bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribose Mediated Glycation of Human Serum Albumin and Their Inhibition by Silibinin and 2-Hydroxy-1,4-Naphthoquinone: In Vitro and Computational Studies
Authors: Elrobh Mohamed , Khan Mohd Shahnawaz , Alenad Amal , Alokail Majed S. , Alharbi Osama M. , Odeibat Hamza Ahmad
Published: January 2025

Under hyperglycemic conditions, proteins undergo structural modifications non-enzymatically, resulting in the formation of advanced glycation end products (AGEs). These AGEs contribute to the production of free radicals, which in turn exacerbate the development of diabetes and its complications. Therefore, inhibiting glycation is anticipated to play a crucial role in managing diabetes. Here, we have examined the effect of 2-hydroxy-1,4-naphthoquinone (NQ) and silibinin on ribose-mediated glycation of HSA. Presence of NQ and silibinin inhibited the fluorescent AGEs formation by 79.18% and 84.10%, respectively. Moreover, the secondary structural loss caused by glycation was restored by NQ and silibinin treatment. Both the compounds showed higher affinity toward native HSA compared to glycated HSA as evident from their binding constants. Molecular docking showed a direct interaction of tested compounds with glycation prone amino acids arginine and lysine residues of HSA. Molecular simulation studies confirmed the NQ or silibinin formed stable complex with HSA. Both the ligands formed hydrogen bonds throughout the trajectory. MM-PBSA calculation showed the overall binding energies for silibinin and NQ with HSA were – 16.863 kcal/mol and – 9.977 kcal/mol, respectively. The findings show the antiglycation potential of NQ and silibinin against ribose mediated glycation of HSA along with mode of action.
Freezing-based Memory and Process Co-design for User Experience on Resource-limited Mobile Devices
Authors: Li Changlong , Zongwei Zhu , Yu Liang , Xuehai Zhou
Published: January 2025

Mobile devices with limited resources are prevalent as they have a relatively low price. Providing a good user experience with limited resources has been a big challenge. This paper found that foreground applications are often unexpectedly interfered by background applications’ memory activities. Improving user experience on resource-limited mobile devices calls for a strong collaboration between memory and process management. This paper proposes a framework, Ice, to optimize the user experience on resource-limited mobile devices. With Ice, processes that will cause frequent refaults in the background are identified and frozen accordingly. The frozen application will be thawed when memory condition allows. Based on the proposed Ice, this paper shows that the refault can be further reduced by revisiting the LRU lists in the original kernel with app-freezing awareness (called Ice
+
). Evaluation of resource-limited mobile devices demonstrates that the user experience is effectively improved with Ice. Specifically, Ice boosts the frame rate by 1.57x on average over the state-of-the-art. The frame rate is further enhanced by 5.14% on average with Ice
+
.
Randle cycle in practice: a student exercise to teach glucose and fatty acid metabolism in fasted, fed, and exercised states
Authors: Petersen Rikke , Nørremark Mie Feldfoss , Færgeman Nils J.
Published: January 2025

Explore our study on how undergraduates learn about glucose and fatty acid metabolism through a blend of lectures and dynamic practical experiments. Our paper highlights how students delve into the Randle cycle and its regulation in various metabolic scenarios, gaining insights through hands-on trials. This innovative approach not only deepens understanding but also enhances collaborative skills. Dive into our findings to see how active learning shapes future scientists.
Word count matters: Features of written language production in progressive apraxia of speech with and without agrammatism
Authors: Tetzloff Katerina A. , Meade Gabriela , Duffy Joseph R. , Clark Heather M. , Botha Hugo , Josephs Keith A. , Whitwell Jennifer L. , Utianski Rene L.
Published: January 2025

Introduction: Apraxia of speech (AOS) is a motor speech disorder characterized by sound distortions, substitutions, deletions, and additions; slow speech rate; abnormal prosody; and/or segmentation between words and syllables. AOS can result from neurodegeneration, in which case it can be accompanied by the primary agrammatic aphasia (PAA), which when presenting together are called AOS+PAA. AOS can also be the sole manifestation of neurodegeneration, termed primary progressive AOS (PPAOS). Together these form the agrammatic-apractic spectrum disorders. Recent work has shown that agrammatic-apractic spectrum patients show reduced quantity of written language production on a picture description task versus controls. However, no study to date has investigated if there are differences in quantity (amount of writing) and quality (grammaticality) in the written language production between PPAOS and AOS+PAA patients, which was the aim of this study.
Methods: Twenty-four AOS+PAA patients, 24 PPAOS patients, and 24 typical controls performed the Western Aphasia Battery (WAB) written picture description task. The total number of words and sentences, as well as the type-token frequency, mean length of utterance, proportion of nouns and function words, and overall sentence grammaticality were compared among groups.
Results: The PPAOS group showed significantly reduced number of words (ß=-44.2, p <.0001) and sentences (ß=-4.04, p<.0001) compared to typical controls, and the AOS+PAA group showed significantly reduced number of words compared to both PPAOS patients (ß=-17.0, p=.02) and controls (ß=-61.20, p<.0001), as well as reduced number of sentences compared to controls (ß=-4.33, p<.0001). AOS+PAA patients also showed grammatical deficits consistent with their concomitant aphasia diagnosis.
Conclusions: This study provides novel quantitative data showing that agrammatic-apractic spectrum disorder patients show decreased written language output on a written picture description task compared to controls, even when there is no overt evidence of aphasia (i.e., PPAOS). Furthermore, these data show that controls, PPAOS patients, and AOS+PAA patients can all be distinguished based on the quantity of information and grammatical errors in a written picture description task. Future studies will explore sources beyond language, such as motoric impairment, that may result in reduced written quantity in agrammatic-apractic spectrum disorders.
Changes in well-being and relationship satisfaction in the years before and after marriage in a sample of New Zealand adults
Authors: Dupuis Hannah E. , Girme Yuthika U. , Overall Nickola C. , Cross Emily J. , Sibley Chris G.
Published: January 2025

