Obesogenic Diet-Induced Neuroinflammation: A Pathological Link between Hedonic and Homeostatic Control of Food Intake.

Obesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NLRP3 inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. In this context, a chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala. This review aims to present the background defining the significant impact of neuroinflammation and how this, when induced by an obesogenic diet, can affect feeding control, triggering metabolic and neurological alterations.

A practical access for fluoroscopically-guided percutaneous sacroplasty: Case report.

BACKGROUND: Sacral metastases represent the lowest percentage of invasion to the spine, however, as chemotherapy treatments progress, the cancer survival rate has become higher, and the percentage of sacral metastases has increased. Treatment options for sacrum metastases are surgery, radiotherapy, and minimally invasive techniques such as sacroplasty and radiofrequency ablation. Knowing the repercussions that advancing the needle anteriorly (viscera) or medially (sacral roots) can have during the sacroplasty we are describing a technique to perform c-arm sacroplasty in coaxial vision, to identify the anterior sacral cortical bone that is in the limits of the pelvic viscera as well as the sacral foraminal line. CASE PRESENTATION: In the current report, we present a 75-year-old male patient with prostate cancer metastatic to S1, S2, S3 and iliac, with severe lumbar axial pain VAS 8/10. With a caudal tilt between 35-45 degrees until aligning the sacrum in a coaxial view, a 11-gauge Jamshidi needle is advanced from s3 to s1. The trajectory of the needle during the procedure is corroborated in AP and lateral, S1 is cemented, and the needle is withdrawn to cement S2 and S3. After the sacroplasty with the coaxial access, the patient reported VAS 1-2/10. CONCLUSIONS: It is important to offer an adequate quality of life to patients with sacral fractures, whether associated with cancer or sacral insufficiency fractures (SIF). Sacroplasty, being a recently described technique, can be a very viable option for these patients, that's why it is important to have safe and reliable techniques to complement the approach of this minimally invasive technique.The coaxial access may be a safe and practical way to perform sacroplasty in these patients.

Light-Initiated C-H Activation via Net Hydrogen Atom Transfer to a Molybdenum(VI) Dioxo.

MoO2Cl2(bpy-tBu) (1) is shown to be a potent one-electron oxidant upon irradiation with 365 nm light in various solvents, while being a weak two-electron oxidant in the dark. Complex 1 is characterized to activate various types of C-H bonds photochemically, including allylic and benzylic positions as well as alkanes and aldehydes. In all of these oxidations, 1 ultimately forms a bimetallic Mo(V)/Mo(V) species with a µ-oxo ligand (2). Depending on the substrate, the major organic product is identified as either an oxygenated or a C-C coupled (homodimerized) compound along with a minor chlorinated species. The product selectivity is proposed to be dependent upon the relative values between the bond dissociation enthalpy (BDE) of a potentially new C-OH bond within the product versus the BDE of a Mo-OH motif within a Mo(V)O(OH) intermediate. Based on this, we can estimate the BDE for Mo-OH to be 83-93 kcal/mol. Mechanistic studies suggest that the C-H activation occurs via a net hydrogen atom transfer (HAT) from 1* occurring either asynchronously or via a stepwise electron-proton transfer (ET-PT) process. Complex 2 is further demonstrated to reform dioxo 1 in the presence of chemical oxidants.

Mesozooplankton taurine production and prokaryotic uptake in the northern Adriatic Sea.

Dissolved free taurine, an important osmolyte in phytoplankton and metazoans, has been shown to be a significant carbon and energy source for prokaryotes in the North Atlantic throughout the water column. However, the extent of the coupling between taurine production and consumption over a seasonal cycle has not been examined yet. We determined taurine production by abundant crustacean zooplankton and its role as a carbon and energy source for several prokaryotic taxa in the northern Adriatic Sea over a seasonal cycle. Taurine concentrations were generally in the low nanomolar range, reaching a maximum of 22 nmol L-1 in fall during a Pseudonitzschia bloom and coinciding with the highest zooplankton taurine release rates. Taurine accounted for up to 5% of the carbon, 11% of the nitrogen, and up to 71% of the sulfur requirements of heterotrophic prokaryotes. Members of the Roseobacter clade, Alteromonas, Thaumarchaeota, and Euryarchaeota exhibited higher cell-specific taurine assimilation rates than SAR11 cells. However, cell-specific taurine and leucine assimilation were highly variable in all taxa, suggesting species and/or ecotype specific utilization patterns of taurine and dissolved free amino acids. Copepods were able to cover the bulk taurine requirements of the prokaryotic communities in fall and winter and partly in the spring-summer period. Overall, our study emphasizes the significance of taurine as a carbon and energy source for the prokaryotic community in the northern Adriatic Sea and the importance of crustacean zooplankton as a significant source of taurine and other organic compounds for the heterotrophic prokaryotic community.

