Tag: pubmed

Sci Rep. 2024 Mar 30;14(1):7560. doi: 10.1038/s41598-024-58221-5.

ABSTRACT

Neurodegenerative diseases, like Alzheimer’s, are associated with the presence of neurofibrillary lesions formed by tau protein filaments in the cerebral cortex. While it is known that different morphologies of tau filaments characterize different neurodegenerative diseases, there are few metrics of global and local structure complexity that enable to quantify their structural diversity rigorously. In this manuscript, we employ for the first time mathematical topology and geometry to classify neurodegenerative diseases by using cryo-electron microscopy structures of tau filaments that are available in the Protein Data Bank. By employing mathematical topology metrics (Gauss linking integral, writhe and second Vassiliev measure) we achieve a consistent, but more refined classification of tauopathies, than what was previously observed through visual inspection. Our results reveal a hierarchy of classification from global to local topology and geometry characteristics. In particular, we find that tauopathies can be classified with respect to the handedness of their global conformations and the handedness of the relative orientations of their repeats. Progressive supranuclear palsy is identified as an outlier, with a more complex structure than the rest, reflected by a small, but observable knotoid structure (a diagrammatic structure representing non-trivial topology). This topological characteristic can be attributed to a pattern in the beginning of the R3 repeat that is present in all tauopathies but at different extent. Moreover, by comparing single filament to paired filament structures within tauopathies we find a consistent change in the side-chain orientations with respect to the alpha carbon atoms at the area of interaction.

PMID:38555402 | DOI:10.1038/s41598-024-58221-5

Spinal Cord. 2024 Mar 30. doi: 10.1038/s41393-024-00968-9. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective study.

OBJECTIVES: To investigate the risk factors of tracheostomy and decannulation after cervical spinal cord injury (CSCI) and their epidemiological changes over the past 8 years in Beijing Bo’ai Hospital, China Rehabilitation Research Center (CRRC), China.

SETTING: Beijing Bo’ai Hospital, CRRC.

METHODS: We reviewed 8 years of patient data (2013.1.1 to 2020.12.31) at CRRC, focusing on those hospitalized and diagnosed with CSCI. We analyzed changes in demographic and clinical data’s trends. Logistic regression analysis was used to determine factors impacting tracheostomy and decannulation.

RESULTS: Finally, 1641 CSCI patients met the inclusion criteria. Over the past 8 years, the proportion of tracheostomized patients with CSCI was 16.3%, and the proportion of successfully decannulated of tracheostomized patients with TCSCI was 77.9%. We found that Traumatic (OR = 1.8, 95% CI = 1.06, 3.22; p = 0.046), Motor level of injury (C5-C8) (OR = 0.32, 95% CI = -1.91,-0.34; p = 0.005), AIS = A/B/C (OR = 22.7/11.1/4.2, 95% CI = 12.16,42.26/5.74,21.56/2.23,7.89; p < 0.001/p < 0.001/p < 0.001), age > 56 (OR = 1.6, 95% CI = 1.04, 2.32; p = 0.031) were the risk factors for tracheostomy. By analyzing the risk factors of decannulation failure in tracheostomized patients with TCSCI through multivariable logistic regression, statistically significant differences were found in age > 45 (OR = 4.1, 95% CI = 1.44, 11.81; p = 0.008), complete injury (OR = 2.7, 95% CI = 1.26, 5.95; p = 0.011), facet dislocation (OR = 2.8, 95% CI = 1.13,7.07; p = 0.027).

CONCLUSIONS: Recent years have witnessed shifts in the epidemiological characteristics of CSCI. Identifying the factors influencing tracheostomy and decannulation in CSCI can aid in improving patient prognosis.

PMID:38555388 | DOI:10.1038/s41393-024-00968-9

Pediatr Res. 2024 Mar 30. doi: 10.1038/s41390-024-03172-w. Online ahead of print.

ABSTRACT

BACKGROUND: Telemedicine has increasingly become a viable option for patient care and may increase access to care. The aim of our study was to evaluate both parent and pediatrician perceptions, preferences, and acceptability regarding the use of different telemedicine modalities.

METHODS: We conducted a cross-sectional survey of both parents and pediatricians in Geneva, Switzerland in 2021. The questionnaire focused on digital literacy, preferences, acceptability, advantages, and disadvantages regarding telemedicine (phone, email, video, and instant message). Descriptive statistics and comparisons of preferences and perceptions (Pearson Chi² and logistic regression) were performed.

RESULTS: Two hundred and twenty-two parents and 45 pediatricians participated. After face-to-face consultations, parents and pediatricians preferred the phone for simple medical advice, discussion of parameters, acute or chronic problems, and psychological support. Email was preferred for communication of results and prescription renewal. Main reasons for using telemedicine were avoiding travel and saving time. Disadvantages were lack of physical examination, technical problems, and unsuitability of the reason for consultation.

