bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking the Mystery: Resident-Led POCUS Intervention in Community Hospital Revealing Pericardial Tamponade in a Complex Case
Authors: Othon-Martinez Diana , Lopez Oscar J. , Daza Jessica , Malaga-Espinoza Barbara X. , Ganiyu Shakirat , Tijani Aramide
Published: February 2025

Pericardial effusions, though relatively rare, can lead to life-threatening complications such as cardiac tamponade. While viral etiologies are common culprits, rapid and accurate diagnosis remains challenging. We present the case of a 74-year-old male with a history of upper respiratory infection who developed sudden onset dyspnea and chest discomfort. Bedside point-of-care ultrasound (POCUS) revealed a large pericardial effusion, prompting urgent intervention. Despite initially stable vital signs, the patient rapidly deteriorated, necessitating emergent pericardiocentesis. Laboratory findings and pathology results eventually ruled out common viral causes, guiding diagnosis toward coxsackieviruses A and B, echovirus, adenoviruses, or influenza. This case highlights the critical role of POCUS in resident-led community hospitals, in expediting the diagnosis of pericardial effusions and underscores the need for prompt intervention in cases of cardiac tamponade to prevent adverse outcomes.
Acute Measurement of Developmental Dysplasia of the Hip: Comparing Two Approaches for Measuring the Alpha Angle Using the Graf Technique
Authors: Dindar Fırat , Aylanç Nilüfer , Aylanç Hakan , Ertem Şenay Bengin , Sıddıkoğlu Duygu , Reşorlu Mustafa
Published: February 2025

Objective:

The Graf method, in ultrasonography screening of developmental hip dysplasia, is based on angle measurements. Using different reference points may cause varied results. The aim of this study was to investigate to what extent the alpha angle obtained, varied at different reference points.

Materials and Methods:

There were 178 hips evaluated by two trained observers. Both measured the alpha angle with different reference points and these were labeled as methods A and B, for all the hips evaluated. The statistical analysis was performed with SPSS Version 21.

Results:

The average of observer 1, based on measurements with method A, were 65.63 (SD ±5.95) and based on method B were 73.39 (SD ±6.29). The average of the measurements of observer 2, utilizing method A were 64.39 (SD ±4.85) and based on method B were 69.92 (SD ±6.08). It was observed that method B showed higher mean and variability compared to method A. The agreement between observers was moderate in method A and poor in method B. The intraobserver correlation coefficient (ICC) was 0.69 for method A and 0.47 for method B. The ICC was considered good (e.g., 95%) for both observers in terms of using methods A and B.

Conclusion:

The use of ultrasonography still maintains its place in the diagnosis of developmental hip dysplasia. The Graf method is based on precise measurements, and the most decisive parameter is the alpha angle. Reference points in method A would be more useful in patient management and may increase the diagnostic accuracy.
Exploring the thrombus niche: Lessons learned and potential therapeutic opportunities
Authors: Weisel John W. , Litvinov Rustem I
Published: February 2025

Thrombus structure and composition are the main determinants of the severity, course, and outcomes of thrombosis. Detailed thrombus morphology has become available due to mechanical thrombectomy, which allows extraction of fresh thrombi from patients followed by scanning electron microscopy. The major structural elements of a thrombus are platelets, erythrocytes, and fibrin, each playing a critical role in determination of biological and physical properties of thrombi, such as permeability, stiffness, lytic and mechanical stability. The minor components include neutrophils, monocytes, von Willebrand factor, cellular microvesicles, plasma proteins, cholesterol crystals, and other structures. Platelets are responsible for contraction (retraction) of thrombi, which results in compaction with very little free space, low permeability and high stiffness. Because of clot contraction, erythrocytes, which are prevalent in all types of thrombi, undergo compressive deformation to polyhedral (polyhedrocytes) and polyhedral-like cells, altogether comprising pressure-deformed cells (piezocytes). Fibrin is the structural and mechanical scaffold of thrombi that changes in time and space both quantitatively and qualitatively during their formation. Fibrin is an equilibrium polymer that can adapt to forced deformations by reorientation at the microscopic level and unfolding at the molecular level. The relative volume fractions of thrombus components, their functional and structural forms vary substantially, providing a basis for the diverse pathogenic mechanisms and clinical manifestations of thrombosis. Modulating any of the components lead to prospective therapeutic approaches. This review summarizes recent research that describes quantitative and qualitative morphologic characteristics of arterial and venous thrombi that provide a basis for new therapeutic opportunities in thrombosis.
The bone marrow NK cell profile predicts MRD negativity in patients with multiple myeloma treated with daratumumab-based therapy
Authors: Korst Charlotte L.B.M. , Tahri Sabrin , Duetz Carolien , Bruins Wassilis S.C. , de Jonge A. Vera , de Jong Madelon M.E. , Fokkema Cathelijne , Smits Febe , Groen Kaz , Verkleij Christie P.M. , Frerichs Kristine A. , Papazian Natalie , van Duin Mark , van Beek Gregory , Hoogenboezem Remco , Baardemans Thomas , Dal Collo Giada , Stoetman Elodie C.G. , Cosovic Meliha , Twickler Inoka , Rentenaar Rosa , Eken Merve , Homan-Weert Paola M. , Saraci Elona , D'Agostino Mattia , van der Velden Vincent H.J. , Sanders Mathijs Arnoud , Gay Francesca , Broijl Annemiek , Moreau Philippe , Sonneveld Pieter , Zweegman Sonja , Mutis Tuna , Cupedo Tom , van de Donk Niels W.C.J.
Published: February 2025