Spin Seebeck Effect from Antiferromagnetic Magnons and Critical Spin Fluctuations in Epitaxial FeF_{2} Films.

We report a longitudinal spin Seebeck effect (SSE) study in epitaxially grown FeF_{2}(110) antiferromagnetic (AFM) thin films with strong uniaxial anisotropy over the temperature range of 3.8-250 K. Both the magnetic-field and temperature-dependent SSE signals below the Néel temperature (T_{N}=70 K) of the FeF_{2} films are consistent with a theoretical model based on the excitations of AFM magnons without any net induced static magnetic moment. In addition to the characteristic low-temperature SSE peak associated with the AFM magnons, there is another SSE peak at T_{N} which extends well into the paramagnetic phase. All the SSE data taken at different magnetic fields up to 12 T near and above the critical point T_{N} follow the critical scaling law very well with the critical exponents for magnetic susceptibility of 3D Ising systems, which suggests that the AFM spin correlation is responsible for the observed SSE near T_{N}.

Taurine Is a Major Carbon and Energy Source for Marine Prokaryotes in the North Atlantic Ocean off the Iberian Peninsula.

Taurine, an amino acid-like compound, acts as an osmostress protectant in many marine metazoans and algae and is released via various processes into the oceanic dissolved organic matter pool. Taurine transporters are widespread among members of the marine prokaryotic community, tentatively indicating that taurine might be an important substrate for prokaryotes in the ocean. In this study, we determined prokaryotic taurine assimilation and respiration throughout the water column along two transects in the North Atlantic off the Iberian Peninsula. Taurine assimilation efficiency decreased from the epipelagic waters from 55 ± 14% to 27 ± 20% in the bathypelagic layers (means of both transects). Members of the ubiquitous alphaproteobacterial SAR11 clade accounted for a large fraction of cells taking up taurine, especially in surface waters. Archaea (Thaumarchaeota + Euryarchaeota) were also able to take up taurine in the upper water column, but to a lower extent than Bacteria. The contribution of taurine assimilation to the heterotrophic prokaryotic carbon biomass production ranged from 21% in the epipelagic layer to 16% in the bathypelagic layer. Hence, we conclude that dissolved free taurine is a significant carbon and energy source for prokaryotes throughout the oceanic water column being utilized with similar efficiencies as dissolved free amino acids.

[Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples]. / Estudio comparativo de equipos INR capilar "point of care" versus INR venoso, en pacientes en tratamiento con antagonistas de vitamina K.

BACKGROUND: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer. AIM: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use. MATERIALS AND METHODS: Patients provided capillary and venous blood samples for parallel tests comparing Xprecia™ Stride with CoaguChek Pro II™ and with venous INR, microINR™ with CoaguChek Pro IITM and with venous INR. The devices' ease of use was assessed surveying the sampling staff. RESULTS: The three tested devices had good correlation coefficients with venous INR: CoaguChek Pro IITM 0.953 and 0.962; Xprecia™ of 0.912 and microINR™ of 0.932. The correlation coefficient of Xprecia™ with CoaguChek Pro IITM was 0.937 and microINR™ with CoaguChek Pro IITM was 0.976. CONCLUSIONS: CoaguChek Pro IITM, Xprecia™ and microINR™ results had a good correlation coefficient with INR measured at the laboratory. Our results indicate that, in the hands of trained users, POC-type coagulometers are reliable and acceptable for routine use in anticoagulant treatment control.

