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Background: Collaterals are a strong determinant of clinical outcome in acute ischemic stroke (AIS) patients undergoing Endovascular Treatment (EVT). Careggi Collateral Score (CCS) is an angiographic score that demonstrated to be superior to the widely suggested ASITN/SIR score. Multi-phase CT-Angiography (mCTA) could be alternatively adopted for collateral assessment. We investigated whether mCTA had an equivalent predictive performance for functional outcome compared to CCS. Methods: Consecutive AIS patients undergoing EVT for large vessel occlusion within 24 h from onset were analyzed. Receiver operating characteristic curves and multivariable logistic regression were investigated to evaluate the predictive performance of mCTA collateral score (range 0–5) and CCS (range 0–4) for good functional outcome (three-months modified Rankin Scale 0–2). Results: We included 201 subjects (59.7% females, mean age 75), of whom 96 (47.7%) had good outcome at three-months. Both CCS (OR = 14.4, 95% CI = 6.3–33.8) and mCTA (OR = 23.8, 95% CI = 10.1–56.4) collateral scores were independent predictors of outcome. The AUC of CCS was 0.80 (95% CI 0.73–0.86) and the best cut-off was ≥ 3 (87% sensitivity, 71% specificity), while the AUC of mCTA collateral score was 0.84 (95% CI 0.78–0.90) with an optimal cut-off of ≥ 4 (85% sensitivity, 87% specificity). Patients with good mCTA collaterals experienced smaller (16.6 vs. 63.7 mL, p < 0.001) infarct lesion as compared to those with mCTA poor collaterals. Conclusion: mCTA discriminative ability for three-months 0–2 mRS was found to be comparable to CCS. mCTA appears a valid, non-invasive imaging modality for evaluating collaterals of AIS patients potentially eligible for EVT. [ABSTRACT FROM AUTHOR]

Objectives: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection. Methods: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented. Results: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted. Conclusion: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Visuospatial circuits (VS) must be preserved during brain tumours' excision. Navigated TMS is a valid tool to preoperatively map VS networks and to optimise functional preservation. In this work, we tested 27 patients with nTMS preoperative mapping and an experimental test for VS abilities, called VISA, demonstrating a good clinical outcome (functional recovery 80–98.86%) and a useful nTMS map for tractography reconstruction (with the main involvement of the second and the third branches of the superior longitudinal fasciculus). Finally, a comparison of nTMS and DCS points in awake surgery (n = 10 patients) documented a sensitivity (Se) of 12%, a specificity (Sp) of 91.21%, a positive predictive value (PPV) of 42%, a negative predictive value (NPV) of 66%, and an accuracy of ~63.7%. According to our preliminary results, nTMS is advantageous to study cognitive functions, minimising neurological impairment. Further analyses are needed to validate our data. Objective: Navigated transcranial magnetic stimulation (nTMS) has seldom been used to study visuospatial (VS) circuits so far. Our work studied (I) VS functions in neurosurgical oncological patients by using repetitive nTMS (rnTMS), (II) the possible subcortical circuits underneath, and (III) the correspondence between nTMS and direct cortical stimulation (DCS) during awake procedures. Methods: We designed a monocentric prospective study, adopting a protocol to use rnTMS for preoperative planning, including VS functions for lesions potentially involving the VS network, including neurosurgical awake and asleep procedures. nTMS-based-DTI tractography allowed the visualization of subcortical circuits. Statistical analyses on nTMS/DCS points were performed. Clinical results were collected pre- and postoperatively. Results: Finally, 27 patients with primitive intra-axial brain lesions were enrolled between April 2023 and March 2024. Specific tests and an experimental integrated VS test (VISA) were used. The clinical evaluation (at 5 ± 7, 30 ± 10, 90 ± 10 days after surgery) documented 33% of patients with neglect in the left hemisphere four days after surgery and, during the 3-month follow-up, preservation of visuospatial function/clinical recovery (90.62% in MMSE, 98.86% in the bell test, 80% in the clock test, and 98% in the OCS test). The surgical strategy was modulated according to the nTMS map. Subcortical bundles were traced to identify those most involved in these functions: SFLII > SLFII > SLFI. A comparison of the nTMS and DCS points in awake surgery (n = 10 patients) documented a sensitivity (Se) of 12%, a specificity (Sp) of 91.21%, a positive predictive value (PPV) of 42%, a negative predictive value (NPV) of 66%, and an accuracy of ~63.7%. Conclusions: Based on our preliminary results, nTMS is advantageous for studying cognitive functions, minimising neurological impairment. Further analyses are needed to validate our data. [ABSTRACT FROM AUTHOR]