Natural killer (NK) cells are important effector cells in antibody-based immune therapies for multiple myeloma (MM) through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry and functional assays to investigate the bone marrow NK cell compartment of MM patients at diagnosis and during treatment. We show reduced proportion of CD16+ cytotoxic NK cells in a subset of patients at diagnosis, which correlated with decreased cytokine production and NK cell degranulation against MM cells in the presence of the anti-CD38 antibody daratumumab. In line with these findings, a low proportion of CD16+ bone marrow NK cells at diagnosis was associated with a reduced likelihood of achieving MRD-negativity post-consolidation in patients treated with daratumumab, bortezomib, thalidomide and dexamethasone in conjunction with autologous stem cell transplantation in the CASSIOPEIA trial. In contrast, NK cell distribution did not predict MRD-negativity in patients treated in the control arm without daratumumab. These findings highlight the impact of the bone marrow NK cell compartment on therapeutic outcomes in MM patients receiving immunotherapy with CD38-targeting antibodies.
Radiological outcomes of surgical techniques for spastic hip in cerebral palsy: a systematic review and meta-analysis
Authors: Menbari Oskouie Iman , Hakiminejad Alireza , Yazdanmehr Amirali , Mostafavi Keihan , Mafhoumi Asma , Sajedi Amir H. , Roosta Ali , Arvin Alireza , Presedo Ana , Nabian Mohammad Hossein , Kasaeian Amir
Published: February 2025

Background

In patients with cerebral palsy (CP), spastic hip is a prevalent complication. Various surgical approaches,, including pelvic osteotomy (PO), femoral osteotomy (FO), combined femoral and pelvic osteotomy (CFPO), and soft tissue surgery (STS), have been used to address this problem. This systematic review and meta-analysis was designed to compare the radiologic outcomes of these interventions for spastic hip in patients with CP.

Methods

To identify relevant studies, databases were searched using specific keywords. Initially, duplicates were removed, then the titles and abstracts were screened, followed by a comprehensive full-text review. Data extraction took place from the studies that met the inclusion criteria. Subsequently, a meta-analysis was conducted.

Results

The analysis of 6116 hips from 4546 patients across 81 studies demonstrated that PO significantly enhanced the center–edge angle (CEA), reduced the acetabular index (AI) and migration percentage (MP), and improved the Sharp and Tönnis angles. FO led to a substantial decrease in AI and MP, though CEA did not show a significant change, while CFPO resulted in significant improvements across AI, MP, neck-shaft angle (NSA), CEA, Sharp angle, and Tönnis angle. STS did not show significant changes in AI or CEA, but MP was notably reduced. Tone-decreasing procedures, such as selective dorsal rhizotomy and botulinum toxin injections, did not significantly alter MP, whereas guided growth techniques showed a significant reduction. MP improvements in FO decreased over time, with other radiologic parameters remaining relatively stable as follow-up increased. Age-specific trends indicated that children under 6 years primarily underwent tone-decreasing procedures and STS, while those around 7 years favored FO and guided growth, and older children (over 9 years) more commonly underwent PO, CFPO, or percutaneous osteotomy. Comparative analysis showed PO and percutaneous osteotomy were particularly more effective in reducing MP, with PO also being superior for AI improvement; whereas CFPO provided better outcomes for enhancing CEA. No significant differences were found among surgical methods for improving NSA.

Conclusions

This systematic review and meta-analysis underscores the superior efficacy of PO and CFPO in correcting spastic hip deformity in children with CP. Radiological outcomes demonstrate significant improvements following these procedures. The findings suggest that these approaches are particularly effective for complex cases where procedures such as FO, STS, or TDS may fall short. Future studies should focus on refining surgical protocols and exploring the long-term functional outcomes of these interventions.
Assessing non-inferiority for binary matched-pairs data with missing values: a powerful and flexible GEE approach based on the risk difference
Authors: Hengelbrock Johannes , Konietschke Frank , Herm Juliane , Audebert Heinrich , Aigner Annette
Published: February 2025

Background

Clinical studies often aim to test the non-inferiority of a treatment compared to an alternative intervention with binary matched-pairs data. These studies are often planned with methods for completely observed pairs only. However, if missingness is more frequent than expected or is anticipated in the planning phase, methods are needed that allow the inclusion of partially observed pairs to improve statistical power.

Methods

We propose a flexible generalized estimating equations (GEE) approach to estimate confidence intervals for the risk difference, which accommodates partially observed pairs. Using simulated data, we compare this approach to alternative methods for completely observed pairs only and to those that also include pairs with missing observations. Additionally, we reconsider the study sample size calculation by applying these methods to a study with binary matched-pairs setting.

Results

In moderate to large sample sizes, the proposed GEE approach performs similarly to alternative methods for completely observed pairs only. It even results in a higher power and narrower interval widths in scenarios with missing data and where missingness follows a missing (completely) at random (MCAR / MAR) mechanism. The GEE approach is also non-inferior to alternative methods, such as multiple imputation or confidence intervals explicitly developed for missing data settings. Reconsidering the sample size calculation for an observational study, our proposed approach leads to a considerably smaller sample size than the alternative methods.

