Medial malleolar osteotomy in the treatment of osteochondral lesions of the Talus - incidence and impact on functional outcome: a retrospective analysis based on data from the German Cartilage Register (KnorpelRegister DGOU).

BACKGROUND: There has long been discussion regarding the impact of medial malleolar osteotomies (MMO) as an adjunctive treatment for osteochondral lesions of the talus (OCLT). MMO may improve the visibility and accessibility of the talus, but they also pose a risk of periprocedural morbidity. There is a lack of research about the prevalence and consequences of MMO in the surgical treatment of OCLT. METHODS: This study retrospectively evaluated data from the German Cartilage Register (KnorpelRegister DGOU) from its implementation in 2015 to December 2020. The impact of MMO on patient-reported outcome measures (PROMs) was investigated. Wherever possible, subgroups were built and matched using a propensity score which matched a group undergoing OCLT without MMO. Matching included age, sex, weight, localization of the OCLT, the international cartilage repair society (ICRS) grading, surgical procedure and preoperative symptoms using the Foot and Ankle Ability Measure (FAAM) and the Activities of Daily Living Subscale (ADL). RESULTS: The prevalence of MMO in the operative treatment of OCLT was 15.9%. Most of the osteotomies were performed in OCL of the medial talar dome (76.8%) and in more serious lesions with an ICRS grade of III (29.1%) and IV (61.4%). More than half of the osteotomies (55.6%) were performed during revision surgery. A matched pair analysis of n = 44 patients who underwent AMIC® via arthrotomy and MMO vs. arthrotomy alone showed no significant differences in patient-reported outcome measures (PROMs, i.e. FAAM-ADL, and FAOS) at 6,12 and 24 months. CONCLUSIONS: MMO are mostly used in the treatment of severe (≥ ICRS grade 3) OCL of the medial talar dome and in revision surgery. Functional and patient-reported outcome measures are not significantly affected by MMO compared to arthrotomy alone. TRIAL REGISTRATION: The German Cartilage Register (KnorpelRegister DGOU) was initially registered at the German Clinical Trials Register ( https://www.drks.de , register number DRKS00005617, Date of registration 03.01.2014) and was later expanded by the ankle module.

Tailored surgical approaches for spinal chordomas: A multidisciplinary perspective.

INTRODUCTION: The treatment of spinal chordomas presents a significant challenge due to their resistance to both radiotherapy and chemotherapy as well as the complexity of the surgical procedures required. This study presents a series of cases of primary spinal chordomas, focusing on the development of a personalized therapeutic strategy that is tailored to each patient's unique clinical status. This approach aims to ensure that treatments are optimally aligned with the patient's overall prognosis and surgical eligibility. METHODS: This retrospective study analyzed 14 patients with primary spinal chordomas treated at our institution. We evaluated surgical strategies, clinical outcomes, and survival rates, The therapeutic strategy was formulated after interdisciplinary conferences with sarcoma management specialists. Data were collected on patient demographics, surgical details, postoperative outcomes, and follow-up status. RESULTS: All patients presented with neurological deficits preoperatively, which generally improved post-surgery. The study included a detailed analysis of two distinct surgical approaches: five patients underwent en bloc resection with dorsal stabilization and nine received decompression only. Patients undergoing en bloc resection showed a reduced need for additional surgery due to the comprehensive removal of the tumor. As anticipated, 40% of the patients who underwent decompression experienced tumor progression within the first three months. However, given the poor overall prognosis, the objective of maintaining neurological function was achieved. CONCLUSIONS: Surgical en bloc resection offers a viable and effective intervention for spinal chordomas, enhancing neurological function. It is imperative to tailor treatment strategies to individual prognoses, integrating insights from multidisciplinary discussions that meticulously evaluate surgical risks. This collaborative approach aids in selecting the most appropriate surgical technique tailored to each patient's specific condition.

IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8+ T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC. DESIGN: Infiltration of Tc17 cells in PDAC tissue was correlated with patient overall survival and tumour stage. Wild-type (WT) or Il17ra-/- quiescent pancreatic stellate cells (qPSC) were exposed to conditional media obtained from Tc17 cells (Tc17-CM); moreover, co-culture of Tc17-CM-induced inflammatory (i)CAF (Tc17-iCAF) with tumour cells was performed. IL-17A/F-, IL-17RA-, RAG1-deficient and Foxn1nu/nu mice were used to study the Tc17 role in subcutaneous and orthotopic PDAC mouse models. RESULTS: Increased abundance of Tc17 cells highly correlated with reduced survival and advanced tumour stage in PDAC. Tc17-CM induced iCAF differentiation as assessed by the expression of iCAF-associated genes via synergism of IL-17A and TNF. Accordingly, IL-17RA controlled the responsiveness of qPSC to Tc17-CM. Pancreatic tumour cells co-cultured with Tc17-iCAF displayed enhanced proliferation and increased expression of genes implicated in proliferation, metabolism and protection from apoptosis. Tc17-iCAF accelerated growth of mouse and human tumours in Rag1-/- and Foxn1nu/nu mice, respectively. Finally, Il17ra-expressed by fibroblasts was required for Tc17-driven tumour growth in vivo. CONCLUSIONS: We identified Tc17 as a novel protumourigenic CD8+ T-cell subtype in PDAC, which accelerated tumour growth via IL-17RA-dependent stroma modification. We described a crosstalk between three cell types, Tc17, fibroblasts and tumour cells, promoting PDAC progression, which resulted in poor prognosis for patients.

Spatially encoded hyperspectral compressive microscope for ultrabroadband VIS/NIR hyperspectral imaging.

Hyperspectral imaging (HSI) has become a valuable tool in sample characterization in various scientific fields. While many approaches have been tested, specific applications and technology usually lead to only a narrow part of the spectrum being studied. We demonstrate the use of a broadband HSI setup based on compressed sensing capable of capturing data in visible (VIS), near-infrared (NIR), and short-wave infrared (SWIR) spectral regions. Using a tested design, we developed a dual configuration and tested its performance on a set of samples demonstrating spatial resolution and spectral reconstruction. Samples showing a potential use of the setup in optical defect detection are also tested. The setup showcases a dual single-pixel camera configuration capable of combining various detectors with a shared spatial modulation, further improving data efficiency and providing an affordable instrument from broadband spectral studies.

Enhanced Fault Type Detection in Covered Conductors Using a Stacked Ensemble and Novel Algorithm Combination.

This study introduces an innovative approach to enhance fault detection in XLPE-covered conductors used for power distribution systems. These covered conductors are widely utilized in forested areas (natural parks) to decrease the buffer zone and increase the reliability of the distribution network. Recognizing the imperative need for precise fault detection in this context, this research employs an antenna-based method to detect a particular type of fault. The present research contains the classification of fault type detection, which was previously accomplished using a very expensive and challenging-to-install galvanic contact method, and only to a limited extent, which did not provide information about the fault type. Additionally, differentiating between types of faults in the contact method is much easier because information for each phase is available. The proposed method uses antennas and a classifier to effectively differentiate between fault types, ranging from single-phase to three-phase faults, as well as among different types of faults. This has never been done before. To bolster the accuracy, a stacking ensemble method involving the logistic regression is implemented. This approach not only advances precise fault detection but also encourages the broader adoption of covered conductors. This promises benefits such as a reduced buffer zone, improved distribution network reliability, and positive environmental outcomes through accident prevention and safe covered conductor utilization. Additionally, it is suggested that the fault type detection could lead to a decrease in false positives.

Versatile compressive microscope for hyperspectral transmission and fluorescence lifetime imaging.

Increasing demand for multimodal characterization and imaging of new materials entails the combination of various methods in a single microscopic setup. Hyperspectral imaging of transmission spectra or photoluminescence (PL) decay imaging count among the most used methods. Nevertheless, these methods require very different working conditions and instrumentation. Therefore, combining the methods into a single microscopic system is seldom implemented. Here we demonstrate a novel versatile microscope based on single-pixel imaging, where we use a simple optical configuration to measure the hyperspectral information, as well as fluorescence lifetime imaging (FLIM). The maps are inherently spatially matched and can be taken with spectral resolution limited by the resolution of the used spectrometer (3 nm) or temporal resolution set by PL decay measurement (120 ps). We verify the system's performance by its comparison to the standard FLIM and non-imaging transmission spectroscopy. Our approach enabled us to switch between a broad field-of-view and micrometer resolution without changing the optical configuration. At the same time, the used design opens the possibility to add a variety of other characterization methods. This article demonstrates a simple, affordable way of complex material studies with huge versatility for the imaging parameters.

Discovering Process Dynamics for Scalable Perovskite Solar Cell Manufacturing with Explainable AI.

Large-area processing of perovskite semiconductor thin-films is complex and evokes unexplained variance in quality, posing a major hurdle for the commercialization of perovskite photovoltaics. Advances in scalable fabrication processes are currently limited to gradual and arbitrary trial-and-error procedures. While the in situ acquisition of photoluminescence (PL) videos has the potential to reveal important variations in the thin-film formation process, the high dimensionality of the data quickly surpasses the limits of human analysis. In response, this study leverages deep learning (DL) and explainable artificial intelligence (XAI) to discover relationships between sensor information acquired during the perovskite thin-film formation process and the resulting solar cell performance indicators, while rendering these relationships humanly understandable. The study further shows how gained insights can be distilled into actionable recommendations for perovskite thin-film processing, advancing toward industrial-scale solar cell manufacturing. This study demonstrates that XAI methods will play a critical role in accelerating energy materials science.

T1ρ relaxation mapping in osteochondral lesions of the talus: a non-invasive biomarker for altered biomechanical properties of hyaline cartilage?

BACKGROUND: To evaluate T1ρ relaxation mapping in patients with symptomatic talar osteochondral lesions (OLT) and healthy controls (HC) at rest, with axial loading and traction. METHODS: Participants underwent 3-T ankle magnetic resonance imaging at rest and with 500 N loading and 120 N traction, without axial traction for a subcohort of 17/29 HC. We used a fast low-angle shot sequence with variable spin-lock intervals for monoexponential T1ρ fitting. Cartilage was manually segmented to extract T1ρ values. RESULTS: We studied 29 OLT patients (age 31.7 ± 7.5 years, 15 females, body mass index [BMI] 25.0 ± 3.4 kg/m2) and 29 HC (age 25.2 ± 4.3 years, 17 females, BMI 22.5 ± 2.3 kg/m2. T1ρ values of OLT (50.4 ± 3.4 ms) were higher than those of intact cartilage regions of OLT patients (47.2 ± 3.4 ms; p = 0.003) and matched HC cartilage (48.1 ± 3.3 ms; p = 0.030). Axial loading and traction induced significant T1ρ changes in the intact cartilage regions of patients (loading, mean difference -1.1 ms; traction, mean difference 1.4 ms; p = 0.030 for both) and matched HC cartilage (-2.2 ms, p = 0.003; 2.3 ms, p = 0.030; respectively), but not in the OLT itself (-1.3 ms; p = 0.150; +1.9 ms; p = 0.150; respectively). CONCLUSION: Increased T1ρ values may serve as a biomarker of cartilage degeneration in OLT. The absence of load- and traction-induced T1ρ changes in OLT compared to intact cartilage suggests that T1ρ may reflect altered biomechanical properties of hyaline cartilage. TRIAL REGISTRATION: DRKS, DRKS00024010. Registered 11 January 2021, https://drks.de/search/de/trial/DRKS00024010 . RELEVANCE STATEMENT: T1ρ mapping has the potential to evaluate compositional and biomechanical properties of the talar cartilage and may improve therapeutic decision-making in patients with osteochondral lesions. KEY POINTS: T1ρ values in osteochondral lesions increased compared to intact cartilage. Significant load- and traction-induced T1ρ changes were observed in visually intact regions and in healthy controls but not in osteochondral lesions. T1ρ may serve as an imaging biomarker for biomechanical properties of cartilage.

Does the Pathologic Fracture Predict Severe Paralysis in Patients with Metastatic Epidural Spinal Cord Compression (MESCC)?-A Retrospective, Single-Center Cohort Analysis.

Currently, there is uncertainty about the predictive factors for metastatic epidural spinal cord compression (MESCC) and consecutive symptomatology in tumor patients. Prognostic algorithms for identifying patients at risk for paralysis are missing. The influence of the pathologic fracture on the patient's symptoms is widely discussed in the literature and we hypothesize that pathologic fractures contribute to spinal cord compression and are therefore predictive of severe paralysis. We tested this hypothesis in 136 patients who underwent surgery for spinal metastases. The most common primary cancers were prostate (24.3%, n = 33), breast (11.0%, n = 15), lung (10.3%, n = 14), and cancer of unknown primary (10.3%, n = 14). MESCC primarily affected the thoracic (77.2%, n = 105), followed by the lumbar (13.2%, n = 18) and cervical (9.6%, n = 13) spine. Pathologic fractures occurred in 63.2% (n = 86) of patients, mainly in osteolytic metastases. On the American spinal injury association (ASIA) impairment scale (AIS), 63.2% (n = 86) of patients exhibited AIS grade D and 36.8% (n = 50) AIS grade C-A preoperatively. The presence of a pathologic fracture alone did not predict severe paralysis (AIS C-A, p = 0.583). However, the duration of sensorimotor impairments, patient age, spinal instability neoplastic score (SINS), and the epidural spinal cord compression (ESCC) grade together predicted severe paralysis (p = 0.006) as did the ESCC grade 3 alone (p = 0.028). This is in contrast to previous studies that stated no correlation between the degree of spinal cord compression and the severity of neurologic impairments. Furthermore, the high percentage of pathologic fractures found in this study is above previously reported incidences. The risk factors identified can help to predict the development of paralysis and assist in the improvement of follow-up algorithms and the timing of therapeutic interventions.

