Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

PURPOSE: The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs. METHODS: An observational study in an area representing one-fifth of England. RESULTS: Data were collected from 89 adult AF recipients. At disclosure, among 57 recipients of a cancer-predisposition-associated AF and 32 recipients of an FH-associated AF, 35% and 88%, respectively, had personal and/or family history evidence of AF-related disease. During post-disclosure investigations, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF. CONCLUSION: Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.

Repeated surgical resections for management of high-grade glioma and its impact on quality of life.

PURPOSE: High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. METHODS: Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. RESULTS: There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. CONCLUSIONS: These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.

Performance of intraoperative neurocognitive tests during awake surgery for patients with diffuse low-grade glioma.

Despite great advancements and the diffusion of awake surgery for brain tumors, the literature shows that the tests applied during the procedure are heterogeneous and non-standardized. This prospective, observational, descriptive study collected data on intraoperative brain mapping and the performance of multiple neurocognitive tests in 51 awake surgeries for diffuse low-grade glioma. Frequency of use and rate of intraoperative findings of different neurocognitive tests were analyzed. Patients mean age at the time of surgery was 35.1 (20-57) years. We performed 26 (51.0%) surgeries on the left hemisphere (LH) and 25 (49.0%) on the right hemisphere (RH). Significant differences were observed between the total number of functional findings (cortical and subcortical) identified in the LH and RH (p = 0.004). In subcortical findings alone, the differences remained significant (p = 0.0004). The RH subcortical region showed the lowest number of intraoperative findings, and this was correlated with functional outcome: Karnofsky performance scale at five days (p = 0.022), three months (p = 0.002) and one year (p = 0.002) post-surgery. On average, more tests were used to map the RH, with a lower frequency of both cortical and subcortical functional findings. Even though subcortical findings were less frequent than cortical findings, they were crucial to defining the resection margins. Based on the intraoperative findings, frequency of use, and rate of findings per use of the tests analyzed, the most relevant tests for each hemisphere for awake brain mapping were identified.

Do Mesocarnivores Respond to the Seasonality in Management Practices in an Agroforestry Landscape?

In the Mediterranean, we find a mosaic of natural and cultural landscapes, where a variety of forest management practices created intermediate disturbance regimes that potentially increased biodiversity values. Nonetheless, it is essential to understand the species' long-term response to the dynamic management in agroecosystems, since the species tolerance to disturbance can change throughout the life cycle. Mammalian carnivores can be sensitive to human disturbance and are an essential part of ecosystems due to their regulatory and community structuring effects. We investigated the spatial response of five mesocarnivores species to spatially- and temporally- varying management practices in an agroforestry landscape. More specifically, we assessed the mesocarnivores' temporal changes in space use by implementing multi-season occupancy models in a Bayesian framework, using seasonal camera-trapping surveys for a 2-year period. All species had a weak response of local extinction to forestry management and livestock grazing pressure. For forest-dwelling species, occupancy was higher where productivity of perennial vegetation was high, while colonization between seasons was positively associated with vegetation cover. For habitat generalist species, we found that occupancy in the wet season increased with the distance to cattle exclusion plots. Most of these plots are pine stands which are subject to forestry interventions during winter. During the 2-year period we found seasonal fluctuations in occupancy for all species, with an overall slight decrease for three mesocarnivore species, while for the two forest-dwelling species there was an increase in occupancy between years. The weak species response to management practices supports the importance of traditional management for upholding a diverse mesocarnivore community in agroforestry systems but could also reflect these species' ecological plasticity and resilience to disturbance.

Spontaneous rhinorrhea and idiopathic intracranial hypertension: a complex and challenging association.

