gamma (IFNγ) and tumor necrosis factor (TNF), resulting in enhanced type I interferon production and induction of interferon-stimulated genes. This feeds back to the T cells, leading to a further increase in effector cytokines and an overall cytotoxic T-cell phenotype, contributing to the beneficial effect of cGAMP/diABZI in enhancing AMG 330-mediated lysis. We established a key role for IFNγ in AMG 330-mediated cytotoxicity against AML cells, and in rendering AML cells responsive to STING agonism. Here, we propose to improve the efficacy of CD33-targeting BsAbs by combining them with a STING agonist.
Venetoclax and Decitabine vs Intensive Chemotherapy as Induction for Young Patients with Newly Diagnosed AML
Authors: Lu Jing , Xue Shengli , Wang Ying , He Xuefeng , Hu Xiaohui , Miao Miao , Zhang Yang , Tang Zaixiang , Xie Jundan , Yang Xiaofei , Xu Mingzhu , Shen Yaoyao , Du Feng , Wu Qian , Xue Mengxing , Wang Yun , Deng Ailing , Dou Xueqing , Xu Yang , Dai Haiping , Wu Depei , Chen Suning
Published: February 2025

Venetoclax combined with hypomethylating agents is approved for frontline therapy in older/unfit acute myeloid leukemia (AML) patients. However, prospective data on this low intensity therapy in treatment-naive younger AML patients are lacking. This study investigated the efficacy and safety of venetoclax plus decitabine (VEN-DEC) as induction in untreated young fit AML patients in a randomized trial. Patients aged 18-59 years eligible for intensive chemotherapy were randomized 1:1 to receive VEN-DEC or IA-12 (idarubicin and cytarabine). All patients achieving CR/CRi underwent high-dose cytarabine consolidation. The primary endpoint was the composite complete remission rate (CRc) rate after induction therapy. Of 255 screened, 188 were enrolled and randomly assigned, with 94 in each group. In the intention-to-treat population, CRc was 89% (84/94) in the VEN-DEC group versus 79% (74/94) in IA-12 (non-inferiority P = 0.0021). MRD negativity after induction was 80% (67/84) versus 76% (56/74), respectively. VEN-DEC showed superior CRc in patients aged ≥40 years (91% vs. 75%), those with adverse risk (91% vs. 42%) or epigenetic mutations (91% vs. 67%) , but lower CRc in RUNX1::RUNX1T1 fusion cases (44% vs. 88%) compared to IA-12. Patients in the VEN-DEC group experienced fewer grade ≥3 infections (32% vs. 67%) and shorter severe thrombocytopenia duration (median 13 vs. 19 days, P < 0.001). At a median follow-up of 12.1 months, overall and progression-free survival were similar between groups. In conclusion, VEN-DEC demonstrated non-inferior response rates with superior safety over IA-12 in young AML patients. The trial was registered at ClinicalTrials.gov as #NCT05177731.
Active Control Method for Frequency Domain Error of Aerostatic Spindle Based on Acoustic Levitation
Authors: Chen Guoda , Chen Zhaoshou , Ge Yifan
Published: February 2025

In the machining of high-end optical components, the aerostatic spindle error of an ultra-precision machine tool has a significant impact on the surface quality of the machined surfaces. The surfaces of many high-end optical components need to meet the extremely stringent requirements of the full-frequency band error, which poses significant challenge to the control of the aerostatic spindle error. In this research, we put forward an active control method for the frequency domain error of the aerostatic spindle based on acoustic levitation, in which the acoustic-magnetism-fluid-solid multi-field coupling rotor dynamics modeling method of the aerostatic spindle was proposed and the corresponding multi-field coupling model was established. Through the numerical simulation and preliminary experiments, the influence law of acoustic levitation on the frequency domain error of the aerostatic spindle is obtained. The results showed that acoustic levitation can be used to control the frequency domain error of the aerostatic spindle to some extent, which verified the effectiveness of the proposed method.
Using deep learning to differentiate among histology renal tumor types in computed tomography scans
Authors: Kan Hung-Cheng , Lin Po-Hung , Shao I-Hung , Cheng Shih-Chun , Fan Tzuo-Yau , Chang Ying-Hsu , Huang Liang-Kang , Chu Yuan-Cheng , Yu Kai-Jie , Chuang Cheng-Keng , Wu Chun-Te , Pang See-Tong , Peng Syu-Jyun
Published: February 2025

Background

This study employed a convolutional neural network (CNN) to analyze computed tomography (CT) scans with the aim of differentiating among renal tumors according to histologic sub-type.

