bluuebunny/crossref_metadata_2025 huggingface dataset:
Celastrol promotes DNA damage and apoptosis in uterine corpus endometrial carcinoma via promotion of KAT2B-mediated RBPJ acetylation and repression of MCM4 transcription
Authors: Pei Lipeng , Zhu Yan , Li Wenpeng , Xu Bin , Sun Jingli
Published: February 2025

Background

Uterine corpus endometrial carcinoma (UCEC) is one of the most frequent female genital malignant tumors. Targeting DNA damage and cell apoptosis are regarded as effective ways for UCEC therapy. Celastrol is a natural anti-cancer product from the Celastraceae plant family, while its role in UCEC has not been investigated.

Methods

UCEC cell lines Ishikawa and HEC-1-A were applied and treated with different concentrations of Celastrol. The appropriate and nontoxic concentrations were used for the subsequent experiments. Functional experiments analyzed the cell viability, cell cycle distribution, DNA damage, apoptosis and the expression of related proteins. We determined tumor growth in xenograft nude mice. Bioinformatic analysis, protein coimmunoprecipitation (Co-IP), luciferase assay, cell experiments were performed to reveal the relationship of Celastrol/KAT2B/RBPJ/MCM4 in UCEC.

Results

Treatment of Celastrol inhibited cell viability in a dose-dependent manner, and caused cell cycle arrest, accompanied by the downregulation of CDK2 and cyclin E expression and the upregulation of p21. Celastrol treatment resulted DNA damage and apoptosis in cultured cells, as demonstrated by increased number of TUNEL-positive cells, activity of caspase-3 and expression of cleaved-caspase-9, cleaved PARP1 and γ-H2AX. In xenograft nude mice, Celastrol also repressed tumor growth. Furthermore, lysine acetyltransferase KAT2B was a putative target of Celastrol, and its expression was upregulated by Celastrol in vitro and in vivo. Overexpression of KAT2B in UCEC inhibited cell proliferation and increased DNA damage and apoptosis. KAT2B knockdown overcame the anti-proliferative and pro-apoptotic roles of Celastrol. Moreover, Co-IP demonstrated that KAT2B bound to RBPJ, a transcriptional repressor, and increased the acetylation of RBPJ. RBPJ could bind to the MCM4 promoter to suppress the luciferase activity. Further functional analysis revealed that the functions of KAT2B in UCEC cell proliferation, DNA damage and apoptosis were mediated by MCM4, and Celastrol enhanced RBPJ acetylation and reduced MCM4 expression.

Conclusions

These results underscore that Celastrol is a promising anti-cancer agent in UCEC with preferential anti-proliferative, pro-apoptotic and DNA damage effects through the KAT2B/RBPJ/MCM4 axis, and KAT2B is a promising therapeutic target for UCEC.

Graphical abstract
Exploring proteomic immunoprofiles: common neurological and immunological pathways in multiple sclerosis and type 1 diabetes mellitus
Authors: Cano-Cano Fátima , Lara-Barea Almudena , Cruz-Gómez Álvaro Javier , Martín-Loro Francisco , Gómez-Jaramillo Laura , González-Montelongo María Carmen , Roca-Rodríguez María Mar , Beltrán-Camacho Lucía , Forero Lucía , González-Rosa Javier J. , Durán-Ruiz Mª Carmen , Arroba Ana I. , Aguilar-Diosdado Manuel
Published: February 2025

Background

Interest in the study of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) has increased because of their significant negative impact on the patient quality of life and the profound implications for the health care system. Although the clinical symptoms of T1DM differ from those of MS, such as pancreatic β-cell failure in T1DM and demyelination in the central nervous system (CNS) in MS, both pathologies are considered as autoimmune-related diseases with shared pathogenic pathways, which include autophagy, inflammation and degeneration, among others. Considering the challenges in obtaining pancreatic β-cells and CNS tissue from patients with T1DM and MS, respectively, it is fundamental to explore alternative methods for evaluating disease status. Proteomic analysis of peripheral blood mononuclear cells (PBMCs) is an ideal approach for identifying novel and potential biomarkers for both autoimmune diseases.

Methods

We conducted a proteomic analysis of PBMCs from patients with T1DM and relapsing remitting Multiple Sclerosis (herein forth MS) patients (n = 9 per condition), using a label-free quantitative proteomics approach. The patients were diagnosed following the American Diabetes Association (ADA) criteria for T1DM and McDonald criteria for MS respectively, and were aged over 18 years and more than 2 years from the onset respectively.

Results

A total of 2476 proteins were differentially expressed in PBMCs from patients with T1DM and MS patients compared with those form healthy controls (H). Predictive analysis highlighted 15 common proteins, up- or downregulated in PBMCs from patients with T1DM and MS patients vs. healthy controls, involved in the immune system activity (BTF3, TTR, CD59, CSTB), diseases of the neuronal system (TTR), signal transduction (STMN1, LAMTOR5), metabolism of nucleotides (RPS21), proteins (TTR, ENAM, CD59, RPS21, SRP9) and RNA (SRSF10, RPS21). In addition, this study revealed both shared and distinct molecular patterns between the two conditions.