The well-being literature reveals that individuals experience increases in well-being leading up to marriage, followed by a return to pre-marriage levels shortly after marriage. In contrast, the relationship/marriage literature suggests that relationship satisfaction may steadily decline across time. However, it is unclear at what point relationship satisfaction may begin to decline. In the current study, we drew data from a nationally representative sample of diverse-aged adults to examine changes in well-being and relationship satisfaction prior to marriage, shortly after marriage, and post marriage. Data were utilized from 14-years of the New Zealand Attitudes and Values Study ( N = 1,520). Participants received annual surveys and reported their well-being (life satisfaction, subjective well-being, belonging) and relationship satisfaction. We examined whether getting married was associated with average within-person changes in well-being and relationship satisfaction across the years before marriage, shortly after marriage, and across the years following marriage. Event-aligned piecewise latent growth models found similar patterns of change across marriage for well-being (life satisfaction, subjective well-being) and relationship satisfaction. On average, well-being and relationship satisfaction increased leading up to marriage, dropped significantly shortly after marriage, and continued to decline following marriage. By integrating well-being and relationship/marriage literatures, these findings provide novel insights that for continuously partnered individuals, the course of well-being and relationship satisfaction change in similar ways leading up to marriage, shortly after marriage, and years following marriage.
Minimum 24-Month Outcomes of Minimally Invasive Paratenon Protection Repair vs Open Giftbox Repair of Ruptured Achilles Tendon
Authors: Yan Xujie , Yue Jixian , Zeng Xinqi , Xu Tonglong , Zhang Yuxuan , Wang Wencheng , Zhao Gang , Mi Jingyi , Rui Yongjun , Liu Shen , Tian Jian
Published: January 2025

Background:

The paratenon has been shown to promote Achilles tendon healing, but the evidence supporting the role of paratenon protection technique in Achilles tendon repair is sparse. We retrospectively assessed the results of a paratenon-sparing repair technique vs an open giftbox repair of Achilles tendon ruptures.

Methods:

Patients with Achilles tendon rupture who underwent surgical treatment at our hospital between January 2015 and August 2021 were retrospectively reviewed. Among them, 61 patients underwent surgical repair using the minimally invasive paratenon protection technique (MI group) and 67 patients using the open repair giftbox technique (OR group). The postoperative rehabilitation protocol was identical in both groups. The operation time, complication rate, length and cross-sectional area (CSA) of Achilles tendon, shear wave elastography (SWE), CSA of the calf triceps muscle, isokinetic strength, Achilles tendon Total Rupture Score (ATRS), and the Victorian Institute of Sports Assessment–Achilles (VISA-A) score were compared between the 2 groups.

Results:

The average follow-up time was 40.0 ± 10.2 months. The operation time and complication rate in the MI group were significantly lower than in the OR group ( P < .001, P = .031). The ATRS score ( P = .015), VISA-A score ( P = .002), isokinetic strength (60 degrees/second: P = .006; 180 degrees/second: P = .036), SWE values ( P = .007), and CSA of Achilles tendon ( P = .043) in the MI group were significantly higher than the OR group. SWE values were significantly positively correlated with the ATRS score ( r = 0.294, P < .001) and the VISA-A score ( r = 0.304, P < .001). And a significant negative correlation was found between Achilles tendon extension length and peak torque (60 degrees/second: r = −0.309, P < .001; 180 degrees/second: r = −0.218, P = .013).

Conclusion:

Compared with the open repair giftbox technique, the minimally invasive paratenon protection technique was associated with likely marginally clinically significant improved clinical outcome scores, greater isokinetic strength, and better mechanical properties of the Achilles tendon.
Upper cervical spinal cord atrophy in MS: Sex, menopause, and neurodegeneration
Authors: Zeydan Burcu , Son Jiye , Neyal Nur , Schwarz Christopher G , Atkinson Elizabeth J , Morrison Holly A , Nathoo Nabeela , Kantarci Kejal , Flanagan Eoin P , Port John D , Kantarci Orhun H
Published: January 2025

Background:

Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective:

Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Methods:

In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCCbrain) was obtained. Impact of sex and menopause on UCCbrain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated.