Methods

Contrast-enhanced CT images were collected from patients with renal tumors. The patient cohort was randomly split to create a training dataset (90%) and a testing dataset (10%). Following image dataset augmentation, Inception V3 and Resnet50 models were used to differentiate between renal tumors subtypes, including angiomyolipoma (AML), oncocytoma, clear cell renal cell carcinoma (ccRCC), chromophobe renal cell carcinoma (chRCC), and papillary renal cell carcinoma (pRCC). 5-fold cross validation was then used to evaluate the models in terms of classification performance.

Results

The study cohort comprised 554 patients, including those with angiomyolipoma (n = 67), oncocytoma (n = 34), clear cell renal cell carcinoma (n = 246), chromophobe renal cell carcinoma (n = 124), and papillary renal cell carcinoma (n = 83). Dataset augmentation of the training dataset included this to 4238 CT images for analysis. The accuracy of the models was as follows: Inception V3 (0.830) and Resnet 50 (0.849).

Conclusion

This study demonstrated the efficacy of using deep learning models for the classification of renal tumor subtypes from contrast-enhanced CT images. While the models showed promising accuracy, further development is necessary to improve their clinical applicability.
Establishing a minimum passing score for the rating scale in simulation training for surfactant administration using the LISA procedure
Authors: Rostoker Hélène , Guillois Bernard , Caradec Amaya , Chollat Clément
Published: February 2025

Introduction

In a previous study, a rating scale for simulation training on surfactant administration using the LISA (Less Invasive Surfactant Administration) procedure was developed and validated. Our objective was to determine a minimum passing score for this rating scale to use it so that it could be used for normative and certifying evaluation.

Methods

The LISA scale comprises 8 categories and 25 items. It was developed and agreed upon by a panel of 12 LISA procedure experts, and subsequently validated through simulation sessions involving 40 learners. Two independent assessors evaluated these 40 simulations. The Cronbach’s alpha score for this scale is 0.72, the R-squared value is 0.99, and the intra-class correlation coefficient is 0.92. Three different methods were employed to establish the minimum passing score: the Angoff method, the Borderline group method, and the Contrasting Group method. For the Angoff method, we enlisted 5 experts from the panel who developed the rating scale. In the Borderline Group method, the two assessors evaluated the 40 simulations following the prescribed methodology. For the Contrasting Group method, the outcomes of various simulation sessions were analyzed.

Results

Using the Angoff method, the minimum passing score was determined to be 35 out of 50, equivalent to 70.6% (standard deviation: 15.8%). Employing the Borderline Group method yielded a minimum passing score of 31.70 out of 50, i.e., 63.4%. Finally, utilizing the Contrasting Group method, the minimum passing score was found to be 33 out of 50, or 66%.

Conclusion

The three methods employed resulted in varying minimum passing scores. A higher score is likely to ensure enhanced safety and quality of patient care, while also facilitating the learner’s progression in simulator training. We recommend considering a minimum passing score of 35 out of 50.
Shared practices among primary health care workers: A time-motion study
Authors: Rewa Talita , de Souza Gonçalves Geisa Colebrusco , Varela Andrea Liliana Vesga , Leonello Valéria Marli , Peduzzi Marina , de Almeida Leticia Yamawaka , Belotti Lorrayne , da Silva Debora Bernardo , Bonfim Daiana
Published: February 2025

Background

Shared activities by health workers in meeting health needs are crucial to improve the health population, patient experience, quality of life of health teams members and the effectiveness of care.

Objective

To identify the activities shared by Primary Health Care (PHC) team workers, whether multiprofessional or uniprofessional.

Method

A descriptive study was, thus, carried out, based on the time-motion technique, in São Paulo-Brazil. Data collection was carried out from 2021 to 2022, through direct observations of workers, family health teams (FHT), oral health teams (OHT) and multiprofessional teams (MultiT). The frequency rates of both activities and time of shared practices and the distribution of workers involved in information exchanges were considered.

Results

A total of 93 workers were observed, recording 21,936 activities (157,653 minutes). Of these, 72.90% were individual activities and 27.10%, shared (36.1% uni-professional and 63.9% multiprofessional). Shared activities represented 26.26% of the time. Dentists presented 60.8% of their activities in the shared modality, uni-professionally (99.26%). Concerning FHT, nurses were most dedicated to shared practices (33.09%) and exchanged information the most with others. According to team practices, the greatest amount of time dedicated to shared practices was spent by FHT (80%), followed by MultiT (71%) and OHT (65%).