Conclusion

Our results indicate that the proposed GEE approach is a powerful alternative to existing methods and can be used for testing non-inferiority, even if the initial sample size calculation was based on a different statistical method. Furthermore, it increases the analytical flexibility by allowing the inclusion of additional covariates, in contrast to other methods.
An early evaluation of team consistency and scope optimization in team-based cancer care
Authors: Lambert Leah K. , Havaei Farinaz , Beck Scott M. , Ma Andy , Larmet John , Kaur Jagbir , Adhami Nassim , Le Dan , Woods Ryan
Published: February 2025

Background

The British Columbia (BC) government has made significant investments towards the implementation of team-based care (TBC) in its provincial comprehensive cancer control program. TBC implementation involves purposeful efforts towards: (a) establishing/expanding multidisciplinary care teams, (b) optimizing scope of practice, and (c) increasing care team consistency. Study objectives include an early-phase evaluation of (i) the association between TBC elements and team effectiveness and (ii) staff perceptions of barrier and facilitators of team effectiveness.

Methods

A series of five surveys over a 2-year period will be administered to prospectively evaluate the ongoing implementation of TBC. This study draws on data from the first of the five planned surveys, administered in May 2023. Eligible respondents included 299 program employees—spanning various roles such as physicians, nurses, and unit clerks—working within TBC at the time of survey deployment. The survey included both validated and researcher-developed questions that were either closed or open-ended, including measures of team composition, team consistency, team effectiveness, scope of practice, and demographics. Quantitative data were analyzed using descriptive and regression analysis; qualitative data were analyzed guided by interpretive description methodology.

Results

Collected responses totaled 121, with the majority of respondents being women (76%), full-time employees (90%), and working in direct patient care (77%). Regression analyses indicated that (i) higher frequency of consistently working with the same team members and (ii) lower proportion of shifts practicing below scope are both significant predictors of higher team effectiveness ratings. Qualitative data highlighted staffing levels as a driver of under- and over-utilized scopes of practice. Furthermore, effective communication, enhanced knowledge of each team member’s scope of practice, and strong interpersonal relationships were highlighted as contributing factors to effectiveness among multidisciplinary care teams.

Conclusions

Preliminary findings from the first of five prospective surveys highlight team consistency and role optimization as drivers of effective teamwork in the early implementation of a team-based model of cancer care. Future research should explore contextual factors that influence cancer care staff and clinicians’ perceptions of effectiveness.
The potential radiosensitization target PFKFB3 is related to response to radiotherapy in SweBCG91RT: a randomized clinical trial with long-term follow-up
Authors: Egelberg Moa , De Marchi Tommaso , Schultz Niklas , Tran Lena , Karlsson Per , Holmberg Erik , Pekar Gyula , Killander Fredrika , Niméus Emma
Published: February 2025

Background

Several cancer types have increased PFKFB3, a glycolytic enzyme for which potent inhibitors have been found. Inhibition of PFKFB3 impairs DNA repair after irradiation of cancer cells, making it a possible radiosensitization target. The SweBCG91RT trial, in which breast cancer patients were randomized to postoperative radiotherapy or not, was used to investigate PFKFB3 as a clinical marker of sensitivity to adjuvant radiotherapy.

Methods

Nuclear protein levels of PFKFB3 were assessed with immunohistochemistry in primary breast tumors (n = 970) and whole-cell RNA levels with microarray gene expression (n = 765). Multivariable competing risks regression analysis was employed for the effect of radiotherapy on incidence of ipsilateral breast tumor recurrence (IBTR), depending on PFKFB3 levels.

Results

Tumors with high levels of nuclear protein and RNA had the largest effect on incidence of IBTR of adjuvant radiotherapy, however without evidence of an interaction. PFKFB3 RNA correlated with subtype, as high levels were more common among the human epidermal growth factor receptor 2 (HER2) positive and Luminal A subtypes than Luminal B and triple negative tumors.

Conclusion

High PFKFB3 is associated with a larger reduction of IBTR after radiotherapy but PFKFB3 cannot reliably be used as a predictive marker of sensitivity to adjuvant radiotherapy in breast cancer. PFKFB3 expression differed with subtype, indicating that it may be a better marker among Luminal A and HER2 positive tumors, but this is yet to be investigated.

Trial registration

The trial has been retrospectively registered at clinicaltrials.gov 2024-10-03 (NCT06637202).
Implementing the flipped classroom model to enhance knowledge retention in pharmacology: a local case study at Semmelweis university
Authors: Onódi Zsófia , Riba Pál , Ferdinandy Péter , Görbe Anikó , Varga Zoltán V.
Published: February 2025

Background

The flipped classroom (FC) approach has demonstrated efficacy in enhancing the learning process, including within higher education contexts such as medical education. Recently, FC has emerged as potential alternative to traditional teaching models across various disciplines, particularly due to its more engaging nature. However, there is limited data available regarding its impact on student performance, particularly in the context of long-term knowledge retention in pharmacology. In this study, our objective was to assess the short- and long-term impact of FC on student performance in Hungarian pharmacology teaching at medical faculty in Semmelweis University (Budapest, Hungary).