This evaluation correlates maxillary sinus 3D morphology with bone regeneration. In 39 patients with crestal bone = 2 mm, mineralized human bone allografts were used to augment the sinus floor through the crestal window sinus elevation approach. CBCT was used to measure the buccopalatal diameter (BPD), mesiodistal diameter (MDD), and hemi-ellipsoidal volume (Vh) in all sinuses. A bone core biopsy sample was taken at implant placement (4 to 5 months after sinus augmentation). Microradiographs of methacrylate-embedded sections were used to evaluate the amounts of bone, residual graft, and soft tissue. All 51 implants placed in the 39 patients successfully osseointegrated. A linear regression analysis showed that as BPD, MMD, and Vh increased, the amount of bone gain decreased and the amount of soft tissue increased (P < .05). The amount of residual graft was little affected by sinus morphology. Microradiographic data were grouped into four different sinus types (from small to great) using BPD and Vh medians. The best amount of bone formation was achieved in the narrow and short sinus type, while no great differences were found in the remaining three sinus types. Understanding of 3D sinus cavity morphology, especially the buccopalatal diameter and mesiodistal dimensions, is fundamental for achieving the best possible sinus augmentation outcomes. [ABSTRACT FROM AUTHOR]

For a compact orientable surface Σ g , 1 of genus 푔 with one boundary component and for an odd prime number 푝, we study the homology of the unordered configuration spaces C ∙ (Σ g , 1) : = ∐ n ≥ 0 C n (Σ g , 1) with coefficients in F p . We describe H ∗ ⁢ (C ∙ ⁢ (Σ g , 1) ; F p) as a bigraded module over the Pontryagin ring H ∗ ⁢ (C ∙ ⁢ (D) ; F p) , where 퐷 is a disc, and compute in particular the bigraded dimension over F p . We also consider the action of the mapping class group Γ g , 1 and prove that the mod-푝 Johnson kernel K g , 1 ⁢ (p) ⊆ Γ g , 1 is the kernel of the action on H ∗ ⁢ (C ∙ ⁢ (Σ g , 1 ; F p)) . [ABSTRACT FROM AUTHOR]

Background: Leptomeningeal enhancement (LME) is considered an MRI marker of leptomeningeal inflammation in inflammatory neurological disorders, including multiple sclerosis (MS). To our knowledge, no disease-modifying therapies (DMTs) have been demonstrated to affect LME number or morphology so far. Methods: Monocentric study investigating the frequency and number of LME in a cohort of people with (pw)MS who performed a 3 T brain MRI with a standardized protocol (including a post-contrast FLAIR sequence), and exploring the impact of autologous hematopoietic stem cell transplantation (AHSCT) on this marker. In a longitudinal pilot study, consecutive MRIs were also analyzed in a subgroup of pwMS, including patients evaluated both pre- and post-AHSCT. Results: Fifty-five pwMS were included: 24/55 (44%) had received AHSCT (AHSCT group) and 31 other treatments (CTRL group). At least one LME was identified in 19/55 (35%) cases (42 and 29% in the AHSCT and CTRL groups, respectively; p = 0.405). In the AHSCT group, LME number correlated with age at AHSCT (R = 0.50; p = 0.014), but not with age at post-treatment MRI. In the longitudinal pilot study (n = 8), one LME disappeared following AHSCT in 1/4 patients, whereas LME number was unchanged in the remaining four pwMS from the CTRL group. Discussion: These results suggest that AHSCT may affect development and persistence of LME, strengthening the indication for early use of effective therapies bioavailable within the central nervous system (CNS), and therefore potentially targeting compartmentalized inflammation. [ABSTRACT FROM AUTHOR]

Optical microscopy videos enable experts to analyze the motion of several biological elements. Particularly in blood samples infected with Trypanosoma cruzi (T. cruzi), microscopy videos reveal a dynamic scenario where the parasites' motions are conspicuous. While parasites have self-motion, cells are inert and may assume some displacement under dynamic events, such as fluids and microscope focus adjustments. This paper analyzes the trajectory of T. cruzi and blood cells to discriminate between these elements by identifying the following motion patterns: collateral, fluctuating, and pan–tilt–zoom (PTZ). We consider two approaches: i) classification experiments for discrimination between parasites and cells; and ii) clustering experiments to identify the cell motion. We propose the trajectory step dispersion (TSD) descriptor based on standard deviation to characterize these elements, outperforming state-of-the-art descriptors. Our results confirm motion is valuable in discriminating T. cruzi of the cells. Since the parasites perform the collateral motion, their trajectory steps tend to randomness. The cells may assume fluctuating motion following a homogeneous and directional path or PTZ motion with trajectory steps in a restricted area. Thus, our findings may contribute to developing new computational tools focused on trajectory analysis, which can advance the study and medical diagnosis of Chagas disease. [ABSTRACT FROM AUTHOR]