Conclusion

Multiprofessional work in PHC is evident as a precursor to interprofessional practice. In this sense, studies and reflections on the way in which PHC indicators have been monitored and evaluated, which mainly refer to individual activities, are required.
Receptor deorphanization in starfish reveals the evolution of relaxin signaling as a regulator of reproduction
Authors: Feng Yuling , Escudero Castelán Nayeli , Hossain Mohammed Akhter , Wu Hongkang , Katayama Hidekazu , Smith Stuart J. , Cummins Scott F. , Mita Masatoshi , Bathgate Ross A. D. , Elphick Maurice R.
Published: February 2025

Background

Relaxins are a family of peptides that regulate reproductive physiology in vertebrates. Evidence that this is an evolutionarily ancient role of relaxins has been provided by the discovery of two relaxin-like gonad-stimulating peptides (RGP1 and RGP2) that trigger spawning in starfish. The main aim of this study was to identify the receptor(s) that mediate(s) the effects of RGP1 and RGP2 in starfish.

Results

Here we show that RGP1 and RGP2 belong to a family of peptides that include vertebrate relaxins, Drosophila insulin-like peptide 8 (Dilp8), and other relaxin-like peptides in several protostome taxa. An ortholog of the human relaxin receptors RXFP1 and RXFP2 and the Drosophila receptor LGR3 was identified in starfish (RXFP/LGR3). In Drosophila, but not in humans and other vertebrates, there is a paralog of LGR3 known as LGR4, and here an LGR4-type receptor was also identified in starfish. In vitro pharmacological experiments revealed that both RGP1 and RGP2 act as ligands for RXFP/LGR3 in the starfish Acanthaster cf. solaris and Asterias rubens, but neither peptide acts as a ligand for LGR4 in these species.

Conclusions

Discovery of the RXFP/LGR3-type receptor for RGP1 and RGP2 in starfish provides a new insight into the evolution of relaxin-type signaling as a regulator of reproductive processes. Furthermore, our findings indicate that RXFP/LGR3-type receptors have been lost in several phyla, including urochordates, mollusks, bryozoans, platyhelminthes, and nematodes.
The application of endoscopic debridement combined with metagenomic next-generation sequencing technology in primary spinal infections: a retrospective study
Authors: Feng Xiaofei , Cheng Jie , Jiang Luyong , Lin Jiayi , Ye Zhewei , Pang Qingjiang , Liu Jiangtao
Published: February 2025

Purpose

Spinal endoscopy is a novel minimally invasive spinal surgery technique used in recent years to treat various degenerative spinal diseases. Metagenomic next-generation sequencing (mNGS) is a new method for identifying infectious microorganisms in infectious diseases. We aim to evaluate the application effect of combining spinal endoscopy with mNGS in diagnosing and treating spinal infections.

Methods

The clinical data of 62 patients with suspected spinal infectious diseases admitted from January 2020 to December 2023 were retrospectively analyzed. All patients underwent spinal endoscopy to obtain tissue specimens, histopathological examination, routine bacterial culture, and mNGS sequencing. Describe the pathogenic microbial spectrum of spinal infection, and compare the differences in sensitivity (true positive rate) and specificity (true negative rate) between the two detection methods. White blood cell (WBC) erythrocyte deposition rate (ESR), C-reactive protein (CRP), visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), and other clinical results were analyzed.

Results

In 62 cases, mNGS, microbiological culture, serologic testing, and pathologic examination results were obtained. 49 cases of spinal infections and 13 cases of non-spinal infections were finally diagnosed clinically. Among the 49 patients with spinal infections, there were 31 cases of purulent bacterial infections, 8 cases of tuberculosis infections, and 10 cases of infections with unspecified etiological microorganisms. Among the 13 cases of non-spinal infections, there were 3 cases of spinal tumors, 6 cases of Modic changes of the endplates, and 4 cases of endplate fracture. The positive rate of microbial culture was 36.73% (18/49), and the positive rate of the mNGS test was 71.43% (35/49), which was statistically different from each other (P < 0.01). The sensitivity of the mNGS test was 71.43%, and the specificity of the mNGS test was 84.62%. At the 3-month follow-up, WBC, ESR, and CRP levels were normalized. The VAS, JOA score, and ODI of the lower back and legs at each follow-up point after surgery were significantly improved compared with those before surgery, and the difference was statistically significant (P < 0.01).

Conclusion

Metagenomic sequencing technology is fast, efficient, and accurate in detecting pathogenic microorganisms, and has high diagnostic value in the diagnosis and treatment of spinal infections. Spinal endoscopic debridement combined with mNGS can achieve good clinical results.
Prioritisation of head, neck, and respiratory outcomes in mucopolysaccharidosis type II: lessons from a rare disease consensus exercise and comparison of parental and clinical priorities
Authors: Dempsey James , Daniels Jessica , Katiri Roulla , Thomas Sophie , Metryka Aleksandra , de Kruijf Mira , Wilkinson Stuart , Jones Simon A. , Bruce Iain A.
Published: February 2025

Background

The mucopolysaccharidoses are a group of rare, inherited metabolic disorders. MPS II is a X-linked recessive disease, also known as Hunter syndrome. Clinical manifestations include upper and lower respiratory tract, and head and neck pathologies influencing quality of life, morbidity, and mortality. Medical and surgical intervention outcomes for MPS are reported inconsistently, creating a challenge when synthesising and contrasting evidence. This study set out to address the inconsistency in outcome measurement in this field. International recommendations for developing a core outcome set were adopted. Available data from qualitative studies and outcomes from a modified e-Delphi surveys were used to develop a list of candidate outcomes for consideration. Three consensus meetings with patients diagnosed with MPS II alongside their parents/carers were ran to help finalise a list of outcome domains.

Results

Survival, airway obstruction, and quality of life were outcomes identified as important to always measure in all MPS II clinical trials and/or in clinical practice. Other outcomes for younger children included swallowing difficulties, cognitive development, ability to participate in education, and communication. The adolescent group included safety of chewing and swallowing, complications of anaesthesia, sleep quality and apnoea, nasal problems, and chronic otitis media. The adult group identified sleep apnoea, and hearing, as additional outcomes to measure.

Conclusions

A novel methodology for determining a core outcome set in rare diseases has been recommended. Both functional and quality of life outcomes were identified by the three age groups of individuals and/or their parents. Adoption of these sets of outcomes in future clinical trials and/or clinical practice will enable comparison of outcomes reported.
Combining molecular characteristics and therapeutic analysis of PDOs predict clinical responses and guide PDAC personalized treatment
Authors: Li Peng , Huang Minli , Li Mengyao , Li Gen , Ma Yifan , Zhao Yong , Wang Xiaowu , Zhang Yongbin , Shi Changhong
Published: February 2025

Background

The emergence of targeted therapies and immunotherapy has broadened treatment options for patients with pancreatic ductal adenocarcinoma (PDAC). Despite this, traditional drug selection, predominantly relies on tumor markers and clinical staging, has underutilized these drugs due to ignoring patient genomic diversity. Patient-derived organoids (PDOs) and corresponding patient-derived organoid xenograft (PDOX) models offer a way to better understand and address this.

Methods

In this study, we established PDOs and PDOX models from PDAC clinical samples. These models were analyzed using immunohistochemistry, H&E staining, and genomic profiling. Drug screening with 111 FDA-approved drugs was performed on PDOs, and drug responses in PDOs and PDOX models were compared to assess consistency with clinical treatment outcomes. Gene analysis was conducted to explore the molecular mechanisms underlying variations in drug responses. Additionally, by analyzing the sequencing results from various drug-sensitive groups, the identified differential gene-drug metabolism gene UGT1A10 were modulated in PDOs to evaluate its impact on drug efficacy. A co-culture system of PDOs with immune cells was developed to study the efficacy of immunotherapies.

Results

PDOs and matched PDOX models retain the morphological, biological, and genomic characteristics of the primary tumor. Exome sequencing and RNA sequencing confirmed both the consistency and heterogeneity among the PDOs. High-throughput drug screening revealed significant variability in drug sensitivity across different organoids, yet PDOs and PDOX derived from the same patient exhibited a high degree of concordance in response to clinical chemotherapy agents. The gene expression analysis of PDOs with significant differences in drug sensitivity revealed UGT1A10 as a crucial regulator. The knockdown of UGT1A10 notably increased drug sensitivity. Furthermore, immune cells demonstrated specific cytotoxicity towards the organoids, underscoring the potential of the co-culture system for application in tumor immunotherapy.

