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Abstract Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix.

Background: Electrical Impedance Tomography (EIT), combined with variable ventilation strategies and Artificial Intelligence (AI), is poised to revolutionize critical care by transitioning from reactive to predictive approaches. This integration aims to enhance patient outcomes through personalized interventions and real-time monitoring. Methods: this narrative review explores the principles and applications of EIT, variable ventilation, and AI in critical care. EIT impedance sensing creates dynamic images of internal physiology, aiding the management of conditions like Acute Respiratory Distress Syndrome (ARDS). Variable ventilation mimics natural breathing variability to improve lung function and minimize ventilator-induced lung injury. AI enhances EIT through advanced image reconstruction techniques, neural networks, and digital twin technology, offering more accurate diagnostics and tailored therapeutic interventions. Conclusions: the confluence of EIT, variable ventilation, and AI represents a significant advancement in critical care, enabling a predictive, personalized approach. EIT provides real-time insights into lung function, guiding precise ventilation adjustments and therapeutic interventions. AI integration enhances EIT diagnostic capabilities, facilitating the development of personalized treatment plans. This synergy fosters interdisciplinary collaborations and sets the stage for innovative research, ultimately improving patient outcomes and advancing the future of critical care.

Background: Mechanical ventilation significantly improves patient survival but is associated with complications, increasing healthcare costs and morbidity. Identifying optimal weaning times is paramount to minimize these risks, yet current methods rely heavily on clinical judgment, lacking specificity. Methods: This study introduces a novel multiparametric predictive score, the MUSVIP (MUltiparametric Score for Ventilation discontinuation in Intensive care Patients), aimed at accurately predicting successful extubation. Conducted at Santo Stefano Hospital’s ICU, this single-center, observational, prospective cohort study will span over 12 months, enrolling adult patients undergoing invasive mechanical ventilation. The MUSVIP integrates variables measured before and during a spontaneous breathing trial (SBT) to formulate a predictive score. Results: Preliminary analyses suggest an Area Under the Curve (AUC) of 0.815 for the MUSVIP, indicating high predictive capacity. By systematically applying this score, we anticipate identifying patients likely to succeed in weaning earlier, potentially reducing ICU length of stay and associated healthcare costs. Conclusion: This study’s findings could significantly influence clinical practices, offering a robust, easy-to-use tool for optimizing weaning processes in ICUs.

High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer (OC), occurring in more than 80% of patients diagnosed with this malignancy. Histological and genetic analysis have confirmed the secretory epithelial of the fallopian tube (FT) as a major site of origin of HGSOC. Although there have been significant strides in our understanding of this disease, early stage detection and diagnosis are still rare. Current clinical imaging modalities lack the ability to detect early stage pathogenesis in the fallopian tubes and the ovaries. However, there are several microscopic imaging techniques used to analyze the structural modifications in the extracellular matrix (ECM) protein collagen in ex vivo FT and ovarian tissues that potentially can be modified to fit the clinical setting. In this perspective, we evaluate and compare the myriad of optical tools available to visualize these alterations and the invaluable insights these data provide on HGSOC initiation. We also discuss the clinical implications of these findings and how these data may help novel tools for early diagnosis of HGSOC.

Physical therapy keeps exploiting more and more the capabilities of the robot of adapting the treatments to patients’ needs. This paper aims at presenting a psychophysiological-aware control strategy for upper limb robot-aided orthopedic rehabilitation. The main features are the capability of i) generating point-to-point trajectories inside an adaptable workspace, ii) providing assistance in guiding the patients’ limbs in accomplishing the assigned task allowing them to freely move with a certain degree of spatial and temporal autonomy and iii) tuning the control parameters according to the patients’ kinematics performance and psychophysiological state. The implemented control strategy is validated in a real clinical setting on eight orthopedic patients undergoing twenty daily robot-aided rehabilitation sessions. The psychophysiological-aware control strategy evidenced a positive impact on the enrolled participants since they are effectively conducted in a calmer condition with respect to the patients who did not receive the psychophysiological adaptation. Moreover, clinical performance indicators suggest that the proposed tailored control strategy improves motor functions.

