Aß1-6A2V(D) peptide, effective on Aß aggregation, inhibits tau misfolding and protects the brain after traumatic brain injury.

Alzheimer's disease (AD), the leading cause of dementia in older adults, is a double proteinopathy characterized by amyloid-ß (Aß) and tau pathology. Despite enormous efforts that have been spent in the last decades to find effective therapies, late pharmacological interventions along the course of the disease, inaccurate clinical methodologies in the enrollment of patients, and inadequate biomarkers for evaluating drug efficacy have not allowed the development of an effective therapeutic strategy. The approaches followed so far for developing drugs or antibodies focused solely on targeting Aß or tau protein. This paper explores the potential therapeutic capacity of an all-D-isomer synthetic peptide limited to the first six amino acids of the N-terminal sequence of the A2V-mutated Aß, Aß1-6A2V(D), that was developed following the observation of a clinical case that provided the background for its development. We first performed an in-depth biochemical characterization documenting the capacity of Aß1-6A2V(D) to interfere with the aggregation and stability of tau protein. To tackle Aß1-6A2V(D) in vivo effects against a neurological decline in genetically predisposed or acquired high AD risk mice, we tested its effects in triple transgenic animals harboring human PS1(M146 V), APP(SW), and MAPT(P301L) transgenes and aged wild-type mice exposed to experimental traumatic brain injury (TBI), a recognized risk factor for AD. We found that Aß1-6A2V(D) treatment in TBI mice improved neurological outcomes and reduced blood markers of axonal damage. Exploiting the C. elegans model as a biosensor of amyloidogenic proteins' toxicity, we observed a rescue of locomotor defects in nematodes exposed to the brain homogenates from TBI mice treated with Aß1-6A2V(D) compared to TBI controls. By this integrated approach, we demonstrate that Aß1-6A2V(D) not only impedes tau aggregation but also favors its degradation by tissue proteases, confirming that this peptide interferes with both Aß and tau aggregation propensity and proteotoxicity.

Evaluating the quality of radiomics-based studies for endometrial cancer using RQS and METRICS tools.

OBJECTIVE: To assess the methodological quality of radiomics-based models in endometrial cancer using the radiomics quality score (RQS) and METhodological radiomICs score (METRICS). METHODS: We systematically reviewed studies published by October 30th, 2023. Inclusion criteria were original radiomics studies on endometrial cancer using CT, MRI, PET, or ultrasound. Articles underwent a quality assessment by novice and expert radiologists using RQS and METRICS. The inter-rater reliability for RQS and METRICS among radiologists with varying expertise was determined. Subgroup analyses were performed to assess whether scores varied according to study topic, imaging technique, publication year, and journal quartile. RESULTS: Sixty-eight studies were analysed, with a median RQS of 11 (IQR, 9-14) and METRICS score of 67.6% (IQR, 58.8-76.0); two different articles reached maximum RQS of 19 and METRICS of 90.7%, respectively. Most studies utilised MRI (82.3%) and machine learning methods (88.2%). Characterisation and recurrence risk stratification were the most explored outcomes, featured in 35.3% and 19.1% of articles, respectively. High inter-rater reliability was observed for both RQS (ICC: 0.897; 95% CI: 0.821, 0.946) and METRICS (ICC: 0.959; 95% CI: 0.928, 0.979). Methodological limitations such as lack of external validation suggest areas for improvement. At subgroup analyses, no statistically significant difference was noted. CONCLUSIONS: Whilst using RQS, the quality of endometrial cancer radiomics research was apparently unsatisfactory, METRICS depicts a good overall quality. Our study highlights the need for strict compliance with quality metrics. Adhering to these quality measures can increase the consistency of radiomics towards clinical application in the pre-operative management of endometrial cancer. CLINICAL RELEVANCE STATEMENT: Both the RQS and METRICS can function as instrumental tools for identifying different methodological deficiencies in endometrial cancer radiomics research. However, METRICS also reflected a focus on the practical applicability and clarity of documentation. KEY POINTS: The topic of radiomics currently lacks standardisation, limiting clinical implementation. METRICS scores were generally higher than the RQS, reflecting differences in the development process and methodological content. A positive trend in METRICS score may suggest growing attention to methodological aspects in radiomics research.

Perceptions of radiologists on structured reporting for cancer imaging-a survey by the European Society of Oncologic Imaging (ESOI).

