bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications
Authors: Hart Stephanie A. , Lee Laura A. , Seegmiller Adam C. , Mason Emily F.
Published: November 2024

The International Consensus (ICC) and World Health Organization fifth edition (WHO5) classifications introduced new, but differing, categories of myeloid disease defined by TP53 mutations. We reviewed a cohort of 188 cases of TP53-mutated myeloid disease to determine how diagnoses and outcomes differ between the 2 classifications. Overall, 120 (64%) cases were classified differently by the ICC and WHO5, including 24 of 80 (30%) cases with <20% blasts. These cases were discrepantly categorized primarily because of inclusion of complex karyotype (CK) as a surrogate for biallelic TP53 inactivation only in the ICC. However, there were no significant differences in clinicopathologic characteristics or overall survival between cases categorized as TP53-mutated disease by both classifications and those with a single TP53 mutation and CK, suggesting that CK reliably identifies TP53-mutated cases with biallelic TP53 inactivation. Most cases of acute myeloid leukemia (AML; 96/102 [94%]) were discrepantly diagnosed between the ICC and WHO5 because of the introduction of AML with mutated TP53 as a distinct category only in the ICC. Nearly all of these were instead diagnosed as AML, myelodysplasia related (AML-MR) by WHO5. However, when compared with a separate cohort of patients with AML-MR without TP53 mutations, patients with TP53-mutated AML showed a distinct genetic profile and significantly worse overall survival, supporting the inclusion of AML with mutated TP53 as a distinct disease category. Overall, our results show that a significant percentage of TP53-mutated myeloid disease is classified differently by the ICC and WHO5 and highlight areas to address in future classification systems.
Rare genetic interstitial lung diseases: a pictorial essay
Authors: Borie Raphael , Berteloot Laureline , Kannengiesser Caroline , Griese Matthias , Cazes Aurelie , Crestani Bruno , Hadchouel Alice , Debray Marie Pierre
Published: November 2024

The main monogenic causes of pulmonary fibrosis in adults are mutations in telomere-related genes. These mutations may be associated with extrapulmonary signs (hepatic, haematological and dermatological) and typically present radiologically as usual interstitial pneumonia or unclassifiable fibrosis. In children, the monogenic causes of pulmonary fibrosis are dominated by mutations in surfactant-related genes. These mutations are not associated with extrapulmonary signs and often manifest radiologically as unclassifiable fibrosis with cysts that can lead to chest wall deformities in adults. This review discusses these mutations, along with most of the monogenic causes of interstitial lung disease, including interferon-related genes, mutations in genes causing cystic lung disease, Hermansky–Pudlak syndrome, pulmonary alveolar proteinosis, lysinuric protein intolerance and lysosomal storage disorders, and their pulmonary and extrapulmonary manifestations.
Predicting paediatric asthma exacerbations with machine learning: a systematic review with meta-analysis
Authors: Votto Martina , De Silvestri Annalisa , Postiglione Lorenzo , De Filippo Maria , Manti Sara , La Grutta Stefania , Marseglia Gian Luigi , Licari Amelia
Published: November 2024

Background

Asthma exacerbations in children pose a significant burden on healthcare systems and families. While traditional risk assessment tools exist, artificial intelligence (AI) offers the potential for enhanced prediction models.

Objective

This study aims to systematically evaluate and quantify the performance of machine learning (ML) algorithms in predicting the risk of hospitalisation and emergency department (ED) admission for acute asthma exacerbations in children.

Methods

We performed a systematic review with meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias and applicability for eligible studies was assessed according to the prediction model study risk of bias assessment tool (PROBAST). The protocol of our systematic review was registered in the International Prospective Register of Systematic Reviews.

Results

Our meta-analysis included seven articles encompassing a total of 17 ML-based prediction models. We found a pooled area under the curve (AUC) of 0.67 (95% CI 0.61–0.73; I2=99%; p<0.0001 for heterogeneity) for models predicting ED admission, indicating moderate accuracy. Notably, models predicting child hospitalisation demonstrated a higher pooled AUC of 0.79 (95% CI 0.76–0.82; I2=95%; p<0.0001 for heterogeneity), suggesting good discriminatory power.

Conclusion

This study provides the most comprehensive assessment of AI-based algorithms in predicting paediatric asthma exacerbations to date. While these models show promise and ML-based hospitalisation prediction models, in particular, demonstrate good accuracy, further external validation is needed before these models can be reliably implemented in real-life clinical practice.
Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity
Authors: Knight Andrea , Houser Josef , Otasevic Tomas , Juran Vilem , Vybihal Vaclav , Smrcka Martin , Piskacek Martin
Published: November 2024

