Scaling of the morphology of African cities.

A large proportion of Africa's infrastructure is yet to be built. Where and how these new buildings are constructed matters since today's decisions will last for decades. The resulting morphology of cities has lasting implications for a city's energy needs. Estimating and projecting these needs has always been challenging in Africa due to the lack of data. Yet, given the sweeping urbanization expected in Africa over the next three decades, this obstacle must be overcome to guide cities toward a trajectory of sustainability and resilience. Based on the location and surface of nearly 200 million buildings on the continent, we estimate the interbuilding distance of almost six thousand cities. Buildings' footprint data enable the construction of urban form indicators to compare African cities' elongation, sprawl, and emptiness. We establish the BASE model, where the mean distance between buildings is a functional relation to the number of Buildings and their average Area, as well as the Sprawl and the Elongation of its spatial arrangement. The mean distance between structures in cities-our proxy for its energy demands related to mobility-grows faster than the square root of its population, resulting from the combined impact of a sublinear growth in the number of buildings and a sublinear increase in building size and sprawl. We estimate that when a city doubles its population, it triples its energy demand from transport.

Performance of the Idylla microsatellite instability test in endometrial cancer.

CONTEXT: DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses. OBJECTIVE: The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status. DESIGN: We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored. RESULTS: The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off. CONCLUSIONS: Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer.

Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.

Prognostic implications of tumor-infiltrating T cells in early-stage endometrial cancer.

Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.

Clinical Correlates of Depression and Suicidality in Huntington Disease: An Analysis of the Enroll-HD Observational Study.

BACKGROUND: Depression and suicidality are commonly experienced by Huntington disease (HD) gene carriers. Research on these behavioral symptoms is imperative, not only to increase our understanding of the symptoms and how they relate to HD, but also to contribute to improving patients' care and quality of life. OBJECTIVE: To identify clinical variables associated with a history of depression and suicidality in HD gene carriers. METHOD: We conducted a cross-sectional study of HD gene carriers from the Enroll-HD database PDS4 (periodic data set 4; N = 11,582). Data from baseline visits were obtained, and binary logistic regression models were used to ascertain the effects of clinical variables on the likelihood that HD gene carriers would have previous depression and suicidal ideation/attempts. RESULTS: Approximately 65% (n = 7526) of the HD gene carriers had a history of depression, and ~27% (n = 3152) had previous suicidal ideation/attempts. Female sex; diagnosis of manifest HD; history of perseverative/obsessive behavior, apathy, and psychosis; and previous suicidal ideation/attempts were significantly associated with a history of depression in the HD gene carriers. Medical history of apathy, psychosis, and depression, as well as worse scores on the Total Functional Capacity and Irritability Scales, were significantly associated with previous suicidal ideation/attempts in the HD gene carriers. CONCLUSION: The prevalence of depression and suicidality is high among HD gene carriers. An improved understanding of the risk factors for depression and suicide in HD gene carriers can assist providers in recognizing at-risk individuals and allow providers to implement therapeutic strategies.

Seronegative Paraneoplastic Limbic Encephalitis Associated with Thymoma.

Paraneoplastic limbic encephalitis is an autoimmune syndrome characterized by the acute or subacute onset of encephalopathy, memory loss, confusion, temporal lobe seizures, and behavioral and mood changes. Although most patients with paraneoplastic limbic encephalitis have antineuronal antibodies, advances in the field now permit the diagnosis without autoantibody test results. In this case illustrating the new diagnostic criteria, we report a 70-year-old woman who was brought to the emergency room after the acute onset of cognitive impairment, altered mental status, and choreoathetoid movements. Brain magnetic resonance imaging showed hyperintense signals in both temporal lobes, and a chest computed tomogram revealed a thymoma. Because the patient met current diagnostic criteria for autoimmune limbic encephalitis, we were able to start treatment before her antibody tests were processed. The patient received immunotherapy and her tumor was resected. Her choreoathetoid movements disappeared and her other neurologic symptoms improved. Her cerebrospinal fluid proved to be negative for paraneoplastic limbic encephalitis antibodies. Most but not all patients with paraneoplastic limbic encephalitis associated with thymoma have evidence of paraneoplastic antibodies. Prompt management of the underlying malignancy determines whether patients survive and may minimize future cognitive and functional impairment. Practicing neurologists and psychiatrists should be aware of this diagnosis.