OBJECTIVES: To assess radiologists' current use of, and opinions on, structured reporting (SR) in oncologic imaging, and to provide recommendations for a structured report template. MATERIALS AND METHODS: An online survey with 28 questions was sent to European Society of Oncologic Imaging (ESOI) members. The questionnaire had four main parts: (1) participant information, e.g., country, workplace, experience, and current SR use; (2) SR design, e.g., numbers of sections and fields, and template use; (3) clinical impact of SR, e.g., on report quality and length, workload, and communication with clinicians; and (4) preferences for an oncology-focused structured CT report. Data analysis comprised descriptive statistics, chi-square tests, and Spearman correlation coefficients. RESULTS: A total of 200 radiologists from 51 countries completed the survey: 57.0% currently utilized SR (57%), with a lower proportion within than outside of Europe (51.0 vs. 72.7%; p = 0.006). Among SR users, the majority observed markedly increased report quality (62.3%) and easier comparison to previous exams (53.5%), a slightly lower error rate (50.9%), and fewer calls/emails by clinicians (78.9%) due to SR. The perceived impact of SR on communication with clinicians (i.e., frequency of calls/emails) differed with radiologists' experience (p < 0.001), and experience also showed low but significant correlations with communication with clinicians (r = - 0.27, p = 0.003), report quality (r = 0.19, p = 0.043), and error rate (r = - 0.22, p = 0.016). Template use also affected the perceived impact of SR on report quality (p = 0.036). CONCLUSION: Radiologists regard SR in oncologic imaging favorably, with perceived positive effects on report quality, error rate, comparison of serial exams, and communication with clinicians. CLINICAL RELEVANCE STATEMENT: Radiologists believe that structured reporting in oncologic imaging improves report quality, decreases the error rate, and enables better communication with clinicians. Implementation of structured reporting in Europe is currently below the international level and needs society endorsement. KEY POINTS: • The majority of oncologic imaging specialists (57% overall; 51% in Europe) use structured reporting in clinical practice. • The vast majority of oncologic imaging specialists use templates (92.1%), which are typically cancer-specific (76.2%). • Structured reporting is perceived to markedly improve report quality, communication with clinicians, and comparison to prior scans.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Comparison of Machine Learning Algorithms Fed with Mobility-Related and Baropodometric Measurements to Identify Temporomandibular Disorders.

Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involves clinical assessment through operator-based physical examination, a self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating the feasibility of using machine-learning algorithms fed with data gathered from low-cost and portable instruments to identify the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as a control group. The diagnosis of TMD was performed by a skilled operator through the typical clinical scale. Participants underwent a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree algorithms were compared. The k-nearest neighbours algorithm based on cosine distance was found to be the best performing, achieving performances of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility of using such methodology to support the diagnosis of TMDs in clinical environments.

4-6 Repetition Maximum (RM) and 1-RM Prediction in Free-Weight Bench Press and Smith Machine Squat Based on Body Mass in Male Athletes.

ABSTRACT: Dhahbi, W, Padulo, J, Russo, L, Racil, G, Ltifi, M-A, Picerno, P, Iuliano, E, and Migliaccio, GM. Four- to 6-repetition maximum and 1-repetition maximum estimation in free-weight bench press and smith machine squat based on body mass in male athletes. J Strength Cond Res 38(8): 1366-1371, 2024-This study aimed to explore the feasibility and face validity of predicting maximum strength 1 repetition maximum (1-RM) and 4-6 RM in athletes across different sports specialties, based on the relationship between muscle strength and BM. One hundred fifteen male athletes, aged 23.63 ± 6.77 years and participating in diverse sports specialties, were included in this study. Muscle strength was assessed using the 4-6 RM and 1-RM tests in free-weight bench press (BP) and Smith machine squat (SQ) exercises, whereas BM was measured using a portable digital scale. A linear regression equation based on muscle strength and BM was performed. The 4-6 RM and 1-RM scores showed excellent intersession relative reliability (intraclass correlation coefficient (2,1) : 0.946-0.989) and absolute reliability (CV: 3.4-4.7%) in both BP and SQ exercises. In addition, the magnitude of the relationship and the coefficients used to estimate the 4-6 RM and 1RM, based on BM, differed among the subjects when they are grouped according to their sports specialties ( R2 ranged from non-significant to 0.998). Overall, the 4-6 RM test showed a stronger correlation with BM ( R : 0.655 for SQ and R : 0.683 for BP) than the 1RM ( R : 0.552 for SQ and R : 0.629 for BP), and the general (i.e., not sport-specific) 4 to 6-RM prediction equations should be preferred over sport-specific ones because they are statistically more robust due to the larger sample size. In conclusion, the 4-6 RM can be predicted from BM with high reliability, a moderate association, and a prediction error that, when considering the 4-6 RM as a starting point for estimating of the 1RM, can be considered entirely acceptable in practical settings.