The overexpression of MYC genes is frequently found in many human cancers, including adult and pediatric malignant brain tumors. Targeting MYC genes continues to be challenging due to their undruggable nature. Using our prediction algorithm, the nine-amino-acid activation domain (9aaTAD) has been identified in all four Yamanaka factors, including c-Myc. The predicted activation function was experimentally demonstrated for all these short peptides in transactivation assay. We generated a set of c-Myc constructs (1–108, 69–108 and 98–108) in the N-terminal regions and tested their ability to initiate transcription in one hybrid assay. The presence and absence of 9aaTAD (region 100–108) in the constructs strongly correlated with their activation functions (5-, 3- and 67-times respectively). Surprisingly, we observed co-activation function of the myc region 69–103, called here acetyl-TAD, previously described by Faiola et al. (Mol Cell Biol 25:10220–10234, 2005) and characterized in this study as a new domain collaborating with the 9aaTAD. We discovered strong interactions on a nanomolar scale between the Myc-9aaTAD activation domains and the KIX domain of CBP coactivator. We showed conservation of the 9aaTADs in the MYC family. In summary for the c-Myc oncogene, the acetyl-TAD and the 9aaTAD domains jointly mediated activation function. The c-Myc protein is largely intrinsically disordered and therefore difficult to target with small-molecule inhibitors. For the c-Myc driven tumors, the strong c-Myc interaction with the KIX domain represents a promising druggable target.
Integrating gene expression and imaging data across Visium capture areas with visiumStitched
Authors: Eagles Nicholas J. , Bach Svitlana V. , Tippani Madhavi , Ravichandran Prashanthi , Du Yufeng , Miller Ryan A. , Hyde Thomas M. , Page Stephanie C. , Martinowich Keri , Collado-Torres Leonardo
Published: November 2024

Background

Visium is a widely-used spatially-resolved transcriptomics assay available from 10x Genomics. Standard Visium capture areas (6.5mm by 6.5mm) limit the survey of larger tissue structures, but combining overlapping images and associated gene expression data allow for more complex study designs. Current software can handle nested or partial image overlaps, but is designed for merging up to two capture areas, and cannot account for some technical scenarios related to capture area alignment.

Results

We generated Visium data from a postmortem human tissue sample such that two capture areas were partially overlapping and a third one was adjacent. We developed the R/Bioconductor package visiumStitched, which facilitates stitching the images together with Fiji (ImageJ), and constructing SpatialExperiment R objects with the stitched images and gene expression data. visiumStitched constructs an artificial hexagonal array grid which allows seamless downstream analyses such as spatially-aware clustering without discarding data from overlapping spots. Data stitched with visiumStitched can then be interactively visualized with spatialLIBD.

Conclusions

visiumStitched provides a simple, but flexible framework to handle various multi-capture area study design scenarios. Specifically, it resolves a data processing step without disrupting analysis workflows and without discarding data from overlapping spots. visiumStitched relies on affine transformations by Fiji, which have limitations and are less accurate when aligning against an atlas or other situations. visiumStitched provides an easy-to-use solution which expands possibilities for designing multi-capture area study designs.
Continuous planting American ginseng (Panax quinquefolius L.) caused soil acidification and bacterial and fungal communities’ changes
Authors: Li Shaoyong , Wei Haiwei , Qi Daqian , Li Wenwen , Dong Yan , Duan Fu-Ang , Ni Shou-Qing
Published: November 2024

Background

American ginseng is an important herb crop and is widely cultivated in China. However, continuous cropping seriously affects the production of American ginseng, and the reason is still unclear and needs more research. We analyzed the soil microbial alpha diversity and community composition as well as soil physicochemical properties in bulk soils to assess the changes in soil associated with planting American ginseng.

Results

The cultivation of American ginseng resulted in a significant decrease in soil pH value. The alpha diversity of soil bacteria and fungi was significantly reduced with the increase of American ginseng planting years. Planting American ginseng also largely altered the community composition of soil bacteria and fungi, in particularly, increased the relative abundance of the pathogenic fungus Fusarium, and reduced the relative abundance of some beneficial microorganisms, such as KD4-96, RB41 and Sphingomonas.

Conclusions

Soil acidification, reduction of beneficial taxa and accumulation of fungal pathogens, therefore, may lead to the replantation problem of American ginseng.
L-arginine impact on inflammatory and cardiac markers in patients undergoing coronary artery bypass graft: a systematic review and meta-analysis of randomized controlled trials
Authors: Mohammadi Zahra , Ravankhah Mahdi , Ahmadi Mohammad , Keshavarzian Omid , Azari Isaac , Abdollahi Mozhan , Rezaei Mehdi , Akbari Hamed
Published: November 2024

Background

Numerous studies have explored the effects of L-arginine, whether administered in the form of a supplement or through infusion during cardioplegia, on cardiac and inflammatory markers in individuals undergoing coronary artery bypass grafting (CABG). However, these studies presented contradictory findings. Consequently, the objective of this study was to investigate the impact of l-arginine on these markers by analyzing available randomized controlled trials (RCTs).

Methods

We performed an extensive search across various databases, including Embase, Medline/PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar, covering research published until December 2023. To analyze the mean changes in inflammatory and cardiac markers between the L-arginine and control groups, we calculated the weighted mean difference (WMD) along with the corresponding 95% confidence interval (CI) using a random-effects model.