Conclusions

Compared with H, patients with T1DM and MS presented a specific expression pattern of common proteins has been identified. This pattern underscores the shared mechanisms involved in their immune responses and neurological complications, alongside dysregulation of the autophagy pathway. Notably, CSTB has emerged as a differential biomarker, distinguishing between these two autoimmune diseases.
Exploring the association between statins use or HMG-CoA reductase inhibition and migraine: a systematic review and meta-analysis
Authors: Makhlouf Hamdy A. , Hassan Amr K. , Almosilhy Nereen A. , Osman Ahmed S.A. , Ramadan Shrouk , Abouelmagd Moaz Elsayed
Published: February 2025

Background

Statins or 3‑hydroxy‑3‑methyl‑glutarylcoenzyme A (HMG‑CoA) reductase inhibitors are medications that act by reducing the cholesterol content of liver cells Moreover, statins have been found to improve endothelial function and reduce vascular wall inflammation. A growing body of research suggests that statins are associated with less risk of migraine, and they can be used to treat symptoms. However, the evidence has been inconclusive, so we aim to investigate the nature and strength of the effect of statins on the prevention and prophylaxis of migraines.

Methods

We conducted a comprehensive systematic search across multiple electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, from inception until October 2024, to include studies on the association between statins use and migraine. The outcomes of interest involved the association of the HMG-CoA reductase gene with the risk of migraine, as well as the association and efficacy of statins in migraine patients.

Results

Thirteen studies were included in our systematic review. Mendelian Randomization (MR) studies revealed that expression of HMGCR was associated with an increased risk of migraine with odds ratio (OR) ranging from 1.38 to 1.55 (P < 0.001). Three observational studies investigating the relationship between statins and migraine risk demonstrated a protective effect, with odds ratios ranging from 0.73 to 0.94 (P < 0.001). The findings suggest a significant reduction in overall migraine risk, particularly for migraines with aura and in patients with higher vitamin D levels. Meta-analysis of randomized controlled trials (RCTs) showed that statins significantly reduced monthly migraine frequency (MD= -3.16, 95%CI= [-5.79, -0.53]; p = 0.02, I2 = 79%; P = 0.03). RCTs supported the efficacy of statins in reducing migraine frequency, days, and intensity compared to placebo.

Conclusions

Statins, already well-established for cardiovascular benefits, emerge as a promising dual-purpose therapy for many neurological disorders. The association between the HMGCR gene and increased migraine risk, coupled with the possible efficacy of statins in reducing migraine frequency, may open new avenues for migraine prophylaxis. However, the variability in study design hinders definitive conclusions, so larger studies with longer follow-ups are required to ascertain both findings.
Safety and accuracy of digitally supported primary and secondary urgent care telephone triage in England: an observational study using routine data
Authors: Sexton Vanashree , Grimley Catherine , Dale Jeremy , Atherton Helen , Abel Gary
Published: February 2025

Background

England’s urgent care telephone triage system comprises non-clinician-led primary triage (NHS111) assessment followed, for approximately 50% patients, by clinician-led secondary triage. Digital decision support is utilised by both. We explore the system’s safety and accuracy relative to patients’ use of emergency departments (EDs) and in-patient care in the subsequent 24 h.

Methods

Descriptive analyses were used to investigate outcomes of 98,946 calls that underwent primary and secondary triage. We investigated sensitivity (safety) and specificity (efficiency/accuracy) in relation to subsequent ED attendance and in-patient hospital admission. Mixed effects regression models were used to explore potential under-estimation of clinical risk (under-triage).

Results

Sensitivity was greater in primary triage, whilst specificity was greater in secondary triage. The positive predictive value for attending ED after being assigned a triage urgency level of within 2 h was 46.0% for secondary triage compared to 20.7% for primary triage; for inpatient admission it was 18.0% and 9.2% respectively. 1.5% (n = 1468) patients triaged to same-day or less urgent care at secondary triage were subsequently admitted for in-patient care. In relation to in-patient admission within 24 h, there were greater odds of potential under-triage for calls made between midnight and 6am, and for shorter duration calls, respectively OR = 1.71; CI:1.32–2.21 and OR: 1.66, CI: 1.30–2.11. The service provider (e.g., service provider 2, OR = 5.61; CI:3.36–9.36) and individual clinician (OR covering the 95% midrange = 16.15) conducting triage were the characteristics most greatly associated with this potential under-triage; p < 0.001 for all.

Conclusions

Clinician-led urgent care triage is more accurate in identifying the likelihood of a need for ED or in-patient care than non-clinician triage. Non-clinician primary triage is risk averse, reflected in its high sensitivity but low specificity. Service and clinician characteristics associated with potential under-triage need further investigation to inform ways of improving the safety and effectiveness of urgent care telephone triage.

Clinical trial number

Not applicable.
“It was simply disturbing“ - evaluation of the stress factors of nursing staff on special COVID-19 wards during the pandemic: a qualitative study
Authors: Kiefer Lea , Volberg Christian , Graw Jan Adriaan , Bösner Stefan
Published: February 2025

Background

The COVID-19 pandemic has posed enormous challenges for healthcare systems worldwide. The strain on nursing staff working in special COVID-19 wards during the pandemic increased dramatically. To support nursing staff more effectively in similar situations in the future, it is important to identify specific stress factors to design effective support measures.

Objective

To collect the experiences and lessons learned from nursing staff who have been affected by COVID-19 pandemic on a special COVID-19 ward that were perceived as stressful. The findings should contribute to the development of specific support measures for healthcare professionals.

Design

Qualitative interview study.