A Data Set of Signals from an Antenna for Detection of Partial Discharges in Overhead Insulated Power Line.

We introduce a data set obtained via a contactless antenna method for detecting partial discharges in XLPE-covered conductors used in medium-voltage overhead power transmission lines. The data set consists of almost three years' worth of data, collected every hour from 9 measuring stations in Czechia and Slovakia. Each sample in the data set represents a single signal gathered for 20 ms. The contactless method is deployed on the same stations as the galvanic contact method, which is used by power distributors and can provide ground truth. Also manually curated data by human expert are present. Successful detection of partial discharges can prevent electricity shutdowns and forest fires resulting from insulation failure due to vegetation contact. The data set is particularly relevant for covered conductors used in mountainous regions where establishing a safe zone is challenging. The contactless method offers advantages such as cheaper and easier installation. The data set has the potential to develop machine learning models to detect partial discharges and facilitate safer and cheaper use of covered conductors.

Neuromuscular adaptations after osseointegration of a bone-anchored prosthesis in a unilateral transfemoral amputee - a case study.

PURPOSE: Many individuals with a lower limb amputation experience problems with the fitting of the socket of their prosthesis, leading to dissatisfaction or device rejection. Osseointegration (OI)- the implantation of a shaft directly interfacing with the remaining bone- is an alternative for these patients. In this observational study, we investigated how bone anchoring influences neuromuscular parameters during balance control in a patient with a unilateral transfemoral amputation. MATERIAL AND METHODS: Center of pressure (CoP) and electromyography (EMG) signals from muscles controlling the hip and the ankle of the intact leg were recorded during quiet standing six months before and one and a half years after this patient underwent an OI surgery. Results were compared to a control group of nine able-bodied individuals. RESULTS: Muscle co-activation and EMG intensity decreased after bone anchoring, approaching the levels of able-bodied individuals. Muscle co-activation controlling the ankle decreased in the high-frequency range, and the EMG intensity spectrum decreased in the lower-frequency range for all muscles when vision was allowed. With eyes closed, the ankle extensor muscle showed an increased EMG intensity in the high-frequency range post-surgery. CoP length increased in the mediolateral direction of the amputated leg. CONCLUSIONS: These findings point to shifts in the patient's neuromuscular profile towards the one of able-bodied individuals.

Mechanisms of PDAC subtype heterogeneity and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is clinically challenging due to late diagnosis and resistance to therapy. Two major PDAC subtypes have been defined based on malignant epithelial cell gene expression profiles; the basal-like/squamous subtype is associated with a worse prognosis and therapeutic resistance as opposed to the classical subtype. Subtype specification is not binary, consistent with plasticity of malignant cell phenotype. PDAC heterogeneity and plasticity reflect partly malignant cell-intrinsic transcriptional and epigenetic regulation. However, the stromal and immune compartments of the tumor microenvironment (TME) also determine disease progression and therapy response. It is evident that integration of intrinsic and extrinsic factors can dictate subtype heterogeneity, and thus, delineating the pathways involved can help to reprogram PDAC towards a classical/druggable subtype.

Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer.

Metastatic pancreatic cancer (PDAC) has a poor clinical outcome with a 5-year survival rate below 3%. Recent transcriptome profiling of PDAC biopsies has identified 2 clinically distinct subtypes - the "basal-like" (BL) subtype with poor prognosis and therapy resistance compared with the less aggressive and drug-susceptible "classical" (CLA) subtype. However, the mechanistic events and environmental factors that promote the BL subtype identity are not very clear. Using preclinical models, patient-derived xenografts, and FACS-sorted PDAC patient biopsies, we report here that the axon guidance receptor, roundabout guidance receptor 3 (ROBO3), promotes the BL metastatic program via a potentially unique AXL/IL-6/phosphorylated STAT3 (p-STAT3) regulatory axis. RNA-Seq identified a ROBO3-mediated BL-specific gene program, while tyrosine kinase profiling revealed AXL as the key mediator of the p-STAT3 activation. CRISPR/dCas9-based ROBO3 silencing disrupted the AXL/p-STAT3 signaling axis, thereby halting metastasis and enhancing therapy sensitivity. Transcriptome analysis of resected patient tumors revealed that AXLhi neoplastic cells associated with the inflammatory stromal program. Combining AXL inhibitor and chemotherapy substantially restored a CLA phenotypic state and reduced disease aggressiveness. Thus, we conclude that a ROBO3-driven hierarchical network determines the inflammatory and prometastatic programs in a specific PDAC subtype.

Organoids at the PUB: The Porcine Urinary Bladder Serves as a Pancreatic Niche for Advanced Cancer Modeling.

Despite intensive research and progress in personalized medicine, pancreatic ductal adenocarcinoma remains one of the deadliest cancer entities. Pancreatic duct-like organoids (PDLOs) derived from human pluripotent stem cells (PSCs) or pancreatic cancer patient-derived organoids (PDOs) provide unique tools to study early and late stage dysplasia and to foster personalized medicine. However, such advanced systems are neither rapidly nor easily accessible and require an in vivo niche to study tumor formation and interaction with the stroma. Here, the establishment of the porcine urinary bladder (PUB) is revealed as an advanced organ culture model for shaping an ex vivo pancreatic niche. This model allows pancreatic progenitor cells to enter the ductal and endocrine lineages, while PDLOs further mature into duct-like tissue. Accordingly, the PUB offers an ex vivo platform for earliest pancreatic dysplasia and cancer if PDLOs feature KRASG12D mutations. Finally, it is demonstrated that PDOs-on-PUB i) resemble primary pancreatic cancer, ii) preserve cancer subtypes, iii) enable the study of niche epithelial crosstalk by spiking in pancreatic stellate and immune cells into the grafts, and finally iv) allow drug testing. In summary, the PUB advances the existing pancreatic cancer models by adding feasibility, complexity, and customization at low cost and high flexibility.

Influence of Augmented Visual Feedback on Balance Control in Unilateral Transfemoral Amputees.

Patients with a lower limb amputation rely more on visual feedback to maintain balance than able-bodied individuals. Altering this sensory modality in amputees thus results in a disrupted postural control. However, little is known about how lower limb amputees cope with augmented visual information during balance tasks. In this study, we investigated how unilateral transfemoral amputees incorporate visual feedback of their center of pressure (CoP) position during quiet standing. Ten transfemoral amputees and ten age-matched able-bodied participants were provided with real-time visual feedback of the position of their CoP while standing on a pressure platform. Their task was to keep their CoP within a small circle in the center of a computer screen placed at eye level, which could be achieved by minimizing their postural sway. The visual feedback was then delayed by 250 and 500 ms and was combined with a two- and five-fold amplification of the CoP displacements. Trials with eyes open without augmented visual feedback as well as with eyes closed were further performed. The overall performance was measured by computing the sway area. We further quantified the dynamics of the CoP adjustments using the entropic half-life (EnHL) to study possible physiological mechanisms behind postural control. Amputees showed an increased sway area compared to the control group. The EnHL values of the amputated leg were significantly higher than those of the intact leg and the dominant and non-dominant leg of controls. This indicates lower dynamics in the CoP adjustments of the amputated leg, which was compensated by increasing the dynamics of the CoP adjustments of the intact leg. Receiving real-time visual feedback of the CoP position did not significantly reduce the sway area neither in amputees nor in controls when comparing with the eyes open condition without visual feedback of the CoP position. Further, with increasing delay and amplification, both groups were able to compensate for small visual perturbations, yet their dynamics were significantly lower when additional information was not received in a physiologically relevant time frame. These findings may be used for future design of neurorehabilitation programs to restore sensory feedback in lower limb amputees.

Interdisciplinary approach to multiple myeloma - time to diagnosis and warning signs.

Delayed diagnosis is a common challenge in the management of multiple myeloma (MM). This prospective interdisciplinary study evaluated symptoms and time to diagnosis (TTD) in 81/295 screened patients at our tertiary center, who were examined by an orthopedist prior to the MM diagnosis. The most frequent complaint was back pain (81%), mainly localized thoracic and/or lumbar. Pain was independent of movement in 85%, occurred at night in 69%, and at multiple localizations in 30% of patients. Notably, 63% patients with an orthopedic disease noticed substantial symptom change before the MM diagnosis was made. The median TTD was 7 months and did not differ significantly between patients with or without a preexisting skeletal disease. To avoid delayed diagnosis, physicians should consider MM as a differential diagnosis, whenever warning signs such as skeletal pain independent from movement, at night, at various localizations, and change in pain characteristics accompanied by fatigue, are reported.

TNF-α-producing macrophages determine subtype identity and prognosis via AP1 enhancer reprogramming in pancreatic cancer.

Large-scale genomic profiling of pancreatic cancer (PDAC) has revealed two distinct subtypes: 'classical' and 'basal-like'. Their variable coexistence within the stromal immune microenvironment is linked to differential prognosis; however, the extent to which these neoplastic subtypes shape the stromal immune landscape and impact clinical outcome remains unclear. By combining preclinical models, patient-derived xenografts, as well as FACS-sorted PDAC patient biopsies, we show that the basal-like neoplastic state is sustained via BRD4-mediated cJUN/AP1 expression, which induces CCL2 to recruit tumor necrosis factor (TNF)-α-secreting macrophages. TNF-α+ macrophages force classical neoplastic cells into an aggressive phenotypic state via lineage reprogramming. Integration of ATAC-, ChIP- and RNA-seq data revealed distinct JUNB/AP1 (classical) and cJUN/AP1 (basal-like)-driven regulation of PDAC subtype identity. Pharmacological inhibition of BRD4 led to suppression of the BRD4-cJUN-CCL2-TNF-α axis, restoration of classical subtype identity and a favorable prognosis. Hence, patient-tailored therapy for a cJUNhigh/TNF-αhigh subtype is paramount in overcoming highly inflamed and aggressive PDAC states.

Collection of micromirror-modulated light in the single-pixel broadband hyperspectral microscope.

A digital micromirror device (DMD) serves in a significant part of computational optical setups as a means of encoding an image by the desired pattern. The most prominent is its usage in the so-called single-pixel camera experiment. This experiment often requires an efficient and homogeneous collection of light from a relatively large chip on a small area of an optical fiber or spectrometer slit. Moreover, this effort is complicated by the fact that the DMD acts as a diffractive element, which causes severe spectral inhomogeneities in the light collection. We studied the effect of light diffraction via a whiskbroom hyperspectral camera in a broad spectral range. Based on this knowledge, we designed a variety of different approaches to the light collection. We mapped the efficiency and spectral homogeneity of each of the configuration, namely, its ability to couple the light into commercially available fiber spectrometers working in the visible and infrared range (up to 1900 nm). We found the integrating spheres to provide homogeneous light collection, which, however, suffers from very low efficiency. The best compromise between the performance parameters was provided by a combination of an engineered diffuser with an off-axis parabolic mirror. We used this configuration to create a computational microscope able to carry out hyperspectral imaging of a sample in a broad spectral range (400 nm-1900 nm). We see such a setup as an ideal tool to carry out spectrally resolved transmission microscopy in a broad spectral range.

Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis, despite surgical resection combined with radio- and chemotherapy. The major clinical obstacles contributing to poor GBM prognosis are late diagnosis, diffuse infiltration, pseudo-palisading necrosis, microvascular proliferation, and resistance to conventional therapy. These challenges are further compounded by extensive inter- and intra-tumor heterogeneity and the dynamic plasticity of GBM cells. The complex heterogeneous nature of GBM cells is facilitated by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. An immunosuppressive tumor microenvironment of GBM provides multiple pathways for tumor immune evasion. Infiltrating immune cells, mostly tumor-associated macrophages, comprise much of the non-neoplastic population in GBM. Further understanding of the immune microenvironment of GBM is essential to make advances in the development of immunotherapeutics. Recently, whole-genome sequencing, epigenomics and transcriptional profiling have significantly helped improve the prognostic and therapeutic outcomes of GBM patients. Here, we discuss recent genomic advances, the role of innate and adaptive immune mechanisms, and the presence of an established immunosuppressive GBM microenvironment that suppresses and/or prevents the anti-tumor host response.