Conclusion

Our results highlight the necessity for personalized treatment strategies that consider genomic diversity beyond tumor markers, thus validating the utility of PDOs and PDOX models in advancing PDAC research and personalized medicine.
Potential application of oxidized cellulose/alginate loaded hydroxyapatite/graphene oxide beads in bone tissue engineering
Authors: Dacrory Sawsan , Ali Lamiaa M. A. , Ouahrani-Bettache Safia , Daurat Morgane , El-Sakhawy Mohamed , Hesemann Peter , Bettache Nadir , Kamel Samir
Published: February 2025

Bone regeneration is one of the most effective methods for treating bone defects. In this work, tricarboxylic cellulose/sodium alginate loaded with hydroxyapatite (HA) and/or graphene oxide (GO) was coagulated by calcium ions to create beads as scaffolds. In the first, cellulose was oxidized to water-soluble tricarboxylic cellulose (TCC) by 2,2,6,6‐tetramethylpiperidine-1-oxyl (TEMPO), periodate, and chlorite oxidation. HA was extracted from eggshells via microwave treatment, and GO was synthesized using the Hummer method. The structural behavior of the formed beads was meticulously investigated through various characterization techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The SEM images confirmed the formation of particles of micrometric size without any specific morphology. Incorporating GO or HA does not affect the morphologies of the materials on the micrometric scale. The cytocompatibility of different bead preparations was studied on murine mesenchymal stem cells. Moreover, the swellability in water and biodegradability by cellulase enzyme of prepared beads were studied. The results show that the prepared beads may be promising for bone tissue engineering.
DrugDiff: small molecule diffusion model with flexible guidance towards molecular properties
Authors: Oestreich Marie , Merdivan Erinc , Lee Michael , Schultze Joachim L. , Piraud Marie , Becker Matthias
Published: February 2025

With the cost/yield-ratio of drug development becoming increasingly unfavourable, recent work has explored machine learning to accelerate early stages of the development process. Given the current success of deep generative models across domains, we here investigated their application to the property-based proposal of new small molecules for drug development. Specifically, we trained a latent diffusion model—DrugDiff—paired with predictor guidance to generate novel compounds with a variety of desired molecular properties. The architecture was designed to be highly flexible and easily adaptable to future scenarios. Our experiments showed successful generation of unique, diverse and novel small molecules with targeted properties. The code is available at https://github.com/MarieOestreich/DrugDiff.

Scientific Contribution

This work expands the use of generative modelling in the field of drug development from previously introduced models for proteins and RNA to the here presented application to small molecules. With small molecules making up the majority of drugs, but simultaneously being difficult to model due to their elaborate chemical rules, this work tackles a new level of difficulty in comparison to sequence-based molecule generation as is the case for proteins and RNA. Additionally, the demonstrated framework is highly flexible, allowing easy addition or removal of considered molecular properties without the need to retrain the model, making it highly adaptable to diverse research settings and it shows compelling performance for a wide variety of targeted molecular properties.
kMoL: an open-source machine and federated learning library for drug discovery
Authors: Cozac Romeo , Hasic Haris , Choong Jun Jin , Richard Vincent , Beheshti Loic , Froehlich Cyrille , Koyama Takuto , Matsumoto Shigeyuki , Kojima Ryosuke , Iwata Hiroaki , Hasegawa Aki , Otsuka Takao , Okuno Yasushi
Published: February 2025

Machine learning is quickly becoming integral to drug discovery pipelines, particularly quantitative structure-activity relationship (QSAR) and absorption, distribution, metabolism, and excretion (ADME) tasks. Graph Convolutional Network (GCN) models have proven especially promising due to their inherent ability to model molecular structures using graph-based representations. However, maximizing the potential of such models in practice is challenging, as companies prioritize data privacy and security over collaboration initiatives to improve model performance and robustness. kMoL is an open-source machine learning library with integrated federated learning capabilities developed to address such challenges. Its key features include state-of-the-art model architectures, Bayesian optimization, explainability, and federated learning mechanisms. It demonstrates extensive customization possibilities, advanced security features, straightforward implementation of user-specific models, and high adaptability to custom datasets without additional programming requirements. kMoL is evaluated through locally trained benchmark settings and distributed federated learning experiments using various datasets to assess the features and flexibility of the library, as well as the ability to facilitate fast and practical experimentation. Additionally, results of these experiments provide further insights into the performance trade-offs associated with federated learning strategies, presenting valuable guidance for deploying machine learning models in a privacy-preserving manner within drug discovery pipelines. kMoL is available on GitHub at https://github.com/elix-tech/kmol.

Scientific contribution The primary scientific contribution of this research project is the introduction and evaluation of kMoL, an open-source machine learning library with integrated federated learning capabilities. By demonstrating advanced customization and security capabilities without additional programming requirements, kMoL represents an accessible yet secure open-source platform for collaborative drug discovery projects. Additionally, the experiment results provide further insights into the performance trade-offs associated with federated learning strategies, presenting valuable guidance for deploying machine learning models in a privacy-preserving manner within drug discovery pipelines.