INTRODUCTION: Spontaneous CSF leak is a known complication of idiopathic intracranial hypertension (IIH). Patients with CSF rhinorrhea present a unique challenge within the IIH population, as the occurrence of a leak can mask the typical IIH symptoms and signs, complicating the diagnosis. Treatment of leaks in this population can also be challenging, with the risk of rhinorrhea recurrence if intracranial hypertension is not adequately treated. OBJECTIVE: The aim of this narrative review was to examine current literature on the association between spontaneous CSF rhinorrhea leaks and IIH, focusing on key clinical features, diagnostic approaches, management strategies, and outcomes. MATERIAL AND METHODS: A literature search was executed using the PubMed and Scopus databases. The search was confined to articles published between January 1985 and August 2023; extracted data was then analysed to form the foundation of the narrative review. RESULTS: This search yielded 26 articles, comprising 943 patients. Average age was 46.8 ± 6.5 years, and average body mass index was 35.8 ± 4.8. Most of the patients were female (74.33%). Presenting symptoms were rhinorrhea, headaches and meningitis. The most common imaging findings were empty sella and encephalocele. The standard treatment approach was endoscopic endonasal approach for correction of CSF rhinorrhea leak, and shunt placement was also performed in 128 (13%) patients. Recurrences were observed in 10% of cases. CONCLUSIONS: The complex relationship between spontaneous CSF leaks and IIH is a challenge that benefits from multidisciplinary evaluation and management for successful treatment. Treatments such as endoscopic repair, acetazolamide, and VP/ /LP shunts reduce complications and recurrence. Personalised plans addressing elevated intracranial pressure are crucial for successful outcomes.

Sustainable approach towards alternatives for the use of iron ore tailings in the construction sector using Data Envelopment Analysis methodology.

Iron ore tailings (IOTs) need to be properly managed to mitigate the environmental, social, and economic impacts of mining activities. To cope with this issue, we use data envelopment analysis (DEA) to evaluate alternatives for using IOT in the construction sector. The classical and weight restriction output-oriented DEA models were used in this analysis. The results show that the ranking of alternatives depends on the aspect being evaluated. Concrete block is the most environmentally friendly alternative when analysing both models. For both social and economic aspects, ceramics produced better results in the classical model, whereas Portland cement showed better outcomes in the weight restriction model. In this sense, the results suggest great potential for the use of IOT in the construction sector, enabling the reduction of risks and social and environmental impacts of tailings dams.

Clinical relevance of the blanking period on late recurrence after catheter ablation of atrial fibrillation.

INTRODUCTION: Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. METHODS AND RESULTS: Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p < .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p < .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively). CONCLUSION: The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.

Simultaneous voltammetric determination of 7-methyl-guanine and 5-methyl-cytosine using a cathodically pre-treated boron-doped diamond electrode.

Given the importance of identifying the presence of biomarkers of human diseases in DNA samples, the main objective of this work was to investigate, for the first time, the electro-catalytic oxidation of 7-methyl-guanine (7-mGua) and 5-methyl-cytosine (5-mCyt) on a boron doped diamond electrode pre-treated cathodically (red-BDDE), using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The anodic peak potentials of 7-mGua and 5-mCyt by DPV were at E = 1.04 V and E = 1.37 V at pH = 4.5, indicating excellent peak separation of approximately 330 mV between species. Using DPV, experimental conditions such as supporting electrolyte, pH and influence of interferents were also investigated to develop a sensitive and selective method for individual and simultaneous quantification of these biomarkers. The analytical curves for the simultaneous quantification of 7-mGua and 5-mCyt in the acid medium (pH = 4.5) were: concentration range of 0.50-5.00 µmol L-1 (r = 0.999), detection limit of 0.27 µmol L-1 for 7-mGua; from 3.00 to 25.00 µmol L-1 (r = 0.998), with a detection limit of 1.69 µmol L-1 for 5-mCyt. A new DP voltammetric method for the simultaneous detection and quantification of biomarkers 7-mGua and 5-mCyt using a red-BDDE is proposed.

The state of art of awake craniotomy in Latin American countries: a scoping review.

BACKGROUND AND OBJECTIVE: Awake craniotomy (AC) is a valuable technique for surgical interventions in eloquent areas, but its adoption in low- and middle-income countries faces challenges like limited infrastructure, trained personnel shortage, and inadequate funding. This scoping review explores AC techniques in Latin American countries, focusing on patient characteristics, tumor location, symptomatology, and outcomes. METHODS: A scoping review followed PRISMA guidelines, searching five databases in English, Spanish, and Portuguese. We included 28 studies with 258 patients (mean age: 43, range: 11-92). Patterns in AC use in Latin America were analyzed. RESULTS: Most studies were from Brazil and Mexico (53.6%) and public institutions (70%). Low-grade gliomas were the most common lesions (55%), most of them located in the left hemisphere (52.3%) and frontal lobe (52.3%). Gross-total resection was achieved in 34.3% of cases. 62.9% used an Asleep-Awake-Asleep protocol, and 14.8% used Awake-Awake-Awake. The main complication was seizures (14.6%). Mean post-surgery discharge time was 68 h. Challenges included limited training, infrastructure, and instrumentation availability. Strategies discussed involve training in specialized centers, seeking sponsorships, applying for awards, and multidisciplinary collaborations with neuropsychology. CONCLUSION: Improved accessibility to resources, infrastructure, and adequate instrumentation is crucial for wider AC availability in Latin America. Despite disparities, AC implementation with proper training and teamwork yields favorable outcomes in resource-limited centers. Efforts should focus on addressing challenges and promoting equitable access to this valuable surgical technique in the region.