Background: Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. Case presentation: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. Conclusions: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent. [ABSTRACT FROM AUTHOR]

Given a couple of subspaces Y ⊂ X of the complex plane C satisfying some mild conditions (a “nice couple”), and given a PMQ-pair (Q , G) , consisting of a partially multiplicative quandle (PMQ) Q and a group G, we introduce a “Hurwitz–Ran” space Hur (X , Y ; Q , G) , containing configurations of points in X \ Y and in Y with monodromies in Q and in G, respectively. We further introduce a notion of morphisms between nice couples, and prove that Hurwitz–Ran spaces are functorial both in the nice couple and in the PMQ-group pair. For a locally finite PMQ Q we prove a homeomorphism between Hur ((0 , 1) 2 ; Q +) and the simplicial Hurwitz space Hur Δ (Q) , introduced in previous work of the author: this provides in particular Hur ((0 , 1) 2 ; Q +) with a cell stratification in the spirit of Fox–Neuwirth and Fuchs. [ABSTRACT FROM AUTHOR]

Although implementing the Pap smear has drastically reduced the mortality rates from cervical cancer, false positives and negatives are related to the quality of the analysis and the cytopathologist experience. An alternative is the insertion of digital cytology in the quality monitoring to assist the screening. However, conventional cytology is still a major challenge, as it presents a lot of cellular overlap and several epithelial structures that make it difficult to implement computational methodologies. This article compares the performance of U-net and SegNet neural networks for nuclei segmentation in cervical images. Experiments were performed with different activation functions, batch sizes, and datasets, ISBI (synthetic images from liquid cytology) and CRIC Cervix-Seg (conventional cytology real images). The models achieved a Dice coefficient of 0.9783 for ISBI2015 and 0.9429 for CRIC Cervix-Seg. These results suggest a methodology capable of segmenting real images of cervical nuclei with quality, even in situations of overlap and artefacts, advancing efforts towards the automation of tasks as part of the cytopathological analysis in the laboratory work routine. [ABSTRACT FROM AUTHOR]

The Lugano classification for response assessment in lymphoma recommends the use of the 5‐point‐scale Deauville Score (DS) to assess response evaluation of end‐of‐treatment FDG‐PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb‐IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re‐evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow‐up was 43 months. The best receiver operator characteristics cut‐off values to distinguish positive and negative patients was 4. The area‐under‐the‐curve was 0.81 (95%CI, 0.70–0.91). Three‐years PFS was 0.95 (95% CI 0.90–0.97) in eotPET negative and 0.22 (95% CI 0.11–0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. Analyses of the NEPA provide additional information to the magnetic resonance imaging (MRI) evaluation of the enhancing part of brain tumors. NEPA analyses of central nervous system malignancies with conventional and advanced MRI techniques give interesting highlights in the differential diagnosis of solid contrast-enhanced brain tumors regarding the prognostic stratification and treatment response. Considering the rapid technological changes in advanced MRI imaging, we assume that an update on this topic might be of interest. The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed. [ABSTRACT FROM AUTHOR]

We consider for d ≥ 1 the graded commutative Q -algebra A (d) : = H ∗ (Hilb d (C 2) ; Q) , which is also connected to the study of generalised Hurwitz spaces by work of the first author. These Hurwitz spaces are in turn related to the moduli spaces of Riemann surfaces with boundary. We determine two distinct, minimal sets of ⌊ d / 2 ⌋ multiplicative generators of A (d) . Additionally, we prove when the lowest degree generating relations occur. For small values of d, we also determine a minimal set of generating relations, which leads to several conjectures about the necessary generating relations for A (d) . [ABSTRACT FROM AUTHOR]

Background: Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. Case presentation: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. Conclusions: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent. [ABSTRACT FROM AUTHOR]