Results:

UCCbrain was smaller in pwMS ( n = 118, 51.4 ± 5.3 mm2) than controls ( n = 118, 54.2 ± 4.4 mm2, p < 0.001) and inversely correlated with older age in pwMS ( r = −0.24, p = 0.010) but not in controls ( r = −0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCCbrain was smaller in men (49.5 ± 5.9 mm2) than women (51.6 ± 5.5 mm2, p = 0.001), postmenopausal women (49.4 ± 5.6 mm2) than premenopausal women (52.9 ± 4.1 mm2, p < 0.001), and progressive (47.5 ± 5.6 mm2) than relapsing MS (52.1 ± 5.2 mm2, p < 0.001). UCCbrain also correlated with disease duration ( r = −0.39, p < 0.001), 9-hole peg test ( r = −0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) ( r = −0.27, p < 0.001).

Conclusion:

UCCbrain, a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.
More than meets the eye: Understanding the importance of the materialities of care at the vaccination encounter in Portugal
Authors: Augusto Fábio Rafael , Hilário Ana Patrícia , Mendonça Joana
Published: January 2025

Caring practices during vaccination encounters are deeply interwoven with materiality, encompassing everyday objects and elements that play a crucial role for all actors involved. However, the significance of these materialities in shaping caring relationships within vaccination practices has been largely overlooked. This research seeks to fill that gap by exploring how mundane elements, such as the objects present during vaccination, contribute to the relational dynamics of the experience. Through a qualitative approach involving participant observation of vaccination encounters and interviews with 30 healthcare professionals, four key themes emerged: (i) objects as comfort devices, (ii) caring as gifts, (iii) reinvented medical instruments, and (iv) creating a friendly environment. These findings suggest that material elements are not merely passive tools but active “co-participants” in the vaccination process, influencing the interactions and emotional exchanges that occur. By acknowledging the role of materiality, this research enhances our understanding of vaccination as a relational experience, highlighting the importance of considering these often-overlooked factors in both practice and policy. The study offers valuable insights into how healthcare professionals can utilize materialities to foster more empathetic and supportive vaccination environments.
Single Versus Dual Therapy for Diabetic Gastroparesis
Authors: Shada Amber L.
Published: January 2025

Gastroparesis is a disorder of gastric motility hallmarked by nausea, vomiting and early satiety. While dietary and medical therapy are the mainstay of treatment, surgery has been useful to palliate symptoms. Two long-used first line surgical therapies for gastroparesis are gastric electrical stimulation and pyloric procedures (including pyloroplasty and pyloromyotomy). This manuscript will focus on the use of these surgical modalities, both separately and in combination, to treat refractory gastroparesis symptoms in patients with diabetes.
Molecular clustering on ctDNA improves the prognostic stratification of DLBCL patients compared to ctDNA levels
Authors: Moia Riccardo , Talotta Donatella , Terzi di Bergamo Lodovico , Almasri Mohammad , Dondolin Riccardo , Salehi Matin , Cosentino Chiara , Soscia Roberta , Della Starza Irene , Bruscaggin Alessio , Andorno Annalisa Giovanna , Mercalli Francesca , Cresta Stefania , Bomben Riccardo , Bittolo Tamara , Vit Filippo , Bulian Pietro , Zucchetto Antonella , Bruna Riccardo , Rivolta Giulia Maria , Schipani Mattia , Secomandi Eleonora , Kogila Sreekar , Bellia Matteo , Mouhssine Samir , Nabki Jana , Al Deeban Bashar , Ghanej Joseph , Cividini Luca , Maher Nawar , Melle Federica , Motta Giovanna , Leutner Monica , Lorenzi Angela , Mahmoud Abdurraouf Mokhtar , Al Essa Wael , Deambrog Clara , Rasi Silvia , Petrucci Luigi , Boldorini Renzo , Di Rocco Alice , Del Giudice Ilaria , Spina Michele , Palazzolo Stefano , Canal Fabio , Canzonieri Vincenzo , Martelli Maurizio , Pileri Stefano A , Gattei Valter , Foà Robin , Rossi Davide , Gaidano Gianluca
Published: January 2025