Impact of Coronary Artery Calcium Score Screening on Cardiovascular Risk Stratification of Patients with Atrial Fibrillation Undergoing Ablation.

INTRODUCTION: There is a well-established association between atrial fibrillation (AF) and coronary artery disease. Coronary artery calcium score (CACS) is a helpful tool to refine cardiovascular (CV) risk stratification and inform on the best strategies for primary CV prevention. This study aims to evaluate the impact of opportunistic screening with CACS on risk stratification and decision of preventive therapies, in patients with AF. METHODS: Cross-sectional study including patients with AF or atrial flutter undergoing cardiac computed tomography for ablation procedure planning, from 2017 to 2019. Baseline clinical and demographical data were collected. CACS was assessed in patients without coronary artery disease using the Agatston method. RESULTS: A total of 474 patients were included (93% with AF, mean age of 58 ± 10 years, 62% male). CACS >0 was present in 254 (54%) patients. According to CACS and the Society of Cardiovascular Computed Tomography recommendations, 25% of the patients would be candidates for statin therapy and 17% would be candidates for changes in the current statin intensity; in 11 patients (8%), acetylsalicylic acid would be recommended. CONCLUSION: In our study, more than half of the patients undergoing cardiac computed tomography before AF catheter ablation had CACS above zero. Our findings suggest that an opportunistic evaluation of CACS at the time of ablation can be an important tool to improve CV risk stratification, with important clinical and therapeutic implications.

Querying semantic catalogues of biomedical databases.

BACKGROUND: Secondary use of health data is a valuable source of knowledge that boosts observational studies, leading to important discoveries in the medical and biomedical sciences. The fundamental guiding principle for performing a successful observational study is the research question and the approach in advance of executing a study. However, in multi-centre studies, finding suitable datasets to support the study is challenging, time-consuming, and sometimes impossible without a deep understanding of each dataset. METHODS: We propose a strategy for retrieving biomedical datasets of interest that were semantically annotated, using an interface built by applying a methodology for transforming natural language questions into formal language queries. The advantages of creating biomedical semantic data are enhanced by using natural language interfaces to issue complex queries without manipulating a logical query language. RESULTS: Our methodology was validated using Alzheimer's disease datasets published in a European platform for sharing and reusing biomedical data. We converted data to semantic information format using biomedical ontologies in everyday use in the biomedical community and published it as a FAIR endpoint. We have considered natural language questions of three types: single-concept questions, questions with exclusion criteria, and multi-concept questions. Finally, we analysed the performance of the question-answering module we used and its limitations. The source code is publicly available at https://bioinformatics-ua.github.io/BioKBQA/. CONCLUSION: We propose a strategy for using information extracted from biomedical data and transformed into a semantic format using open biomedical ontologies. Our method uses natural language to formulate questions to be answered by this semantic data without the direct use of formal query languages.

Identification of traits to improve co-assimilation of glucose and xylose by adaptive evolution of Spathaspora passalidarum and Scheffersomyces stipitis yeasts.

Lignocellulosic biomass is a renewable raw material for producing several high-value-added chemicals and fuels. In general, xylose and glucose are the major sugars in biomass hydrolysates, and their efficient utilization by microorganisms is critical for an economical production process. Yeasts capable of co-consuming mixed sugars might lead to higher yields and productivities in industrial fermentation processes. Herein, we performed adaptive evolution assays with two xylose-fermenting yeasts, Spathaspora passalidarum and Scheffersomyces stipitis, to obtain derived clones with improved capabilities of glucose and xylose co-consumption. Adapted strains were obtained after successive growth selection using xylose and the non-metabolized glucose analog 2-deoxy-D-glucose as a selective pressure. The co-fermentation capacity of evolved and parental strains was evaluated on xylose-glucose mixtures. Our results revealed an improved co-assimilation capability by the evolved strains; however, xylose and glucose consumption were observed at slower rates than the parental yeasts. Genome resequencing of the evolved strains revealed genes affected by non-synonymous variants that might be involved with the co-consumption phenotype, including the HXT2.4 gene that encodes a putative glucose transporter in Sp. passalidarum. Expression of this mutant HXT2.4 in Saccharomyces cerevisiae improved the cells' co-assimilation of glucose and xylose. Therefore, our results demonstrated the successful improvement of co-fermentation through evolutionary engineering and the identification of potential targets for further genetic engineering of different yeast strains. KEY POINTS: • Laboratory evolution assay was used to obtain improved sugar co-consumption of non-Saccharomyces strains. • Evolved Sp. passalidarum and Sc. stipitis were able to more efficiently co-ferment glucose and xylose. • A mutant Hxt2.4 permease, which co-transports xylose and glucose, was identified.