Simple Summary: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. Seventeen Italian centers analyzed the role of serial [18F]FDG PET/CT scans in patients candidates and, later undergoing immunotherapy for some solid cancers. Serial [18F]FDG PET/CT can be useful in evaluating the response to therapy, soon after 3 and 6-months from the start of immunotherapy. The evidences were foud both in patients affected by lung cancer and malignant melanoma, although large prospective trials are needed for definitively confirmed these findings. AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31–89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1–137) months, 113 (36.3%) patients had died. On Kaplan–Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory. [ABSTRACT FROM AUTHOR]

Screening of Pap smear images continues to depend upon cytopathologists' manual scrutiny, and the results are highly influenced by professional experience, leading to varying degrees of cell classification inaccuracies. In order to improve the quality of the Pap smear results, several efforts have been made to create software to automate and standardize the processing of medical images. In this work, we developed the CEA (Cytopathologist Eye Assistant), an easy-to-use tool to aid cytopathologists in performing their daily activities. In addition, the tool was tested by a group of cytopathologists, whose feedback indicates that CEA could be a valuable tool to be integrated into Pap smear image analysis routines. For the construction of the tool, we evaluate different YOLO configurations and classification approaches. The best combination of algorithms uses YOLOv5s as a detection algorithm and an ensemble of EfficientNets as a classification algorithm. This configuration achieved 0.726 precision, 0.906 recall, and 0.805 F1-score when considering individual cells. We also made an analysis to classify the image as a whole, in which case, the best configuration was the YOLOv5s to perform the detection and classification tasks, and it achieved 0.975 precision, 0.992 recall, 0.970 accuracy, and 0.983 F1-score. [ABSTRACT FROM AUTHOR]

We introduce ordered and unordered configuration spaces of 'clusters' of points in an Euclidean space |$\mathbb{R}^d$|⁠ , where points in each cluster satisfy a 'verticality' condition, depending on a decomposition |$d=p+q$|⁠. We compute the homology in the ordered case and prove homological stability in the unordered case. [ABSTRACT FROM AUTHOR]

Anti‐EGFRs plus doublet chemotherapy is considered the optimal upfront option for RAS/BRAF wild‐type left‐sided metastatic colorectal cancer (mCRC). Early‐onset (EO) mCRC has an increasing incidence and its prognostic/predictive role and management is debatable. We performed a post hoc analysis of Valentino study, that randomized RAS wild‐type mCRC patients to two panitumumab‐based maintenance regimens after FOLFOX/panitumumab induction. We assessed the safety and efficacy outcomes in patients stratified for age (<50/≥50 years old). We assessed progression‐free survival (PFS), overall survival (OS), response rate (ORR), rate of treatment‐related and panitumumab‐related adverse events (AEs) and quality of life (QoL). In 229 patients enrolled, 35 (15%) had EO mCRC, with a higher rate of female sex (P =.020) and lower rate of primary tumor resection (P =.001). Median PFS and OS were 10.9 vs 10.8 months (P =.593) and 28.1 vs 27.5 months (P =.865) in patients <50 and ≥50 years old, respectively, with no significant impact of maintenance arm. ORR and disease control rate were 74% vs 65% (P =.337) and 97% vs 81% (P =.013) in patients <50 or ≥50 years old. In younger patients, a trend for increased chemotherapy‐related AEs (peculiarly anemia) was shown, while significantly decreased EGFR‐related hypomagnesemia and increased skin rash were reported. No significant differences in treatment intensity or QoL were observed. In patients with EO mCRC and RAS wild‐type status, we found no differences in terms of survival outcomes based on age when selecting maintenance strategies. Management of treatment‐related AEs should consider the differential toxicity profile of age and sex. [ABSTRACT FROM AUTHOR]

Intelligent healthcare systems are a topic of interest in recent approaches due to novel possibilities created from edge hardware and software development. In 2020, the COVID-19 pandemic displayed the urge to speed up technological systems development to aid medical facilities. In this context, solutions must enhance the experience of both patients and healthcare professionals. Thus, we propose a novel cooperative architecture to improve healthcare facilities involved in pandemic control. On the one hand, this solution helps a faster recognition and link to the patients' data using reality augmentation resources. On the other hand, it helps monitor the conditions of medical professionals working in the facility and exposed to contamination danger. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. Methods: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. Results: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. Conclusions: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.Methods: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.Results: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population.Conclusions: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. Despite recent improvements in treatment and prevention, most of the current therapeutic options are weighted by side effects impacting patients' quality of life. Better patient selection towards systemic treatments represents an unmet clinical need. The recent multidisciplinary and molecular advancements in the treatment of CRC patients demand the identification of efficient biomarkers allowing to personalise patient care. Currently, core tumour biopsy specimens represent the gold-standard biological tissue to identify such biomarkers. However, technical feasibility, tumour heterogeneity and cancer evolution are major limitations of this single-snapshot approach. Genotyping circulating tumour DNA (ctDNA) has been addressed as potentially overcoming such limitations. Indeed, ctDNA has been retrospectively demonstrated capable of identifying minimal residual disease post-surgery and post-adjuvant treatment, as well as spotting druggable molecular alterations for tailoring treatments in metastatic disease. In this review, we summarise the available evidence on ctDNA applicability in CRC. Then, we review ongoing clinical trials assessing how liquid biopsy can be used interventionally to guide therapeutic choice in localised, locally advanced and metastatic CRC. Finally, we discuss how its widespread could transform CRC patients' management, dissecting its limitations while suggesting improvement strategies. [ABSTRACT FROM AUTHOR]