Methods and results

161 medical students and 10 teachers were involved in this study. We flipped four seminars, then we assessed the academic performance by using multiple choice tests immediately and two weeks after the flipped class. A follow-up assessment was conducted six months after the initial two FC sessions. Our findings indicated that the FC approach enhanced both short- and long-term knowledge retention across most topics. Notably, this long-term improvement was evident even six months after the original seminars on specific subjects. However, despite these topic-specific benefits, the overall performance, including exam grades, did not show significant improvement when compared to the conventional teaching approach. Additionally, we assessed student and teacher perceptions using two questionnaires immediately after practice and at the end of the year. According to the questionnaire responses, students perceived positively the FC approach, emphasizing its interactive and thought-provoking aspects. However, they identified the time-consuming nature of preparation as a significant concern. Teachers also viewed the FC approach favorably, particularly appreciating its interactivity and potential for greater effectiveness. Interestingly, more experienced teachers were less receptive to the FC method, and their perceptions of it were less favorable compared to those of their younger colleagues.

Conclusions

The flipped classroom approach presents a viable strategy for teaching pharmacology, with the potential to enhance student performance and engagement. However, student occupation and faculty resistance may pose significant challenges to the implementation of such alternative teaching methods.
Between duty and despair: the ethical toll of brain drain on Nepalese nurse managers
Authors: Ghimire Animesh , Neupane Mamata Sharma
Published: February 2025

Background

The relentless exodus of skilled healthcare professionals from low- and middle-income countries to wealthier nations, known as the 'brain drain,' poses a grave threat to global health equity. Nepal, a prime example of a source country, faces a critical shortage of nurses due to this migration. Nurse managers, uniquely positioned at the intersection of leadership and frontline care, face considerable challenges in times of crisis. These challenges encompass ethical dilemmas associated with resource allocation, staffing shortages, and maintaining quality care standards. Additionally, nurse managers must navigate their own experiences of moral distress, further complicating their decision-making processes and overall effectiveness in managing healthcare teams and patient outcomes. This study delves into their lived experiences, aiming to expose the far-reaching consequences of brain drain and spark a global dialogue on ethical and sustainable healthcare workforce practices.

Methods

This qualitative descriptive study examined the lived experiences of ten nurse managers in Nepal, employing semi-structured interviews and inductive content analysis. Participants were chosen through a combination of purposive, snowball, and convenience sampling methods, ensuring representation from both urban and rural settings.

Results

Thematic analysis revealed five core themes: (1) Moral Distress on the Frontlines; (2) Unequal Burden, Unequal Access; (3) The Ripple Effects of Exodus; (4) Beyond the Hippocratic Oath; and (5) Policy at the Crossroads.

Conclusion

Policy interventions prioritizing improving working conditions, investing in the domestic healthcare workforce, and promoting ethical recruitment practices are essential to ensure equitable and sustainable healthcare. The voices of nurse managers at the forefront of this crisis provide a powerful call to action. Their experiences and insights urge national and global stakeholders to recognize the human cost of brain drain and work collaboratively towards a more just and resilient healthcare system.
Molecular evolution of dietary shifts in ladybird beetles (Coleoptera: Coccinellidae): from fungivory to carnivory and herbivory
Authors: Huang Yu-Hao , Escalona Hermes E. , Sun Yi-Fei , Zhang Pei-Fang , Du Xue-Yong , Gong Sen-Rui , Tang Xue-Fei , Liang Yuan-Sen , Yang Dan , Chen Pei-Tao , Yang Huan-Ying , Chen Mei-Lan , Hüttel Bruno , Hlinka Ondrej , Wang Xingmin , Meusemann Karen , Ślipiński Adam , Zwick Andreas , Waterhouse Robert M. , Misof Bernhard , Niehuis Oliver , Li Hao-Sen , Pang Hong
Published: February 2025

Background

Dietary shifts are major evolutionary steps that shape ecological niches and biodiversity. The beetle family Coccinellidae, commonly known as ladybirds, first transitioned from a fungivorous to an insectivorous and subsequently a plant diet. However, the molecular basis of this dietary diversification remained unexplored.

Results

We investigated the molecular evolution of dietary shifts in ladybirds, focusing on the transitions from fungivory to carnivory (Coccinellidae) and from carnivory to herbivory (Epilachnini), by comparing 25 genomes and 62 transcriptomes of beetles. Our analysis shows that chemosensory gene families have undergone significant expansions at both nodes of diet change and were differentially expressed in feeding experiments, suggesting that they may be related to foraging. We found expansions of digestive and detoxifying gene families and losses of chitin-related digestive genes in the herbivorous ladybirds, and absence of most plant cell wall-degrading enzymes in the ladybirds dating from the transition to carnivory, likely indicating the effect of different digestion requirements on the gene repertoire. Immunity effector genes tend to emerge or have specific amino acid sequence compositions in carnivorous ladybirds and are downregulated under suboptimal dietary treatments, suggesting a potential function of these genes related to microbial symbionts in the sternorrhynchan prey.