CONCLUSIONS: Understanding the factors that influence acceptance and satisfaction with telemedicine is vital for its successful implementation. Convenience, quality of care, trust, strong pediatrician-parent relationships, technical reliability, user-friendliness, and privacy considerations play significant roles in shaping parent and pediatrician attitudes toward telemedicine.

IMPACT: The COVID-19 pandemic spurred the expansion of the use of telemedicine in pediatric care. Few studies have addressed parent and pediatrician perceptions and preferences regarding telemedicine. Both parents and pediatricians consider certain telemedicine modalities (phone, email, video, and instant message) pertinent in only specific clinical situations. Advantages of telemedicine outweigh disadvantages with parents and pediatricians appreciating the increased access to care, time savings, and avoiding transport. However, the lack of a physical examination remains a significant disadvantage. Convenience, quality of care, trust, strong pediatrician-parent relationship, technical reliability, user-friendliness, and privacy considerations play significant roles in shaping attitudes towards telemedicine.

PMID:38555380 | DOI:10.1038/s41390-024-03172-w

Ther Innov Regul Sci. 2024 Mar 30. doi: 10.1007/s43441-024-00634-5. Online ahead of print.

ABSTRACT

In June 2021, FDA released a Draft Guidance on Sponsor Responsibilities for IND Safety Reporting and cited components of a recommended Safety Surveillance Plan (SSP). To meet the expectations of the 2021 FDA guidance, sponsors should document their plan for aggregate safety assessment. The Drug Information Association-American Statistical Association Interdisciplinary Safety Evaluation scientific working group has proposed an Aggregate Safety Assessment Plan (ASAP) that addresses this recommendation. The 2021 FDA guidance also discusses potential strategies for unblinded review of safety data from ongoing studies by an independent Assessment Entity, which could occur via planned periodic evaluations or “triggered” reviews based on blinded data assessments. The Assessment Entity reviewing unblinded data makes recommendations as to whether the threshold has been met for submission of an aggregate IND safety report. In this paper, we discuss how the ASAP supports IND aggregate safety reporting decisions, including elements to be included in a proposed SSP appendix to the ASAP. In addition, the authors advocate for the benefits of developing a charter (or specific section of the Data Monitoring Committee charter, if applicable) that describes the responsibilities and conduct of the Assessment Entity. With these components in place, study sponsors will meet the objective of having clearly defined processes for the monitoring of clinical trial safety data in aggregate and making IND safety reporting decisions.

PMID:38555342 | DOI:10.1007/s43441-024-00634-5

Bull Math Biol. 2024 Mar 30;86(5):48. doi: 10.1007/s11538-024-01277-1.

ABSTRACT

Carcinomas often utilize epithelial-mesenchymal transition (EMT) programs for cancer progression and metastasis. Numerous studies report SNAIL-induced miR200/Zeb feedback circuit as crucial in regulating EMT by placing cancer cells in at least three phenotypic states, viz. epithelial (E), hybrid (h-E/M), mesenchymal (M), along the E-M phenotypic spectrum. However, a coherent molecular-level understanding of how such a tiny circuit controls carcinoma cell entrance into and residence in various states is lacking. Here, we use molecular binding data and mathematical modeling to report that the miR200/Zeb circuit can essentially utilize combinatorial cooperativity to control E-M phenotypic plasticity. We identify minimal combinatorial cooperativities that give rise to E, h-E/M, and M phenotypes. We show that disrupting a specific number of miR200 binding sites on Zeb as well as Zeb binding sites on miR200 can have phenotypic consequences-the circuit can dynamically switch between two (E, M) and three (E, h-E/M, M) phenotypes. Further, we report that in both SNAIL-induced and SNAIL knock-out miR200/Zeb circuits, cooperative transcriptional feedback on Zeb as well as Zeb translation inhibition due to miR200 are essential for the occurrence of intermediate h-E/M phenotype. Finally, we demonstrate that SNAIL can be dispensable for EMT, and in the absence of SNAIL, the transcriptional feedback can control cell state transition from E to h-E/M, to M state. Our results thus highlight molecular-level regulation of EMT in miR200/Zeb circuit and we expect these findings to be crucial to future efforts aiming to prevent EMT-facilitated dissemination of carcinomas.

PMID:38555331 | DOI:10.1007/s11538-024-01277-1

Br J Cancer. 2024 Mar 30. doi: 10.1038/s41416-024-02663-1. Online ahead of print.

ABSTRACT

BACKGROUND: Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking.

METHODS: We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month).

RESULTS: The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87).

CONCLUSION: Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes.

PMID:38555316 | DOI:10.1038/s41416-024-02663-1

Sci Rep. 2024 Mar 30;14(1):7568. doi: 10.1038/s41598-024-57814-4.

ABSTRACT

The aim of this study was to investigate and analyse the predictive value of systemic inflammatory markers based on peripheral blood biomarkers for the prognosis of non-small cell lung cancer (NSCLC) patients. Based on a retrospective monitoring cohort of 973 NSCLC patients from an Affiliated Tumor Hospital from 2012 to 2023. The log-rank test and Cox proportional risk regression model were used to identify independent prognostic inflammatory markers. Subsequently, a nomogram prediction model was constructed and evaluated. The results of multivariate Cox regression analysis showed that patients with high NLR group (HR = 1.238, 95% CI 1.015-1.510, P = 0.035), and high CAR group (HR = 1.729, 95% CI 1.408-2.124, P < 0.001) were risk factors affecting the prognosis of NSCLC patients. The nomogram that includes age, tumor stage, smoking history, BMI, NLR, and CAR can effectively predict the prognosis of NSCLC patients.The inflammatory markers NLR and CAR, which combine inflammatory and nutritional status, are effective predictors of the prognosis of NSCLC patients. The combination of clinical information and these easily accessible inflammatory markers has significant research value for prognostic assessment, clinical treatment, and follow-up monitoring of NSCLC patients.

PMID:38555313 | DOI:10.1038/s41598-024-57814-4

Sci Rep. 2024 Mar 30;14(1):7581. doi: 10.1038/s41598-024-57989-w.

ABSTRACT

There are 16 species in the genus Satureja L. (Lamiaceae), of which 10 are native. This research aimed to investigate the effect of gamma rays and storage conditions and duration on the percentage and components of the essential oil and some biochemical characteristics of Satureja mutica Fisch & C.A. Mey at the Research Institute of Forests and Rangelands. Plants were collected at the full flowering stage and exposed to different doses of gamma rays (0, 2.5, 5, 7.5, and 10 kGy) at the Atomic Energy Organization, Iran. The samples were kept in a refrigerator (4 °C) and in the shade (25 ± 2 °C) for 0, 120, and 240 h. This experiment was performed in a completely randomized design. Essential oil extraction was done by water distillation for 2 h. The composition of their essential oil components was identified using GC and GC/MS. Some biochemical traits, including phenol content, antioxidant capacity, and carbohydrate content, were measured. The results indicated that irradiation on the percentage of essential oil showed a statistically significant difference. In addition, the interaction effect of irradiation × storage conditions, irradiation × duration of storage, on the percentage of essential oil was significant. According to a comparison of the means, 2.5 kGy irradiation produced the highest percentage of essential oil (0.4%); in contrast, a significant decrease was detected in components with 7.5 and 10 kGy irradiation. It was observed that the percentage of some essential oil compounds decreased with the gamma-ray intensity increase. 2.5 kGy of gamma rays and shade storage conditions for 240 h led to the highest content of p-cymene and carvacrol. Nevertheless, the highest thymol content was obtained under refrigeration conditions without irradiation. The maximum phenol content and antioxidant capacity were obtained when the plants were irradiated with 2.5 and 7.5 kGy gamma rays. However, the maximum carbohydrate rate was observed in non-irradiated plants. It was concluded that low-intensity gamma rays could improve the percentage of essential oil and main components like p-cymene and carvacrol in S. mutica Fisch & C.A. Mey.

PMID:38555296 | DOI:10.1038/s41598-024-57989-w

Sci Rep. 2024 Mar 30;14(1):7588. doi: 10.1038/s41598-024-57470-8.

ABSTRACT

Establishing sustainable communities requires bridging the gap between academic knowledge and societal requirements; this is where entrepreneurial education comes in. The first phase involved a comprehensive review of the literature and extensive consultation with experts to identify and shortlist the components of entrepreneurship education that support sustainable communities. The second phase involved Total Interpretative Structural Modelling to explore or ascertain how the elements interacted between sustainable communities and entrepreneurial education. The factors are ranked and categorized using the Matrice d’impacts croises multiplication appliquee an un classement (MICMAC) approach. The MICMAC analysis classifies partnerships and incubators as critical drivers, identifying Student Entrepreneurship Clubs and Sustainability Research Centers as dependent elements. The study emphasizes alumni networks and curriculum designs as key motivators. The results highlight the critical role that well-designed entrepreneurial education plays in developing socially conscious entrepreneurs, strengthening communities, and generating long-term job prospects. The study provides a valuable road map for stakeholders dedicated to long-term community development agendas by informing the creation of strategic initiatives, curriculum updates, and policies incorporating entrepreneurial education.

PMID:38555294 | DOI:10.1038/s41598-024-57470-8

Nat Commun. 2024 Mar 30;15(1):2805. doi: 10.1038/s41467-024-47215-6.

ABSTRACT

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS < 6 months]. Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.

PMID:38555285 | DOI:10.1038/s41467-024-47215-6