Let F_n(\Sigma _{g,1}) denote the configuration space of n ordered points on the surface \Sigma _{g,1} and let \Gamma _{g,1} denote the mapping class group of \Sigma _{g,1}. We prove that the action of \Gamma _{g,1} on H_i(F_n(\Sigma _{g,1});\mathbb {Z}) is trivial when restricted to the ith stage of the Johnson filtration \mathcal {J}(i)\subset \Gamma _{g,1}. We give examples showing that \mathcal {J}(2) acts nontrivially on H_3(F_3(\Sigma _{g,1})) for g\ge 2, and provide two new conceptual reinterpretations of a certain group introduced by Moriyama. [ABSTRACT FROM AUTHOR]

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association and agreement between magnetic resonance dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) and computed tomography perfusion (CTP) in determining vascularity and permeability of primary and secondary brain tumors. Material and methods: DSC-PWI and CTP studies from 97 patients with high-grade glioma, low-grade glioma and solitary brain metastasis were retrospectively reviewed. Normalized cerebral blood flow (nCBF), cerebral blood volume (nCBV), capillary transfer constant (nK2) and permeability surface area product (nPS) values were obtained. Variables among groups were compared, and correlation and agreement between DSC-PWI and CTP were tested. Results: All DSC-PWI and CTP parameters were higher in high-grade than in low-grade gliomas (p < 0.01 and p < 0.001). Metastases had greater DSC-PWI nCBV (p < 0.05), nCTP-CBF (p < 0.05), nCTP-CBV (p < 0.01) and nCTP-PS (p < 0.0001) than low-grade gliomas and more elevated nCTP-PS (p < 0.01) than high-grade gliomas. The correlation was strong between DSC-PWI nCBF and CTP nCBF (r = 0.79; p < 0.00001) and between DSC-PWI nCBV and CTP nCBV (r = 0.83; p < 0.00001), weaker between DSC-PWI nK2 and CTP nPS (r = 0.29; p < 0.01). Bland–Altman plots indicated that the agreement was strong between DSC-PWI nCBF and CTP nCBF, good between DSC-PWI nCBV and CTP nCBV and poorer between DSC-PWI nK2 and CTP nPS. Conclusion: DSC-PWI and CTP CBF and CBV maps were comparable and interchangeable in the assessment of tumor vascularity, unlike DSC-PWI K2 and CTP PS maps that were more discordant in the analysis of tumor permeability. CTP could be an alternative method to quantify tumor neoangiogenesis when MRI is not available or when the patient does not tolerate it. [ABSTRACT FROM AUTHOR]

Open-plan workspaces are becoming common because of their compact footprint, economic advantages, and capacity for fostering communication. However, users of open-plan workspaces often report a high level of distraction, undermining their performance especially on individual cognitive tasks. Existing common solutions require recurrent physical changes, which are neither practical for companies and employees nor desired by interior architects. In this paper, we examine the use of augmented reality (AR) midair pervasive displays and visual separators to address the problem of visual distractions in open-plan workspaces. While past applications of AR in workspaces mostly focused on content creation and manipulation, we use AR to superimpose visual barriers—what we refer to as virtual partitions. To evaluate the impact of virtual partitioning on the occupants' cognitive performance, we conducted two user studies with a total of 48 participants. The design of assessed virtual partitions was informed by interviews that we conducted with 11 professional space designers. The analysis of collected data suggests that virtual partitions can reduce visual distractions and enable users to personalize the visual attributes of their space leading to an improved experience of shared workspaces. [ABSTRACT FROM AUTHOR]