Setting

We interviewed 14 members of nursing staff who worked on COVID-19 wards at two University Hospitals about their working experiences during the pandemic.

Results

We were able to identify 10 key stress factors. These included an increased workload, communication deficits, a difficult personnel situation, subjective pressure, the establishment of a new ward, a shortage of material resources, inadequate hygiene conditions, a lack of opportunities to cope with the situation, the absence of relatives and decision making.

Conclusion

The identification of various stress factors highlights the urgent need for comprehensive support measures. These measures could include concepts for dealing with physical and psychosocial stress, the provision of resources and sufficient personnel support. It remains crucial to proactively take preventive and supportive measures to reduce the burden and moral distress of nursing staff and protect their health in the long term. Despite the pandemic, the implications of our findings remain relevant for the future.
Hospitalization outcomes in people living with HIV on Dolutegravir-based regimen in Mwanza, Tanzania: a comparative cohort
Authors: Kisigo Godfrey A. , Barongo Eric , Issarow Benson , Cichowitz Cody , Wajanga Bahati , Kalluvya Samuel , Peck Robert N.
Published: February 2025

Introduction

Hospitalized people living with HIV (PLWH) experienced extremely high mortality rates in the first year after an index hospitalization in the pre-Dolutegravir (DTG) era. We conducted a multi-center study in Mwanza, Tanzania to (1) describe causes of hospitalization for PLWH on DTG; (2) determine in-hospital and 3-month post-hospital mortality; (3) examine factors associated with overall mortality; and (4) determine changes in trends and predictors of mortality pre- and post-DTG era.

Methods

Between August 2020 and February 2021, hospitalized PLWH on dolutegravir-based antiretroviral therapy were enrolled and followed for three months after hospitalization. The primary outcome was mortality within 3-months of hospitalization. Cox regression analysis was used to calculate hazard ratios to identify predictors of mortality.

Results

Of the 154 enrolled patients, the median [interquartile range] age was 42 [33–50] years and 57% were female. Suspected immune reconstitution inflammatory syndrome (IRIS) and antiretroviral therapy (ART) non-adherence leading to an HIV-associated admission were common. The overall all-cause mortality was 42%. Male sex, using DTG-based regimen for < 3 months, diagnosis of suspected IRIS, diagnosis of ART side effect, advanced WHO clinical stage, CD4 count < 200 cells/mm3, hemoglobin level 7–11.9 gm/dl and hemoglobin level < 7 gm/dl were all independent risk factors for death.

Conclusion

In conclusion, the mortality rate of hospitalized PLWH in Africa remains high in the DTG era. Clinical trials are urgently needed to test novel interventions for improving survival in this high-risk group. In the meantime, hospital clinicians should be aware of the very high mortality among PLWH with IRIS and those with ART side effect to ensure that all possible diagnostic and therapeutic options are explored.
Point-of-care tests in the emergency medical services: a scoping review
Authors: Moore T. H. M. , Dawson S. , Kirby K. , Body R. , Thompson A. , Adepoju Y. O. , Perry R. , Nicholson H. , Dinnes J. , Mitchell K. , Savović J. , Voss S. , Benger J. R.
Published: February 2025

Background

This scoping review aimed to summarize existing research on point-of-care tests (POCTs) within emergency medical services (EMS). There is a lack of comprehensive reviews covering the breadth and scope of application of POCTs in EMS despite growing interest and potential benefits in this setting. A review of the research will inform how we target future research efforts to support effective implementation and avoid duplication.

Methods

We searched three databases to April 2023 using comprehensive terms for POCTs. One author screened titles and abstracts, full-text papers and extracted data with a second author checking the data. A scoping review framework was used to categorise studies according to demographics, study design, medical conditions, biomarkers and test devices.

Results

We found 141 papers that included 158 reports of 9 study designs, 155 reports of 40 combinations of biomarker and condition and 161 reports of 41 test-devices. The majority of research was done in the UK (19%), US (17%), and the Netherlands (16%), mostly in land-based EMS (82%). Most frequently assessed were troponin for acute coronary syndromes (26%), lactate for sepsis (14%) or lactate for trauma/critical illness (13%). The majority of research designs investigated the accuracy of the tests (43%). Few studies were of a design to inform guidelines to change patient pathways and the associated outcomes, including, randomised controlled trials (RCTs) (4%), non-randomised studies able to assess causality (6%), economic analyses (1%) or qualitative work on acceptability (3%). In those few cases where RCTs were done there were long delays between initial test-accuracy research and publication of the first RCT, for example 11 years delay for troponin for acute coronary syndromes.

Conclusions

We identified a thriving base of research on POCT in the EMS, however most studies established the diagnostic accuracy of the tests with few RCTs, economic analyses or qualitative research on acceptability. The time-lag from diagnostic accuracy to developing an RCT is considerable. Investment in funding and infrastructure is needed to support the research pathway for potential POCTs beyond diagnostic accuracy to designs able to assess clinical effectiveness, acceptability and economic effectiveness.
Long-term outcome of a treat-to-target strategy in late-onset rheumatoid arthritis with chronic lung disease: 5-year results of a prospective observational study
Authors: Nomura Manami , Sugihara Takahiko , Baba Hiroyuki , Hosoya Tadashi , Kamiya Mari , Ishizaki Tatsuro , Matsumoto Takumi , Kubo Kanae , Hirano Fumio , Kojima Masayo , Miyasaka Nobuyuki , Yasuda Shinsuke , Harigai Masayoshi
Published: February 2025

Background

Controlling disease activity and improving physical function would be more difficult in patients with late-onset rheumatoid arthritis (LORA) who have chronic lung disease (CLD) at baseline. Our aim was to evaluate 5-year outcomes of following a treat-to-target (T2T) strategy targeting low disease activity (LDA) in LORA with CLD.