Leptin, Ghrelin, Irisin, Asprosin and Subfatin Changes in Obese Women: Effect of Exercise and Different Nutrition Types.

Background and Objectives: In this study, the effects of a six-week training program and various diets on subfatin, asprosin, irisin, leptin, ghrelin and the lipid profile were investigated in overweight women. Materials and Methods: A total of 78 women voluntarily participated in the study. Groups: The study was divided into eight groups: Healthy Control, Obese Control, Obese + Vegetarian, Obese + Ketogenic, Obese + Intermittent Fasting, Obese + Exercise + Vegetarian, Obese + Exercise + Ketogenic and Obese + Exercise + Intermittent Fasting. While there was no intervention in the healthy and obese control groups, the other groups followed predetermined exercise and diet programs for 6 weeks. Blood samples were taken from the participants in the research group twice (before and after the interventions). An autoanalyzer was used to determine the lipid profile in the blood samples taken, and the ELISA method was used to analyze other parameters. Results: Overall, a significant difference was found in the values of weight, BMI, subfatin, ghrelin, leptin, cholesterol, triglyceride, HDL and LDL as a result of the exercise and diet interventions (p < 0.05). There was no significant difference in asprosin and irisin values (p > 0.05). Conclusions: In conclusion, regular exercise and dietary interventions in obese women can regulate lipid profile, ghrelin, leptin and asprosin levels, and increasing irisin with exercise can activate lipid metabolism and support positive changes in lean mass.

PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target.

Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose-response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.

The value of MRI in quantification of parametrial invasion and association with prognosis in locally advanced cervical cancer: the "PLACE" study.

OBJECTIVE: This retrospective observational study aims to evaluate the association between the extent of parametrial invasion (PMI) and disease-free survival (DFS) and cancer-specific survival (CSS) in patients with locally advanced cervical cancer (LACC). MATERIALS AND METHODS: This study included patients with LACC showing parametrial invasion at Magnetic Resonance Imaging (MRI). They were treated with neoadjuvant chemo-radiotherapy (CT/RT) before undergoing radical hysterectomy. The staging MRIs were reviewed retrospectively. Measurements of maximum PMI (PMImax) and parametrial length were taken bilaterally. After that, PMIratio was calculated by dividing PMImax by parametrial length. Analysis was conducted on homogeneous subsets of patients, grouped based on their pathological lymph nodal evaluation (N- and N+). Correlations between PMImax and PMIratio with DFS and CSS were evaluated in both the N- and N+ groups, employing univariable Cox regression analysis. RESULTS: Out of 221 patients, 126 (57%) had non-metastatic lymph nodes (N-), while 95 (43%) had metastatic lymph nodes (N+). The median observation period for all these patients was 73 months (95% confidence interval [CI]: 66-77). The 5-year DFS and CSS probability rates were 75% and 85.7%, respectively, for the N- group and 54.3% and 73.6%, respectively, for the N+ group. A higher PMImax (hazard ratio [HR] = 1.09) and PMIratio (HR = 1.04) correlated with worse overall survival in patients in the N- group (p = 0.025 and p = 0.042). These parameters did not show a significant statistical association in the N+ group. CONCLUSIONS: The degree of PMI evaluated on MRI affects outcome in N- patients with LACC. CLINICAL RELEVANCE STATEMENT: The degree of MRI parametrial invasion affects disease-free survival and cancer-specific survival in patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. This MRI finding can be easily incorporated into routine clinical practice. KEY POINTS: • Visual assessment of parametrial invasion on MRI was not significantly associated with prognosis in locally advanced cervical cancer (LACC). • A greater degree of parametrial invasion is associated with poorer disease-free survival and cancer-specific survival in patients with LACC without metastatic lymph node involvement. • The degree of parametrial invasion at MRI has no correlation with prognosis in LACC with metastatic lymph nodes.

Radiomics systematic review in cervical cancer: gynecological oncologists' perspective.

OBJECTIVE: Radiomics is the process of extracting quantitative features from radiological images, and represents a relatively new field in gynecological cancers. Cervical cancer has been the most studied gynecological tumor for what concerns radiomics analysis. The aim of this study was to report on the clinical applications of radiomics combined and/or compared with clinical-pathological variables in patients with cervical cancer. METHODS: A systematic review of the literature from inception to February 2023 was performed, including studies on cervical cancer analysing a predictive/prognostic radiomics model, which was combined and/or compared with a radiological or a clinical-pathological model. RESULTS: A total of 57 of 334 (17.1%) screened studies met inclusion criteria. The majority of studies used magnetic resonance imaging (MRI), but positron emission tomography (PET)/computed tomography (CT) scan, CT scan, and ultrasound scan also underwent radiomics analysis. In apparent early-stage disease, the majority of studies (16/27, 59.3%) analysed the role of radiomics signature in predicting lymph node metastasis; six (22.2%) investigated the prediction of radiomics to detect lymphovascular space involvement, one (3.7%) investigated depth of stromal infiltration, and one investigated (3.7%) parametrial infiltration. Survival prediction was evaluated both in early-stage and locally advanced settings. No study focused on the application of radiomics in metastatic or recurrent disease. CONCLUSION: Radiomics signatures were predictive of pathological and oncological outcomes, particularly if combined with clinical variables. These may be integrated in a model using different clinical-pathological and translational characteristics, with the aim to tailor and personalize the treatment of each patient with cervical cancer.

Fetal MRI prior to intrauterine surgery of open neural tube defects: What does the radiologist need to know.

The management of myelomeningocele study trial showed significant prognostic improvement in fetal repair before 26 weeks of gestation. Hence, surgery in utero represents the best treatment option for open-neural tube defects (NTDs). Fetal surgery of open-NTDs has specific inclusion and exclusion criteria, which can be adequately studied with fetal MRI. The main concern: the spine (spinal defects other than Myelomeningocele and Myeloschisis, the level of the lesion higher than T1 or lower than S1 and the degree of kyphosis ≥ 30°), the skull/brain (no cerebellum herniation and Chiari II malformation and the presence of any intracranial abnormality unrelated to open NTDs), the uterus (cervix length less than 2 cm, multiple gestations and placental and uterine abnormalities) and any other fetal abnormality not attributed to spinal defect. In this review, we describe the fundamental role of fetal MRI in supporting therapeutic decisions in pre-surgery intrauterine planning through the accurate and comprehensive description of findings, providing a proposal of a structured report. In addition, we describe how post-surgical MRI is important in investigating the effectiveness of surgery and detecting repairing complications.

Marathon shoes vs. track spikes: a crossover pilot study on metabolic demand at different speeds in experienced runners.

The aim of this study was to assess the metabolic cost (Cr) with marathon shoes (Adidas Adizero 3 [AA]) vs. track spikes (Nike Zoom Matumbo 3 [NZM]) on track. For this, five experienced runners were randomly assessed (NZM/AA) on a running track at 73% and 85% of best performance speed on 1500-m race. At first, speed (4.39 ± 0.53 m·s-1), Crs with AA and NZM resulted 3.63 ± 0.29 and 3.64 ± 0.43 J·kg-1·m-1 (+0.3% with NZM, effect size [ES] small and p = 0.951), respectively. Besides, at second speed (5.20 ± 0.18 m·s-1), Crs were 4.09 ± 0.28 and 4.07 ± 0.22 J·kg-1·m-1 (-0.5% with NZM, ES small and p = 0.919) with AA and NZM, respectively. It resulted in an increased Cr (+12.2%) between s1 and s2 with both shoe conditions (ES large and p = 0.009 and 0.011 with AA and NZM, respectively). There is a pattern yet to be confirmed for track spikes to become more beneficial at higher speeds (when duty factor becomes lower and therefore grip on track is crucial).

Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC).

BACKGROUND: Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality. METHODS: RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models. RESULTS: The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06-2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56-2.62; P = 0.00647). CONCLUSIONS: RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells.

BACKGROUND: With the success of recent non-viral gene delivery-based COVID-19 vaccines, nanovectors have gained some public acceptance and come to the forefront of advanced therapies. Unfortunately, the relatively low ability of the vectors to overcome cellular barriers adversely affects their effectiveness. Scientists have thus been striving to develop ever more effective gene delivery vectors, but the results are still far from satisfactory. Therefore, developing novel strategies is probably the only way forward to bring about genuine change. Herein, we devise a brand-new gene delivery strategy to boost dramatically the transfection efficiency of two gold standard nucleic acid (NA)/polymer nanoparticles (polyplexes) in vitro. RESULTS: We conceived a device to generate milli-to-nanoscale vibrational cues as a function of the frequency set, and deliver vertical uniaxial displacements to adherent cells in culture. A short-lived high-frequency vibrational load (t = 5 min, f = 1,000 Hz) caused abrupt and extensive plasmalemma outgrowths but was safe for cells as neither cell proliferation rate nor viability was affected. Cells took about 1 hr to revert to quasi-naïve morphology through plasma membrane remodeling. In turn, this eventually triggered the mechano-activated clathrin-mediated endocytic pathway and made cells more apt to internalize polyplexes, resulting in transfection efficiencies increased from 10-to-100-fold. Noteworthy, these results were obtained transfecting three cell lines and hard-to-transfect primary cells. CONCLUSIONS: In this work, we focus on a new technology to enhance the intracellular delivery of NAs and improve the transfection efficiency of non-viral vectors through priming adherent cells with a short vibrational stimulation. This study paves the way for capitalizing on physical cell stimulation(s) to significantly raise the effectiveness of gene delivery vectors in vitro and ex vivo.

Radiomics-based prediction of two-year clinical outcome in locally advanced cervical cancer patients undergoing neoadjuvant chemoradiotherapy.

PURPOSE: The aim of this study is to determine if radiomics features extracted from staging magnetic resonance (MR) images could predict 2-year long-term clinical outcome in patients with locally advanced cervical cancer (LACC) after neoadjuvant chemoradiotherapy (NACRT). MATERIALS AND METHODS: We retrospectively enrolled patients with LACC diagnosis who underwent NACRT followed by radical surgery in two different institutions. Radiomics features were extracted from pre-treatment 1.5 T T2w MR images. The predictive performance of each feature was quantified in terms of Wilcoxon-Mann-Whitney test. Among the significant features, Pearson correlation coefficient (PCC) was calculated to quantify the correlation among the different predictors. A logistic regression model was calculated considering the two most significant features at the univariate analysis showing the lowest PCC value. The predictive performance of the model created was quantified out using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 175 patients were retrospectively enrolled (142 for the training cohort and 33 for the validation one). 1896 radiomic feature were extracted, 91 of which showed significance (p < 0.05) at the univariate analysis. The radiomic model showing the highest predictive value combined the features calculated starting from the gray level co-occurrence-based features. This model achieved an AUC of 0.73 in the training set and 0.91 in the validation set. CONCLUSIONS: The proposed radiomic model showed promising performances in predicting 2-year overall survival before NACRT. Nevertheless, the observed results should be tested in larger studies with consistent external validation cohorts, to confirm their potential clinical use.

Micro- and Nanoplastics' Effects on Protein Folding and Amyloidosis.

A significant portion of the world's plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood-brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications.

The role of apparent diffusion coefficient (ADC) in the evaluation of lymph node status in patients with locally advanced cervical cancer: our experience and a review.

Purpose: To evaluate the role of apparent diffusion coefficient (ADC) value measurement in the diagnosis of meta-static lymph nodes (LNs) in patients with locally advanced cervical cancer (LACC) and to present a systematic review of the literature. Material and methods: Magnetic resonance imaging (MRI) exams of patients with LACC were retrospectively eva-luated. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of enlarged LNs were measured and compared between positron emission tomography (PET)-positive and PET-negative LNs. Comparisons were made using the Mann-Whitney U-test and Student's t-test. ROC curves were generated for each parameter to identify the optimal cut-off value for differentiation of the LNs. A systematic search in the literature was performed, exploring several databases, including PubMed, Scopus, the Cochrane library, and Embase. Results: A total of 105 LNs in 34 patients were analysed. The median ADC value of PET-positive LNs (0.907 × 10-3 mm2/s [0.780-1.080]) was lower than that in PET-negative LNs (1.275 × 10-3 mm2/s [1.063-1.525]) (p < 0.05). rADC and cADC values were lower in PET-positive LNs (rADC: 0.120 × 10-3 mm2/s [-0.060-0.270]; cADC: 1.130 [0.980-1.420]) than in PET-negative LNs (rADC: 0.435 × 10-3 mm2/s [0.225-0.673]; cADC: 1.615 [1.210-1.993]) LNs (p < 0.05). ADC showed the highest area under the curve (AUC 0.808). Conclusions: Mean ADC, rADC, and cADC were significantly lower in the PET-positive group than in the PET-negative group. The ADC cut-off value of 1.149 × 10-3 mm2/s showed the highest sensitivity. These results confirm the usefulness of ADC in differentiating metastatic from non-metastatic LNs in LACC.