Conclusions

Our study provides a comprehensive comparative genomic analysis to address evolution of chemosensory, digestive, detoxifying, and immune genes associated with dietary shifts in ladybirds. Ladybirds can be considered a ubiquitous example of dietary shifts in insects, and thus a promising model system for evolutionary and applied biology.
Non-invasive diagnosis of vulvar dysplasia using cervical methylation markers—a case control study
Authors: Becker Sabeth , Dübbel Lena , Behrens Dana , Knoll Kristin , Hippe Juliane , Loser Karin , Malik Eduard , Schild-Suhren Meike
Published: February 2025

Background

Diagnostic screenings for vulvar squamous intraepithelial lesions (VSIL) are limited and without information on disease trends. A panel of six methylation markers (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671; GynTect® assay) has shown promise in diagnosing cervical intraepithelial neoplasia (CIN). Given the similarities between the carcinogenesis of cervix and vulva, this study aimed to investigate the suitability of these markers for diagnosing vulvar lesions.

Methods

One hundred twenty-one vulvar FFPE samples and 237 vulvar cell smears with different VSIL grades, HPV status, and with or without lichen sclerosus and planus were tested. Additionally, dysplasia-free vulvar cell smears from patients with cervical dysplasia were analyzed. The expression of DNA methyltransferases (DNMTs) in the FFPE samples was measured.

Results

The markers demonstrated high specificity in vulvar smears, with sole 5.45% of dysplasia-free smears testing positive. Yet, 75.00% of vulvar carcinoma smears appear positive in the methylation kit, similar to VHSIL (VIN III) smears with 77.78%. In FFPE samples, dysplasia-free samples from the tumor microenvironment of high-grade vulvar neoplasia showed 43.75% positivity. The positivity rates for VSIL and carcinoma samples were 76.92%, 64.71%, 64.71%, and 80.49%, respectively. DNMT3a expression was the highest in VLSIL (VIN I) samples, while DNMT1 was only expressed in VHSIL (VIN III) and carcinoma samples. Lichen sclerosis and planus showed a high false positive rate of 45.45% for dysplasia-free and 54.54% for smears with dVIN. Cervical HSIL was associated with a significantly higher number of positive results in the kit than in patients without cervical dysplasia.

Conclusions

The findings suggest that the methylation markers comprising GynTect® may be suitable for detecting vulvar neoplasia, as they exhibit high sensitivity. Nonetheless, adjustments are needed for comparable specificity. Lichen should be considered in result interpretation, and the kit should be used with caution for patients with lichen. Moreover, we observed methylation changes as an early event with the highest positivity of VLSIL. Surprisingly, changes in methylation pattern are not as local as presumed. Cervical SIL led to changed methylation in the vulva. Patients with positive kit results should be monitored regularly for all genital dysplasia. This sheds new light on the epigenetics in cancer.
Insights into the complex relationship between triglyceride glucose-waist height ratio index, mean arterial pressure, and cardiovascular disease: a nationwide prospective cohort study
Authors: Xu Jie , Cai Dihui , Jiao Yuheng , Liao Yingying , Shen Yinyin , Shen Yunli , Han Wei
Published: February 2025

Background

Both the triglyceride glucose-waist height ratio (TyG-WHtR) index and elevated arterial blood pressure are risk factors for cardiovascular disease (CVD). However, it is uncertain whether the TyG-WHtR index can increase the risk of CVD by influencing arterial blood pressure, and the extent to which the TyG-WHtR index may mediate the association between arterial blood pressure and CVD. The purpose of this study is to evaluate complex association of the TyG-WHtR index and mean arterial pressure (MAP) with CVD.

Methods

All data in this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS) free of CVD at baseline. CVD was defined as self-reporting heart disease and stroke. Cox proportional hazards model and restricted cubic spline (RCS) were used to analyze the association of the TyG-WHtR index and MAP with the risk of CVD. Time-dependent receiver operating characteristic (ROC) analysis was used to assess the predictive performance of TyG-WHtR, MAP for CVD. Four-way decomposition method explored the mediating effects of the TyG-WHtR index and MAP in CVD.

Results

A total of 7976 participants were included in this study. The mean age of the participants was 58.68 ± 9.60 years, and 4263 (53.45%) were females. During a maximum follow-up of 7.0 years, 1326 (16.62%) people developed CVD. Both the TyG-WHtR index and MAP were signifcantly associated with CVD. The RCS regression analyses demonstrated a positive linear association of the TyG-WHtR index and MAP with the incidence of CVD. Compared with participants with TyG-WHtR < median and MAP < median, those with TyG-WHtR ≥ median and MAP ≥ median had the highest risk of CVD (HR 1.961; 95%CI 1.660–2.317). The combination of TyG-WHtR and MAP demonstrated incremental predictive utility over either biomarker alone, as evidenced by improvements in integrated discrimination improvement (IDI) and net reclassification improvement (NRI). While absolute predictive performance remained moderate. Increased MAP signifcantly mediated 52.43% of the associations between TyG-WHtR index and CVD, and increased TyG-WHtR index signifcantly mediated 83.40% of the associations between MAP and CVD.

Conclusion

The combination of a higher TyG-WHtR index and a higher MAP was associated with the highest risk of CVD. The combined model of the TyG-WHtR index and MAP showed improved predictive ability, as indicated by IDI and NRI, although its overall predictive performance was still moderate. The MAP could partially mediate the association between TyG-WHtR index and CVD, as well as TyG-WHtR index could also partially mediate the association between MAP and CVD. These findings suggested that the combination of TyG-WHtR index and MAP helps identify populations at early risk of CVD and improve risk stratifcation.