Circulating tumor DNA (ctDNA) levels can help predict outcomes in diffuse large B-cell lymphoma (DLBCL), but its integration with DLBCL molecular clusters remains unexplored. Using the LymphGen tool in 77 DLBCL with both ctDNA and tissue biopsy, a 95.8% concordance rate in molecular cluster assignment was observed, showing the reproducibility of molecular clustering on ctDNA. A multicenter, prospective cohort of 166 newly diagnosed DLBCL was analyzed for ctDNA levels and molecular clusters using CAPP-seq. Patients with ctDNA levels < 2.5 log10hGE/mL had a 4-year progression-free survival (PFS) and overall survival (OS) of 71.7% and 85.7%, respectively, compared to 50.3% and 61.0% for those with higher ctDNA levels (p=0.0018 and p=0.0017). Recursive partitioning showed that patients with ctDNA levels > 2.5 log10hGE/mL were further stratified by clusters ST2/BN2. In this group, ST2/BN2 patients associated with a favorable outcome with a 4-year PFS and OS of 87.5% and 100%, respectively, compared to 38.0% and 47.1% for other clusters (p=0.003 and p=0.001). Combining ctDNA levels and ST2/BN2 clusters improved outcome prediction. Low-risk patients (N=51), characterized by ctDNA levels < 2.5 log10hGE and/or BN2/ST2 cluster, had a 4-year PFS and OS of 75.3% and 87.8%. High-risk patients (N=115), with ctDNA levels > 2.5 log10hGE and no BN2/ST2 cluster, had a 4-year PFS and OS of 38.0% and 47.1%. Adding cluster assignment to ctDNA levels improved the model's C statistics (0.63 vs. 0.59 for PFS and 0.68 vs. 0.63 for OS). Liquid biopsy thus provides a multi-layered approach for outcome prediction in DLBCL.
Final Analysis of the Phase 1b Chemotherapy And Venetoclax in Elderly Acute Myeloid Leukaemia Trial (CAVEAT)
Authors: Chua Chong Chyn , Loo Sun , Fong Chun Yew , Ting Stephen B , Tiong Ing S , Fleming Shaun A , Anstee Natasha S , Ivey Adam , Ashby Michael , Teh Tse-Chieh , Reynolds John , Roberts Andrew W , Wei Andrew H
Published: January 2025

Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The chemotherapy and venetoclax in elderly AML trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients ≥65 years. In this final analysis, 85 patients (median age 71 years) were followed for a median of 41.8 months. The CAVEAT induction combined cytarabine and idarubicin with 5 dose levels of venetoclax (50-600 mg) for up to 14 days. Two additional cohorts explored adjusted-dose venetoclax (50 mg, 100 mg) with posaconazole. CAVEAT induction was well tolerated, with low mortality (4%) and limited high-grade gastrointestinal toxicity (4%). Delayed hematological recovery after consolidation was ameliorated by omitting idarubicin from post-remission therapy. The overall response rate (ORR: CR + CRh + CRi) was 75% with a median overall survival (OS) of 19.3 months (95% CI 11.1-31.3). Among de novo AML, ORR was 88% and median OS 33.1 months (95% CI 19.3-54.3). Almost one-third have not relapsed, many benefiting from prolonged treatment-free remission (median 17.9 months). CAVEAT induction was well tolerated and associated with high ORR that was durable, particularly for de novo AML. CAVEAT represents an effective time-limited treatment option for fit older patients with AML. (https://www.anzctr.org.au; ACTRN12616000445471).
Ipsilateral concomitant fractures of the clavicle and coracoid process of the scapula: incidence, characteristics, and outcomes
Authors: Zhang Nan , Bai Guoyang , Kang Xiaomin , Zhu Yangjun , Feng Dongxu
Published: January 2025

Background

Clavicle fractures associated with ipsilateral coracoid process fractures are very rare, with limited literature reporting only a few cases. This study reports on 27 patients with ipsilateral concomitant fractures of the clavicle and coracoid process who were followed for more than 12 months.

Material and methods

This retrospective study reviewed the charts of skeletally mature patients with traumatic ipsilateral clavicle and coracoid process fractures treated at the authors’ institution. Each patient was regularly followed post-treatment. Radiographs assessed bone union and implant integrity, while clinical evaluations included the Constant–Murley score for shoulder function; disability of the arm, shoulder, and hand (DASH) questionnaire for upper limb function; and visual analog scale score for pain. Complications were also recorded.

Results

From October 2012 to February 2023, 40 patients were diagnosed with ipsilateral fractures of the clavicle and coracoid process of the scapula, accounting for 1.4% (40/2877) of all clavicle fractures and 5.2% (40/786) of all scapular fractures. This study included 27 patients with follow-up exceeding 12 months: 6 had medial-third clavicle fractures, 12 had middle-third fractures, and 9 had distal-third fractures. According to Eyres’ classification, the coracoid fractures included two type I, five type II, eight type III, seven type IV, and five type V fractures. Twenty-two patients received operative treatment, with clavicle fractures fixed with internal plating and 11 coracoid fractures with internal fixation. Bone union was achieved in all patients. The mean Constant–Murley score was 91.2 ± 9.4 and the mean DASH score was 6.4 ± 7.6. Five patients reported mild shoulder pain and five patients developed complications.

Conclusions

Ipsilateral concomitant fractures of the clavicle and coracoid process can occur at various clavicle locations, with shaft and medial fractures more common than previously thought. Displaced fractures can be effectively managed with operative treatment, and coracoid process fixation may not be necessary if satisfactory indirect reduction is achieved after clavicle fixation.

Level of evidence: Level III, retrospective cohort study.
Perspectives on which health settings geriatricians should staff: a qualitative study of patients, care providers and health administrators
Authors: Wong Eric Kai-Chung , Tricco Andrea C. , Isaranuwatchai Wanrudee , Naimark David M. J. , Straus Sharon E. , Sale Joanna E. M.
Published: January 2025

Background

With a shortage of geriatricians and an aging population, strategies are needed to optimise the distribution of geriatricians across different healthcare settings (acute care, rehabilitation and community clinics). The perspectives of knowledge users on staffing geriatricians in different healthcare settings are unknown. We aimed to understand the acceptability and feasibility (including barriers and facilitators) of implementing a geriatrician-led comprehensive geriatric assessment (CGA) in acute care, rehabilitation, and community clinic settings.

Methods

A qualitative description approach was used to explore the experience of those implementing (administrative staff), providing (healthcare providers), and receiving (patients/family caregivers) a geriatrician-led CGA in acute care, rehabilitation and community settings. Semi-structured interviews were conducted in Toronto, Canada. The theoretical domains framework and consolidated framework for implementation research informed the interview guide development. Analysis was conducted using a thematic approach.

Results

Of the 27 participants (8 patients/caregivers, 9 physicians, 10 administrators), the mean age was 53 years and 14 participants (52%) identified as a woman (13 [48%] identified as a man). CGAs were generally perceived as acceptable but there was a divergence in opinion about which healthcare setting was most important for geriatricians to staff. Acute care was reported to be most important by some because no other care provider has the intersection of acute medicine skills with geriatric training. Others reported that community clinics were most important to manage geriatric syndromes before hospitalization was necessary. The rehabilitation setting appeared to be viewed as important but as a secondary setting. Facilitators to implementing a geriatrician-led CGA included (i) a multidisciplinary team, (ii) better integration with primary care, (iii) a good electronic patient record system, and (iv) innovative ways to identify patients most in need of a CGA. Barriers to implementing a geriatrician-led CGA included (i) lack of resources or administrative support, (ii) limited team building, and (iii) consultative model where recommendations were made but not implemented.

Conclusions

Overall, participants found CGAs acceptable yet had different preferences of which setting to prioritise staffing if there was a shortage of geriatricians. The main barriers to implementing the geriatrician-led CGA related to lack of resources.

Clinical trial number

Not applicable.
Responsiveness of hand-held dynamometry for measuring changes in trunk muscle strength in people with chronic low back pain
Authors: Althobaiti Shouq , Deane Janet A. , Falla Deborah
Published: January 2025

Objective

To assess the responsiveness of a hand-held dynamometer (HHD) in evaluating changes in trunk isometric strength in people with chronic low back pain (LBP).

Background

Reduced trunk muscle strength has been associated with pain incidence and severity in people with chronic LBP. Trunk muscle strength is an important functional outcome that is measured in clinical practice and research. However, the responsiveness of clinical tools such as HHD for measuring changes in trunk muscle strength remains underexplored.

Methods

Maximum isometric trunk strength was measured using both a HHD and an isokinetic dynamometer (ID) in 21 participants with chronic LBP both before and after 6 weeks of progressive trunk resistance exercises. Effect sizes (ES) and standardised response mean (SRM) were used to evaluate the internal responsiveness of the HHD measures. External responsiveness was determined by correlating the change scores measured with the HHD with those obtained using the ID.

Results

Following the progressive resistance exercise programme, there was a significant improvement in trunk muscle strength measured with the HHD with moderate to large ES (0.40–0.85) and SRM (0.60- 0.74), indicating moderate to high internal responsiveness. Pearson's correlations revealed a weak correlation between changes in trunk strength measured with the HHD and those measured with the ID (r = 0.22- 0.26), indicating inadequate external responsiveness.

Conclusions

Although the use of a HHD was shown to have internal responsiveness for detecting changes in trunk muscle strength, the inadequate external responsiveness warrants further investigation. Future research should also explore the responsiveness of HHD in people with chronic LBP with higher pain and disability levels using comparable measurement setups.
Improving general practitioners’ approaches to functional somatic syndromes: a pilot training program with a focus on compassion and communication
Authors: Ariane Gonthier , Audrey Linder , Johanna Sommer , Jean-Nicolas Despland , Gilles Ambresin
Published: January 2025

Background

Functional somatic syndromes are common in primary care and represent a challenge for general practitioners (GPs), with a risk of deterioration in the doctor-patient relationship, and of compassion fatigue on the part of the physician. Little is known about how to teach better management of these symptoms.

Methods

The aim of our scientific team was to develop a training session about functional somatic syndromes for GPs, with the objective to improve the therapeutic attitude of the participants. The first session of the training was constructed as a pilot session, followed by a qualitative study to complete content validation. The educational framework of the training session is multimodal and includes theory on the pathophysiology of functional somatic syndromes, communication skills, and introspective learning including an introduction to compassion meditation. 20 physicians attended the pilot training session. 10 of them participated in the qualitative study. The qualitative study consisted of five individual semi-structured interviews and one focus group of five persons, investigating the impact of the training session on the clinical practices, as perceived by the participants. The interviews were analysed through an inductive method inspired by Malterud’s systematic text condensation strategy.