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PURPOSE: In GI cancers, anaplastic lymphoma kinase (ALK) rearrangements are extremely less frequent than in non–small-cell lung cancer but may be important to offer personalized strategies of treatment in selected patients. Data about the activity and efficacy of ALK inhibitors (ALKi) in GI cancers are scarce. MATERIALS AND METHODS: We assembled a clinical and molecular international data set of pretreated patients with metastatic or nonresectable cancers of GI primary tumor origin with documented ALK rearrangement treated with at least one line of ALKi. Measurable disease as per RECIST 1.1 was required for response analysis. RESULTS: Primary tumor sites were distributed as follows: 5 (38%) pancreas, 3 (23%) right colon, and 1 (8%) for each one of gastric, duodenal, rectal, left colon, and biliary tract sites. Seven patients (54%) were treated with alectinib, 5 (38%) with crizotinib, and 1 (8%) with entrectinib. After disease progression, five patients (38%) received a subsequent ALKi treatment line, and at the time of data cutoff date, treatment was still ongoing in two patients. Five of 12 evaluable patients (41%) achieved a partial response to first-line ALKi, five patients (41%) had stable disease, and 2 (17%) had progressive disease. No complete responses were registered. At a median follow-up of 39.6 months (interquartile range: 19.8-59.5), the median progression-free survival was 5.0 months (95% CI, 3.68 to no response) and the median overall survival was 9.3 months (95% CI, 5.46 to no response). CONCLUSION: Treatment with ALKi provides remarkable responses and clinical benefit in pretreated patients with ALK fusion–positive GI malignancies. Despite the rarity, ALK rearrangements represent an important therapeutic target in individual pretreated patients with GI solid tumors. Further work providing prospective clinical validation of this target is needed. ALK inhibitors are active in patients with ALK fusion–positive GI cancers. [ABSTRACT FROM AUTHOR]

The contribution of brain regions to visuospatial abilities according to sex differences and gender identity is inconsistently described. One potential explaining factor may be the different tasks employed requiring a variable load of working memory and other cognitive resources. Here we asked to 20 cis and 20 transgender participants to undergo functional Magnetic Resonance Imaging during performance of a judgement line of orientation test that was adapted to explore the basic visuospatial processing while minimizing the working memory load. We show that V1 activation may be viewed as a brain area with enhanced activation in males, regardless of participants' gender identity. On its turn, gender identity exclusively influences the visuospatial processing of extrastriate visual areas (V5) in women with gender dysphoria. They showed enhanced V5 activation and an increased functional connectivity between V5 and V1. Overall our neuroimaging results suggest that the basic visuospatial abilities are associated with different activations pattern of cortical visual areas depending on the sex assigned at birth and gender identity. [ABSTRACT FROM AUTHOR]

Simple Summary: Anticancer treatments commonly cause adverse events (AE). Among others, pneumatosis intestinalis (PI) is reported to be infrequent, though it can lead to severe consequences. The aim of our systematic review was to investigate the concurrency of PI and oncological therapy exposure; moreover, we defined the characteristics of patients and the primarily involved tumor types. We analyzed 88 different episodes of PI. The median time of onset was 6 weeks and oncological patients with respiratory system cancers and those treated with targeted therapies appeared be at higher risk. Symptoms were frequently mild to absent; nevertheless, life-threatening complications were reported. Therefore, this AE, although uncommon, should be considered in the case of specific symptoms. Potential pharmacological mechanisms of anticancer drugs in inducing PI are also discussed. Pneumatosis intestinalis (PI) is a rare condition due to the presence of gas within the bowel wall; it is mainly caused by endoscopic procedures, infections and other gastrointestinal diseases. Oncological therapies have been reported to be a cause of PI as well, but their role is not clearly defined. This systematic review investigates the concurrency of PI and antitumor therapy in cancer patients, considering both solid tumors and onco-hematological ones. We performed a literature review of PubMed, Embase and the Web of Science up to September 2021 according to the PRISMA guidelines. A total of 62 papers reporting 88 different episodes were included. PI was mainly reported with targeted therapies (sunitinib and bevacizumab above all) within the first 12 weeks of treatment. This adverse event mostly occurred in the metastatic setting, but in 10 cases, it also occurred also in the neoadjuvant and adjuvant setting. PI was mostly localized in the large intestine, being fatal in 11 cases, while in the remaining cases, symptoms were usually mild, or even absent. A significant risk of PI reoccurrence after drug reintroduction was also reported (6/18 patients), with no fatal outcomes. Potential pharmacological mechanisms underlying PI pathogenesis are also discussed. In conclusion, although uncommonly, PI can occur during oncological therapies and may lead to life-threatening complications; therefore, consideration of its occurrence among other adverse events is warranted in the presence of clinical suspicion. [ABSTRACT FROM AUTHOR]