Expanded-access use of elamipretide in a patient with membrane protein-associated neurodegeneration.

This case report presents a progressively declining 17-year-old patient with membrane protein-associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6-minute walk test and 5 times sit-to-stand test during elamipretide treatment.

Obsessive-compulsive and perseverative behaviors in Huntington's disease.

Obsessive-compulsive and perseverative behaviors (OCBs/PBs) are characteristic features of Huntington's Disease (HD). Although a few recent research have attempted to discriminate between OCBs and PBs, most of the available evidence on OCBs does not consistently make this distinction. In this article, we aimed to explore the current inconsistencies in assessing and reporting OCBs/PBs and map the body of existing evidence. Up to half of the patients with motor manifest HD can experience OCBs. Separate reporting of PBs in HD patients has been uncommon among the studies and was frequently reported as a part of obsessive-compulsive symptoms. The structural limitation of the currently used rating scales and the overlaps in neuropathology and definition of OCBs and PBs are among the main reasons for the mixed reporting of OCBs/PBs. Perseverative thinking or behavior as a separate item is found in a few assessment tools, such as the Problem Behaviors Assessment - Short form (PBA-s). Even when the item exists, it is commonly reported as a composite score in combination with the obsessive-compulsive item. In addition to the significant psychological burden in individuals with HD, PBs are associated with somatic effects (e.g., cardiovascular symptoms) and high-risk behaviors (e.g., suicide). Recognition and monitoring of PBs in HD can aid in early detection of concerning symptoms and differentiating overlapping illnesses.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods: In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results: This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract (d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [rsp] = -0.56, p < 0.001), and forceps minor of corpus callosum (rsp = -0.45, p < 0.01). Conclusion: MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

Unusual primary central nervous system T-cell/histiocyte-rich large B-cell lymphoma: a case report.

We report the case of a 54-year-old immunocompetent woman who presented with a primary T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL) of the central nervous system without systemic involvement, diagnosed by means of a brain biopsy. She was treated with corticosteroids and we subsequently started chemotherapy with rituximab, methotrexate, ifosfamide and intrathecal cytarabine. The patient's symptoms gradually improved over the first weeks and we followed-up with autologous haematopoietic cell transplantation. The patient has been in complete remission for a year. Primary TCHRLBCL of the central nervous system in an immunocompetent patient is an extremely rare condition that requires a multidisciplinary approach. This case highlights the importance of undergoing a sequential work-up and establishing a treatment despite the absence of evidence-based guidelines.

Empiric recommendations for population disaggregation under different data scenarios.

High-resolution population mapping is of high relevance for developing and implementing tailored actions in several fields: From decision making in crisis management to urban planning. Earth Observation has considerably contributed to the development of methods for disaggregating population figures with higher resolution data into fine-grained population maps. However, which method is most suitable on the basis of the available data, and how the spatial units and accuracy metrics affect the validation process is not fully known. We aim to provide recommendations to researches that attempt to produce high-resolution population maps using remote sensing and geospatial information in heterogeneous urban landscapes. For this purpose, we performed a comprehensive experimental research on population disaggregation methods with thirty-six different scenarios. We combined five different top-down methods (from basic to complex, i.e., binary and categorical dasymetric, statistical, and binary and categorical hybrid approaches) on different subsets of data with diverse resolutions and degrees of availability (poor, average and rich). Then, the resulting population maps were systematically validated with a two-fold approach using six accuracy metrics. We found that when only using remotely sensed data the combination of statistical and dasymetric methods provide better results, while highly-resolved data require simpler methods. Besides, the use of at least three relative accuracy metrics is highly encouraged since the validation depends on level and method. We also analysed the behaviour of relative errors and how they are affected by the heterogeneity of the urban landscape. We hope that our recommendations save additional efforts and time in future population mapping.

Cerebral blood flow is associated with markers of neurodegeneration in Huntington's disease.