Results

A total of 393 RCTs were identified during the initial search. After screening and selection, 7 trials were included. In a meta-analysis of three trials that reported troponin T levels, we found a significant impact of L-arginine on reducing troponin T levels (WMD = -0.61 ng/ml; 95% CI: -1.07, -0.15). Our analysis also showed that L-arginine had a noticeable impact on decreasing interleukin-6 (IL-6) levels (WMD = -7.72 pg/ml; 95% CI: -15.05, -0.39). However, we found no considerable impact of L-arginine treatment on creatine phosphokinase-MB (CPK-MB), tumor necrosis factor-alpha (TNF-α), and troponin I compared to the placebo groups.

Conclusions

Our findings suggest that L-arginine may benefit patients undergoing CABG, as it helps reduce inflammatory reactions and limits myocardial ischemia. This study registered in the PROSPERO database (Registration No. CRD42024508341).
geessbin: an R package for analyzing small-sample binary data using modified generalized estimating equations with bias-adjusted covariance estimators
Authors: Ishii Ryota , Ohigashi Tomohiro , Maruo Kazushi , Gosho Masahiko
Published: November 2024

Background

The generalized estimating equation (GEE) method is widely used for analyzing longitudinal and clustered data. Although the GEE estimate for regression coefficients and sandwich covariance estimate are consistent regardless of the choice of covariance structure, they are generally biased for small sample sizes. Various researchers have proposed modified GEE methods and covariance estimators to handle small-sample bias.

Results

We briefly present bias-corrected and penalized GEE methods, along with 11 bias-adjusted covariance estimators. In addition, we focus on analyzing longitudinal or clustered data with binary outcomes using the logit link function and introduce package in R to implement conventional and modified GEE methods with bias-adjusted covariance estimators. Finally, we illustrate the implementation and detail a usage example of the package. The package is available from the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/geessbin/index.html.

Conclusions

The package provides three GEE estimates with numerous covariance estimates. It is useful for analyzing correlated data such as longitudinal and clustered data. Additionally, the is designed to be user-friendly, making it accessible to non-statisticians.
Gait abnormalities and longitudinal fall risk in older patients with end-stage kidney disease and sarcopenia
Authors: Sun Chien-Yao , Hsu Lin-Chieh , Su Chien-Chou , Li Chung-Yi , Chao Chia-Ter , Chang Yu-Tzu , Chang Chia-Ming , Wang Wen-Fong , Lien Wei-Chih
Published: November 2024

Background

Sarcopenia, gait disturbance, and intradialytic hypotension are among the various factors that contribute to fall risk. This study aimed to investigate the relationship between risk of sarcopenia, hemodialysis (HD) session, and long-term fall risk in older end-stage kidney disease (ESKD) patients by analyzing their spatiotemporal gait characteristics.

Methods

We recruited 22 non-demented patients aged ≥ 65 years who were undergoing maintenance HD. Participants were divided into two groups based on their SARC-F score (< 4 and ≥ 4) to identify those with higher and lower risk of sarcopenia. Demographics, comorbidities, and renal parameters were compared between groups. Inertial measurement unit-based technology equipped with triaxial accelerometry and gyroscope was used to evaluate gait characteristics. The gait task was assessed both before and after dialysis using the Timed-Up and Go (TUG) test and a 10-meter walking test at a regular pace. Essential gait parameters were thoroughly analyzed, including gait speed, stride time, stride length, double-support phase, stability, and symmetry. We investigated the interaction between the dialysis procedure and gait components. Outcome of interest was any occurrence of injurious fall during follow-up period. Logistic regression models were employed to examine the relationship between baseline gait markers and long-term fall risk.

Results

The SARC-F ≥ 4 group showed various gait abnormalities, including longer TUG time, slower gait speed, longer stride time, shorter stride length, and longer double support time compared to counterpart (SARC-F < 4). After HD sessions, the SARC-F ≥ 4 group showed a 2.0-second decrease in TUG task time, an 8.0 cm/s increase in gait speed, an 11.6% lower stride time, and a 2.4% increase in gait symmetry with significant group-time interactions. Shorter stride length and longer double support time were associated with injurious falls during the two-year follow-up.

Conclusion

Our study demonstrated the utility of triaxial accelerometers in extracting gait characteristics in older HD patients. High-risk sarcopenia (SARC-F ≥ 4) was associated with various gait abnormalities, some of which partially improved after HD sessions. These gait abnormalities were predictive of future falls, highlighting their prognostic significance.
The economic burden of nosocomial infections for hospitals: evidence from Germany
Authors: Asegu Lulseged M. , Kitschen Anne , Neuwirth Meike M. , Sauerland Dirk
Published: November 2024

Background

Nosocomial infections (NI) significantly worsen patient outcomes, resulting in higher mortality rates and reduced health-related quality of life. Furthermore, they pose substantial economic strain on healthcare systems and hospitals. For instance, patients with nosocomial infections (NIs) experience prolonged hospital stays compared to those without NIs. These extended stays result in occupied bed-days, leading to opportunity costs for hospitals. This study aimed to estimate the opportunity costs for a German hospital based on hospital stays, daily revenue, and occupancy rates (OCR).

Methods

We analysed cost data obtained from routine records maintained by the accounting department of a German hospital's surgical and orthopedic units from 2018 to 2019 for the “HygArzt” research project. To ensure balance, we employed genetic matching. We estimated the differences in length of stay (LOS) and daily revenue between patients with and without nosocomial infections (NI) using linear regression. Finally, we calculated the opportunity cost borne by the hospital by treating NI patients instead of non-NI patients. All costs are reported in 2018 Euros.