Methods

Data from 197 methotrexate (MTX)-naïve LORA patients (mean age 74.4 years) from a prospective, monocentric registry were analyzed. Patients were treated with MTX if they had one or more poor prognostic features. If they had interstitial lung disease (ILD), tacrolimus could be administered instead of MTX at the discretion of the attending physician. If patients exhibited no response according to the European League Against Rheumatism criteria at week 12 or had not achieved LDA by week 24, biological disease-modifying antirheumatic drugs (bDMARDs) were started targeting LDA. The primary outcomes were the 5-year simplified disease activity index (SDAI) remission and Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 by non-responder imputation analysis. Secondary outcomes were serious adverse events (SAEs).

Results

Of the 197 LORA patients, 47 had CLD at baseline. The proportion of patients using MTX at baseline was significantly lower in those with than without CLD. Tacrolimus was initiated in 25.5% of the CLD group. The proportion of patients on bDMARDs was higher in those with CLD at year 5. Achievement of SDAI remission at year 5 was 29.8% in patients with CLD and 44.0% in those without CLD (p = 0.555). Achievement of HAQ-DI ≤ 0.5 at year 5 was 36.2% and 45.3% in patients with and without CLD, respectively (p = 0.939). Non-adherence to T2T due to comorbidities or adverse events was observed in 34.0% and 18.7% of the patients with and without CLD, respectively (p = 0.027). Infections requiring hospitalization, deterioration of extra-articular manifestations and fractures were more frequently reported as SAEs in patients with CLD, and multivariable analysis showed that patients with CLD had a higher risk of developing these SAEs (adjusted hazard ratio:2.53, 95% CI 1.60–4.00, p < 0.001).

Conclusion

For LORA patients with CLD, the T2T strategy is effective, but comorbidities and SAEs make the implementation of the T2T more difficult.
Technology license agreements as public–private partnerships for economic development: evaluations using surveys, input–output modeling, and regression analysis
Authors: Raile Eric D. , Austin Eric K. , Wallner Michael P. , Peterson Jeffrey , Lewandowski Brian , Kapps Derek , Sellegren Bridger , Hutton Joe
Published: February 2025

We evaluate license agreements as a form of technology transfer that constitutes a public–private partnership (PPP) with the primary goal of economic development. These license agreements permit entrepreneurs and other businesses to turn government innovations into earnings. We constructed a complete database of all license agreements between the U.S. Department of Defense and private industry from 2000 to 2021. We first surveyed the companies involved, achieving a 96% response rate. The subsequently anonymized responses allowed us to generate sales numbers and to model a variety of other national economic impacts. We tallied approximately $32 billion in direct sales across 590 license agreements. While the majority of license agreements with sales belong to smaller companies (which often attract additional investment), some large companies generate higher revenues. Further statistical modeling with the heavily anonymized data identifies features of license agreement situations that influence economic outcomes. Technology license agreements are a form of PPP that performs well against its goal of economic development without the downsides of some PPPs. Importantly, entrepreneurs can use this form of PPP to attract investment and to generate jobs and other societal benefits.
Phantom-based investigation of block sequential regularised expectation maximisation (BSREM) reconstruction for zirconium-89 PET-CT for varied count levels
Authors: Bonney Lara M. , Walker Matthew D. , McGowan Daniel R.
Published: February 2025

Background

Zirconium-89 (Zr-89) PET tracers have become increasingly significant in the field of nuclear medicine due to their 3-day physical half-life, allowing for the study of dynamic biological processes over relatively long timeframes. To date there has been limited publication of studies focused on optimisation of acquisition parameters for Zr-89 PET. This paper outlines a short phantom study investigating the optimal beta regularization parameter for quantitation and noise in block sequential regularised expectation maximisation (BSREM) also known as Bayesian penalized likelihood (BPL) reconstruction, for varying image noise characteristics (acquisition duration).

Results

The choice of the beta regularisation parameter substantially impacts image quality and quantitation. For larger volumes, BSREM reconstruction enhanced image quality (lower noise) and maintained quantitation, whereas for smaller volumes quantitation worsened as compared to OSEM for high regularisation parameters.

Conclusion

Where BSREM reconstruction is used for Zr-89 images, careful attention must be paid to the choice of weighting factor, especially for quantitative clinical studies. The effect of varying beta on several measures of image quality was characterised for the case of a phantom, with the results indicating that the value of beta for optimal Zr-89 quantitation is lower than what is generally used for optimal visualisation. This work demonstrates the need for careful attention to the reconstruction methods used for quantitative imaging studies, such as those required for theragnostic imaging.
Incorporation of kiwifruit peel improved the property of carboxymethyl cellulose-gum Arabic active film and its effects on the quality of beef sausages
Authors: Boateng Evans Frimpong , Yang Ziyi , Zhang Jian , Zhou Lei , Xing Lujuan , Zhang Wangang
Published: February 2025

In the present study, different doses of lyophilized kiwifruit peel powder extract (KPE) were incorporated into carboxymethyl cellulose (CMC) and gum Arabic (GA) based polymer matrices to fabricate films CG-CT (control film), CG-KPE1 (1% KPE), CG-KPE2 (2% KPE), and CG-KPE3 (3% KPE) to investigate their effects on active packaging functionality and sliced-beef sausage quality. Consequently, CG-KPE films demonstrated a superior antimicrobial effect on Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria and antioxidant efficacy compared to CG-CT films. The scanning electronic microscopy (SEM) of CG-KPE films revealed an enhanced micrograph. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) evidenced the intramolecular interaction between KPE and CG and the improved thermal stability of film matrix. Film X-ray diffraction (XRD) peaks revealed a good crystallinity. CG-KPE films exhibited better physical and mechanical properties, increased opacity, and better ultraviolet (UV) emission barrier due to KPE addition and pigmentation compared to CG-CT films. The quick biodegradability of CG-KPE film suggested potential for KPE as a biopolymer. Subsequently, sliced-beef sausages were packaged with CG-CT, CG-KPE1, CG-KPE2, and CG-KPE3 (respective to CT, TI, T2, and T3) and stored for 12 d (4 ± 1 °C). The product’s pH and moisture content were controlled due to KPE addition in CG-KPE films. The products revealed that during storage CG-KPE treatments had a positive impact on the textural property, the color stability, and the sensory quality compared to CG-CT treatments. CG-KPE treatments showed antimicrobial effectiveness and lesser TBARS values than CG-CT treatments during storage.

Graphical Abstract
Effect of atrial high-rate episodes (AHREs) on functional status and quality of life (QoL) in heart failure—cardiac resynchronization therapy population
Authors: Allam Lamyaa Elsayed , Moneim Youssef Abdel , Eldamanhoury Hayam Mohammad , Eltoukhy Sherif Mohammad Aziz
Published: February 2025

Background

New type of arrhythmia called atrial high-rate episodes (AHREs) has been discovered thanks to the ability of cardiac electronic implantable devices to track, record, and analyze complex arrhythmias. The aim is to determine factors associated with AHRE in HFrEF/CRT patients and the effect of AHRE on functional capacity and quality of life (QoL).

Results

We interrogated 100 patients' devices to gauge the incidence and burden of AHRE, then assessed their functional capacity using the standard 6-min walk test (6MWT), and evaluated their QoL using the Minnesota Living with HF questionnaire (MLHFQ) score. 34% of patients had AHRE, and 91.2% of them had AF. By multivariate logistic regression analysis, smoking (OR 9.426, 95% CI [1.33, 66.65], P 0.025), higher BMI (OR 1.336, 95% CI [1.09, 1.635], P 0.005), and increased LAVI (OR 1.16, 95% CI [1.063, 1.262], P < 0.001) are independent predictors for AHRE. There was a significant correlation between AHRE and the distance walked during 6MWT when compared to the distance expected for an equivalent healthy individual (82.02 ± 17.22% in the non-AHRE group vs. 75.15 ± 15.78% in the AHRE group, P < 0.001). It was found that AHRE was statistically linked to a higher total MLHFQ score (46.76 ± 9.82 in the AHRE group vs. 36.97 ± 7.76 in the non-AHRE group, P 0.032), with higher physical scores in the AHRE group.

Conclusion

AHRE significantly reduces functional status and perceived quality of life in HFrEF patients receiving CRT. Longer than five minutes of AHRE was associated with a higher MLHFQ score and worse performance on the 6MWT. In that patient population, smoking, obesity, and elevated LAVI were independent predictors of AHRE.
Comparative efficacy of clopidogrel-aspirin combination therapy versus aspirin monotherapy in preventing recurrent events in transient ischemic attack and minor stroke: a systematic review and meta-analysis
Authors: Bhutto Ahmad Mujtaba , Raza Rana Ali , Abbasi Mohammad Bilal , Jauhar Iman , Arbani Naeemullah , Mubashir Muhammad , Raheem Abdul , Ameen Taha Basit , Ali Syed Muhammad Sinaan
Published: February 2025

Background and objective

Stroke is a leading cause of disability and death globally. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a common intervention for acute ischemic stroke (AIS) and transient ischemic attack (TIA). This meta-analysis aims to evaluate the efficacy and safety of DAPT compared to aspirin monotherapy in preventing recurrent stroke.

Methods

We performed a systematic search of electronic databases including PubMed, MEDLINE, Embase, and Scopus up to April 1, 2024. Eligible studies involved adult patients with acute stroke or TIA receiving either DAPT with clopidogrel and aspirin or aspirin monotherapy, with follow-up durations between 30 and 90 days. Data were extracted on recurrent stroke, hemorrhagic stroke, myocardial infarction, all-cause mortality, and functional outcomes measured by the modified Rankin Scale (mRS). Statistical analyses were conducted using relative risk (RR) and odds ratio (OR) with 95% confidence intervals, and heterogeneity was evaluated using I
2 statistics.

Results

From 2344 articles screened, 33 studies involving 15,376 participants were included. DAPT significantly reduced the risk of recurrent stroke (RR 0.85, 95% CI 0.75–0.97, I
2 = 42%, p = 0.02). However, DAPT was associated with an increased, but not statistically significant, risk of hemorrhagic stroke (RR 1.27, 95% CI 0.55–2.90, I
2 = 51%, p = 0.23). There were no significant differences in the risk of myocardial infarction or all-cause mortality between the two groups. Functional outcomes indicated that DAPT reduced the risk of disability (OR 0.80, 95% CI 0.70–0.92, I
2 = 35%, p = 0.004).

Conclusion

DAPT with clopidogrel and aspirin is more effective than aspirin monotherapy in reducing recurrent strokes but may increase the risk of hemorrhagic stroke. Individualized patient assessment is crucial to balance the benefits and risks of DAPT. Further high-quality, long-term studies are needed to confirm these findings and inform clinical practice.
Shift in the profile and prognostic implications in invasive fungal rhinosinusitis: experience of 10 years in a tertiary center
Authors: Mellidez-Acosta Raúl , Torres-García Lidia , Saro-Buendía Miguel , Jaramillo-Ángel Natalia , Cabrera-Guijo Javier , Bancalari-Díaz Catalina , Muñoz-Fernández Noelia , Fito-Martorell Lucas , Armengot-Carceller Miguel , García-Piñero Alfonso
Published: February 2025

Background

Despite appropriate treatment, mortality of acute invasive fungal rhinosinusitis remains exceedingly high, surpassing 50%. Evidence on how to optimize its management is still limited. We present a case series from our institution aiming to fill the knowledge gap.

Methods

A retrospective descriptive study was conducted, selecting cases treated at our institution between January 2012 and January 2022. The following variables were analyzed: gender, age, underlying conditions, symptoms, histological study outcomes, microbiological study outcomes, administered antifungal treatment, surgical interventions, and survival following diagnosis.

Results

Seventeen patients were included in our study. The mean age was 55 years, with 12 males and 5 females. The most frequents underlying conditions were hematological malignancies (76.5%) and solid organ transplantation (11.8%). Surgical interventions were performed on 15 patients (88%), with 6 patients (35.3%) requiring a second intervention and 2 patients (11.8%) undergoing at least 3 interventions.3% patients succumbed to causes directly related to rhinosinusitis, with an average survival of 22 days, and 52.9% patients subsequently passed away due to complications related to their underlying condition, with an average survival of 171 days. Mid-term overall mortality was 88.2%, with an average survival of 111 days.

Conclusion

A shift in the patient profile was observed. Less fulminant courses have been evidenced, being oncohematotological disease and solid organ transplantation the main predisposing conditions, instead of poorly controlled diabetes. Even if direct mortality rates from AIFR are reduced (around 35%), the overall mortality rate of these patients is close to 90% with a median survival of less than 6 months. Then, an intense focus on the underlying disease and related complications is essential.
Effect of endoscopic sinus surgery on eustachian tube function in adult patients with chronic rhinosinusitis
Authors: Youssef Mahmoud Atef Abdelghaffar , Nassim Nassim Talaat , Alkeeb MohamedNourEddin Bashir , Algarf Tareq Muhammad
Published: February 2025

Background

Chronic rhinosinusitis (CRS) is a frequent chronic heterogeneous inflammatory disease of the upper airways and paranasal sinuses persistent for ≥ 12 weeks causing considerable healthcare expenses and reduction of patients’ quality of life due to severe tiredness and disappointment as well as diminished cognitive function. CRS is commonly associated with eustachian tube (ET) dysfunction.

Aim of the study

To evaluate the effect of endoscopic sinus surgery on ET function in the form of (tympanogram, Valsalva maneuver, and total ET dysfunction questionnaire score), in adult patients with CRS.

Method

This non-randomized clinical trial study was conducted at the Otorhinolaryngology department, the Faculty of Medicine, Cairo University, on 40 patients > 18 years old, suffering from CRS with or without sinonasal polyposis who are indicated for endoscopic sinus surgery (ESS) and were recruited from Otorhinolaryngology department’s outpatient clinic in the period from November 2022 to June 2023. All selected patients were subjected to a full history taken, a full general examination, and a local otorhinolaryngology examination. Routine preoperative laboratory investigation including complete blood count (CBC), liver and kidney function tests, and coagulation profile. An electrocardiogram (ECG) examination was done routinely for all patients above 40 years old. Radiological examination included the following: preoperative CT nose and paranasal sinus, axial and coronal soft tissue cuts, and bone windows. Assessment of ET function was done using the ET dysfunction questionnaire (ETDQ-7), Valsalva maneuver, and tympanogram. ET function was reevaluated 6 weeks post-operative in the form of an ETDQ-7, Valsalva maneuver, and tympanogram.

Results

The ages of selected patients ranged from 21 to 45 years old with mean ± SD = 30.98 ± 10.24 years old. 52.5% of patients were males. Our results showed a statistically significant postoperative improvement in the Valsalva maneuver and the tympanogram type of both ears compared to preoperative with a p-value < 0.001. Similar results were found regarding the assessment of ET function using ETDQ-7 items and the total score (15.35 ± 4.92 vs 26.12 ± 7.79 respectively) with p-value < 0.001.

Conclusion

A significant improvement in ET function in the form of tympanogram, Valsalva maneuver, and total ET dysfunction questionnaire score, following endoscopic sinus surgery in adult patients with CRS with or without sinonasal polyposis.
5-Aminolevulinic acid activates the MdWRKY71-MdMADS1 module to enhance anthocyanin biosynthesis in apple
Authors: Zhang Liuzi , Tao Huihui , Zhang Jianting , An Yuyan , Wang Liangju
Published: February 2025

5-Aminolevulinic acid (ALA), as a natural plant growth regulator, is well known for promoting red fruit coloring by enhancing anthocyanin accumulation. However, the underlying mechanisms remain elusive. In this study, we firstly demonstrated that ALA upregulates gene expression of the transcription factor MdMADS1, which in turn directly binds to and activates transcription of the key anthocyanin biosynthetic genes, MdCHS and MdUFGT. Then, we identified a novel WRKY transcription factor, MdWRKY71, that interacts with MdMADS1. Through gene manipulation, we revealed that MdWRKY71 plays a pivotal role in ALA-induced anthocyanin accumulation, highlighting its regulatory significance in this process. Further investigation unveiled that MdWRKY71 not only activates MdMADS1 transcription but also enhances its transcriptional activation on its target genes, MdCHS and MdUFGT. Additionally, we discovered that MdWRKY71 independently binds to and activates the transcription of two other anthocyanin biosynthetic genes, MdANS and MdDFR. The protein–protein interaction between MdWRKY71 and MdMADS1 amplifies the transcriptional activation of these genes by MdWRKY71. These findings delineate a fine and complex regulatory framework where MdWRKY71 and MdMADS1 coordinately regulate anthocyanin biosynthesis in apples, providing new insights into the molecular control of fruit coloration and offering potential target genes for breeding aimed at enhancing fruit quality.
Multidisciplinary surgical strategy for an invasive thymoma in an immunocompromised patient: a case of a successful resection and postoperative troubleshooting
Authors: Oki Tomonari , Iizuka Shuhei , Nakamura Toru
Published: February 2025

Background

Robot-assisted thoracoscopic surgery has become prevalent as a feasible approach for anterior mediastinal tumor resections, while conventional open surgery, such as a median sternotomy, remains preferred for a combined resection of adjacent organs. However, an additional thoracotomy may be necessary when tumors extend into one hemithorax. This complex approach can cause significant damage to the osseous thoracic cage, increasing the risk of surgical morbidity especially in immunocompromised patients.

Case presentation

A 77-year-old man presented with an anterior mediastinal thymoma measuring 71 mm, detected during an annual health check with suspected involvement of the left brachiocephalic vein and upper lobe of the left lung. The patient had a medical history of recurrent surgical site infections and fasciitis panniculitis syndrome requiring immunosuppressive therapy. To minimize any thoracic cage destruction, a multidisciplinary approach combining robotic surgery with open surgery according to vascular or pulmonary invasion was planned. The patient, initially placed in the supine position with the robot docked over the right side, underwent a thymic dissection, revealing a firm adhesion to the left brachiocephalic vein. The robot was then undocked, and a transmanubrial osteomuscular sparing approach was initiated, enabling a tumor dissection under the proximal and distal control of the left brachiocephalic vein. As invasion into the proximal upper pulmonary vein and extensive dorsal adhesions were observed, the patient was repositioned to the right lateral decubitus position, and a thoracoscopic left upper segmentectomy with adhesiolysis was performed, achieving an R0 resection. The patient was extubated on day 1 but required non-invasive ventilation until day 5. Mediastinitis, likely due to a sternal wire infection, developed on day 9, necessitating debridement, sternal wire removal, and negative pressure wound therapy. After 17 days of treatment, the infection subsided, allowing for a sequestrectomy and chest wall reconstruction with a pedicled pectoralis major myocutaneous flap. By avoiding a total sternotomy, the extent of the mediastinitis was localized, allowing for a limited sequestrectomy. Wound healing was satisfactory, with no recurrent infection at 12 months and minimal functional impairment.

Conclusions

A multidisciplinary approach offers a feasible option for managing an invasive thymoma to minimize postoperative morbidity, particularly in immunocompromised patients. Preoperative surgical planning is essential for guiding intraoperative decision-making and ensuring optimal outcomes.
Casual associations between frailty and nine mental disorders: bidirectional Mendelian randomisation study
Authors: Zhou Yong , Duan Jiayue , Zhu Jiayi , Huang Yunying , Tu Tao , Wu Keke , Lin Qiuzhen , Ma Yingxu , Liu Qiming
Published: February 2025

Background

An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.

Aims

To assess the bidirectional causal relationship between frailty and nine mental disorders.

Method

We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's Q-test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.

Results

Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36–2.53, P = 8.1 × 10−5), anxiety (odds ratio 2.76, 95% CI 1.56–4.90, P = 5.0 × 10−4), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69–3.87, P = 9.9 × 10−6), neuroticism (β = 0.25, 95% CI 0.11–0.38, P = 3.3 × 10−4) and insomnia (β = 0.50, 95% CI 0.25–0.75, P = 1.1 × 10−4). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: β = 0.071, 95% CI 0.033–0.110, P = 2.8 × 10−4; neuroticism: β = 0.269, 95% CI 0.173–0.365, P = 3.4 × 10−8; insomnia: β = 0.160, 95% CI 0.141–0.179, P = 3.2 × 10−61; suicide attempt: β = 0.056, 95% CI 0.029–0.084, P = 3.4 × 10−5). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.