Diagnostic accuracy of nucleic acid amplification tests (NAATs) in urine for genitourinary tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Genitourinary tuberculosis is the third most common form of extrapulmonary tuberculosis. Diagnosis is difficult because of unspecific clinical manifestations and low accuracy of conventional tests. Unfortunately, the delayed diagnosis impacts the urinary tract severely. Nucleic acid amplification tests yield fast results, and among these, new technologies can also detect drug resistance. There is lack of consensus regarding the use of these tests in genitourinary tuberculosis; we therefore aimed to assess the accuracy of nucleic acid amplification tests in the diagnosis of genitourinary tuberculosis and to evaluate the heterogeneity between studies. METHODS: We did a systematic review and meta-analysis of research articles comparing the accuracy of a reference standard and a nucleic acid amplification test for diagnosis of urinary tract tuberculosis. We searched Medline, EMBASE, Web of Science, LILACS, Cochrane Library, and Scopus for articles published between Jan 1, 1990, and Apr 14, 2016. Two investigators identified eligible articles and extracted data for individual study sites. We analyzed data in groups with the same index test. Then, we generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when studies were not heterogeneous. RESULTS: We identified eleven relevant studies from ten articles, giving information on PCR, LCR and Xpert MTB/RIF tests. All PCR studies were "in-house" tests, with different gene targets and had several quality concerns therefore we did not proceed with a pooled analysis. Only one study used LCR. Xpert studies were of good quality and not heterogeneous, pooled sensitivity was 0·87 (0·66-0·96) and specificity was 0·91 (0·84-0·95). CONCLUSION: PCR studies were highly heterogeneous. Among Xpert MTB/RIF studies, specificity was favorable with an acceptable confidence interval, however new studies can update meta-analysis and get more precise estimates. Further high-quality studies are urgently needed to improve diagnosis of genitourinary tuberculosis. PROTOCOL REGISTRATION: PROSPERO CRD42016039020.

Transcriptional regulation of the sodium-coupled neutral amino acid transporter (SNAT2) by 17ß-estradiol.

The sodium-coupled neutral amino acid transporter 2 (SNAT2) translocates small neutral amino acids into the mammary gland to promote cell proliferation during gestation. It is known that SNAT2 expression increases during pregnancy, and in vitro studies indicate that this transporter is induced by 17ß-estradiol. In this study, we elucidated the mechanism by which 17ß-estradiol regulates the transcription of SNAT2. In silico analysis revealed the presence of a potential estrogen response element (ERE) in the SNAT2 promoter. Reporter assays showed an increase in SNAT2 promoter activity when cotransfected with estrogen receptor alpha (ER-α) after 17ß-estradiol stimulation. Deletion of the ERE reduced estradiol-induced promoter activity by 63%. Additionally, EMSAs and supershift assays showed that ER-α binds to the SNAT2 ERE and that this binding competes with the interaction of ER-α with its consensus ERE. An in vivo ChIP assay demonstrated that the binding of ER-α to the SNAT2 promoter gradually increased in the mammary gland during gestation and that maximal binding occurred at the highest 17ß-estradiol serum concentration. Liquid chromatography-elevated energy mass spectrometry and Western blot analysis revealed that the SNAT2 ER-α-ERE complex contained poly(ADP-ribose) polymerase 1, Lupus Ku autoantigen protein p70, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) proteins and that the silencing of each of these proteins nearly abolished 17ß-estradiol-stimulated SNAT2 promoter activity. Nuclear levels of GAPDH increased progressively during gestation in the mammary gland, and GAPDH binding was nucleotide-specific for the SNAT2 ERE. Thus, this study provides new insights into how the mammary epithelium adapts to control amino acid uptake through the transcriptional regulation of the SNAT2 transporter via 17ß-estradiol.

Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation.

The sodium coupled neutral amino acid transporter 2 (SNAT2/SAT2/ATA2) is expressed in the mammary gland (MG) and plays an important role in the uptake of alanine and glutamine which are the most abundant amino acids transported into this tissue during lactation. Thus, the aim of this study was to assess the amount and localization of SNAT2 before delivery and during lactation in rat MG, and to evaluate whether prolactin and the dietary protein/carbohydrate ratio might influence SNAT2 expression in the MG, liver and adipose tissue during lactation. Our results showed that SNAT2 protein abundance in the MG increased during lactation and this increase was maintained along this period, while 24 h after weaning it tended to decrease. To study the effect of prolactin on SNAT2 expression, we incubated MG explants or T47D cells transfected with the SNAT2 promoter with prolactin, and we observed in both studies an increase in the SNAT2 expression or promoter activity. Consumption of a high-protein/low carbohydrate diet increased prolactin concentration, with a concomitant increase in SNAT2 expression not only in the MG during lactation, but also in the liver and adipose tissue. There was a correlation between SNAT2 expression and serum prolactin levels depending on the amount of dietary protein/carbohydrate ratio consumed. These findings suggest that prolactin actively supports lactation providing amino acids to the gland through SNAT2 for the synthesis of milk proteins.

Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells.

MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol.

The expression of RNA helicase DDX5 is transcriptionally upregulated by calcitriol through a vitamin D response element in the proximal promoter in SiHa cervical cells.

The DEAD box RNA helicase DDX5 is a multifunctional protein involved in the regulatory events of gene expression. Herein, we presented evidence indicating that DDX5 is transcriptionally upregulated by calcitriol, the hormonal form of vitamin D3. In silico analysis revealed the presence of two putative vitamin D response elements (VDREs) in the DDX5 promoter region. Using luciferase reporter assays, we demonstrated that the DDX5 promoter containing these putative VDREs significantly increased the luciferase activity in vitamin D receptor (VDR)-positive SiHa cells upon calcitriol treatment. Electrophoretic mobility shift assays showed the ability of VDR and retinoid X receptor to interact only with the most proximal VDRE, while chromatin immunoprecipitation analysis confirmed the occupancy of this VDRE by the VDR. Finally, we demonstrated that calcitriol significantly increased both DDX5 mRNA and protein in SiHa cells. In summary, this study shows that DDX5 gene is transcriptionally upregulated by calcitriol through a VDRE located in its proximal promoter. Given the importance of DDX5 as a master regulator of differentiation programs, our study suggests that the pro-differentiating properties of calcitriol may be related with the induction of DDX5.

Bipolar radiofrequency ablation for cancer pain in the trigeminal distribution.

Tumours in patients with head and neck cancer (HNC) are associated with a more significant decrease in quality of life compared with the rest of patients with cancer. We present a patient with pain due to HNC successfully treated with bipolar radiofrequency ablation. A man in his 70s presented with a tumour in the left V2 and V3 region, with disabling pain, Visual Analogue Scale (VAS) score of 10/10, pain on swallowing, chewing and speaking, 3 months of evolution. The patient was evaluated in the pain management department, and the interventional treatment proposed consisted of bipolar pulsed radiofrequency, followed by bipolar thermal radiofrequency of the left V2 and V3 branches with fluoroscopic guidance to achieve better control and coverage of the affected trigeminal branches. Immediately after the procedure, the patient reported a significant improvement in pain with a 0-10 VAS; hypoesthesia in the affected V2 and V3 territory was identified, but no motor weakness. The improvement in pain was maintained for 6 months with a significant improvement in quality of life and pain, which allowed him to speak, chew and swallow without pain. Later, the patient died from complications associated with the disease. The treatment approach in these patients is both pain treatment and achieving independence by allowing better speech ability and improving eating, the above as a pillar of treatment focused on improving the patient's quality of life. This approach is a potential tool in the early stage of the disease in patients with pain due to HNC.

Sacroiliac Joint Denervation-A Novel Approach to Target Sacral Lateral Branches: A Practical Approach.

INTRODUCTION: Sacroiliac joint (SIJ) pain is a relatively common cause of low back pain. Percutaneous radiofrequency (RF) techniques for SIJ are limited to ablation of the posterior SIJ innervation. Different techniques have been described for SIJ radiofrequency ablation, including conventional thermal, cooled RF, pulsed RF, bipolar RF, and specialized tip RF needle (i.e., multi-tined); however, additional costs may limit these applications. METHODS: This new technique for SIJ denervation uses anatomical landmarks and a single RF cannula. Two spinal needles are placed lateral to the posterior S1 and S2 sacral foramina; then, with caudal tilt we get a coaxial view of the sacral bone, we advance an 18-G curved 15-mm active tip RF cannula just lateral to the aligned finder needles. Ablation is performed, and then the RF cannula is retracted 2 cm and ablation is repeated for a total of four lesions. RESULTS: The two spinal needles placed lateral to the posterior sacral foramina S1 and S2 guide the final needle in the posterior aspect of the sacrum, lateral to the sacral foramina, where the lateral sacral branches are located. CONCLUSION: We introduce a cost and time efficient technique to perform radiofrequency ablation of the sacral lateral branches using a single RF needle. This technique utilizes the sacrum's reliable anatomy and angulation and maximizes the surface area of the active tip lesioning. This technique creates a strip lesion lateral to the sacral foramina and reduces time and cost efficacy compared to several of the other techniques and/or commercially available special devices designed for sacroiliac denervation.

Percutaneous Foraminal Neuroplasty Using Reference Spinal Needles: Technical Description.