Graphical abstract
Automatic gait EVENT detection in older adults during perturbed walking
Authors: Wang Shuaijie , Omar Kazi Shahrukh , Miranda Fabio , Bhatt Tanvi
Published: February 2025

Accurate detection of gait events in older adults, particularly during perturbed walking, is essential for evaluating balance control and fall risk. Traditional force plate-based methods often face limitations in perturbed walking scenarios due to the difficulty in landing cleanly on the force plates. Subsequently, previous studies have not addressed gait event automatic detection methods for perturbed walking. This study introduces an automated gait event detection method using a bidirectional gated recurrent unit (Bi-GRU) model, leveraging ground reaction force, joint angles, and marker data, for both regular and perturbed walking scenarios from 307 healthy older adults. Our marker-based model achieved over 97% accuracy with a mean error of less than 14 ms in detecting touchdown (TD) and liftoff (LO) events for both walking scenarios. The results highlight the efficacy of kinematic approaches, demonstrating their potential in gait event detection for clinical settings. When integrated with wearable sensors or computer vision techniques, these methods enable real-time, precise monitoring of gait patterns, which is helpful for applying personalized programs for fall prevention. This work takes a significant step forward in automated gait analysis for perturbed walking, offering a reliable method for evaluating gait patterns, balance control, and fall risk in clinical settings.
Effect of bronchofiberscopic lavage with acetylcysteine instillation on refractory mycoplasma pneumoniae pneumonia in children: a retrospective clinical observation
Authors: Li Pei-long , Fu Hong-min , Liu Kai , Li Feng , Yang Jia-wu
Published: February 2025

Background

Bronchofiberscopic lavage is a therapeutic treatment for mycoplasma infection. However, there are limited reports on the use of bronchofiberscopic lavage with acetylcysteine instillation. The aim of our study was to investigate the clinical effect of bronchofiberscopic lavage with acetylcysteine instillation on refractory mycoplasma pneumoniae pneumonia in children.

Methods

This was a retrospective study. Clinical and laboratory data were collected from 280 children hospitalized with MPP in the Department of Pulmonary and Critical Care Medicine at Kunming Children′s Hospital from January 2021 to January 2023, and these were divided into two groups: the study group and the control group. Children in the control group were treated with anti-infective, antitussive, and antipyretic routine symptomatic treatment and nebulization of acetylcysteine suspension, while children in the study group were treated with bronchofiberscopic lavage with acetylcysteine instillation along with standard treatment as in the control group. The clinical characteristics, adverse reactions, pulmonary imaging changes, and laboratory examination indicators were compared between the two groups.

Results

The treatment effective rate and the absorption area of lung lesions in the study group were significantly higher than those in the control group (P < 0.05). Before treatment, there were no statistically significant differences in WBC, IgG, IgE, CRP, and IL-6 levels between the two groups (P > 0.05). After 7 days of treatment, IgG levels in both groups were higher than those before treatment, while WBC, IgE, CRP, and IL-6 levels were lower than those before treatment (P < 0.05).

Conclusions

The bronchofiberscopic lavage with acetylcysteine instillation constitutes a safe and efficacious therapeutic regimen, which might alleviate the clinical symptoms experienced and reduce the levels of inflammatory factors for children with RMPP.
Sublingual sufentanil after orthopaedic and abdominal surgery: long-term outcome and safety
Authors: Borck Michael , Wandrey Jan D. , Spies Claudia , Tafelski Sascha
Published: February 2025

Background

Acute postoperative pain management often requires opioid treatment with patient-controlled analgesia (PCA). Non-invasive PCA with a sublingual sufentanil tablet system (SSTS) may reduce acute pain sufficiently, but opioids are associated with central nerve system side effects and risk of long-term opioid use postoperatively. The objective of this study was to observe the SSTS to assess the incidence of postoperative chronic pain (PCP) and postoperative delirium (POD).

Methods

This was a longitudinal cohort study based at a university hospital between November 2017 and November 2021. Adults undergoing elective orthopaedic knee or abdominal surgery planned for PCA as postoperative pain management were included. They received the SSTS in addition to a standardised pain medication protocol depending on the surgery they underwent. Exclusion criteria were pregnancy, emergency surgery, concurrent participation in another clinical trial and chronic opioid use before surgery. Patients were followed after surgery in hospital and over 3 and 12 months for pain, cognitive function and side effects.

Results

Altogether N = 80 patients were included with SSTS postoperatively. Daily pain experience decreased from pre-operatively 89.2% of patients to 45.7% and 22.5% at 3 and 12 months. None of our patients developed postoperative delirium after surgery. Patients reported high overall satisfaction with SSTS (median 8.0/10 points, IQR 3). However, 51% of patients had difficulties with handling the SSTS and required acute replacement of the authentication tag.

Conclusions

SSTS sufficiently treated acute postoperative pain without incidence of POD and demonstrated good tolerability and overall ease. Postoperative pain improved significantly over time but 22% still reported chronic pain related to surgery. Technical issues with the identification thumb tag limited the feasibility of SSTS.