Endoscopic endonasal surgery for prolactinomas: prognostic factors for disease control and management of persistent disease.

Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion.

Different Approaches in Skull Base Surgery Carry Risks for Different Types of Complications.

Complications are not uncommon in the complex field of skull base surgery. The intrinsic relationship of lesions in this region to important neurovascular structures, dura mater, and bone may lead to significant morbidity and mortality. The evolution of endoscopic endonasal surgery has had a significant impact on this field as a less invasive option for treatment of selected lesions, but major morbidity may still occur; moreover, endoscopic approaches have been associated with higher rates of some specific complications, such as cerebrospinal fluid leaks. Based on a presented case report, the authors discuss the management of various complications associated with different approaches for resection of skull base malignancies, including epidural and intradural pneumocephalus, subdural hematoma, and subdural empyema. Important lessons learned by the senior author throughout more than 30 years of his skull base surgery practice are highlighted. The inherent risk of complications in skull base surgery emphasizes the importance of their avoidance, prevention, and learning from one's unfavorable experience so as not to repeat them.

Predictive factors for post operative seizures following meningioma resection in patients without preoperative seizures: a multicenter retrospective analysis.

PURPOSE: Meningiomas are the most common primary brain tumor and represent 35% of all intracranial neoplasms. However, in the early post-operative period approximate 3-5% of patients experience an acute symptomatic seizure. Establishing risk factors for postoperative seizures will identify those patients without preoperative seizures at greatest risk of postoperative seizures and may guide antiseizure medications (ASMs) management. METHODS: Adult seizure naïve patients who underwent primary resection of a World Health Organization (WHO) Grade 1-3 meningioma at the three Mayo Clinic Campuses between 2012-2022 were retrospectively reviewed. Multivariate regression analyses were used to identify radiological, surgical, and management features with the development of new-onset seizures in patients undergoing meningioma resection. RESULTS: Of 113 seizure naïve patients undergoing meningioma resection 11 (9.7%) experienced a new-onset post-operative seizure. Tumor volume ≥ 25 cm3 (Odds Ratio (OR) 5.223, 95% Confidence Interval (CI) 1.546 - 17.650, p = 0.008) and cerebral convexity meningiomas (OR 4.742, 95% CI 1.255 - 14.336, p = 0.016) were most associated with new onset postoperative seizures in multivariate analysis. ASMs and corticosteroid therapies did not display a significant difference among those with and without a new onset postoperative seizure. CONCLUSION: In the current study, a larger tumor volume (≥ 25 cm3) and/or convexity meningiomas predicted the development of new onset post-operative seizures. Those who present with these factors should be counseled for their increased risk of new onset post-operative seizures and may benefit from prophylactic ASMs therapy.

Single-cell mtDNA heteroplasmy in colorectal cancer.

Human mitochondria can be genetically distinct within the same individual, a phenomenon known as heteroplasmy. In cancer, this phenomenon seems exacerbated, and most mitochondrial mutations seem to be heteroplasmic. How this genetic variation is arranged within and among normal and tumor cells is not well understood. To address this question, here we sequenced single-cell mitochondrial genomes from multiple normal and tumoral locations in four colorectal cancer patients. Our results suggest that single cells, both normal and tumoral, can carry various mitochondrial haplotypes. Remarkably, this intra-cell heteroplasmy can arise before tumor development and be maintained afterward in specific tumoral cell subpopulations. At least in the colorectal patients studied here, the somatic mutations in the single-cells do not seem to have a prominent role in tumorigenesis.