Purpose. Nerve growth factor efficacy was demonstrated for corneal lesions treatment, and recombinant human NGF (rhNGF) was approved for neurotrophic keratitis therapy. However, NGF-induced molecular responses in cornea are still largely unknown. We analyzed microRNAs expression in human epithelial corneal cells after time-dependent rhNGF treatment. Methods. Nearly 700 microRNAs were analyzed by qRT-PCR. MicroRNAs showing significant expression differences were examined by DIANA-miRpath v.3.0 to identify target genes and pathways. Immunoblots were performed to preliminarily assess the strength of the in silico results. Results. Twenty-one microRNAs (miR-26a-1-3p, miR-30d-3p, miR-27b-5p, miR-146a-5p, miR-362-5p, mir-550a-5p, mir-34a-3p, mir-1227-3p, mir-27a-5p, mir-222-5p, mir-151a-5p, miR-449a, let7c-5p, miR-337-5p, mir-29b-3p, miR-200b-3p, miR-141-3p, miR-671-3p, miR-324-5p, mir-411-3p, and mir-425-3p) were significantly regulated in response to rhNGF. In silico analysis evidenced interesting target genes and pathways, including that of neurotrophin, when analyzed in depth. Almost 80 unique target genes (e.g., PI3K, AKT, MAPK, KRAS, BRAF, RhoA, Cdc42, Rac1, Bax, Bcl2, FasL) were identified as being among those most involved in neurotrophin signaling and in controlling cell proliferation, growth, and apoptosis. AKT and RhoA immunoblots demonstrated congruence with microRNA expression, providing preliminary validation of in silico data. Conclusions. MicroRNA levels in response to rhNGF were for the first time analyzed in corneal cells. Novel insights about microRNAs, target genes, pathways modulation, and possible biological responses were provided. Importantly, given the putative role of microRNAs as biomarkers or therapeutic targets, our results make available data which might be potentially exploitable for clinical applications. [ABSTRACT FROM AUTHOR]

Since Saul Kripke's and Hilary Putnam's groundbreaking work in the Seventies, the idea has emerged that natural kind terms are semantically special among common nouns. Stephen P. Schwartz, for example, has argued that an artifactual kind term like "pencil" functions very differently from a natural kind term like "tiger." This, however, blatantly violates a principle that I call Semantic Uniformity. In this paper, I defend the principle. In particular, I outline a picture of how natural kind terms function based on Kripke's and Putnam's considerations, and I use it to rebut Schwartz's arguments, showing that if it works for natural kind terms, it can work for artifactual kind terms too (and, arguably, for common nouns in general), or at least that Schwartz did not provide good enough reasons to the contrary. [ABSTRACT FROM AUTHOR]

We consider the Birman–Hilden inclusion $\phi\colon\Br_{2g+1}\to\Gamma_{g,1}$ of the braid group into the mapping class group of an orientable surface with boundary, and prove that $\phi$ is stably trivial in homology with twisted coefficients in the symplectic representation $H_1(\Sigma_{g,1})$ of the mapping class group; this generalises a result of Song and Tillmann regarding homology with constant coefficients. Furthermore we show that the stable homology of the braid group with coefficients in $\phi^*(H_1(\Sigma_{g,1}))$ has only 4-torsion. [ABSTRACT FROM AUTHOR]

We give an upper bound on the topological complexity of varieties V obtained as complements in ℂm of the zero locus of a polynomial. As an application, we determine the topological complexity of unordered configuration spaces of the plane. [ABSTRACT FROM AUTHOR]

Background In patients with RAS / BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy. Methods We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan–Meier method and Cox proportional hazards regression were used for the survival analysis. When comparing the outcomes of anti-EGFR-based reinduction versus any second line, a propensity score–based matching was used. Results Liver-limited/single site of disease (P <.001 and P =.002), left-sidedness (P =.029), surgery of metastases (P =.003), early tumor shrinkage, and deeper responses (P =.018 and P =.036) were associated with the use of anti-EGFR-based reinduction versus any other second line. All patients treated with reinduction had an anti-EGFR-free interval of at least 3 months. In the propensity score–matched population, progression-free survival (PFS) was similar in the 2 treatment groups, the overall survival (OS) was significantly longer for patients treated with reinduction (P =.029), and the response rate was higher in patients treated with reinduction (P =.033). An oxaliplatin-free interval ≥12 months, left-sidedness, and molecular hyperselection beyond RAS/BRAF were associated with significantly better outcomes after anti-EGFR-based reinduction. Conclusions Reinduction strategies with anti-EGFR-based regimens are commonly used in clinical practice. Our data highlight the importance of clinical–molecular selection for re-treatments and the need for prospective strategy trials in selected populations. [ABSTRACT FROM AUTHOR]

Climate policies encourage the search for greenhouse gas (GHG) mitigation options in all economic sectors and peatland rewetting is one of the most efficient mitigation measures in agriculture and land use. The benefits shown in the national GHG inventories, however, depend not only on the actual mitigation actions on the ground but also how well the effects can be reported. Currently there are no specific emission factors for reporting GHG emissions from rewetted agricultural soils as the current emission factors are aggregated for several pre-rewetting land use types. Also, rewetting can aim at either restoration or different forms of paludiculture which may differ in their GHG profile and thus demand disaggregated emission factors. We compiled the current knowledge on GHG emissions on sites where rewetting has occurred on former agricultural peatland in temperate or boreal climate zones. The recent data suggest that on average the current emission factors for rewetting nutrient-rich sites published by the Intergovernmental Panel for Climate Change (IPCC) provide a good estimate for reporting emissions from rewetting in the temperate zone. However, the total GHG balances differed widely in restoration, Sphagnum farming and production of emergent plants in paludiculture and it is evident that disaggregated emission factors will be needed to improve the accuracy of reporting the effects of mitigation measures in the GHG inventories. [ABSTRACT FROM AUTHOR]

Background: Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. Case presentation: We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. Conclusion: To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients. Methods: Seventeen patients with genetically confirmed CADASIL, aged <60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12‐lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg‐MBF) by 13NH3 positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg‐MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched. Results: Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg‐MBF and CFR were blunted in CADASIL patients compared with controls (Reg‐MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p < 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p < 0.01). No correlations were found between Reg‐MBF values and neuropsychological performance or cerebral lesion burden on MRI. Conclusions: CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients. [ABSTRACT FROM AUTHOR]

The definition of oligometastatic colorectal cancer (CRC) identifies a peculiar subpopulation of patients characterized by a limited metastatic spread of disease.[1] Oligometastatic disease is defined as the involvement of up to two or occasionally three sites with five or sometimes more metastases that for their anatomic localization is amenable to local ablative therapies, thus rendering the patient free of disease.[1] [3] Thus, this subgroup is wide and has a significant cohort of patients with CRC. Thus, we hypothesize that PDOs testing might be more helpful in patients with a low tumor burden, because of intrapatient heterogeneity that is expected to be lower in these patients.[34],[35] Indeed, diffused metastatic disease is more likely to be widely heterogeneous and patients do not achieve the same results observed on PDOs.[21],[36],[37] Second, PDOs drug sensitivity testing constitutes a relatively expensive method to choose a systemic cytotoxic regimen. Suggested Clinical Contexts Better Allowing the Use of Data From Drug Screening on PDOs as a Tool to Implement Treatment Choice and Prioritization in Metastatic Colorectal Cancer Treatment implementation driven by PDOs drug sensitivity testing has intrinsic limitations potentially hampering its applicability in the daily clinical practice. [Extracted from the article]

In recent years, deep learning methods have outperformed previous state-of-the-art machine learning techniques for several problems, including image classification. Classifying cells in Pap smear images is very challenging, and it is still of paramount importance for cytopathologists. The Pap test is a cervical cancer prevention test that tracks preneoplastic changes in cervical epithelial cells. Carrying out this exam is important in that early detection. It is directly related to a greater chance of curing or reducing the number of deaths caused by the disease. The analysis of Pap smears is exhaustive and repetitive, as it is performed manually by cytopathologists. Therefore, a tool that assists cytopathologists is needed. This work considers 10 deep convolutional neural networks and proposes an ensemble of the three best architectures to classify cervical cancer upon cell nuclei and reduce the professionals' workload. The dataset used in the experiments is available in the Center for Recognition and Inspection of Cells (CRIC) Searchable Image Database. Considering the metrics of precision, recall, F1-score, accuracy, and sensitivity, the proposed ensemble improves previous methods shown in the literature for two- and three-class classification. We also introduce the six-class classification outcome. [ABSTRACT FROM AUTHOR]