Results

We identified three main themes in the responses of the participants: (1) the crucial issue of putting a name to chronic psychosomatic suffering; (2) the importance of self-compassion for physicians; (3) changes in therapeutic attitude fostering a reconciliation between “self” and “care”. Participants expressed a need for more regular meetings of this type. The opportunity to share their negative feelings about therapeutic relationship within a peer group, with compassionate supervision of the trainers, seemed to play an important role in the improvement of their self-compassion

Conclusion

A multimodal teaching session seems to help the physicians to feel more comfortable and competent when treating patients with functional somatic syndromes. Including compassion meditation in the teaching seems a promising tool to prevent compassion fatigue.
Assessing psychosocial risk factors in children with Sickle Cell Disease
Authors: Frey Nicole , LaMotte Julia E. , Bouck Jillian R. , Fancher Lauren , Parker Genese T. , Carter Allie , Jacob Seethal A.
Published: January 2025

Background

Individuals with Sickle Cell Disease (SCD) are a minoritized and marginalized community that have disparate health outcomes as a result of systemic racism and disease-related stigma. The purpose of this study was to determine the psychosocial risk factors for families caring for children with SCD at a pediatric SCD center through use of the Psychosocial Assessment Tool (PAT), a validated caregiver-report screener.

Methods

The PAT was administered annually during routine clinical visits and scored by the SCD Social Worker to provide tailored resources to families. The PAT stratifies scores into 3 categories of psychosocial concern: Universal, Targeted, Clinical. PATs administered between September 2021-December 2022 were analyzed.

Results

Two hundred twenty-five PATs were included for analysis. Most caregivers identified as Black, single Women over 21 years old with a high school degree or more. The average patient age was 8.2 years (0–22 years). Sixty-seven percent of PATs fell into the Universal category. Dyads that scored in the Targeted or Clinical categories were more likely to report financial hardship, caregiver mental health concerns, and family stressors (p < 0.001). Nearly 50% of all families reported some form of financial difficulty, including almost 40% in the Universal category.

Conclusions

Universal implementation of a psychosocial risk screener identified financial challenges for many families, as well as caregiver burden and mental health concerns, allowing for timely resource support. However, overall risk for many of these families was categorized as Universal or low risk, indicating that distribution of resources and support cannot be based on PAT category alone.
Aspergillus fumigatus is responsible for inflammation in a murine model of chronic obstructive pulmonary disease exacerbation
Authors: Bouyssi Alexandra , Trecourt Alexis , Déméautis Tanguy , Persat Florence , Glehen Olivier , Wallon Martine , Devouassoux Gilles , Bentaher Abderrazzak , Menotti Jean
Published: January 2025

Background

In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD.

Methods

The inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 105 spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses.

Results

In co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung.

Conclusions

There was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.
Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study
Authors: Lai Liye , Juntilla Dave Laurence , Del Monica , Del C Gomez-Alonso Monica , Grallert Harald , Thorand Barbara , Farzeen Aiman , Rathmann Wolfgang , Winkelmann Juliane , Prokisch Holger , Gieger Christian , Herder Christian , Peters Annette , Waldenberger Melanie
Published: January 2025

Background

Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.

Methods

In this longitudinal study, we examined data from the Cooperative Health Research in the Region of Augsburg (KORA) F4 and FF4 studies, conducted approximately seven years apart. Leucocyte DNA methylation was assessed using the Illumina EPIC and 450K arrays. Linear mixed-effects models were employed to identify significant associations between methylation sites and diabetes status, as well as with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homoeostasis model assessment of beta cell function (HOMA-B), and homoeostasis model assessment of insulin resistance (HOMA-IR). Interaction effects between diabetes status and follow-up time were also examined. Additionally, we explored CpG sites associated with persistent prediabetes or T2D, as well as the progression from normal glucose tolerance (NGT) to prediabetes or T2D. Finally, we assessed the associations between the identified CpG sites and their corresponding gene expression levels.

Results

A total of 3,501 observations from 2,556 participants, with methylation measured at least once across two visits, were included in the analyses. We identified 64 sites associated with T2D including 15 novel sites as well as known associations like those with the thioredoxin-interacting protein (TXNIP) and ATP-binding cassette sub-family G member 1 (ABCG1) genes. Of these, eight CpG sites exhibited different rates of annual methylation change between the NGT and T2D groups, and seven CpG sites were linked to the progression from NGT to prediabetes or T2D, including those annotated to mannosidase alpha class 2a member 2 (MAN2A2) and carnitine palmitoyl transferase 1 A (CPT1A). Longitudinal analysis revealed significant associations between methylation and FPG at 128 sites, HbA1c at 41 sites, and HOMA-IR at 57 sites. Additionally, we identified 104 CpG-transcript pairs in whole blood, comprising 40 unique CpG sites and 96 unique gene transcripts.

Conclusions

Our study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development.

Graphical abstract
Application of stem cells alone and in combination with low-level laser therapy for sciatic nerve repair in rats
Authors: Shalalvand Mohsen , Mahaseni Aghdam Hamidreza , Asghari Ahmad , Nehzat Siamak , Shahsavari Fatemeh , Ardalani Rojin
Published: January 2025

This study evaluated the efficacy of tubular constructs containing stem cells and Type I collagen, both independently and in conjunction with low-level laser therapy (LLLT), in repairing the sciatic nerve in a rat model. In this animal study, the right sciatic nerve of 30 male Wistar rats, each weighing 250–300 g, was surgically excised to a length of 8 mm. The rats were then randomly allocated to three groups (n = 10 per group). In Group 1, the excised nerve segment was utilized as an autograft and sutured at the defect site. In Group 2, a tubular construct containing stem cells and Type I collagen was used to bridge the proximal and distal ends of the nerve. Group 3 received the same intervention as group 2, supplemented with 5 weeks of LLLT. After 5 and 12 weeks, rats underwent histological, behavioral, and electrophysiological assessments. Data were statistically analyzed using analysis of variance (ANOVA), Bonferroni post-hoc test, and Kruskal–Wallis test. At both 5 and 12 weeks, axonal count and nerve repair scores showed no significant differences among the three groups (P > 0.05). Notably, the Sciatic Functional Index (SFI) was the most favorable (lowest) in the autograft group, whereas the stem cell-only group exhibited the least favorable (highest) SFI at 5 weeks (P < 0.001). Additionally, distal latency was highest in the stem cell group and lowest in the stem cell combined with LLLT group at 5 weeks (P < 0.001). A significant difference was observed between the autograft and stem cell plus LLLT groups (P < 0.05). In conclusion, the application of stem cell-laden tubular constructs in conjunction with LLLT demonstrated efficacy for sciatic nerve repair in rats.
Assessment of greenness, blueness, and whiteness profiles of a validated HPLC-DAD method for quantitation of Donepezil HCl and Curcumin in their laboratory prepared co-formulated nanoliposomes
Authors: Abd Elwahab Mennah M. , Saad Samar , Sheribah Zeinab A. , El-Enany Nahed
Published: January 2025

White and Green Analytical Chemistry are innovative approaches in analytical chemistry that prioritize both sustainability and efficiency. Together, these approaches aim to advance scientific research while minimizing environmental impact and enhancing safety. This integration of environmental consciousness into analytical practices represents a significant step forward in achieving sustainable scientific progress. In the present study, a sensitive eco-friendly HPLC-DAD method was carried out and validated to allow concurrent determination of Donepezil HCl (DPZ) and Curcumin (CUR) in their pure form and laboratory made nano-liposome formulation. Optimum seperation was accomplished by utilising Zobrax Eclipse Plus C18 column (4.6*100 mm,5 μm) with gradient elution of the mobile phase composed of 0.02 M phosphate buffer at pH 3.2 and ethanol at flow rate of 1.5 ml/min. A diode array detector (DAD) was implemented for detection at 273 nm and 435 nm for DPZ and CUR, respectively, with the column oven set at 40 °C. The method was validated according to ICH specifications in terms of accuracy, precision, linearity range, detection and quantification limit. The calibration plots were linear with correlation coefficients (r2) = 0.999 over the range (0.1–100 µg/ml) and (0.1–100 µg/ml) for DPZ and CUR, successively. The validated HPLC-DAD approach was adopted to analyse both medications in laboratory prepared nano-liposomal formulation in which the analytes were successfully quantified with good recovery values and no disrubtion from the added excipients. The investigation of whiteness, blueness, and greenness metrics revealed a major benefit of the suggested approach over previous reported ones.
Optimizing Phaeodactylum tricornutum cultivation: integrated strategies for enhancing biomass, lipid, and fucoxanthin production
Authors: Elshobary Mostafa E. , Abo-Shanab Walaa A. , Ende Stephan S. W. , Alquraishi Mohammed , El-Shenody Rania A.
Published: January 2025

Background

Phaeodactylum tricornutum is a versatile marine microalga renowned for its high-value metabolite production, including omega-3 fatty acids and fucoxanthin, with emerging potential for integrated biorefinery approaches that encompass biofuel and bioproduct generation. Therefore, in this study we aimed to optimize the cultivation conditions for boosting biomass, lipid, and fucoxanthin production in P. tricornutum, focusing on the impacts of different nutrient ratios (nitrogen, phosphorus, silicate), glycerol supplementation, and light regimes.

Results

Optimized medium (− 50%N%, + 50% P, Zero-Si, 2 g glycerol) under low-intensity blue light (100 μmol m⁻2 s⁻1) improved biomass to 1.6 g L⁻1, with lipid productivity reaching 539.25 mg g⁻1, while fucoxanthin increased to 20.44 mg g−1. Total saturated fatty acid (ΣSFA) content in the optimized culture increased approximately 2.4-fold compared to the control F/2 medium. This change in fatty acid composition led to improved biodiesel properties, including a higher cetane number (59.18 vs. 56.04) and lower iodine value (53.96 vs 88.99 g I2/100 g oil). The optimized conditions also altered the biodiesel characteristics, such as kinematic viscosity, cloud point, and higher heating value.

Conclusion

Our optimization approach reveals the significant potential of P. tricornutum as a versatile microbial platform for biomass, lipid, and fucoxanthin production. The tailored cultivation strategy successfully enhanced biomass and lipid accumulation, with notable improvements in biodiesel properties through strategic nutrient and light regime manipulation. These findings demonstrate the critical role of precise cultivation conditions in optimizing microalgal metabolic performance for biotechnological applications.
Headache in radiologically isolated syndrome: a hint toward imminent conversion: a case report
Authors: Etemadifar Masoud , Kaveyee Hasan , Zohrabi Parto , Jozaie Amir Mohammad , Salari Mehri , ebne-ali-heydari Yasin
Published: January 2025

Background

Headaches are more prevalent in patients with multiple sclerosis compared with the general population. However, headaches are still considered a rare symptom of multiple sclerosis, especially when they appear as an initial symptom. The occurrence of a headache as a symptom of radiologically isolated syndrome (RIS) is uncommon, and it can significantly increase the likelihood of developing multiple sclerosis.

Case presentation

We report the case of a 36-year-old Iranian woman experiencing severe unilateral headaches without other multiple sclerosis symptoms. Despite normal physical and laboratory exams, cerebrospinal fluid analysis showed positive oligoclonal bands. Magnetic resonance imaging (MRI) revealed multiple demyelinating plaques consistent with RIS. She was treated with dimethyl fumarate. Subsequent MRI confirmed multiple sclerosis by showing new gadolinium-enhanced lesions. After 3 months of dimethyl fumarate treatment, her headache intensity decreased, and she remained otherwise symptom free. Written informed consent was obtained from the patient.

Conclusion

Effectively managing headaches in patients with RIS is a challenge for clinicians to improve their quality of life and delay the progression of multiple sclerosis.
Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis
Authors: Asgarpur Golschan , Weber Franz , Kiessling Peggy , Akbari Nilufar , Stroben Fabian , Kleikamp Bernadette , Kloft Charlotte , Treskatsch Sascha , Angermair Stefan
Published: January 2025

Purpose

CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22). There is limited clinical data on the effect of CS on the plasma concentrations of beta-lactams. We aimed to evaluate the statistical and clinical impact of CS in a post-filter CKRT-CS setting on the plasma concentrations of the antibiotics meropenem and piperacillin in critically ill patients.

Methods

Patients admitted to the intensive care unit (ICU) who received a prolonged infusion of piperacillin or meropenem with CS-combined CKRT were included in this retrospective analysis. TDM (therapeutic drug monitoring) plasma blood samples were collected at three different points. The differences in antibiotic concentrations between Pre, Intra, and Post were statistically compared to evaluate the total and isolated contributions of CKRT and CS to antibiotic removal. CS, CKRT and combined clearance (CL) values were calculated. The hypothesis was that the CS filter would have no clinically relevant impact on antibiotic levels.

Results

207 TDM samples were taken from 24 critically ill patients requiring beta-lactam antibiotics. Among these, 129 were meropenem samples, and 78 were piperacillin samples. A decrease in both antibiotic levels was observed between Pre and Intra, and Pre and Post, and the median relative difference between was >15% (meropenem: Pre–Intra 34.8%, Pre–Post 35.8%; piperacillin: Pre–Intra 41.1%, Pre–Post 34.7%), indicating a statistically and clinically significant effect of CKRT on both antibiotic exposures. No significant difference was observed between Intra and Post indicating no clinically relevant drug removal via the CS filter. Changes in CL attributed to CS were minimal, with combined CL differing by ≤8.60% compared to CKRT clearance.

Conclusion

The application of CS does not appear to significantly affect plasma concentrations of meropenem and piperacillin in critically ill patients.
Analysis of stiffness changes and factors induced by smart suit with trunk kinetic chain SLIP model
Authors: Mori Hiromu , Tanaka Takayuki , Murai Akihiko , Kusaka Takashi , Imamura Yumeko
Published: January 2025

We are currently developing a suit that assists human running motion based on the Smart Suit (SS). The SS is a wearable assistive device that intervenes in trunk kinetic chain movements by linking trunk rotation to hip flexion and extension through elastic belts. By intervening in the trunk kinetic chain, our goal is to enhance stiffness, thereby improving running economy and speed. The purpose of this study is to acquire fundamental insights into the changes in leg and trunk rotational stiffness induced by the SS, as well as the underlying mechanisms. We defined the SS torque intervention rate

$$p_{ss}$$

p

ss

, which focuses on the magnitude of force, and the peak time difference index,

$$e_{lag}$$

e

lag

, between SS and humans, which focuses on the timing of force, and analyzed the relationship between the stiffness change rate due to SS wearing. The results of the analysis suggest that SS affects human running sensitively rather than mechanically. We also confirmed that the degree of adaptation to SS, assessed by the timing gap between SS exertion and human exertion, contributes significantly to changes in trunk rotation stiffness.