INTRODUCTION: The ultimate cause of neuronal death in Huntington's disease (HD) is still uncertain. Apart from impairment in systems handling abnormal proteins, other mechanisms might contribute to neurodegeneration and progression of HD. Decreased cerebral blood flow (CBF) has been described in other neurodegenerative disorders and may play a role in HD. OBJECTIVES: To investigate CBF changes in HD gene carriers. METHODS: A group of 39 HD gene carriers (18 premanifest and 21 manifest HD) and 16 controls underwent a comprehensive clinical evaluation and a brain magnetic resonance imaging protocol that included pseudo-continuous arterial spin labeling to quantify CBF. Regions of interest (ROI) analyses were performed to compare CBF in controls vs premanifest HD vs manifest HD. Correlation analyses were performed to ascertain the relationship between CBF and clinical and biomarkers data. RESULTS: We found a decrease in CBF in bilateral caudate and putamen of patients with manifest HD in comparison with controls. CBF of premanifest HD carriers in the same ROIs was midway between controls and the HD patients, with differences not reaching statistical significance. Lower CBF in caudate and putamen was associated with worse motor symptoms, functionality, and cognitive performance. CBF was also associated with markers of neurodegeneration: higher CBF in caudate and putamen significantly correlated to higher volumes in the same ROI and to lower levels of neurofilament light chain. CONCLUSION: As CBF changes in caudate and putamen nuclei were associated with markers of neurodegeneration and with clinical outcomes, decreased CBF and oxygen supply could emerge as a relevant mechanism contributing to degeneration in HD.

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia.

To date, the therapeutic use of cannabinoids in chronic pain management remains controversial owing to the limited clinical evidence found in randomized clinical trials (RCTs), the heterogeneous nature of the clinical indication, and the broad range of cannabis-based medicinal products (CBMPs) used in both experimental and observational clinical studies. Here we evaluate patient-reported clinical outcomes (PROMS) in a cohort of adult patients, diagnosed with chronic pain of diverse etiology, who received adjuvant treatment with oral, cannabis-based, magistral formulations between May and September 2021 at the Latin American Institute of Neurology and Nervous System (ILANS-Zerenia) in Bogotá, Colombia. During this period, 2,112 patients completed a PROMS questionnaire aimed at capturing the degree of clinical improvement of their primary symptom and any potential side effects. Most participants were female (76.1%) with an average age of 58.7 years old, and 92.5% (1,955 patients) reported some improvement in their primary symptom (p < 0.001). Two monovarietal, full-spectrum, cannabis formulations containing either cannabidiol (CBD 30 mg/mL; THC <2 mg/mL) or a balanced composition (THC 12 mg/mL; CBD 14 mg/mL) accounted for more than 99% of all prescriptions (59.5 and 39.8%, respectively). The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment. Sex-specific differences were also found in prescription patterns, with male patients increasing the intake of the balanced chemotype overtime. For many patients (71.7%) there were no adverse side effects associated to the treatment and those most reported were mild, such as somnolence (13.0%), dizziness (8.1%) and dry mouth (4.2%), which also appeared to fade over time. Our results constitute the first real-world evidence on the clinical use of medicinal cannabis in Colombia and suggest that cannabis-based oral magistral formulations represent a safe and efficacious adjuvant therapeutic option in the management of chronic pain.

iRECIST and atypical patterns of response to immuno-oncology drugs.

With the advent of immunotherapy as one of the keystones of the treatment of our patients with cancer, a number of atypical patterns of response to these agents has been identified. These include pseudoprogression, where the tumor initially shows objective growth before decreasing in size, and hyperprogression, hypothesized to be a drug-induced acceleration of the tumor burden. Despite it being >10 years since the first immune-oncology drug was approved, neither the biology behind these paradoxical responses has been well understood, nor their incidence, identification criteria, predictive biomarkers, or clinical impact have been fully described. Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines have been published as a revision to the RECIST V.1.1 criteria for use in trials of immunotherapeutics, and the iRECIST subcommittee (of the RECIST Working Group) is working on elucidating these aspects, with data sharing a current major challenge to move forward with this unmet need in immuno-oncology.

Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (including patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation.

Blind microscopy image denoising with a deep residual and multiscale encoder/decoder network.

In computer-aided diagnosis (CAD) focused on microscopy, denoising improves the quality of image analysis. In general, the accuracy of this process may depend both on the experience of the microscopist and on the equipment sensitivity and specificity. A medical image could be corrupted by several perturbations during image acquisition. Nowadays, CAD deep learning applications pre-process images with image denoising models to reinforce learning and prediction. In this work, an innovative and lightweight deep multiscale convolutional encoder-decoder neural network is proposed. Specifically, the encoder uses deterministic mapping to map features into a hidden representation. Then, the latent representation is rebuilt to generate the reconstructed denoised image. Residual learning strategies are used to improve and accelerate the training process using skip connections in bridging across convolutional and deconvolutional layers. The proposed model reaches on average 38.38 of PSNR and 0.98 of SSIM on a test set of 57458 images overcoming state-of-the-art models in the same application domain.Clinical relevance - Encoder-decoder based denoiser enables industry experts to provide more accurate and reliable medical interpretation and diagnosis in a variety of fields, from microscopy to surgery, with the benefit of real-time processing.