ABSTRACT Enteroviruses are one of the most abundant viruses causing mild to serious acute infections in humans and also contributing to chronic diseases like type 1 diabetes. Presently, there are no approved antiviral drugs against enteroviruses. Here, we studied the potency of vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, as an antiviral against enteroviruses. We showed that vemurafenib prevented enterovirus translation and replication at low micromolar dosage in an RAF/MEK/ERK-independent manner. Vemurafenib was effective against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Forest virus, adenovirus, and respiratory syncytial virus. The inhibitory effect was related to a cellular phosphatidylinositol 4-kinase type IIIβ (PI4KB), which has been shown to be important in the formation of enteroviral replication organelles. Vemurafenib prevented infection efficiently in acute cell models, eradicated infection in a chronic cell model, and lowered virus amounts in pancreas and heart in an acute mouse model. Altogether, instead of acting through the RAF/MEK/ERK pathway, vemurafenib affects the cellular PI4KB and, hence, enterovirus replication, opening new possibilities to evaluate further the potential of vemurafenib as a repurposed drug in clinical care. IMPORTANCE Despite the prevalence and medical threat of enteroviruses, presently, there are no antivirals against them. Here, we show that vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, prevents enterovirus translation and replication. Vemurafenib shows efficacy against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Forest virus, adenovirus, and respiratory syncytial virus. The inhibitory effect acts through cellular phosphatidylinositol 4-kinase type IIIβ (PI4KB), which has been shown to be important in the formation of enteroviral replication organelles. Vemurafenib prevents infection efficiently in acute cell models, eradicates infection in a chronic cell model, and lowers virus amounts in pancreas and heart in an acute mouse model. Our findings open new possibilities to develop drugs against enteroviruses and give hope for repurposing vemurafenib as an antiviral drug against enteroviruses.

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.

Background: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. Methods: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant’s posture in accordance with the patient’s needs). Results: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). Conclusions: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.

Abstract Background Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. Methods In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio

IntroductionRobotic therapy allow to propose sessions of controlled and identical exercises, customizing settings, and characteristics on the individual patient. The effectiveness of robotic assisted therapy is still under study and the use of robots in clinical practice is still limited. Moreover, the possibility of treatment at home allows to reduce the economic costs and time to be borne by the patient and the caregiver and is a valid tool during periods of pandemic such as covid. The aim of this study is to assess whether a robotic home-based treatment rehabilitation using the iCONE robotic device has effects on a stroke population, despite the chronic condition of patients involved and the absence of a therapist next to the patient while performing the exercises.Materials and methodsAll patients underwent an initial (T0) and final (T1) assessment with the iCONE robotic device and clinical scales. After T0 evaluation, the robot was delivered to the patient's home for 10 days of at-home treatment (5 days a week for 2 weeks).ResultsComparison between T0 and T1 evaluations revealed some significant improvements in robot-evaluated indices such as Independence and Size for the Circle Drawing exercise and Movement Duration for Point-to-Point exercise, but also in the MAS of the elbow. From the analysis of the acceptability questionnaire, a general appreciation of the robot emerged: patients spontaneously asked for the addition of further sessions and to continue therapy.DiscussionTelerehabilitation of patients suffering from a chronic stroke is an area that is still little explored. From our experience, this is one of the first studies to carry out a telerehabilitation with these characteristics. The use of robots can become a method to reduce the rehabilitation health costs, to ensure continuity of care, and to arrive in more distant places or where the availability of resources is limited.ConclusionFrom the data obtained, this rehabilitation seems to be promising for this population. Moreover, promoting the recovery of the upper limb, iCONE can improve patient's quality of life. It would be interesting to conduct RCT studies to compare a conventional treatment in structure with a robotic telematics treatment.

Background & Aims: Type 1 autoimmune pancreatitis (AIP) is an IgG4-related disease whose diagnosis is challenging. The aim of this study was to investigate the diagnostic value of circulating total and IgG4+ plasmablasts in differentiating this condition from the other main pancreatic diseases. Methods: Patients with type 1 AIP (n = 19) were prospectively enrolled in a tertiary center together with patients suffering from type 2 or not otherwise specified (NOS) AIP (n = 10), pancreatic adenocarcinoma (n = 17), chronic pancreatitis (n = 20), and intraductal papillary mucinous neoplasia or chronic asymptomatic pancreatic hyperenzymemia (n = 21) as control groups. Flow cytometry was used to measure the total plasmablast and IgG4+ plasmablast number by gating peripheral blood CD45+CD19+CD38hiCD20-CD24-CD27+ and CD45+CD19+CD38hiCD20-CD24-CD27+IgG4+ cells, respectively. In patients with AIP, these cell populations were also evaluated after 1 month of therapy, after 2–4 months from the end of treatment, and after 1 year from the enrollment. The study was approved by the local ethics committee (protocol number: 59133, 30/11/2017). Results: Total plasmablast quantification was capable of discriminating type 1 AIP from all the other pancreatic disorders with a sensitivity of 47% and a specificity of 81%, according to a cutoff of 4500 cells/mL (AUC = 0.738), whereas IgG4+ plasmablast count distinguished type 1 AIP from all the other pancreatic disorders with a sensitivity of 80% and a specificity of 97% when applying a cutoff of 210 IgG4+ cells/mL (AUC = 0.879). The basal IgG4+ plasmablast number was significantly higher (P = .0001) in type 1 AIP than in type 2/NOS AIP, decreased after steroid therapy, and increased at disease relapse. Conclusion: IgG4+ plasmablast count represents a potentially useful biomarker to differentiate type 1 from type 2/NOS AIP and from other pancreatic diseases.

Background. Direct access in physiotherapy (DAPT) occurs when a patient has the ability to self-refer to physical therapy without physician referral. This model of care in musculoskeletal diseases (MSDs) has shown better outcomes than the traditional-based medical model of care that requires physician referral to access physiotherapist services. This traditional physician referral often results in a delay in care. Unfortunately, DAPT is still not permitted in many countries. Objectives. The primary objective of this systematic review was to compare the effectiveness, safety, and the accuracy of DAPT compared to the physician-led model of care for the management of patients with musculoskeletal disorders. The secondary objective of the present study is to define the physiotherapists’ characteristics or qualifications involved in DAPT. Materials and methods. Databases searched included: Medline, Scopus and Web of Science. Databases were searched from their inception to July 2022. Research strings were developed according to the PICO model of clinical questions (patient, intervention, comparison, and outcome). Free terms or synonyms (e.g., physical therapy; primary health care; direct access; musculoskeletal disease; cost-effectiveness) and when possible MeSH (Medical Subject Headings) terms were used and combined with Boolean operators (AND, OR, NOT). Risk of bias assessment was carried out through Version 2 of the Cochrane risk-of-bias tool (ROB-2) for randomized controlled trials (RCTs) and the Newcastle Ottawa Scale (NOS) for observational studies. Authors conducted a qualitative analysis of the results through narrative analysis and narrative synthesis. The narrative analysis was provided for an extraction of the key concepts and common meanings of the different studies, while the summary narrative provided a textual combination of data. In addition, a quantitative analysis was conducted comparing the analysis of the mean and differences between the means. Results. Twenty-eight articles met the inclusion criteria and were analyzed. Results show that DAPT had a high referral accuracy and a reduction in the rate of return visits. The medical model had a higher use of imaging, drugs, and referral to another specialist. DAPT was found to be more cost-effective than the medical model. DAPT resulted in better work-related outcomes and was superior when considering patient satisfaction. There were no adverse events noted in any of the studies. In regard to health outcomes, there was no difference between models. ROB-2 shows an intermediate risk of bias risk for the RCTs with an average of 6/9 points for the NOS scale for observational studies. Conclusion. DAPT is a safe, less expensive, reliable triage and management model of care that results in higher levels of satisfaction for patients compared to the traditional medical model. Prospero Registration Number: CRD42022349261.

We introduce the feature issue on the Optics in the Life Sciences Congress held on April 2-5, 2017 in San Diego, CA. The Congress consisted of 5 topical symposia: (i) Bio-optics Design and Application; (ii) Novel Techniques in Microscopy; (iii) Optical Molecular Probes, Imaging and Drug Delivery; (iv) Optical Trapping Applications; and (v) Optics and the Brain. These separate symposia also held joint sessions of common interest. The following highlights some of the topics from the Congress.

Objective: This qualitative study utilises the Behaviour Change Wheel (BCW) approach to identify barriers and enablers to the delivery of email communication in a mental health helpline service for young people, which are then linked to specific intervention strategies for improvement. Methods: Semi-structured interviews were conducted with ten volunteers working for a free online helpline service for young people. Transcripts of the interviews were coded according to deductive then inductive themes. Results: Ten core themes were identified. These were barriers or enablers, depending on the volunteers’ level of experience with the email service. Enablers included the volunteers’ skills, the resources and support offered to them. Barriers related to the asynchronous nature of email communication, need for additional training and volunteers’ lack of confidence and motivation in responding to emails. Innovation: This study expands current research on online mental health support by showing how the BCW can be a useful tool to identify influences on email helpline provision and offer strategies for its optimisation. Conclusion: Offering training targeted to the email service, increasing the level of practice with mock-up emails, and introducing newsletters featuring positive feedback on the email service may improve the delivery of email helpline services for young people.