Core versus Surface Sensors for Reinforced Concrete Structures: A Comparison of Fiber-Optic Strain Sensing to Conventional Instrumentation.

High-resolution distributed reinforcement strain measurements can provide invaluable information for developing and evaluating numerical and analytical models of reinforced concrete structures. A recent testing campaign conducted at UCLouvain in Belgium used fiber-optic sensors embedded along several longitudinal steel rebars of three reinforced concrete U-shaped walls. The resulting experimental dataset provides an opportunity to evaluate and compare, for different types of loading, the strain measurements obtained with the fiber-optic sensors in the confined core of the structural member against more conventional and state-of-the-practice sensors that monitor surface displacements and deformations. This work highlights the need to average strain measurements from digital image correlation techniques in order to obtain coherent results with the strains measured from fiber optics, and investigates proposals to achieve this relevant goal for research and engineering practices. The longitudinal strains measured by the fiber optics also provide additional detailed information on the behavior of these wall units compared to the more conventional instrumentation, such as strain penetration into the foundation and head of the wall units, which are studied in detail.

A Modular In-Vehicle C-ITS Architecture for Sensor Data Collection, Vehicular Communications and Cloud Connectivity.

The growth of the automobile industry in recent decades and the overuse of personal vehicles have amplified problems directly related to road safety, such as the increase in traffic congestion and number of accidents, as well as the degradation of the quality of roads. At the same time, and with the contribution of climate change effects, dangerous weather events have become more common on road infrastructure. In this context, Cooperative Intelligent Transport Systems (C-ITS) and Internet of Things (IoT) solutions emerge to overcome the limitations of human and local sensory systems, through the collection and distribution of relevant data to Connected and Automated Vehicles (CAVs). In this paper, an intra- and inter-vehicle sensory data collection system is presented, starting with the acquisition of relevant data present on the Controller Area Network (CAN) bus, collected through the vehicle's On-Board-Diagnostics II (OBD-II) port, as well as on an on-board smartphone device and possibly other additional sensors. Short-range communication technologies, such as Bluetooth Low Energy (BLE), Wi-Fi, and ITS-G5, are employed in conjunction with long-range cellular networks for data dissemination and remote cloud monitoring. The results of the experimental tests allow the analysis of the road environment, as well as the notification in near real-time of adverse road conditions to drivers. The developed data collection system reveals itself as a potentially valuable tool for improving road safety and to iterate on the current Road Weather Models (RWMs).

Computational Approaches Drive Developments in Immune-Oncology Therapies for PD-1/PD-L1 Immune Checkpoint Inhibitors.

Computational approaches in immune-oncology therapies focus on using data-driven methods to identify potential immune targets and develop novel drug candidates. In particular, the search for PD-1/PD-L1 immune checkpoint inhibitors (ICIs) has enlivened the field, leveraging the use of cheminformatics and bioinformatics tools to analyze large datasets of molecules, gene expression and protein-protein interactions. Up to now, there is still an unmet clinical need for improved ICIs and reliable predictive biomarkers. In this review, we highlight the computational methodologies applied to discovering and developing PD-1/PD-L1 ICIs for improved cancer immunotherapies with a greater focus in the last five years. The use of computer-aided drug design structure- and ligand-based virtual screening processes, molecular docking, homology modeling and molecular dynamics simulations methodologies essential for successful drug discovery campaigns focusing on antibodies, peptides or small-molecule ICIs are addressed. A list of recent databases and web tools used in the context of cancer and immunotherapy has been compilated and made available, namely regarding a general scope, cancer and immunology. In summary, computational approaches have become valuable tools for discovering and developing ICIs. Despite significant progress, there is still a need for improved ICIs and biomarkers, and recent databases and web tools have been compiled to aid in this pursuit.

Colonic perineurioma of the transverse colon: presentation of a rare neoplasm in an atypical location.

A 51-year-old male with previous medical history of dyslipidemia performed screening colonoscopy, which revealed a sessile polypoid lesion with a diameter of approximately 8 mm located at the proximal transverse colon, which was resected en bloc with a cold snare. Remarkably, histopathological examination revealed a proliferation of spindle cells in the lamina propria entrapping colonic crypts without evidence of nuclear pleomorphism, mitotic figures or necrosis. On immunohistochemistry, spindle cells were diffusely positive for glucose transporter-1 and negative for S100, DOG1, CD34 and smooth muscle actin. These features were consistent with a diagnosis of colonic perineurioma.