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Purpose: Trans-foraminal endoscopic discectomy (TELD) is an alternative surgical technique for lumbar disc herniation (LDH). Compared with microscope-assisted open discectomy, TELD is expected to result in less postoperative low back pain (LBP) and has a lower likelihood of complications. However, some clinical analysis report patients still had persistent LBP at follow-up. Several studies have identified different known risk factors for LBP after TELD, including the preoperative presence of disc height loss and "microinstability" of the lumbar spine, which can be detrimental to a patient's successful outcome., Methods: We conducted a retrospective review of a cohort of 86 patients with symptomatic LDH who underwent TELD surgery in a single Neurosurgery Unit from 2021 to 2023 and subjected themselves to a clinical and radiological follow-up program up to one year, focusing on the presence of collapsed disc (Group A) and the presence of normal intersomatic height (Group B) at the site of lumbar herniation., Results: The two groups demonstrated no significant differences in the pain and disability scales at the preoperative and postoperative phases, both after surgery and during follow-up. However, at the 1-year clinical evaluation, patients who had signs of a collapsed disc before surgery experienced less recovery on the ODI scale compared to the other group CONCLUSION: Our study showed that the presence of severe intervertebral disc height loss, accompanied by pre-operative signs of a collapsed disc at the site of the LDH, may serve as a predictor of poor postoperative pain recovery., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nasal vestibule squamous cell carcinoma (NVSCC) is an exceedingly rare malignancy, often misclassified due to its anatomical location and lack of a standardized definition. This review aims to consolidate current evidence on NVSCC, focusing on epidemiology, risk factors, classification, clinical presentation, treatment modalities, and prognostic factors. The NV anatomy is delineated, emphasizing the need for a clear definition to avoid misclassification. Risk factors include smoking, sunlight exposure, and debated associations with chalk exposure or viral factors. Clinical presentation includes symptoms like nasal obstruction, pain, burning, and bleeding, often misdiagnosed as inflammatory conditions. NVSCC exhibits distinct local spread patterns along cartilaginous surfaces, with the facial and submandibular lymph nodes at higher metastatic risk. Current classifications lack consensus, hindering comparison of outcomes. Treatment varies, with surgery or radiotherapy for early-stage tumors and multimodality approaches for advanced cases. The choice between surgery and radiotherapy is debated, with potential advantages and drawbacks for each. Radiotherapy, especially with Interventional RadioTherapy (IRT, previously known as brachytherapy), is gaining prominence, showing promising outcomes in terms of local control and cosmetic results. Prophylactic neck treatment remains controversial, with indications based on tumor characteristics. Prognostic factors include T classification, tumor size, surgical margins, nodal involvement, and histological features. Long-term survival rates range widely, emphasizing the need for further studies to refine management strategies for this rare malignancy. In conclusion, NVSCC poses diagnostic and therapeutic challenges, warranting multidisciplinary approaches and continued research efforts to optimize patient outcomes., (© 2024. The Author(s).)

Purpose: Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos., Methods: Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation., Results: The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%., Conclusions: The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Large cohort studies and variant-specific electrophysiology have enabled the delineation of different SCN2A-epilepsy phenotypes, phenotype-genotype correlations, prediction of pharmacosensitivity to sodium channel blockers, and long-term prognostication for clinicians and families. One of the most common clinical presentations of SCN2A pathological variants is benign familial neonatal-infantile seizures (BFNIS), which are characterized by seizure onset between the first day of life and 23 months of age and typically resolve, either spontaneously or with the aid of sodium channel blockers, within the first 2 years of life. In 2004, Berkovic et al. reported the case of a young boy affected by SCN2A-related BFNIS whose mother, who carried the same pathological variant, had also presented with BFNIS in infancy. Our case report focuses on the aforementioned woman who, more than 40 years later, presented two additional seizures, therefore opening the possibility of a role for SCN2A-related seizures in adulthood., (© 2024 Wiley Periodicals LLC.)

Introduction: The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimer's disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment., Methods: URPs include ethnoculturally minoritized, lower education (≤ 12 years), and rural populations. The CI-CER model includes: (1) culturally informed methodology (e.g., less restrictive inclusion/exclusion criteria, sociocultural measures, financial compensation, results disclosure, Spanish Language Capacity Workgroup) and (2) inclusive engagement methods (e.g., the Engagement Core team; Hub Sites; Community-Science Partnership Board)., Results: As of April 2024, 60% of ADNI-4 new in-clinic enrollees were from ethnoculturally or educationally URPs. This exceeds ADNI-4's ≥ 50% URP representation goal for new enrollees but may not represent final enrollment., Discussion: Findings show a CI-CER model increases URP enrollment in AD/ADRD clinical research and has important implications for clinical trials to advance health equity., Highlights: The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) uses a culturally informed, community-engaged research (CI-CER) approach. The CI-CER approach is scalable and sustainable for broad, multisite implementation. ADNI-4 is currently exceeding its inclusion goals for underrepresented populations., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Despite the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), most patients with non-small-cell lung cancer (NSCLC) eventually develop resistance to these agents. Notably, EGFR _C797S mutations confer resistance to the third-generation EGFR-TKI osimertinib and no approved post-osimertinib targeted pharmacology options are currently available. BLU-945 is a novel, reversible, and orally available next-generation EGFR-TKI that selectively targets EGFR-activating ( EGFR m) and resistance mutations (including EGFR_C797S) with nanomolar potency while sparing wild-type EGFR in vitro., Methods: In vitro activity of BLU-945 as a single agent and in combination with osimertinib was tested in engineered EGFR -mutant cell lines as well as patient-derived cells and patient-derived organoids. In vivo activity was evaluated in osimertinib-resistant patient-derived xenograft mouse models. Three patient cases from the global, first-in-human, phase I/II SYMPHONY trial (NCT04862780) demonstrating the clinical efficacy of BLU-945 were reported., Results: In vitro BLU-945 demonstrated inhibited cell viability and growth of EGFR -mutant/osimertinib-resistant cell lines. BLU-945 demonstrated in vivo tumor shrinkage in osimertinib-resistant models of NSCLC (osimertinib second line: EGFR _L858R/C797S and third line: EGFR _ex19del/T790M/C797S and L858R/T790M/C797S) both as monotherapy and in combination with osimertinib. BLU-945 also demonstrated tumor shrinkage in patients from the SYMPHONY trial., Conclusion: Our findings demonstrate the preclinical and early clinical activity of BLU-945 in EGFR m NSCLC progressing on previous EGFR-TKIs., Competing Interests: S.M.L. reports grants from AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer-Ingelheim, Bridge BioTherapeutics, Daichii-Sankyo, Eli Lily, Gilead, GlaxoSmithkline, Jiangsu Hengrui Medicine, J Ints Bio, Oscotec, Roche, Takeda, and Yuhan. S.S.S. is a shareholder of Blueprint Medicines Corporation. C.C. is an employee of and a shareholder of Blueprint Medicines Corporation. Y.A.M. is an employee of and a shareholder of Blueprint Medicines Corporation. R.W. is a shareholder of Blueprint Medicines Corporation. Z.Z. is a shareholder of Blueprint Medicines Corporation. L.E.T.-M. reports work was conducted as an employee of Blueprint Medicines Corporation and is currently a shareholder of Blueprint Medicines Corporation. F.S. is a shareholder of Blueprint Medicines Corporation. F.A. is an employee of and a shareholder of Blueprint Medicines Corporation. T.A.D. is an employee of and a shareholder of Blueprint Medicines Corporation. J.H. is an employee of Blueprint Medicines Corporation and a shareholder of Blueprint Medicines Corporation. A.Z. is a shareholder of Blueprint Medicines Corporation. J.R. reports consulting fees or honoraria from Amgen, AstraZeneca, BioAtla, G1 Therapeutics, Genentech, Guardant Health, Jazz, Janssen, Sanofi-Genzyme, Summit, and Takeda Pharmaceuticals, and has also been contracted for research (institutional) with AstraZeneca, BioAtla, Blueprint Medicines, Enliven, EpimAb Biotherapeutics, LOXO Oncology, ORIC, and Redcloud. D.H.L. reports personal fees from AbbVie, AstraZeneca, BC World Pharm, Boehringer-Ingelheim, Bristol-Myers Squibb, ChongKeunDang, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Roche, ST Cube, Takeda Oncology, and Yuhan, and non-financial support from Blueprint Medicines Corporation and Takeda Oncology outside the submitted work. B.C.C. reports grants from AbbVie, AstraZeneca, Bayer, Blueprint Medicines Corporation, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Janssen, MedPacto, Merck Sharp & Dohme, MOGAM Institute, Novartis, Ono, Yuhan, and consultancy fees from AstraZeneca, Blueprint Medicines Corporation, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, Janssen, MedPacto, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan and currently owns stock in BridgeBio Therapeutics, Gencurix Inc, KANAPH Therapeutic Inc, TheraCanVac Inc., has served on a scientific advisory board for KANAPH Therapeutic Inc, receives royalties for Champions Oncology and is the founder of Daan Biotherapeutics., (© The Author(s), 2024.)

For the first time is reported the comparison of solid biocatalysts derived from Candida rugosa lipase (CRL) immobilized on different lignocellulosic wastes (rice husk, brewer's spent grain, hemp tea waste, green tea waste, vine bark, and spent coffee grounds) focusing on the characterization of these materials and their impact on the lipase-support interaction. The wastes were subjected to meticulous characterization by ATR-FTIR, BET, and SEM analysis, besides lignin content and hydrophobicity determination. Investigating parameters influencing immobilization performance revealed the importance of morphology, textural properties, and hydrophobic interactions revealed the importance of morphology, textural properties and especially hydrophobic interactions which resulted in positive correlations between surface hydrophobicity and lipase immobilization efficiency. Hemp tea waste and spent coffee grounds demonstrated superior immobilization performances (7.20 U/g and 8.74 U/g immobilized activity, 102.3% and 33.5% efficiency, 13.4% and 15.4% recovery, respectively). Moreover, they demonstrated good temporal stability (100% and 92% residual activity after 120 days, respectively) and retained 100% of their immobilized activity after five reuses in the hydrolysis of p-nitrophenyl palmitate in hexane. In addition, the study of enzymatic desorption caused by ionic strength and detergent treatments indicated mixed hydrophobic and electrostatic interactions in rice husk, vine bark, and spent coffee grounds supports, while hemp tea waste and green tea waste were dominated by hydrophobic interactions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: We evaluated preliminary feasibility of a digital, culturally-informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4)., Methods: Participants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12-item Everyday Cognition Scale [ECog-12]), Novoic Storyteller speech-based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non-URPs., Results: Of 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty-seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog-12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level., Discussion: Preliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges., Highlights: A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally-informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Chronic pain, with its complex and multidimensional nature, poses significant challenges in identifying effective long-term treatments. There is growing scientific interest in how psychopathological and personality dimensions may influence the maintenance and development of chronic pain. This longitudinal study aimed to investigate whether alexithymia can predict the improvement of pain severity following a treatment-as-usual programme for chronic musculoskeletal pain over and above psychological cofactors (emotional distress, catastrophizing, and self-efficacy). A consecutive sample of 129 patients with diagnosed chronic musculoskeletal pain referred to two tertiary care centres was recruited and treated for 16 weeks. Clinical pain, psychological distress, self-efficacy, catastrophizing, and alexithymia were assessed with validated self-report measures at the first medical visit (T0) and at 16-week follow-up (T1). Compared with non-responder patients (n = 72, 55.8%), those who responded (i.e., reduction of >30% in pain severity; n = 57, 44.2%) reported an overall improvement in psychological variables except alexithymia. Alexithymia showed relative stability between baseline and follow-up within the entire sample and remained a significant predictor of treatment outcome even when other predictive cofactors (i.e., pain interference, depressive symptoms, and catastrophizing) were considered simultaneously. Our results suggest that identifying patients with a co-occurrence between alexithymia, depressive symptoms, catastrophizing, and the stressful experience of chronic pain can be clinically relevant in pain prevention and intervention programs., (© 2024 John Wiley & Sons Ltd.)

Purpose: The primary aim of this systematic review is to assess the efficacy, safety, and cost-effectiveness of high-volume steroid nasal irrigation (SNI) for treating chronic rhinosinusitis (CRS) and allergic rhinitis (AR)., Methods: A systematic review of literature from 2012 to 2024 was conducted using PubMed to identify relevant studies. The search focused on terms related to AR, CRS, and steroid nasal irrigation. Studies were screened for relevance and duplicates removed, resulting in 20 studies being included in the final analysis. These studies were categorized based on their focus on efficacy, safety, or both, and underwent a risk of bias assessment using Cochrane and ROBINS-I tools., Results: Of the 20 studies included, 13 examined the effectiveness of high-volume nasal steroid irrigations, 4 investigated safety, and 3 covered both. High-volume irrigations demonstrated superior efficacy in symptom improvement for CRS and AR compared to nasal sprays, particularly post-surgery. Budesonide was the most commonly used steroid. Safety evaluations indicated no significant hypothalamic-pituitary-adrenal axis suppression or increases in intraocular pressure, although minor adverse events were reported., Conclusion: High-volume steroid nasal irrigations are more effective than standard nasal sprays for CRS and AR, particularly post-surgery, without significant safety concerns. However, no studies on cost-effectiveness were found, suggesting a need for further research in this area., (© 2024. The Author(s).)

Purpose: In the present study, we investigated how tumor distance from midline (TDFM) and depth of invasion (DOI) may affect survival outcomes after compartmental tongue surgery (CTS) for oral tongue squamous cell carcinoma (OTSCC)., Methods: A retrospective series of cT2-T3 OTSCC treated with upfront CTS at our Department from 2010 to 2021 was evaluated. Radiological and pathological DOI and TDFM were correlated. The main outcomes were overall (OS) and loco-regional recurrence free survival (LRRFS). The linear relationship between DOI and TDFM with 2-year OS and LRRFS was tested. Survival estimates were obtained by the Kaplan-Meier method. Univariate analysis was performed for variables of interest, and results expressed in terms of hazard ratios and 95% confidence intervals., Results: A total of 64 patients underwent CTS and neck dissection. No significant difference was found between pathological (pDOI) and radiological DOI (rDOI) (p = 0.321) or between pathological (pTDFM) and radiological TDFM (p = 0.435). Two- and 5-year OS and LRRFS were 85.7% and 70.4%, 84.3% and 76.1%, respectively. A linear and significant relationship with OS (p = 0.020) and LRRFS (p = 0.013) was found for pDOI; although linear, the relationship between pTDFM was not statistically significant for either survival outcomes. Once categorized, the ideal cut-off for pDOI according to OS was set at 10 mm (p = 0.023)., Conclusion: In patients undergoing CTS for primary OTSCC, magnetic resonance-derived rDOI represents an accurate estimate of pDOI, In contrast, TDFM was not associated with OS suggesting that the median raphe is a safe deep margin for CTS., Protocol N: BS/231,009 retrospectively registered., (© 2024. The Author(s).)

Background: Binge eating (BE) is associated with a range of cognitive control deficits related to impulsivity, including lower response inhibition, preference for immediate gratification, and maladaptive decision-making. The aim was to investigate whether impulsivity and BE may interact with the decision process and underlying brain activity in outpatients with overweight or obesity who are starting a treatment to achieve weight loss., Methods: A sample of 26 treatment-seeking outpatients with overweight or obesity was evaluated for impulsivity, BE, and temporal discounting rates. Impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11), according to which two groups were composed: high BIS and low BIS; BE was assessed with the eating disorders module of the Structured Clinical Interview for DSM5-Research Version, according to which two groups were composed: with (BE group) or without BE (NBE group). Changes in subjective value of rewards were measured with the Temporal Discounting Task (TDt) where participants had to choice between sooner but smaller vs. later but larger monetary rewards. These choices were made in two differently delayed conditions ("Now" and "Not-now"). Brain rhythms were recorded through high-density electroencephalogram (hd-EEG) during the TDt., Results: Patients with BE reported more impulsive tendencies and perceived sooner rewards as more gratifying when both options were delayed (Not-now condition, p = 0.02). The reward choice in the TDt was accompanied by a general EEG alpha band desynchronization in parietal areas observed without differences between experimental conditions and patients groups. No effects were observed within the Now condition or in the other EEG bands., Conclusions: The tendency to favor immediate rewards may constitute an obstacle to adhering to treatment plans and achieving weight loss goals for outpatients with overweight or obesity. Clinicians are therefore encouraged to include psychological factors, such as impulsivity and dysfunctional eating behaviors, when designing weight loss programs. By addressing these psychological aspects, clinicians can better support patients in overcoming barriers to adherence and achieving sustainable weight loss., Trial Registration: This study was approved by the Ethics Committee of the Department of Psychological, Health, and Territorial Sciences of the University G. d'Annunzio of Chieti-Pescara (Prot. n. 254 of 03/14/2017)., (© 2024. The Author(s).)

This study presents an application of an Artificial Neural Network (ANN) to detect fluids in an annular flow regime using Prompt-Gamma Neutron Activation Analysis (PGNAA). The ANN was trained using gamma-ray spectra resulting from neutron interactions with chemical elements found in fluids typical of multiphase flow in oil exploration. These spectra were generated through mathematical simulation using the MCNP6 Monte Carlo computer code to model nuclear particle transport. A 241 Am-Be polyenergetic neutron source was simulated for these calculations. Several combinations of fluid fractions were developed to create a dataset used for both training and evaluation of the ANN. The ANN demonstrated robust generalization capabilities by accurately predicting the volume fraction of the three investigated fluids (saltwater, oil, and gas), even for cases not included in the training phase. The combination of ANN and PGNAA proved effective for analyzing multiphase systems, with over 92% of all showing errors of less than 5%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1-3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1-3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0-2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1-2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group., (© 2024. The Author(s).)

The overarching challenge of this research is setting up a procedure to select the most appropriate fraction from complex, heterogeneous materials such as historic mortars in case of radiocarbon dating. At present, in the international community, there is not a unique and fully accepted way of mortar sample preparation to systematically obtain accurate results. With this contribution, we propose a strategy for selecting suitable mortar samples for radiocarbon dating of anthropogenic calcite in binder or lump. A four-step procedure is proposed: (I) good sampling strategies along with architectural and historical surveys; (II) mineralogical, petrographic, and chemical characterization of mortars to evaluate the feasibility of sample dating; (III) a non-destructive multi-analytical characterization of binder-rich portions to avoid geogenic calcite contamination; (IV) carbonate micro-sample preparation and accelerator mass spectrometer (AMS) measurements. The most innovative feature of the overall procedure relies on the fact that, in case of positive validation in step III, exactly the same material is treated and measured in step IV. The paper aims to apply this procedure to the ancient mortar of the Florentine historical building (Trebbio Castle), selecting micro-samples suitable for dating in natural hydraulic mortars. The discussion of the mortar dating results with the historical-archaeological hypotheses provided significant insights into the construction history of the building., (© 2024. The Author(s).)

Spatially offset Raman spectroscopy (SORS) is typically used to non-invasively investigate stratified samples that possess features on a millimeter scale, whereas micro-SORS usually deals with micrometer-thick layered samples. However, there are many instances where these boundaries are intertwined, sometimes indicating the possibility of using both techniques as well as circumstances that present mutual exclusion to their applicability. The aim of this study is to establish an application protocol that provides better insight into their suitability for deployment in various scenarios. The differences and similarities between the two approaches are investigated highlighting their strengths and limitations considering both theoretical and practical aspects. Diverse available parameters entail prospects and restrictions of both techniques and give rise to specific instrumental effects, namely, the overlap between the collection and excitation areas, the percentage of collected area for a given spatial offset, and the accuracy in the definition of the spatial offset (spread effect). These aspects are studied and exemplified on mockup samples relevant to the field of cultural heritage. The samples are characterized by high compositional complexity comprising features ranging from micrometer to millimeter scales. The conclusions reached are also relevant to other scientific areas such as biomedical, forensic, or energy harvest., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this paper.

The REarranged during Transfection (RET) receptor tyrosine kinase plays a crucial role in the development of various anatomical structures during embryogenesis and it is involved in many physiological cellular processes. This protein is also associated with the initiation of various cancer types, such as thyroid cancer, non-small cell lung cancer, and multiple endocrine neoplasms. In breast cancer, and especially in the estrogen receptor-positive (ER+) subtype, the activity of RET is of notable importance. Indeed, RET seems to be involved in tumor progression, resistance to therapies, and cellular proliferation. Nevertheless, the ways RET alterations could impact the prognosis of breast cancer and its response to treatment remain only partially elucidated. Several inhibitors of RET kinase have been developed thus far, with various degrees of selectivity toward RET inhibition. These molecules showed notable efficacy in the treatment of RET-driven tumors, including some breast cancer cases. Despite these encouraging results, further investigation is needed to fully understand the potential role RET inhibition in breast cancer. This review aims to recapitulate the existing evidence about the role of RET oncogene in breast cancer, from its pathogenic and potentially prognostic role, to the clinical applications of RET inhibitors., Competing Interests: FM advisory role and honoraria from Amgen; Daiichi-Sankyo; Eli-Lilly; Gilead; GSK; Novartis; Pfizer; Roche. Support for travels and accommodations from Eli-Lilly; Gilead; Pfizer; Roche; Sophos. MG advisory role and honoraria from AstraZeneca, Daichii Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini Stemline; MSD, Novartis, Pfizer, Roche, Seagen. Support for travels and accommodations from Lilly, Pfizer, AstraZeneca. Research funding to the institution from AstraZeneca. PV advisory role and honoraria from Astra-Zeneca; Daiichi-Sankyo; Eli-Lilly; Gilead; Incyte; Istituto Gentili; Novartis; Pfizer; Roche; Seagen; Teva. Support for travel and accommodation from Daiichi-Sankyo; Eli-Lilly; Novartis. Research funding to the institution from Novartis and AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Di Grazia, Conti, Nucera, Motta, Martorana, Stella, Massimino, Giuliano and Vigneri.)

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults., Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3., Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease., Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board., Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion., Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources)., Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples ( p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy ( p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.

Antibody-drug conjugates (ADCs) represent an effective class of agents for the treatment of several tumor types, including breast cancer (BC), featuring approved molecules such as trastuzumab-emtansine, trastuzumab-deruxtecan, and sacituzumab-govitecan. Immune-checkpoint inhibitors (ICIs) also showed activity in selected BC subtypes, and two agents, pembrolizumab and atezolizumab, are currently approved for the treatment of triple-negative BC patients. The potential synergy between ADCs and immunotherapy in BC remains an area of active investigation. Preclinical studies suggest that ADCs promote immune surveillance, modulating tumor microenvironment, inducing immunogenic cell death, and enhancing antitumor immunity. Translational evidence has shown potential predictive biomarkers for ADCs alone or in combination with immunotherapy, including expression of target antigen, oncogenic pathways, tumor-infiltrating lymphocytes, and neutrophil-to-lymphocyte ratio. Given this background, several clinical trials evaluated ADC-ICI combinations in BC patients, demonstrating promising outcomes with an overall manageable toxicity profile, and many studies are currently ongoing to confirm the efficacy and feasibility of this therapeutic approach. In the present review, we summarized the available evidence about the integration of ADCs and immunotherapy for the management of BC, emphasizing the need for further translational and clinical investigations to optimize this treatment strategy and elucidate predictive biomarkers, eventually improving patient outcomes.

Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alain Hendlisz: Consultancy, advisory roles, honoraria from Amgen, Bayer, Eli Lilly, Merck, Pierre Fabre, Servier, Sirtex. Research funding (institutional) from Amgen, Astra Zeneca, Ipsen, Leo Pharma, Merck, Roche, Sanofi, Teva Pharma. Support for travel/accomodation from Merck, Roche, Sirtex. Francesco Sclafani: Consultancy, advisory roles, honoraria from AMAL Therapeutics, Amgen, Bayer, BMS, Dragonfly Therapeutics, GSK, Merck, Nordic Pharma, Roche, Servier. Research funding (institutional) from Amgen, Astellas, Astra Zeneca, Bayer, BMS, Merck, MSD, Pierre-Fabre, Roche, Sanofi. Support for travel/accomodation from Amgen, Bayer, Lilly, Merck, Roche, Servier. Leadership role: Secretary of the EORTC Gastrointestinal Tract Cancer Group. All other Authors do not have conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Optical beams with nonuniform polarization offer enhanced capabilities for information transmission, boasting increased capacity, security, and resilience. These beams possess vectorial features that are spatially organized within localized three-dimensional regions, forming tensors that can be harnessed across a spectrum of applications spanning quantum physics, imaging, and machine learning. However, when subjected to the effect of the transmission channel, the tensorial propagation leads to a loss of data integrity due to the entanglement of spatial and polarization degrees of freedom. The challenge of quantifying this spatial-polarization coupling poses a significant obstacle to the utilization of vector beams in turbulent environments, multimode fibers, and disordered media. Here, we introduce and experimentally investigate mosaic vector beams, which consist of localized polarization tesserae that propagate in parallel, demonstrating accurate measurement of their behavior as they traverse strongly disordered channels and decoding their polarization structure in single-shot experiments. The resultant transmission tensor empowers polarization-based optical communication and imaging in complex media. These findings also hold promise for photonic machine learning, where the engineering of tensorial flow can enable optical computing with high throughput.

Background: Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8 + T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity., Results: One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1β, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8 + T cells, and (ii) decreased early precursors CD8 + T stem cell-like memory cells (TSCM) and CD27 + CD28 + . The cytokines mentioned above were found at higher concentrations in the COVID-19 + older cohort compared to a younger cohort in which they were not associated with disease severity., Conclusions: Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care., (© 2024. The Author(s).)

Objective: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer., Design: prospective, observational, multicenter cohort., Setting and Participants: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score., Statistical Methods: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni' correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care)., Results: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19-1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39-2.29] (p < 0.001)., Conclusion: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Study Design: A prospective cohort study., Objectives: To examine the use of a circle-tracing task in quantifying hand functional recovery in cervical spinal cord injury patients., Methods: Ten cervical spinal cord injury (SCI) patients and 10 healthy age-matched controls performed a circle-tracing task, using a computerized tablet at the beginning of the study and after 4 weeks. Data relative to performance accuracy as well as pen pressure throughout the performances were collected, and clinical assessment for all patients was performed at the beginning and at the end of the study., Results: Significant differences were found in pen pressure profiles in the SCI patients between the initial assessment and after 4 weeks of assessment. SCI patients, when compared with controls, apply less pressure during the execution, though no significant differences were found for the other parameters. Examination of pen pressure profiles of both controls and SCI patients reveals that, in addition to the lower pressure registered, SCI patients present a more oscillating pressure profile which is direction-dependent. No significant correlations were found between clinical assessments and pen pressure, both within the initial assessment as well as after 4 weeks., Conclusions: This study emphasizes the potential of simple computerized means for quantifying upper limb functions in SCI patients. These results of this study could be helpful for both highlighting specific functional deficits in patients as well tailoring specific interventions.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers., Research Question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy., Materials and Methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers., Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request., Discussion and Conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

We investigate the subsurface composition of turbid materials at the micro scale by means of a portable non-invasive technique, micro-spatially offset Raman spectroscopy (micro-SORS), combined with shifted excitation Raman difference spectroscopy (SERDS). This combination enables the microscale layer analysis and allows to deal effectively with highly fluorescing samples as well as ambient light, all in a form of an in-house portable prototype device optimised for applications in heritage science. The instrument comprises ability to simultaneously collect multiple spectra by means of an optical fibre bundle, thus reducing the dead time and simplifying the ease of deployment of the technique. The performance of the synergy between micro-SORS and 785 nm SERDS dual-wavelength diode laser is demonstrated on a stratified mock-up painting samples including highly fluorescing painted layers. This instrumental approach could be ground-breaking in heritage science, due to the largely unmet need of analysing the molecular composition of subsurface of artworks non-invasively and in situ , and in the presence of fluorescent background and ambient light. Moreover, many other fields are expected to benefit from this technological advancement such as solar energy, forensic and food analytical areas.

The issue of preserving carbonatic stones of cultural heritage (CH) restored in the past that have undergone new decay phenomena is strongly emerging and conservation science has not yet found a reliable solution. In this paper, we propose the application of synchrotron radiation X-ray diffraction computed tomography (XRDCT) to explore the effects of using inorganic-mineral products (ammonium oxalate; ammonium phosphate) in sequence as a novel, compatible and effective re-treatment approach to consolidate decayed carbonatic stones already treated with inorganic-mineral treatments. High-quality XRDCT datasets were used to qualitatively/quantitatively investigate and 3D localize the complex mixture of crystalline phases formed after the conservation re-treatments within a porous carbonatic stone substrate. The XRDCT reconstruction images and the structural refinements of XRD patterns with the Rietveld methods showed that the phase composition of reaction products, their volume distribution, and weight fraction vary as a function of the treatment sequence and penetration depth. The high potential of XRDCT allows (i) assessment of peculiar trends of each treatment/treatment sequence; (ii) exploration of the reaction steps of the sequential treatments and (iii) demonstration of the consolidating effect of inorganic re-treatments, non-destructively and at the micron scale. Above all, our study (i) provides new analytical tools to support the conservation choices, (ii) showcases new analytical possibilities for XRDCT in conservation science, including in investigations of CH materials and decay processes, and (iii) opens up new perspectives in analytical chemistry and material characterisation for the non-destructive and non-invasive analysis of reactions within heterogeneous polycrystalline systems.

This study explores the possibility of using microspatially offset Raman spectroscopy (micro-SORS) imaging to reconstruct noninvasively letters and figures hidden by opaque layers. Micro-SORS experiments were conducted on mockup samples that mimic real situations encountered in the cultural heritage field, such as sealed letters with inaccessible text and original documents. Subsurface images were obtained using both the characteristic Raman bands of the hidden compounds and their different optical properties from the remaining matrix. In the latter case, contrast obtained through observing a difference in the overall spectral intensity and fluorescence profile rather than any specific Raman bands were used to track the images within the hidden layer. This approach opens new prospects for the use of micro-SORS in heritage science, with applications in the field that include the study of objects covered by opaque overlayers not only through their Raman signatures but also through differences in their optical properties (e.g., fluorescence emission, absorption).

Background: There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment., Methods: Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19.  Results: The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma)., Conclusion: In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.

Background: Chronic pain is one of the most common and critical long-term effects of breast cancer. Digital health technologies enhance the management of chronic pain by monitoring physical and psychological health status and supporting pain self-management and patient treatment decisions throughout the clinical pathway., Objective: This pilot study aims to evaluate patients' experiences, including usability, with a novel digital integrated health ecosystem for chronic pain named PainRELife. The sample included patients with breast cancer during survivorship. The PainRELife ecosystem comprises a cloud technology platform interconnected with electronic health records and patients' devices to gather integrated health care data., Methods: We enrolled 25 patients with breast cancer (mean age 47.12 years) experiencing pain. They were instructed to use the PainRELife mobile app for 3 months consecutively. The Mobile Application Rating Scale (MARS) was used to evaluate usability. Furthermore, pain self-efficacy and participation in treatment decisions were evaluated. The study received ethical approval (R1597/21-IEO 1701) from the Ethical Committee of the European Institute of Oncology., Results: The MARS subscale scores were medium to high (range: 3.31-4.18), and the total app quality score was 3.90. Patients with breast cancer reported reduced pain intensity at 3 months, from a mean of 5 at T0 to a mean of 3.72 at T2 (P=.04). The total number of times the app was accessed was positively correlated with pain intensity at 3 months (P=.03). The engagement (P=.03), information (P=.04), and subjective quality (P=.007) subscales were positively correlated with shared decision-making. Furthermore, participants with a lower pain self-efficacy at T2 (mean 40.83) used the mobile app more than participants with a higher pain self-efficacy (mean 48.46; P=.057)., Conclusions: The data collected in this study highlight that digital health technologies, when developed using a patient-driven approach, might be valuable tools for increasing participation in clinical care by patients with breast cancer, permitting them to achieve a series of key clinical outcomes and improving quality of life. Digital integrated health ecosystems might be important tools for improving ongoing monitoring of physical status, psychological burden, and socioeconomic issues during the cancer survivorship trajectory., International Registered Report Identifier (irrid): RR2-10.2196/41216., (©Marianna Masiero, Chiara Filipponi, Elisa Fragale, Silvia Francesca Maria Pizzoli, Elisabetta Munzone, Alessandra Milani, Luca Guido, Vittorio Guardamagna, Sara Marceglia, Roberto Prandin, Marco Prenassi, Annamaria Caruso, Vania Manzelli, Chiara Savino, Costanza Conti, Federica Rizzi, Alice Casalino, Giulia Candiani, Francesca Memini, Luca Chiveri, Andrea Luigi Vitali, Massimo Corbo, Roberto Grasso, Florence Didier, Roberta Ferrucci, Gabriella Pravettoni. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.02.2024.)

Background: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression., Methods: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated., Results: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment., Discussion: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Classical and quantum systems are used to simulate the Ising Hamiltonian, an essential component in large-scale optimization and machine learning. However, as the system size increases, devices like quantum annealers and coherent Ising machines face an exponential drop in their success rate. Here, we introduce a novel approach involving high-dimensional embeddings of the Ising Hamiltonian and a technique called "dimensional annealing" to counteract the decrease in performance. This approach leads to an exponential improvement in the success rate and other performance metrics, slowing down the decline in performance as the system size grows. A thorough examination of convergence dynamics in high-performance computing validates the new methodology. Additionally, we suggest practical implementations using technologies like coherent Ising machines, all-optical systems, and hybrid digital systems. The proposed hyperscaling heuristics can also be applied to other quantum or classical Ising devices by adjusting parameters such as nonlinear gain, loss, and nonlocal couplings.

Intraoperative neurophysiological monitoring (IONM) is needed for evaluating and demonstrating the integrity of the central and peripheral nervous system during surgical manoeuvres that take place in proximity to eloquent motor and somatosensory nervous structures. The integrity of the monitored motor pathways is not always followed by consistent clinical normality, particularly in the first hours/days following surgery, when surgical resection involves brain structures such as the supplementary motor areas (SMA). We report the case of a patient who underwent surgical excision of a right frontal glioblastoma with normal preoperative, intraoperative (IONM), and postoperative central motor conduction, but with persistent postoperative hemiplegia (> 6 months). The literature regarding SMA syndrome and its diagnosis and prognosis is reviewed., (© 2023. Fondazione Società Italiana di Neurologia.)

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines., Competing Interests: Declaration of interests S.P. is founder, CSO, and shareholder (>5%) of CITC Ltd. and Chair of the Scientific Advisory Board at ReNeuron plc., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications., Materials and Methods: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion., Results: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases., Conclusions: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management., (© 2023. Fondazione Società Italiana di Neurologia.)

This longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lanzara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diagnosis and prognostic stratification of myelodysplastic syndromes (MDS) have been complemented by new techniques, including flow cytometry and NGS. To analyze the relationship between molecular and cytofluorimetric data, we enrolled in this retrospective study, 145 patients, including 106 diagnosed with MDS and 39 controls. At disease onset, immunophenotypic (IF), cytogenetic tests, and cytomorphological (CM) examination on bone marrow were carried out in all patients, while NGS was performed in 58 cases. Ogata score presented a specificity of 100% and a sensitivity of 59%. The detection of at least two phenotypic aberrancies in Ogata negative patients increased the sensitivity to 83% and specificity to 87%. Correlations were identified between IF aberrancies and mutations, including positive Ogata>2 and mutations in SRSF2 (p=0.035), CD15 and U2AF1 (0.032), CD56 and DNMT3A (p=0.042), and CD38 and TP53 (p=0.026). In multivariate analysis, U2AF1 mutations, associated with del(20q) and/or abnormalities of chromosome 7 (group 4 as defined by the EuroMDS score), significantly correlated with an inferior overall survival (p=0.019). These parameters and Ogata score>2 also showed a significant correlation with inferior event-free survival (p=0.023 and p=0.041, respectively). Both CM and FC features correlated with prognosis and mutational patterns. In an integrated MDS work-up, these tools may guide indications for mutational screening for optimal risk stratification., (© 2023. The Author(s).)

Chronic pain is a condition in which the use of digital health technologies, ecological momentary assessments, and digital communication tools may boost patient's engagement and coping. Here we present the results of the PainRE-Life a project, financed by the Lombardy Region (Italy), aimed to develop a dynamic and integrated technology ecosystem based on big data management and analysis to allow care continuity in patients with pain, and able to act as a decision aid for patients and caregivers.

In this work, we present a method to characterize the transmission matrices of complex scattering media using a physics-informed, multi-plane neural network (MPNN) without the requirement of a known optical reference field. We use this method to accurately measure the transmission matrix of a commercial multi-mode fiber without the problems of output-phase ambiguity and dark spots, leading to up to 58% improvement in focusing efficiency compared with phase-stepping holography. We demonstrate how our method is significantly more noise-robust than phase-stepping holography and show how it can be generalized to characterize a cascade of transmission matrices, allowing one to control the propagation of light between independent scattering media. This work presents an essential tool for accurate light control through complex media, with applications ranging from classical optical networks, biomedical imaging, to quantum information processing.