Abstract Background Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation. Methods Preterm infants with gestational age

Gait impairment is one of the most common disorders of patients with chronic stroke, which hugely affects the ability to carry out the activities of daily living and the quality of life. Recently, traditional rehabilitation techniques have been associated with non-invasive brain stimulation (NIBS) techniques, which enhance brain plasticity, with the aim of promoting recovery in patients with chronic stroke. NIBS effectiveness in improving gait parameters in patients with chronic stroke has been in several studies evaluated. Robotic devices are emerging as promising tools for the treatment of stroke-related disabilities by performing repetitive, intensive, and task-specific treatments and have been proved to be effective for the enhancement of motor recovery in patients with chronic stroke. To date, several studies have examined the combination of NIBS with robotic-assisted gait training, but the effectiveness of this approach is not yet well established. The main purpose of this systematic review is to clarify whether the combination of NIBS and robot-assisted gait training may improve walking function in patients with chronic stroke. Our systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Studies eligible for review were identified through PubMed/MEDLINE, Embase, Scopus, and PEDro from inception to March 15, 2021, and the outcomes considered were gait assessments. Seven studies were included in the qualitative analysis of this systematic review, with a total population of 186 patients with chronic stroke. All studies specified technical characteristics of robotic devices and NIBS used, with high heterogeneity of protocols. Methodological studies have shown a significantly greater improvement in walking capacity recorded with 6MWT. Finally, research studies have highlighted a positive effect on walking recovery by combination of robot-assisted gait training with non-invasive brain stimulation. Furthermore, future studies should identify the best characteristics of the combined therapeutic protocols.Systematic Review RegistrationCRD42021244869.

Background: cervical spinal cord injury leads to loss of upper limb functionality, which causes a decrease in autonomy to perform activities of daily living. The use of robotic technologies in rehabilitation could contribute to improving upper limb functionality and treatment quality. This case report aims to describe the potential of robotic hand treatment with Gloreha Sinfonia, in combination with conventional rehabilitation, in a tetraparetic patient. Material: fifteen rehabilitative sessions were performed. Evaluations were conducted pre-treatment (T0), post-treatment (T1), and at two-months follow-up (T2) based on: the upper-limb range of motion and force assessment, the FMA-UE, the 9-Hole Peg Test (9HPT), and the DASH questionnaire. A virtual reality game-based rating system was used to evaluate the force control and modulation ability. Results: the patient reported greater ability to use hands with less compensation at T1 and T2 assessments. Improvements in clinical scales were reported in both hands at T1, however, at T2 only did the dominant hand show further improvement. Improved grip strength control and modulation ability were reported for T1. However a worsening was found in both hands at T2, significant only for the non-dominant hand. The maximum force exerted increased from T0 to T2 in both hands. Conclusion: hand treatment combining physical therapy and Gloreha Sinfonia seems to have benefits in functionality and dexterity in tetraparetic patient in the short term. Further studies are needed to confirm these findings, to verify long-term results, and to identify the most appropriate modalities of robotic rehabilitation.

Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of neurons. Towards this goal, we combined spatially precise optogenetic stimulation with multicellular recording to deeply characterize intralaminar and translaminar monosynaptic connections to supragranular (L2/3) neurons in the mouse visual cortex. The reliability and specificity of multiphoton optogenetic stimulation were measured across multiple Cre lines, and measurements of connectivity were verified by comparison to paired recordings and targeted patching of optically identified presynaptic cells. With a focus on translaminar pathways, excitatory and inhibitory synaptic connections from genetically defined presynaptic populations were characterized by their relative abundance, spatial profiles, strength, and short-term dynamics. Consistent with the canonical cortical microcircuit, layer 4 excitatory neurons and interneurons within L2/3 represented the most common sources of input to L2/3 pyramidal cells. More surprisingly, we also observed strong excitatory connections from layer 5 intratelencephalic neurons and potent translaminar inhibition from multiple interneuron subclasses. The hybrid approach revealed convergence to and divergence from excitatory and inhibitory neurons within and across cortical layers. Divergent excitatory connections often spanned hundreds of microns of horizontal space. In contrast, divergent inhibitory connections were more frequently measured from postsynaptic targets near each other.