Conclusions

Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.
Epilepsy Genetics
Authors: Kessler Sudha Kilaru
Published: February 2025

OBJECTIVE

This article reviews essential concepts and terminology in epilepsy genetics, discusses current guidance on when and how to pursue genetic evaluation, provides an overview of genetic syndromes, and offers illustrative examples of the effect of genetic diagnosis in epilepsy patient care.

LATEST DEVELOPMENTS

The growing availability of next-generation genetic sequencing methods for clinical use provides an opportunity to make etiologic diagnoses in a larger number of epilepsy patients, which can affect therapeutic management, prognostic counseling, surveillance for comorbid conditions, and other aspects of epilepsy care. Exome and genome sequencing may have high diagnostic yields in patients with unexplained epilepsy. The body of knowledge in epilepsy genetics is growing more complex, not only because of gene discovery but also because of an increasingly nuanced understanding of the varying pathophysiologic effects of specific types of variation within epilepsy genes.

ESSENTIAL POINTS

Genetic testing plays a key role in the evaluation of epilepsy patients. Clinicians caring for patients with epilepsy should understand patient selection, test selection, and result interpretation in genetic testing. The recommended first-line test in most patients is exome or genome sequencing.
EEG in Epilepsy
Authors: Weber Daniel
Published: February 2025

OBJECTIVE

The purpose of this article is to review the fundamentals and limitations of EEG, guide the selection of EEG type to answer clinical questions, and provide instruction on the interpretation of results within the patient's clinical context.

LATEST DEVELOPMENTS

EEG is the single most useful ancillary test to support the clinical diagnosis of epilepsy, but if used incorrectly it can cause great harm. Misapplication of EEG findings can lead to misdiagnosis and long-term mental and physical health sequelae. Although all neurologists may not have sufficient training for independent EEG interpretation, most should be able to review and apply the findings from the report accurately to guide patient care. Longer-term EEGs with similar recording electrodes tend to have higher diagnostic yields. Common EEG findings are described in this article, along with diagnostic limitations of some classically described patterns. There is an updated definition for an epileptiform discharge, along with a consensus on EEG patterns in the critically ill.

ESSENTIAL POINTS

EEG continues to be the most useful ancillary test to assist in the diagnosis of epilepsy. Its application requires proper understanding of its limitations and variability of testing results.
Neuroimaging in Epilepsy
Authors: Skidmore Christopher T.
Published: February 2025

OBJECTIVE

The goal of this article is to review the use of neuroimaging in the treatment of new-onset seizures and epilepsy. The article will focus predominantly on MRI because this is the most common modality, but it will also review others that are often used in individuals being considered for epilepsy surgery. The article also reviews common causes of epilepsy and their appearance on imaging and various imaging tools that can be combined to assist in the care of people with epilepsy.

LATEST DEVELOPMENTS

MRI has revolutionized the ability to diagnose the cause of many forms of epilepsy. However, to maximize the diagnostic power of MRI, it is essential to order the correct imaging sequences. In this article, the harmonized neuroimaging of epilepsy structural sequences (HARNESS) MRI protocol proposed by the International League Against Epilepsy is discussed.

ESSENTIAL POINTS

MRI is the preferred imaging modality to identify lesions associated with epilepsy. Protocols should include thin-cut, no-gap sequences to permit the identification of small epileptogenic lesions, and studies should be reviewed with an understanding of all the clinical information to help guide the identification of potential lesions.
Implementing Guidelines and Measures in Epilepsy Care
Authors: Baca Christine M.
Published: February 2025

People with epilepsy must receive up-to-date, high-quality care that aligns with current understanding of basic disease mechanisms, improved diagnostic testing, and evolving medical and surgical treatments. Varying progress has been made in identifying, measuring, and mitigating epilepsy care gaps. Epilepsy guidelines and quality measures should be developed using rigorous processes informed by systematic reviews of best evidence in conjunction with prioritization of need. Epilepsy measures help operationalize guidelines and practice parameters. Most epilepsy quality indicators are process-based metrics defined by delivering care to the patient. Systematic and reliable tracking and documentation of seizure frequency using consistent language is required as a patient-reported outcome within individuals over time and across populations. Emerging literature has demonstrated gaps in epilepsy care, perhaps highlighting limitations in the dissemination and implementation of guidelines and quality measures in clinical practice. Quality improvement methods applied to clinical data registries and learning health systems may afford new opportunities to iteratively, collaboratively, and feasibly disseminate guidelines and quality measures, measure epilepsy care quality, allow for the testing of interventions to mitigate identified care gaps, and, ultimately, improve care for patients with epilepsy.
Erector Spinae Plane Block Together With Inter-Transverse Process Block for Open Gastrectomy: Case Report
Authors: Marrone Francesco , Failli Simone , Fabbri Fabio , Paventi Saverio , Lepre Luca , Virno Vincenzo , Pullano Carmine
Published: February 2025

Fascial plane blocks of the posterior thoracic wall (erector spinae plane [ESP] and intertransverse plane [ITP]) may offer advantages for high-risk patients requiring open abdominal surgery in whom thoracic epidural analgesia (TEA) combined with general anesthesia (GA) may be relatively contraindicated. As a primary anesthesia method, ESP/ITP (paravertebral by proxy) blocks proved effective in a case of open gastrectomy by avoiding airway intervention, mechanical ventilation, and effectively managing visceral pain. This article highlights the use of ESP/ITP blocks in a high-risk patient for whom GA and TEA posed substantial risks, with the patient who experienced favorable perioperative outcomes.