During chronic kidney disease (CKD) progression, an increase in fibroblast growth factor (FGF23) is present. In stage 5, a positive correlation between FGF23 and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) emerges. Hypothesizing that the rising positive correlation between monocyte chemoattractant protein 1 (MCP1) and n-6 in stage 4 could be the cause, we previously explored FGF23 and MCP1's roles in dyslipidemia and cardiovascular risk in CKD. In the present paper, we retraced the study evaluating 40 kidney transplant patients (KTx), a cohort where several factors might modify the previous relationships found. An ELISA and gas chromatography assessed the MCP1, FGF23, and PUFA levels. Despite the FGF23 increase ( p < 0.0001), low MCP1 levels were found. A decrease in the n-6/n-3 ratio ( p = 0.042 CKD stage 4 vs. 5) lowered by the increase in both n-3 αlinolenic ( p = 0.012) and docosapentaenoic acid ( p = 0.049) was observed. A negative correlation between FGF23 and the n-6/n-3 ratio in CKD stage 4 (r 2 -0.3 p = 0.043) and none with MCP1 appeared. According to our findings, different mechanisms in the relationship between FGF23, PUFAs, and MCP1 in CKD and KTx patients might be present, which is possibly related to the immunosuppressive status of the last. Future research will further clarify our hypothesis.

Extreme waves are intense and unexpected wavepackets ubiquitous in complex systems. In optics, these rogue waves are promising as robust and noise-resistant beams for probing and manipulating the underlying material. Localizing large optical power is crucial especially in biomedical systems, where, however, extremely intense beams have not yet been observed. We here discover that tumor-cell spheroids manifest optical rogue waves when illuminated by randomly modulated laser beams. The intensity of light transmitted through bio-printed three-dimensional tumor models follows a signature Weibull statistical distribution, where extreme events correspond to spatially-localized optical modes propagating within the cell network. Experiments varying the input beam power and size indicate that the rogue waves have a nonlinear origin. We show that these nonlinear optical filaments form high-transmission channels with enhanced transmission. They deliver large optical power through the tumor spheroid, and can be exploited to achieve a local temperature increase controlled by the input wave shape. Our findings shed light on optical propagation in biological aggregates and demonstrate how nonlinear extreme event formation allows light concentration in deep tissues, paving the way to using rogue waves in biomedical applications, such as light-activated therapies., (© 2023. Springer Nature Limited.)

Breast cancer (BC) remains the most diagnosed cancer in women, accounting for 12% of new annual cancer cases in Europe and worldwide. Advances in surgery, radiotherapy and systemic treatment have resulted in improved clinical outcomes and increased survival rates in recent years. However, BC therapy-related cardiotoxicity, may severely impact short- and long-term quality of life and survival. This study presents the CARDIOCARE platform and its main components, which by integrating patient-specific data from different categories, data from patient-oriented eHealth applications and wearable devices, and by employing advanced data mining and machine learning approaches, provides the healthcare professionals with a valuable tool for effectively managing BC patients and preventing or alleviating treatment induced cardiotoxicity.Clinical Relevance- Through the adoption of CARDIOCARE platform healthcare professionals are able to stratify patients for their risk for cardiotoxicity and timely apply adequate interventions to prevent its onset.

Morgagni hernia (MH) is a rare congenital diaphragmatic hernia (CDH) that accounts for less than 2% of surgically repaired CDH in adulthood. Even if this condition is often asymptomatic, surgery is advised due to the risk of life-threatening complications such as volvulus or bowel strangulation. Surgery for MH repair can be performed by transthoracic, transabdominal, laparoscopic, or thoracoscopic approaches. Though laparoscopy has recently improved surgical outcomes, the use of prosthetic meshes and the need for reduction of the hernia sac are still the most debated issues. We present the video of a laparoscopic repair of a large MH with the use of a double mesh technique and no resection of the hernia sac., Competing Interests: Conflict of interest All authors have no conflicts of interest to declare., (© 2023 The Korean Society of Endo-Laparoscopic & Robotic Surgery.)

Here, we demonstrate, for the first time, the possibility of distinguishing between geogenic and anthropogenic calcite in a non-destructive and effective way. Geogenic calcite derives from natural sedimentary and metamorphic rocks whereas anthropogenic calcite is formed artificially due to the carbonation process in mortars and plaster lime binders. Currently, their distinction is a major unaddressed issue although it is crucial across several fields such as 14 C dating of historical mortars to avoid contamination with carbonate aggregates, investigating the origins of pigments, and studying the origins of sediments, to name a few. In this paper, we address this unmet need combining high-resolution micro-Raman spectroscopy with data mining and machine learning methods. This approach provides an effective means of obtaining robust and representative Raman datasets from which samples' origins can be effectively deduced; moreover, a distinction between sedimentary and metamorphic calcite has been also highlighted. The samples, chemically identical, exhibit systematic and reliable differences in Raman band positions, band shape and intensity, which are likely related to the degree of structural order and polarization effects.

Introduction: Emerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values., Methods: Retrospective analysis of patients who underwent surgery for CRC at our center (2005 - 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed., Results: Pre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery., Conclusion: To our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Turri, Caligola, Ugel, Conti, Zenuni, Barresi, Ruzzenente, Lippi, Scarpa, Bronte, Guglielmi and Pedrazzani.)