The editors introduce the feature issue on "Novel Techniques in Microscopy," which was the topic of a symposium held on April 12-15, 2015, in Vancouver, BC. This symposium was part of the Optics in the Life Sciences Congress.

Background: Stroke in childhood presents a serious rehabilitation challenge since it leads to physical, cognitive and psychosocial disability. The objective of our study was to describe the effectiveness of robot-mediated therapy (RMT) with Gloreha Sinfonia in addition to a conventional treatment in the recovery of the sensory-motor capabilities of the paretic hand and the quality of life in a ten-year-old child after a stroke. Methods: The girl was enrolled to undergo 10 sessions of RMT with Gloreha Sinfonia. She was evaluated with functional scales and with upper limb kinematic analysis at pre-treatment (T0) and at the end of treatment (T1). Outcome measures were Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Visual Analogic Scale (VAS) and Activities and Participation of Daily Life (ADL). In addition, a Force Assessment System based on Virtual Reality games was used to assess the force control and modulation capability at T0 and T1. Results: At the end of treatment, the patient improved in functional scales and in quality of life for greater involvement in some activity of daily living. Force control and modulation capability significantly increased after the treatment. Conclusions: This clinical case highlights possible positive effects of a combined (conventional plus robotic) rehabilitation treatment for the upper limb in pediatric stroke outcomes from both a sensorimotor and functional point of view, also improving the motivational and affective aspects of the patient and of family members. Further studies are needed to validate these results and to identify the most appropriate modalities and doses.

Second harmonic generation (SHG) and third harmonic generation (THG) microscopies have emerged as powerful imaging modalities to examine structural properties of a wide range of biological tissues. Although SHG and THG arise from very different contrast mechanisms, the two are complimentary and can often be collected simultaneously using a modified multiphoton microscope. In this review, we discuss the needed instrumentation for these modalities as well as the underlying theoretical principles of SHG and THG in tissue and describe how these can be leveraged to extract unique structural information. We provide an overview of recent advances showing how SHG microscopy has been used to evaluate collagen alterations in the extracellular matrix and how this has been used to advance our knowledge of cancers, fibroses, and the cornea, as well as in tissue engineering applications. Specific examples using polarization-resolved approaches and machine learning algorithms are highlighted. Similarly, we review how THG has enabled developmental biology and skin cancer studies due to its sensitivity to changes in refractive index, which are ubiquitous in all cell and tissue assemblies. Lastly, we offer perspectives and outlooks on future directions of SHG and THG microscopies and present unresolved questions, especially in terms of overall miniaturization and the development of microendoscopy instrumentation.

Background: The collagen architecture in high grade serous ovarian cancer (HGSOC) is highly remodeled compared to the normal ovary and the fallopian tubes (FT). We previously used Second Harmonic Generation (SHG) microscopy and machine learning to classify the changes in collagen fiber morphology occurring in serous tubal intraepithelial carcinoma (STIC) lesions that are concurrent with HGSOC. We now extend these studies to examine collagen remodeling in pure p53 signatures, STICs and normal regions in tissues that have no concurrent HGSOC. This is an important distinction as high-grade disease can result in distant collagen changes through a field effect mechanism. Methods: We trained a linear discriminant model based on SHG texture and image features as a classifier to discriminate the tissue groups. We additionally performed mass spectrometry analysis of normal and HGSOC tissues to associate the differential expression of collagen isoforms with collagen fiber morphology alterations. Results: We quantified the differences in the collagen architecture between normal tissue and the precursors with good classification accuracy. Through proteomic analysis, we identified the downregulation of single α-chains including those for Col I and III, where these results are consistent with our previous SHG-based supramolecular analyses. Conclusion: This work provides new insights into ECM remodeling in early ovarian cancer and suggests the combined use of SHG microscopy and mass spectrometry as a new diagnostic/prognostic approach.

Though presenting typological and construction-related features different from other European countries, Italian residential buildings as a whole fail to meet the performances required by the European Union before the 2050 deadline. Among the hypotheses meant to upgrade residential buildings, adding floors is regarded as capable of meeting the demand for new lodgings without any further soil consumption as well as of being the driving force leading to the overall upgrading of the building. The research has been aimed at focusing on the problems arising from upward extensions within the Italian seismic context, by means of digital environment surveys, defining intervention guidelines that can be applied to adding floors to 1950-2000 buildings.