C. elegans detects toxicity of traumatic brain injury generated tau.

Traumatic brain injury (TBI) is associated with widespread tau pathology in about 30% of patients surviving late after injury. We previously found that TBI in mice induces the formation of an abnormal form of tau (tauTBI) which progressively spreads from the site of injury to remote brain regions. Intracerebral inoculation of TBI brain homogenates into naïve mice induced progressive tau pathology, synaptic loss and late cognitive decline, suggesting a pivotal role of tauTBI in post-TBI neurodegeneration. However, the possibility that tauTBI was a marker of TBI-associated neurodegeneration rather than a toxic driver of functional decline could not be excluded. Here we employed the nematode C. elegans as a biosensor to test the pathogenic role of TBI generated tau. The motility of this nematode depends on efficient neuromuscular transmission and is exceptionally sensitive to the toxicity of amyloidogenic proteins, providing a tractable model for our tests. We found that worms exposed to brain homogenates from chronic but not acute TBI mice, or from mice in which tauTBI had been transmitted by intracerebral inoculation, had impaired motility and neuromuscular synaptic transmission. Results were similar when worms were given brain homogenates from transgenic mice overexpressing tau P301L, a tauopathy mouse model, suggesting that TBI-induced and mutant tau have similar toxic properties. P301L brain homogenate toxicity was similar in wild-type and ptl-1 knock-out worms, indicating that the nematode tau homolog protein PTL-1 was not required to mediate the toxic effect. Harsh protease digestion to eliminate the protein component of the homogenates, pre-incubation with anti-tau antibodies or tau depletion by immunoprecipitation, abolished the toxicity. Homogenates of chronic TBI brains from tau knock-out mice were not toxic to C. elegans, whereas oligomeric recombinant tau was sufficient to impair their motility. This study indicates that tauTBI impairs motor activity and synaptic transmission in C. elegans and supports a pathogenic role of tauTBI in the long-term consequences of TBI. It also sets the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds.

Birds seen and not seen during the COVID-19 pandemic: The impact of lockdown measures on citizen science bird observations.

In early 2020, the rapid spread of the novel coronavirus disease 2019 (COVID-19) led multiple countries to introduce strict lockdown measures to contain the pandemic. Movement restrictions may have influenced the ability of the public to contribute to citizen science projects. We investigated how stay-at-home orders affected data submitted by birdwatchers in Italy, Spain and the United Kingdom (UK) to a widely-used citizen science platform, iNaturalist, depending on whether observations were collected in urban or non-urban areas. We found significant trends in the daily number of observations in all three countries, indicating a surge in urban observation during lockdowns. We found an increase in the mean daily number of urban observations during the lockdown in Italy and Spain, compared to previous years. The mean daily number of non-urban observations decreased in Italy and Spain, while remained similar to previous years in the UK. We found a general decrease of new records during the lockdowns both in urban and non-urban areas in all countries. Our results suggest that the citizen science community remained active during the lockdowns and kept reporting birds from home. However, limitations to movements may have hampered the possibility of birdwatchers to explore natural areas and collect new records. Our findings suggest that future research and conservation applications of citizen science data should carefully consider the bias and gaps in data series caused by the pandemic. Furthermore, our study highlights the potential of urban areas for nature activities, such as birdwatching, and its relevance for sustainable urban planning.

The role of MRI in cervical cancer > 2 cm (FIGO stage IB2-IIA1) conservatively treated with neoadjuvant chemotherapy followed by conization: a pilot study.

INTRODUCTION: MRI is very accurate in selecting young women with cervical cancer for fertility-sparing surgery (FSS), in particular radical hysterectomy (RH). In order to improve obstetrical outcomes, neoadjuvant chemotherapy (NACT) followed by cold knife conization (CKC) has been proposed as alternative technique. OBJECTIVE: To investigate the role of MRI in evaluation of response to treatment after neoadjuvant chemotherapy (NACT), followed by CKC, in patients with cervical cancer FIGO stage IB2-IIA1 with tumor size 2 - 4 cm, desiring to preserve their fertility. METHODS: 13 young women (23-36 years old) with cervical cancer stage IB2-IIA1 desiring to preserve their fertility were included. Tumor diameter at baseline and after treatment was detected on 1.5 T MRI. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and then compared to histopathology result. RESULTS: MRI correctly assessed 11 out of 13 cases, according to RECIST 1.1, compared to histopathology. Among these 7 patients with partial response (PR), 2 cases of CR, 1 SD and 1 PD with persistence or enlargement of primary tumor. CONCLUSION: Our pilot study supports the usefulness of MRI in assessment of treatment response after NACT, followed by CKC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02323841.