BACKGROUND: Lumbar foraminal stenosis is a common cause of chronic lower back pain and radiculopathy often treated by epidural steroid injections. In the absence of imaging findings with a positive physical exam demonstrating symptoms, percutaneous neuroplasty (PNP) may be an alternative to transforaminal epidural steroid injections that have otherwise failed. CASE PRESENTATION: We present two cases (55-year-old man and 65-year-old woman) with chronic low back pain and radiculopathy with otherwise normal imaging demonstrating no lumbar foraminal stenosis refractory to transforaminal epidural steroid injections. PNP was performed using reference spinal needles with both patients achieving sustained > 50-75% pain relief. CONCLUSION: PNP offers interventional chronic pain physicians and patients with refractory chronic low back pain with lumbar radiculopathy due to fibrosis an alternative, safe treatment that offers sustained results. Furthermore, this is the first of its kind to offer a step-by-step procedural step of PNP using a reference spinal needle.

Hepatic amino acid-degrading enzyme expression is downregulated by natural and synthetic ligands of PPARα in rats.

Body nitrogen retention is dependent on the amount of dietary protein consumed, as well as the fat and carbohydrate content in the diet, due to the modulation of amino acid oxidation. PPARα is a transcription factor involved in the upregulation of the expression of enzymes of fatty acid oxidation. However, the role of putative PPARα response elements (PPREs) in the promoter of several amino acid-degrading enzymes (AADEs) is not known. The aim of this work was to study the effect of the synthetic ligand Wy 14643 and the natural ligands palmitate, oleate, and linoleate in rats fed graded concentrations of dietary protein (6, 20, or 50 g/100 g of total diet) on the expression of the AADEs histidase, serine dehydratase, and tyrosine aminotransferase. Thus, we fed male Wistar rats diets containing 6, 20, or 50% casein for 10 d. The results showed that addition of Wy 14643 to the diet significantly reduced the expression of the AADEs. Furthermore, the incubation of hepatocytes with natural ligands of PPARα or feeding rats with diets containing soybean oil, safflower oil, lard, or coconut oil as sources of dietary fat significantly repressed the expression of the AADEs. Gene reporter assays and mobility shift assays demonstrated that the PPRE located at -482 bp of the histidase gene actively bound PPARα in rat hepatocytes. These data indicate that PPARα ligands may reduce amino acid catabolism in rats.

The Gut Microbiota-Brain Axis during Aging, Mild Cognitive Impairment and Dementia: Role of Tau Protein, ß-Amyloid and LPS in Serum and Curli Protein in Stool.

Currently, there is an increasing number of people with mild cognitive (MCI) impairment and dementia (D). In the present work we studied the role of tau protein, ß-amyloid, LPS (lipopolysaccharide), and curli protein of elderly adults with MCI or D and the contribution of gut microbiota. Four groups were studied: young subjects, healthy adults older than 60 years (A), elderly adults with MCI (MCI), and elderly adults with dementia (D). A preclinical study was conducted in old male Wistar rats to evaluate the impact of gut microbiota on curli protein abundance in feces and brain. The results showed that with increasing age, tau protein, ß-amyloid, and LPS significantly increased in serum during MCI and D, and this was associated with an increase in the abundance of E. coli that synthesize the amyloid protein curli, that may promote the aggregation of amyloid proteins. Rats showed a clear increase in the abundance of curli protein in the brain during aging. Thus, cognitive impairment and dementia are in part due to an alteration in the gut microbiota-brain axis via increase in curli protein and LPS leading to an increase in tau and ß-amyloid protein.

Properties for Thermally Conductive Interfaces with Wide Band Gap Materials.

The goal of this study is to determine how bulk vibrational properties and interfacial structure affect thermal transport at interfaces in wide band gap semiconductor systems. Time-domain thermoreflectance measurements of thermal conductance G are reported for interfaces between nitride metals and group IV (diamond, SiC, Si, and Ge) and group III-V (AlN, GaN, and cubic BN) materials. Group IV and group III-V semiconductors have systematic differences in vibrational properties. Similarly, HfN and TiN are also vibrationally distinct from each other. Therefore, comparing G of interfaces formed from these materials provides a systematic test of how vibrational similarity between two materials affects interfacial transport. For HfN interfaces, we observe conductances between 140 and 300 MW m-2 K-1, whereas conductances between 200 and 800 MW m-2 K-1 are observed for TiN interfaces. TiN forms exceptionally conductive interfaces with GaN, AlN, and diamond, that is, G > 400 MW m-2 K-1. