bluuebunny/crossref_metadata_2025_split huggingface dataset:
A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study
Authors: Ali Samir , Moors Xavier , van Schuppen Hans , Mommers Lars , Weelink Ellen , Meuwese Christiaan L. , Kant Merijn , van den Brule Judith , Kraemer Carlos Elzo , Vlaar Alexander P. J. , Akin Sakir , Lansink-Hartgring Annemiek Oude , Scholten Erik , Otterspoor Luuk , de Metz Jesse , Delnoij Thijs , van Lieshout Esther M. M. , Houmes Robert-Jan , Hartog Dennis den , Gommers Diederik , Dos Reis Miranda Dinis 
Published: April 2024

Abstract
Background
The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients.

Methods
The ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18–50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months.

Discussion
The ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment.

Trial registration
Clinicaltyrials.gov under NCT04620070, registration date 3 November 2020.
Outcomes of sentinel node biopsy according to MRI response in an association with the subtypes in cN1–3 breast cancer after neoadjuvant systemic therapy, multicenter cohort study
Authors: Bae Soong June , Chun Jung Whan , Lee Sae Byul , Ryu Jai Min , Nam Seok Jin , Jeong Joon , Park Hyung Seok , Ahn Sung Gwe 
Published: April 2024

Abstract
Background
This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden.

Methods
In the multicenter retrospective cohort, 388 individuals with cN1–3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST.

Results
In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2− (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6–54.0] and 20.9% [95% CI 14.1–27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0–0), whereas that of non-complete responders was 33.3% (95% CI 20.8–45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0–16.7).

Conclusions
Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.
Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway
Authors: Zhong Yue , Qin Cheng , Wang Qing , Ding Maoyuan , Qiu Chong , Xu Yunzhao , Chen Jinling 
Published: April 2024

Abstract
Background
Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii.

Methods
Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining.
To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells.

Results
In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site.

Conclusions
T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes.

Graphical Abstract
Twenty-four hour physical activity, sedentary behaviour and sleep profiles in adults living with rheumatoid arthritis: a cross-sectional latent class analysis
Authors: Feehan Lynne , Xie Hui , Lu Na , Li Linda C. 
Published: April 2024

Abstract
Background
Rheumatoid Arthritis (RA), an autoimmune systemic inflammatory disease, affects more than 17 million people globally. People with RA have higher risk of premature mortality; often experience chronic fatigue, pain and disrupted sleep; and are less physically active and more sedentary than healthy counterparts. It remains unclear how people with RA may balance sleep and awake movement activities over 24-hours, or how differences in 24-hour behaviours may be associated with determinants of health, or alignment with published activity guidelines.

Methods
Cross-sectional exploration of objective measures of 24-hour sleep-wake activities in 203 people with RA. Latent Class Analysis (LCA) derived classes from time, by tertile, in six sleep-awake activities over 24 h. Comparisons of model fit statistics, class separation and interpretability defined best fit for number of classes. Variations in sleep-awake behaviour across classes and association of profile allocation with determinants of health, quality metrics for sleep, sitting and walking and alignment with published guidelines were explored. Multinomial logistic regression identified factors associated with likelihood of profile allocation.

Results
LCA identified 2 to 6 classes and a 4-class model was determined as best fit for 24-hour sleep-awake behaviour profiles. One profile (26%) presented with more balanced 24-hour sleep, sitting and walking behaviours. The other three profiles demonstrated progressively less balanced 24-hour behaviours including: having low (< 7 h), high (> 8 h), or recommended (7–8 h) sleep duration in respective combination with high sitting (> 10 h), limited walking (< 3 h) or both when awake. Age, existing sitting and walking habit strength and fatigue were associated with likelihood of belonging to different profiles. More balanced 24-hour behaviour was aligned with better quality metrics for sleep, sitting and walking and published guidelines.

Discussion
For people living with RA it is important to understand the ‘whole person’ and their ‘whole day’ to define who may benefit from support to modify 24-hour sleep-awake behaviours and which behaviours to modify. Supports should be informed by an understanding of personal or health-related factors that could act as barriers or facilitators for behavioural change, including exploring existing habitual sitting and walking behaviours.

Trial registrations
ClinicalTrials.gov ID: NCT02554474 (2015-09-16) and ClinicalTrials.gov ID: NCT03404245 (2018-01-11)
Point-of-Care 3-Dimensional–Printed Polyetheretherketone Customized Implants for Cranioplastic Surgery of Large Skull Defects
Authors: Pöppe Johannes P. , Spendel Mathias , Griessenauer Christoph J. , Gaggl Alexander , Wurm Werner , Enzinger Simon 
Published: April 2024

BACKGROUND AND OBJECTIVES:
3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital.

METHODS:
A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed.

RESULTS:
Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient.

CONCLUSION:
This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.
Intrinsic motivation between face-to-face and blended learning in surgical clinical education
Authors: Jawaid Masood , Masood Zubia , Imran Nazish 
Published: April 2024

Objective: The variability and opportunistic nature of surgical clinical education is the main problem for effective teaching and training of medical students. Incorporating online mediums including discussion forums, interactive videos/scenarios, static pages, and quizzes is known as blended learning (BL). This study aimed to compare the intrinsic motivation of surgical students enrolled in blended learning to those enrolled in face-to-face teaching (f2f teaching).
Methods: A quasi-experimental, cross-over study was conducted in Surgical Unit-I and Surgical Unit-II of Dow University Hospital, Karachi, from March to August 2014. A total of 31 students participated and were exposed to two different teachings. For the first four weeks, Group A was posted in Surgical-I (f2f teaching) and Group B in Surgical-II (BL). Both groups were taught the same contents with the same schedule. The F2F group had clinical exposure to real patients, and small group discussions (SGDs) while The BL group students were exposed to an additional online learning component. Intrinsic Motivation Inventory (IMI) was administered at the end of four weeks and groups were swapped. Exchanged groups were again taught the same contents with the same schedule for another four weeks and IMI was administered.
Results: Fifty-eight students completed IMI; 28 in f2f and 30 in BL group. There was a significant difference in all four subscales of IMI between the two groups. In three subscales, students in BL were more motivated as compared to f2f (p<0.01). Students in f2f experienced more perceived tension than in BL (p<0.048).
Conclusion: This study concluded that blended surgical learning programs keep medical students more intrinsically motivated to learn. By utilizing online learning, superior educational opportunities for students can be cultivated. It can result in enhanced faculty effectiveness and efficiency as well.
doi: https://doi.org/10.12669/pjms.40.5.1048
How to cite this: Jawaid M, Masood Z, Imran N. Intrinsic motivation between face-to-face and blended learning in surgical clinical education. Pak J Med Sci. 2024;40(5):913-917. doi: https://doi.org/10.12669/pjms.40.5.1048
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effect of Clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction: A retrospective single-center analysis
Authors: Huang Huiying , Zhang Shan , Du Hong , Guo Yonghua , Zheng Hui 
Published: April 2024

Objective: To explore the effect of clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction (APCI).
Methods: We retrospectively analyzed the records of 190 patients with APCI admitted to Chengdu First People’s Hospital from September 2020 to April 2023. The records were divided into an aspirin group (76 cases), a clopidogrel group (72 cases), and a clopidogrel plus aspirin group (42 cases) according to the treatment records. We compared the efficacy of the three treatment outcomes by analyzing the National Institutes of Health Stroke Scale (NIHSS) scores, and the levels of serum inflammatory factors (IL-8, TNF-α, and IL-1β), cone like protein-1 (VILIP-1), and caveolin-1 (Cav-1).
Results: The total efficacy of the combination group (97.62%) was significantly higher than those of the aspirin group (73.68%) or the clopidogrel group (79.17%) (p<0.05). After treatment, the NIHSS scores, inflammatory factor levels, serum VILIP-1 and Cav-1 levels were significantly lower than those before treatment in the three groups, but all the levels were significantly lower in the combination group (all p<0.05).
Conclusions: Our results indicate that compared with aspirin alone or clopidogrel alone, the combination of aspirin and clopidogrel is more effective for the treatment of APCI. The combination regimen effectively lowers serum inflammatory factors (IL-8, TNF-α, and IL-1β), as well as the VILIP-1 and Cav-1 levels.
doi: https://doi.org/10.12669/pjms.40.5.9206
How to cite this: Huang H, Zhang S, Du H, Guo Y, Zheng H. Effect of Clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction: A retrospective single-center analysis. Pak J Med Sci. 2024;40(5):891-895. doi: https://doi.org/10.12669/pjms.40.5.9206
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Physical activity and life-limiting conditions
Authors: Sheill Gráinne , Afolabi Jide , McMahon Margaret , Crowley Jonathon , Guinan Emer 
Published: April 2024

Background: Physical activity can assist people with life-limiting conditions to maintain their wellbeing and quality of life. Aims: To explore the views of clinical nurse specialists (CNS) working in community palliative care towards the role of physical activity for people with life-limiting conditions, and to explore the physical activity needs of patients with life-limiting conditions identified by CNSs. Methods: A purposive sample of CNSs working in community palliative care received an anonymous online survey via email. Findings: The response rate was 66% (n=20). Most respondents were practicing for over 20 years (60%, n=12). All respondents (100%, n=20) reported they would like further information on the role of exercise for palliative populations. The main perceived benefit of physical activity was to improve quality of life (95%, n=18). A lack of physical activity guidelines for people living with life-limiting conditions was the most commonly reported barrier to engaging in discussions around physical activity (74%, n=14). Conclusion: Further education opportunities on the role of physical activity for patients living with life-limiting conditions are needed.
The academic TikTok: Academics’ perceptions and uses of Microsoft Flip as a vlogging platform
Authors: Dianati Seb , Spinelli Franciele , Gazmuri Sanhueza Alicia 
Published: April 2024

Vlogs, asynchronous video blogs where individuals film themselves to share personal experiences, have been widely used in educational settings. This study explores the integration of Microsoft Flip (Flip), a vlogging platform, in higher education, focusing on its use by academics during a 3-year pilot preceding institution-wide adoption. Grounded in Driscoll and Burner’s (2005) constructivist theory, this research involved interviews with 10 academics from an Australian university, examining their experiences, challenges and recommendations for using Flip. The findings reveal that Flip facilitates innovative activity design, promoting user-friendliness, interaction and self-directed learning. However, privacy concerns, technical difficulties and engagement shortfalls were identified consistent with broader educational technology adoption issues. To minimise these challenges, academics suggested setting clear guidelines on how to use Flip to enhance learning and offered suggestions on how to organise the activities effectively. This research offers insights for academics and learning designers considering Flip in the tertiary educational context, highlighting its potential as a tool for enhancing learning experiences.

Implications for practice or policy:

Implement scaffolded teaching in higher education, emphasising peer interaction, sequential assessments, and clear instructions to boost student learning outcomes.
Provide academics with targeted resources and training to effectively integrate vlogs in teaching, addressing technological barriers.
Use vlogging for summative assessments to ensure authentic uptake which also mitigates challenges within identity verification and artificial intelligence misuse in higher education.
Voluntary exercise fails to prevent metabolic dysfunction‐associated steatotic liver disease progression in male rats fed a high‐fat high‐cholesterol diet
Authors: Besqueut‐Rougerie Clément , Chavanelle Vivien , Michaux Arnaud , Otero Yolanda F. , Sirvent Pascal , King James A. , Ennequin Gaël 
Published: April 2024

AbstractMetabolic dysfunction‐associated steatotic liver disease (MASLD) is a major public health issue with a worldwide prevalence of 30%–32%. In animal models, voluntary exercise may be an alternative to forced physical activity, avoiding stress, potential injuries, and being logistically simpler. Here, we assessed voluntary exercise (Vex) in Sprague–Dawley rats fed a high‐fat, high‐cholesterol diet for 18 weeks to induce MASLD. We quantified workload (speed and distance) using exercise wheels and evaluated energy expenditure using calorimetric cages. MASLD progression was assessed using circulating and hepatic biochemical and gene markers of steatosis, inflammation, and fibrosis. The animals ran an average of 301 km during the study period, with the average daily distance peaking at 4937 m/day during Weeks 3–4 before decreasing to 757 m/day by the end of the study. Rats exposed to Vex showed no improvement in any of the MASLD‐associated features, such as steatosis, inflammation, or fibrosis. Rats exposed to Vex exhibited a higher total energy expenditure during the night phase (+0.35 kcal/h; p = 0.003) without resulting in any effect on body composition. We conclude that, in our experimental conditions, Vex failed to prevent MASLD progression in male Sprague–Dawley rats exposed to a high‐fat high‐cholesterol diet for 18 weeks.