Trial registration

This prospective longitudinal cohort study was approved by the ethics committee of the Charité Universitätsmedizin Berlin (Ethics committee 2, Campus Charité Virchow Klinikum, EA2/041/17, Prof. Dr. jur. R. Seeland, 21.03.2017) and was registered in the study register (https://clinicaltrials.gov/ct2/show/NCT03133858).
Enterocloster clostridioformis protects against Salmonella pathogenesis and modulates epithelial and mucosal immune function
Authors: Beresford-Jones Benjamin S. , Suyama Satoshi , Clare Simon , Soderholm Amelia , Xia Wangmingyu , Sardar Puspendu , Lee Junhee , Harcourt Katherine , Lawley Trevor D. , Pedicord Virginia A.
Published: February 2025

Background

Promoting resistance to enteric pathogen infection is a core function of the gut microbiota; however, many of the specific host–commensal interactions that mediate this protection remain uncharacterised. To address this knowledge gap, we monocolonised germ-free mice with mouse-derived commensal microbes to screen for microbiota-induced resistance to Salmonella Typhimurium infection.

Results

We identified Enterocloster clostridioformis as a protective species against S. Typhimurium infection. E. clostridioformis selectively upregulates resistin-like molecule β and cell cycle pathway expression at the level of caecal epithelial cells and increases T-regulatory cells in the underlying mucosal immune system, potentially contributing to reduced infection-induced pathology.

Conclusions

We highlight novel mechanisms of host–microbe interactions that can mediate microbiota-induced resistance to acute salmonellosis. In the backdrop of increasing antibiotic resistance, this study identifies novel potential avenues for further research into protective host responses against enteric infections and could lead to new therapeutic approaches.
Prevalence and risk factors of acute respiratory infection and diarrhea among children under 5 years old in low-middle wealth household, Indonesia
Authors: Purnama Tri Bayu , Wagatsuma Keita , Saito Reiko
Published: February 2025

Background

Acute respiratory infection (ARI) and diarrhea remain critical public health concerns. In Indonesia, various interventions have been implemented to reduce the prevalence of ARIs and diarrhea among children in low- and middle-income households. Hence, the absence of detailed data on the prevalence of ARIs and diarrhea among children under five in low- and middle-income households in Indonesia restricts the formulation of targeted health interventions and policies. This study sought to evaluate the prevalence of ARI and diarrhea while examining modifiable risk factors related to malnutrition, sanitation, and social protection characteristics in Indonesia.

Methods

This study utilized a cross-sectional design based on data from the Nutrition Status Survey 2022 covering 514 districts/cities in Indonesia. It analyzed 289,631 children under five years out of 334,848 households with low and middle wealth indices. Multivariable binary logistic regression analysis was employed to calculate the risk associated with cases of ARI and diarrhea.

Results

The prevalence of ARI and diarrhea among low- and middle-wealth households were 5.7% and 6.0%, respectively, with infants under six months being the most vulnerable group to these infections, including malnutrition. The most significant risk factors for ARI and diarrhea are unclean cooking fuel [adjusted odds ratio (aOR) = 1.53, 95% CI 1.47–1.60] and shared toilet facilities (aOR = 1.45, 95% CI 1.38–1.51), with households using shared toilets having 1.45 times higher risk of diarrhea (aOR = 1.45, 95% CI 1.38–1.51) compared to those with private access. Additionally, households lacking social protection support are also at increased risk for these infections and malnutrition issues.

Conclusions

This study revealed a notable prevalence of ARI and diarrhea among low- and middle-wealth households, particularly affecting infants under six months. Vulnerable children, especially those who were stunted or underweight, and households lacking sanitation and social protection faced heightened risks for these health issues.

Graphical Abstract
Associations Between Lactate Thresholds and 2000 m Rowing Ergometer Performance: Implications for Prediction—A Systematic Review
Authors: Kilbey Timothy , Vecchi Eugenio , Salbany Paulo , Handa Ashok , Stride Eleanor , Sheth Mihir
Published: February 2025

Background

Various exercise thresholds have been evaluated to predict athlete performance. However, a systematic review of the literature assessing the association between lactate-based exercise thresholds and 2000 m rowing ergometer performance is still lacking. These may have utility in the prediction of 2000 m rowing ergometer performance due to the close relationship between metabolic parameters and development of endurance capacity. The aim of the present study is to review and assess the extent, quality, and reliability of lactate-based exercise testing and methodologies in their association with 2000 m rowing ergometer performance, and to discuss the potential implications for performance prediction.

Methods

The systematic review was performed following PRISMA 2020 guidelines. The databases searched were EMBASE, MEDLINE and SPORTDiscus. The initial search took place in July 2022, with an update search performed in September 2023, and again in August 2024. Studies which reported a lactate test and its correlation to 2000 m ergometer performance were included. No meta-analysis was performed.

Results

Twenty-four studies comprising 797 athletes (513 male, 257 female, 27 not stated) met the eligibility criteria for inclusion in the review. The most commonly used testing protocol involved the use of incremental step-tests. A range of exercise intensity parameters, lactate-based exercise thresholds and interpretation methodologies were employed. Of these, the power or velocity at a blood lactate concentration of 4 mmol l−1 was the most common test, with correlation coefficients ranging from 0.53 to 0.96 suggesting that 28–92% of the variance in rowing performance can be explained by this metric. Six studies that rated as GOOD on the risk of bias assessment found very strong correlations > 0.85 (p < 0.05).