Results

The final sample included 81 patients with NI matched with 207 patients without NI. The majority of the NI patients (77.0%) had surgical site infection (SSI). Compared to non-NI patients, we observed that NI patients had a longer LOS (10 days, p < 0.001) and lower daily revenue (€400, p < 0.001). We also found that comorbidities and the frequency of operations had significant impact on the LOS. Using a baseline 30 to 50% preventable NIs, successful prevention of a single NI could potentially reduce the length of hospital stay by 3 to 5 days and increase hospital revenue by approximately €120 to €200 per day per prevented NI. Consequently, the hospital saves 3 to 5 more bed-days to backfill and generate more revenue, and/or make more efficient resource allocation by changing bed-capacity and staffing. The resulting opportunity costs can potentially exceed €1,000 per preventable case.

Conclusion

NIs pose a substantial economic burden for hospitals. From a health economics’ perspective, there are strong economic incentives for hospitals to implement infection control interventions, such as the involvement of a prevention link physician/nurse.
A systematic literature review on how consumer and community involvement have shaped and influenced pre-pregnancy care interventions for women with diabetes
Authors: Hicks Rachel , Dune Tinashe , Gu Veronica , Simmons David , MacMillan Freya
Published: November 2024

Background

Diabetes and pregnancy studies have found better outcomes when interventions were developed with consumer (individuals with lived experience of diabetes) and community involvement. When consumers are central to development and delivery of interventions, study participants have better engagement and outcomes, particularly for individuals from culturally and linguistically diverse (CALD) and/or lower socio-economic backgrounds. Our study aims to examine the scope of consumer and community involvement (CCI) in the construction and implementation of pre-pregnancy care (PPC) interventions and discuss a framework for consumer-lead intervention development.

Methods

A systematic literature review was conducted, examining 3 electronic databases. A meta synthesis analysis of tabulated data summarized in a literature matrix was undertaken with a phenomenological approach to develop a Pre-Pregnancy Care CCI-Driven Intervention Framework.

Results

Overall, 4642 papers were identified, with 29 meeting inclusion criteria. The meta-synthesis and literature matrix identified several common themes across previous studies. These were: barriers to accessing (PPC) such as negativity and stigma in care from behaviours, attitudes and perceptions of HCPs; limited appointment availability not aligning with work and family commitments; fear of losing a “normal” pregnancy journey; awareness of risk but unwillingness to discuss if consumers have not established trust with HCPs; inaccessibility to CALD appropriate PPC and contraception; and digitisation of PPC information resources including peer support and social media. From these results, a PPC Consumer-Driven Intervention Framework for Women with Pregestational Diabetes was developed with recommendations.

Conclusion

Consumers have been under-involved in the majority of previous developments and implementation of interventions for women with diabetes and pregnancy, and their representation as stakeholders in interventions is paramount to the longevity of intervention outcomes. To assist community involvement in diabetes pregnancy intervention design and delivery we created a new framework, for improving clinical and social outcomes in healthcare, empowering relationships between HCPs and consumers, and highlighting the value of lived experience and women-centred care for increased community engagement.
Nutritional status and factors associated with gestational weight gain in the city of São Paulo, 2012 to 2020: a retrospective cohort study
Authors: Corrêa Fernanda Ferreira , de Aquino Bonilha Eliana , da Silva Wesley Pereira , de Melo Tarcisio Cantos , dos Santos Quaresma Marcus V. L. , Diniz Carmen Simone G.
Published: November 2024

Background

Gestational weight gain (GWG) is a critical issue related to postpartum health in newborns and mothers. In Brazil, pregnant women’s public health recommends monitoring GWG. Therefore, the objective of this study is to evaluate gestational weight gain and associated health factors of pregnant women monitored at Unified Health System (SUS) in the city of São Paulo between 2012 and 2020.

Methods

This is a retrospective cohort study of pregnant women seen from 2012 to 2020 in São Paulo, Brazil. The database used was from the Integrated Health Care Management System related to the Live Birth Information System. Data distribution was assessed using the Kolmogorov-Smirnov test. Comparisons between groups according to weight gain (LWG vs. AWG vs. EWG) were performed using analysis of variance (ANOVA) with Tukey post hoc. Inclusion criteria considered that pregnant women had a recorded initial weight before 13 weeks and up to 15 days before delivery and a single pregnancy. The final database includes 276.220 pregnant women.

Results

The frequency of women according to initial body mass index (BMI) was 12.004 (4.4%) underweight, 132.049 (48.3%) normal weight, 78.856 (28.8%) overweight, and 50.660 (18.5%) living with obesity. The population consisted of 59.881 (21.9%), 37.217 (13.6%) and 176.471 (64.5%) women with LWG, AWG and EWG, respectively. Weight gain was associated with initial BMI, type of birth, color/ethnicity, marital status, women’s age and antenatal care visits.