The heartbeat of the city.

Human activity is organised around daily and weekly cycles, which should, in turn, dominate all types of social interactions, such as transactions, communications, gatherings and so on. Yet, despite their strategic importance for policing and security, cyclical weekly patterns in crime and road incidents have been unexplored at the city and neighbourhood level. Here we construct a novel method to capture the weekly trace, or "heartbeat" of events and use geotagged data capturing the time and location of more than 200,000 violent crimes and nearly one million crashes in Mexico City. On aggregate, our findings show that the heartbeats of crime and crashes follow a similar pattern. We observe valleys during the night and peaks in the evening, where the intensity during a peak is 7.5 times the intensity of valleys in terms of crime and 12.3 times in terms of road accidents. Although distinct types of events, crimes and crashes reach their respective intensity peak on Friday night and valley on Tuesday morning, the result of a hyper-synchronised society. Next, heartbeats are computed for city neighbourhood 'tiles', a division of space within the city based on the distance to Metro and other public transport stations. We find that heartbeats are spatially heterogeneous with some diffusion, so that nearby tiles have similar heartbeats. Tiles are then clustered based on the shape of their heartbeat, e.g., tiles within groups suffer peaks and valleys of crime or crashes at similar times during the week. The clusters found are similar to those based on economic activities. This enables us to anticipate temporal traces of crime and crashes based on local amenities.

Sex Differences in Huntington's Disease: Evaluating the Enroll-HD Database.

BACKGROUND: Identifying sex-related differences is critical for enhancing our understanding of factors that may impact prognosis and advance treatments in Huntington's disease (HD). OBJECTIVES: To investigate if sex-related differences exist in clinical HD. METHODS: Longitudinal study of the Enroll-HD database. Manifest HD patients were included in the analysis (N = 8401). Linear mixed models were used to assess motor, behavioral, and cognitive functioning over a series of four annual visits, and compared male and female HD gene carriers. RESULTS: HD patients showed significant sex-dependent differences in motor, cognitive, and behavioral symptoms. Both sexes had worsened motor symptoms over the course of four visits, but there was a significant disparity between sexes, with females consistently presenting with more symptoms than males. For behavioral symptoms, specifically depressive symptoms, females had significantly more depressive symptoms, although self-reported symptoms in both sexes became less severe throughout time. CONCLUSIONS: Our analyses suggest that women have worse symptoms than men during the course of HD.

Neighbourhood green space and health disparities in the global South: Evidence from Cali, Colombia.

Increasing attention has been given to the role of green space in reducing health disparities. However, robust evidence to support decision making is lacking in the global South. We investigate the relationship between green space and health as well as its underlying mechanism in Cali, Colombia. Results indicate that neighbourhood greenness is associated with enhanced self-rated 'good' health and reduced physical and mental distress. The health benefits of green space appear to be stronger for people living in wealthier neighbourhoods than those in poor neighbourhoods. Results highlight the importance of considering health disparities for future green infrastructure planning in the global South context.

Olfactory Dysfunction in Huntington's Disease.

Olfactory dysfunction is a common symptom in patients with neurodegenerative disorders, including Huntington's disease (HD). Understanding its pathophysiology is important in establishing a preventive and therapeutic plan. In this literature review, we cover the physiology of olfaction, its role in neurodegeneration, and its characteristics in patients with HD. In the general population, olfactory dysfunction is present in 3.8-5.8%and the prevalence increases significantly in those older than 80 years. For HD, data regarding prevalence rates are lacking and the scales used have been inconsistent or have been restructured due to concerns about cross-cultural understanding. Pathogenic huntingtin deposits have been found in the olfactory bulb of individuals with HD, although no studies have correlated this with the grade of olfactory impairment. Olfactory dysfunction is present in both premanifest and manifest patients with HD, showing a progressive decline over time with more severe deficits at advanced stages. No specific treatment for olfactory impairment in HD has been proposed; identifying and avoiding potential medications that cause olfactory dysfunction, as well as general safety recommendations remain the basis of the therapeutic strategy.