Conclusions

This systematic review found that there is good evidence that the power generated at a blood lactate concentration of 4 mmol l−1 correlates strongly to 2000 m rowing ergometer performance and may have useful predictive power. However, the review also identified the varying quality of the available literature, with a variety of parameters, exercise protocols, testing methods, and performance metrics being used to report performance making it difficult to compare results between studies. Other tests such as

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at a blood lactate concentration of 4 mmol l−1 and power at the initial non-linear inflection blood lactate threshold merit further investigation as the extent and reliability of the available data is currently insufficient to draw firm conclusions.

Protocol registration: The protocol was registered on Open Science Framework on 17/11/2022. https://doi.org/10.17605/OSF.IO/D8YCE
Unexpected negative-pressure pulmonary edema after tracheostomy: two case reports
Authors: Kotani Taichi , Naito Yusuke , Okuda Chie , Sonobe Shota , Egawa Junji , Kawaguchi Masahiko
Published: February 2025

Background

Negative-pressure pulmonary edema (NPPE) often develops with upper airway obstruction, and is uncommon in secured airways, for example, after tracheostomy. Herein, we report two cases of NPPE post-tracheostomy.

Case presentation

Case 1: A 69-year-old man underwent prophylactic tracheotomy for possible airway obstruction secondary to glottic carcinoma. Two hours after awakening from general anesthesia, he had difficulty expectorating and developed NPPE due to airway secretions obstructing the tracheostomy tube.

Case 2: An 11-year-old boy was admitted to the intensive care unit for continuous hemodiafiltration on a ventilator under sedation. On the 76th day, the day after the tracheostomy was performed, the patient developed patient-ventilator asynchrony due to sedative withdrawal syndrome. The postulated primary mechanism was functional airway obstruction due to patient-ventilator asynchrony.

Conclusion

These cases highlight the need to consider NPPE, even in patients with an airway secured with a tracheostomy.
Catheter diameter and infection control are important in neonatal continuous kidney replacement therapy: a single-center retrospective study
Authors: Otsuka Hiroki , Kibe Masaya , Ishihara Chie , Tokuhisa Takuya
Published: February 2025

Background

Neonates have smaller bodies than children; reports on circuit lifetime in neonates remain scarce, even though the mortality rate is high with continuous kidney replacement therapy (CKRT). In this study, we determined the circuit lifetime of CKRT in neonates and examined the associated factors.

Methods

We retrospectively identified patients who were admitted to our neonatal intensive care unit and underwent CKRT from 1 January 2014 to 31 December 2022. A survival analysis of circuit lifetime was performed, and the Cox proportional hazards model was developed to analyze the impact on circuit occlusion.

Results

In total, 88 circuits were assembled, with 69 occluded and 19 detached circuits. The median corrected age at CKRT therapy was 39.6 (interquartile range [IQR] 35.4–42.3) weeks, weight was 2508 (1500–3090) g, catheter diameter was 1.2 (0.8–1.8) mm, and circuit lifetime was 16.0 (7.5–38.1) h. The hazard ratio for circuit lifetime was 1.04 (95% confidence interval [CI] 0.97–1.11), 1.00 (1.00–1.00), 0.62 (0.40–0.96), and 0.41 (0.21–0.80) for corrected age, weight, catheter diameter, and bacteremia, respectively.

Conclusions

Appropriate selection of catheter and infection management are important for safe CKRT.
Barriers and facilitators for treatment-seeking among women with genital fistula: a facility-based qualitative study in Bangladesh
Authors: Kon Kanako , Imoto Atsuko , Rashid Sabina Faiz , Masuda Ken
Published: February 2025

Background

Women living with genital fistula often endure prolonged suffering and face multiple barriers to accessing treatment. Bangladesh’s government has enhanced referral mechanisms, enabling case detection in communities and facilitating surgical interventions at medical college hospitals through nationwide initiatives. However, research on barriers and facilitators for fistula treatment in Bangladesh remains limited. Detailed insights into treatment-seeking paths with time sequences are scarce. This study aimed to explore facilitators and barriers to completing fistula treatment with the description of treatment-seeking paths. This study is important to assist with future policy and program strategies for fistula treatment.

Methods

A facility-based qualitative study was conducted at Dhaka Medical College Hospital, Dhaka, Bangladesh. Data were collected from February to May 2024 through 18 in-depth interviews (IDIs) with in-patients, five IDIs with families, and 11 key informant interviews with health service providers. Participants’ treatment-seeking paths were described chronologically and identified patterns of treatment-seeking paths. Thematic analysis, guided by the Partners for Applied Social Sciences model for health-seeking behavior and access to care, was used to analyze case histories.

Results

The average duration of treatment-seeking by the women was 39 months, with a maximum of 22 years. Women with fistula often sought care at multiple facilities (up to eight), suspended treatment, and encountered systemic obstacles that delayed treatment. Key barriers included scarce information on illness and treatment in the community, less decision-making power, failure of medical communication, and systemic failures in cost, treatment, and referral systems. Facilitators that motivated women to complete treatment included informal peer support through shared treatment experiences and emotional, physical, and financial support.

Conclusions

Analysis of treatment-seeking paths revealed the absence of standardized treatment routes for women with fistula. To ensure effective care, raising societal awareness about fistula, improving treatment and referral systems, enhancing medical communication, and providing peer and emotional support are strongly recommended.