Conclusion

The proportion of pregnant women with inadequate weight gain is high, relating initial BMI, type of birth, color/ethnicity, marital status, women’s age and antenatal care visits. Interventions such as nutritional education should be suggested to help achieve adequate GWG.
Stigma trajectories, disclosure, access to care, and peer-based supports among African, Caribbean, and Black im/migrant women living with HIV in Canada: findings from a cohort of women living with HIV in Metro Vancouver, Canada
Authors: Samnani Faaria , Deering Kathleen , King Desire , Magagula Patience , Braschel Melissa , Shannon Kate , Krüsi Andrea
Published: November 2024

Background

African, Caribbean, and Black im/migrant women experience a disproportionate burden of HIV relative to people born in Canada, yet there is scarce empirical evidence about the social and structural barriers that influence access to HIV care. The objectives of this study is to estimate associations between African, Caribbean, and Black background and stigma and non-consensual HIV disclosure outcomes, and to understand how experiences of stigma and im/migration trajectories shape access to HIV care and peer supports among African, Caribbean, and Black im/migrant women living with HIV in Canada.

Methods

This mixed-methods analysis draws on interviewer-administered questionnaires and semi-structured interviews with self-identifying African, Caribbean, and Black women living with HIV in the community-based SHAWNA (Sexual Health and HIV/AIDS: Women’s Longitudinal Needs Assessment) cohort. Bivariate and multivariable logistic regression using generalized estimating equations (GEE) were performed to estimate associations between African, Caribbean, and Black background and stigma and non-consensual HIV disclosure outcomes. Drawing on a social and structural determinants of health framework, qualitative analysis of interviews elucidated the interplay between migration trajectories, stigma, racialization, and HIV.

Results

Amongst our participants (n = 291), multivariable GEE analysis revealed that African, Caribbean, and Black participants (n = 15) had significantly higher odds of recently being outed without consent as living with HIV (AOR 2.34, 95% CI 0.98–5.57). Additionally, African, Caribbean, and Black participants had higher odds of recent verbal or physical abuse due to their HIV status (AOR 2.11, 95% CI 0.65–6.91). Reflecting on their im/migration trajectories, participants’ narratives (n = 9) highlighted experiences of political violence and conflict, trauma, stigma, and discrimination associated with HIV in their place of origin and the racialization and stigmatization of HIV in Canada. Fear of disclosure without consent was linked to barriers of accessing care and peer-based supports.

Conclusion

Our findings indicate that im/migration trajectories of African, Caribbean, and Black women living with HIV are critically related to accessing HIV care and supports in Canada and compound HIV stigma and discrimination. HIV disclosure without consent complicates access to care and social/peer support, underscoring the need for privacy, confidentiality, and the importance of building trust in the context of clinical encounters. The results of this study emphasize the critical need for culturally sensitive trauma-informed care models rooted in peer-based approaches.
Volatiles extracted from Melaleuca Rugulosa (Link) Craven leaves: comparative profiling, bioactivity screening, and metabolomic analysis
Authors: Mady Mohamed S. , Elsayed Heba E. , Tawfik Nashwa F , Moharram Fatma A.
Published: November 2024

Background

Melaleuca species (family Myrtaceae) are characterized by their wide-ranging applications as antimicrobials and in skin-related conditions. Herein, we estimated the volatile profile and biological significance of M. rugulosa (Link) leaves for the first time supported by a dereplication protocol.

Materials and methods

Volatile components were extracted using hydrodistillation (HD), supercritical fluid (SF), and headspace (HS) techniques and identified using GC/MS. The variations among the three extracts were assessed using principal component analysis and orthogonal partial least square discriminant analysis (OPLS-DA). The extracted volatiles were tested for radical scavenging activity, anti-aging, and anti-hyperpigmentation potential. Finally, disc diffusion and broth microdilution assays were implemented to explore the antibacterial capacity against Streptococcus pyogenes, Staphylococcus aureus, Clostridium perfringens, and Pseudomonas aeruginosa.

Results

The yield of the SF technique (0.8%) was three times higher than HD. GC/MS analysis revealed that the oxygenated compounds are the most proponents in the three extracts being 95.93% (HD), 80.94% (HS), and 48.4% (SF). Moreover, eucalyptol (1,8-cineol) represents the major component in the HD-EO (89.60%) and HS (73.13%) volatiles, while dl-α-tocopherol (16.27%) and α-terpineol (11.89%) represent the highest percentage in SF extract. Regarding the bioactivity profile, the HD-EO and SF-extract showed antioxidant potential in terms of oxygen radical absorbance capacity, and β- carotene assays, while exerting weak activity towards DPPH. In addition, they displayed potent anti-elastase and moderate anti-collagenase activities. The HD-EO exhibited potent anti-tyrosinase activity, while the SF extract showed a moderate level compared to tested controls. OPLS-DA and dereplication studies predicted that the selective antibacterial activity of HD-EO to S. aureus was related to eucalyptol, while SF extract to C. perfringens was related to α-tocopherol.

Conclusions

M. rugulosa leaves are considered a vital source of bioactive volatile components that are promoted for controlling skin aging and infection. However, further safety and clinical studies are recommended.
Higher interest to continue COVID-19 practice recommendations in non-pandemic times among German GPs with better crisis leadership skills (egePan study)
Authors: Aretz Benjamin , Krumpholtz Yelda , Kugai Simon , Amarell Nicola , Schmidt Manuela , Weltermann Birgitta
Published: November 2024

Background

The German College of General Practitioners and Family Physicians (DEGAM) issued a COVID-19 guideline with eleven recommendations to support primary care services during the pandemic. Their use in general practices beyond the pandemic can contribute to pandemic preparedness. This study analysed general practitioners’ (GPs) interest in applying recommended organisational changes in non-pandemic times.

Methods

Data from the German egePan GP survey (n = 516 GPs) - a multi-level clustered randomised web-based survey - were analysed. GPs’ interest in the future application of the eleven guideline recommendations was calculated. In addition, each recommendation was evaluated by the GPs using a Net-Promoter-Score (NPS range − 100 to 100). A linear regression model identified GP and practice characteristics associated with a higher interest in applying recommendations in non-pandemic times.

Results

98.5% of the GPs indicated the intention to implement at least one guideline recommendation prospectively: disinfectant dispensers at the entrance (86%), optimised consultation scheduling to reduce waiting times (83%), and glass screens in the reception area (72%), which also received the highest NPS scores. In contrast, lower interest was observed for items such as insurance card readers handled by patients (48%), only selected staff treating infectious patients (44%), and video consultations for patients with infections (26%). A higher interest to implement recommendations in non-pandemic times was associated with a higher crisis leadership score (p < 0.001), using the Corona-Warn-App (p = 0.007), and being a female GP (p = 0.045). In addition, GPs from Western, Northern, and Southern, and those with a higher patient volume per three months, were more interested in future implementation.

Conclusions

Overall, GPs demonstrated the readiness to follow the DEGAM COVID-19 guideline outside pandemic periods, establishing them as key contributors to pandemic preparedness in Germany.
The Implementation Process Assessment Tool: translation, contextualization, and psychometric evaluation of a Swedish version in a municipal elderly care context
Authors: Kaltenbrunner Monica , Hagerman Heidi , Fagerström Cecilia , Hartveit Miriam , Nordheim Espen , Ekstedt Mirjam
Published: November 2024

Background

The number of older adults with complex healthcare needs is growing alongside limited resources available in health services. To meet this challenge, it is urgent that healthcare staff are motivated and able to continuously translate new knowledge and working methods into daily practice. To facilitate such implementation, supportive measures responding to the healthcare personnel’s needs seem essential. The present study aims to translate, contextualize and test a Swedish version of the Implementation Process Assessment Tool (IPAT) for measuring the facilitation needs among staff implementing a new working process in municipal elderly care.

Methods

A mixed-method design was used. First, the existing instrument was translated into Swedish. Thereafter, twelve staff members with different professions working in healthcare and at the municipal elderly care were interviewed using Think-aloud interviews to contextualize and test the face validity of the translated instrument. Lastly, the adjusted instrument (Swe-IPAT) was psychometrically evaluated through a cross-sectional survey among 305 staff members working in municipal elderly care.

Results

The psychometric evaluation of the Swe-IPAT revealed satisfying properties. Three factors, largely in line with the original IPAT, are suggested. Internal consistency assessed using Cronbach’s alpha was 0.93 for the factor individual phases for behavioral change and perception of the intervention, 0.84 for the factor individual activities, and 0.95 for the factor collective readiness and support.

Conclusions

The 27-item Swe-IPAT, translated into Swedish and contextualized, demonstrated satisfactory psychometric properties when tested in an elderly care context. The instrument is suggested to be useful in providing feedback to managers in tailoring support and assessing implementation efforts among healthcare staff in elderly care. However, more research is needed to evaluate its properties throughout the entire implementation process and to test the usability of Swe-IPAT in other settings.
Declining genetic polymorphism of the C-terminus Merozoite Surface Protein-1 amidst increased Plasmodium knowlesi transmission in Thailand
Authors: Tapaopong Parsakorn , Chainarin Sittinont , Mala Abdulrohman , Rannarong Arnuwat , Kangkasikorn Nikom , Kusolsuk Teera , Roobsoong Wanlapa , Cui Liwang , Nguitragool Wang , Sattabongkot Jetsumon , Bantuchai Sirasate
Published: November 2024

Background

Recent reports from Thailand reveal a substantial surge in Plasmodium knowlesi cases over the past decades, with a more than eightfold increase in incidence by 2023 compared to 2018. This study investigates temporal changes in genetic polymorphism associated with the escalating transmission of P. knowlesi malaria in Thailand over time using the prominent vaccine candidate, pkmsp1 as a marker.

Methods

Twenty-five P. knowlesi samples collected in 2018–2023 were sequenced for the 42-kDa region of pkmsp1 and compared with 24 retrieved sequences in 2000–2009, focusing on nucleotide diversity, natural selection, recombination rate, and population differentiation.

Results

Seven unique haplotypes were identified in recent samples, compared to 15 in earlier samples. Nucleotide and haplotype diversity were lower in recent samples (π = 0.016, Hd = 0.817) than in earlier samples (π = 0.018, Hd = 0.942). Significantly higher synonymous substitution rates were observed in both sample sets (dS–dN = 2.77 and 2.43, p < 0.05), indicating purifying selection and reduced genetic diversity over time. Additionally, 8 out of 17 mutation points were located on predicted B-cell epitopes, suggesting an adaptive response by the parasites to evade immune recognition. Population differentiation analysis using the fixation index (Fst) revealed high genetic differentiation between parasite populations in central and southern Thailand or Malaysia. Conversely, the relatively lower Fst value between southern Thailand and Malaysia suggests a closer genetic relationship, possibly reflecting historical gene flow.

Conclusion

This study highlights a decline in genetic diversity and evidence of purifying selection associated with the recently increased incidence of P. knowlesi malaria in Thailand. The minor genetic differentiation between P. knowlesi populations from southern Thailand and Malaysia suggests a shared recent ancestry of these parasites and underscores the need for coordinated efforts between the two countries for the elimination of P. knowlesi.
Adipokines and their potential impacts on susceptibility to myocardial ischemia/reperfusion injury in diabetes
Authors: Han Ronghui , Huang Hemeng , Zhu Jianyu , Jin Xiaogao , Wang Yongyan , Xu Youhua , Xia Zhengyuan
Published: November 2024

Coronary artery disease has a high mortality rate and is a striking public health concern, affecting a substantial portion of the global population. On the early onset of myocardial ischemia, thrombolytic therapy and coronary revascularization could promptly restore the bloodstream and nutrient supply to the ischemic tissue, efficiently preserving less severely injured myocardium. However, the abrupt re-establishment of blood flow triggers the significant discharge of previously accumulated oxidative substances and inflammatory cytokines, leading to further harm referred to as ischemia/reperfusion (I/R) injury. Diabetes significantly raises the vulnerability of the heart to I/R injury due to disrupted glucose and lipid processing, impaired insulin sensitivity and metabolic signaling, and increased inflammatory responses. Numerous studies have indicated that adipokines are crucial in the etiology and pathogenesis of obesity, diabetes, hyperlipidemia, hypertension, and coronary artery disease. Adipokines such as adiponectin, adipsin, visfatin, chemerin, omentin, and apelin, which possess protective properties against inflammatory activity and insulin resistance, have been shown to confer myocardial protection in conditions such as atherosclerosis, myocardial hypertrophy, myocardial I/R injury, and diabetic complications. On the other hand, adipokines such as leptin and resistin, known for their pro-inflammatory characteristics, have been linked to elevated cardiac lipid deposition, insulin resistance, and fibrosis. Meteorin-like (metrnl) exhibits opposite effects in various pathological conditions. However, the data on adipokines in myocardial I/R, especially in diabetes, is still incomplete and controversial. This review focuses on recent research regarding the categorization and function of adipokines in the heart muscle, and the identification of different signaling pathways involved in myocardial I/R injury under diabetic conditions, aiming to facilitate the exploration of therapeutic strategies against myocardial I/R injury in diabetes.
Periplaneta americana L. extract exerts neuroprotective effects by inhibiting endoplasmic reticulum stress via AKT-dependent pathway in experimental models of Parkinson’s disease
Authors: Cao Ting , Wang Xue-lian , Rao Jiang-yan , Zhu Hui-feng , Qi Hong-yi , Tian Zhen
Published: November 2024

Background

Parkinson’s disease (PD) is a chronic neurodegenerative disorder that currently has no curable strategies. More and more evidence suggests that endoplasmic reticulum (ER) stress plays an essential role in PD pathogenesis. Periplaneta americana L. (P. americana) is a traditional Chinese medicine with diverse therapeutic properties. This study aims to investigate the neuroprotective effect and underlying mechanism of P. americana in in vitro and in vivo PD models.

Methods

The exposure of SH-SY5Y cells to 1-methyl-4-phenyl-pyridinium (MPP+) was used as the in vitro PD model. MTT assay, Hoechst staining, Calcein AM-PI staining and flow cytometry were performed to measure the cell viability and apoptosis. DCFH-DA and JC-1 assay were used to measure the intracellular ROS and mitochondrial membrane potential (Δψm), respectively. Western-blot and immunostaining were conducted to detect the expression of key molecules related with ER stress. For the in vivo PD model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP), the motor function of mice was assessed by behavioral tests, the level of TH was examined by western-blot and immunostaining, the expression of key molecules related with ER stress was measured by western-blot.

Results

Periplaneta americana ethanol extract (PAE) concentration-dependently inhibited MPP+-induced cell loss and increased cell viability. PAE also remarkably attenuated ROS accumulation, the decline of Δψm as well as the excessive ER stress. The neuroprotective effects of PAE could be blocked by ROS inducer trimethylamine N-Oxide or ER stress activator tunicaymycin, while the antioxidant N-Acetyl-L-cysteine or ER stress inhibitor sodium 4-phenylbutyrate mimicked the effects of PAE. Furthermore, we found that PAE could activate AKT/GSK3β/β-catenin pathway. The effect of PAE on ROS production, Δψm and ER stress was blocked by AKT inhibitor MK-2206. In in vivo model, PAE significantly improved motor function, prevented dopaminergic neuronal loss and attenuated ER stress in substantia nigra and striatum of MPTP-treated mice. Similarly, the effects of PAE on MPTP-treated mice were also abolished by MK-2206.

Conclusions

Our results suggest that P. americana exerts neuroprotective effects through inhibiting ER stress via AKT-dependent pathway. Periplaneta americana may represent a promising therapeutic agent for PD treatment and is worthy of further being exploited.
Characteristics and therapeutic outcomes of subcutaneous panniculitis-like T-cell lymphoma with and without germline HAVCR2 mutations in Thai children and adolescents
Authors: Youthong Pimpitcha , Pakakasama Samart , Komvilaisak Patcharee , Rujkijyanont Piya , Choed-Amphai Chane , Phuakpet Kamon , Moonla Chatphatai , Polprasert Chantana , Sosothikul Darintr
Published: November 2024

Background

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma associated with hemophagocytic lymphohistiocytosis (HLH)/HLH-like systemic illnesses and germline HAVCR2 mutations. Although previous studies suggested successful treatment of SPTCL with immunosuppressive therapy (IST) without chemotherapy, IST data in pediatric SPTCL remain scarce. To explore characteristics and therapeutic outcomes, comparing IST-based and chemotherapy-based regimens in pediatric SPTCL, in this retrospective cohort study, patients with SPTCL diagnosed at age ≤20 years during 2007-2023 were enrolled from 6 hematology/oncology centers in Thailand. HAVCR2 exon 2 sequencing was performed using DNA extracted from peripheral blood or bone marrow. Presence of HLH/HLH-like systemic illnesses, treatment outcomes, and adverse events (AEs) were reviewed and analyzed.

Results

Of 22 patients with SPTCL (median age at diagnosis, 11.5 years [range, 6.0-19.0]; 63.6% males), 86.4% harbored germline HAVCR2 mutation, either homozygous (77.3%) or heterozygous (9.1%) p.Y82C variant, while 68.2% developed HLH/HLH-like systemic illnesses. Overall, 36.4% received IST as first-line treatment. Durable complete remission (CR) was achieved in 71.4% and 50.0% after first-line chemotherapy and IST, respectively (P=0.45); however, chemotherapy tended to increase any AEs compared to IST (57.1% vs. 12.5%; P=0.07). The most common AEs were hypertension (27.3%), febrile neutropenia (18.2%), and fungal infection (13.6%). Among the relapsed cases, 71.4% could reach CR after subsequent-line therapy. Fatality (4.5%) only occurred in the chemotherapy group.

Conclusions

Pediatric SPTCL in Thailand frequently involves germline HAVCR2 mutations and/or HLH/HLH-like systemic illnesses. With comparable response and modest therapy-related toxicity, IST-based regimens may alternatively be considered as first-line treatment for pediatric SPTCL.
Phase angle and body composition in long-term type 1 diabetes in adults: a comparative study in a Brazilian public reference outpatient clinic
Authors: Fenner-Pena Natália , Fajardo Virgínia Capistrano , Froes Lívia , Carvalho Paulo Augusto Miranda , Comim Fábio Vasconcellos , Sahade Viviane , Lauria Márcio Weissheimer , Torres Henrique Oswaldo da Gama
Published: November 2024

Introduction

Type 1 Diabetes Mellitus (DM1) affects a small percentage of the population. Nevertheless, its prevalence is currently growing with alarming data on uncontrolled cases. The importance of body composition and Phase Angle (PA), assessed by Bioelectrical Impedance (BIA), in long- term DM1 patients lies in the fact that alterations in cellular integrity and body compartments may affect risk profiles and metabolic control. The objective of this study was to compare PA and body composition parameters between adults with DM1 and healthy controls.

Methods

A comparative study was carried out in a public university outpatient clinic including a cohort of adult patients of both sexes diagnosed with DM1 and healthy controls matched by age and sex in a 2:1 ratio. Anthropometric measurements included weight, height and BMI. Using the raw BIA data of Resistance and Reactance, fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), fat mass index (FMI), PA and standardized PA (SPA) were calculated. Means or medians were compared between the groups. Regression models were used to identify distinguishing characteristics of the groups and associations within the DM1 group (i.e. glycated hemoglobin (HbA1c), disease duration, presence of microvascular complications, capillary blood glucose, BMI and FMI).

Results

88 patients with DM1and 46 healthy controls were evaluated. PA (6.05 vs. 6.85, p = 0.000) and SPA (-1.47 vs. -0,37, p = 0.000) were lower in patients with DM1 compared to healthy controls. People with DM1 displayed higher adiposity (%FM = 29.6 vs. 27.6, p = 0.016; FMI = 7.00 vs. 6.33, p = 0.016) and lower %FFM compared to healthy controls. Most of the differences were maintained after sex stratification; however, men with DM1 showed a lower FFMI than male controls (18.2 vs. 20.16, p = 0.029).

Conclusion

Patients with DM1 present lower PA than healthy controls, which may be related to worse cell membrane integrity. Significant body composition differences between the groups and between sexes were identified, with data showing greater adiposity in women with DM1 and men displaying lower muscle mass. These findings suggest the importance of including PA and body composition evaluations in the follow-up of patients with DM1. The ultimate goal is to obtain a better metabolic control and, consequently, a better prognosis.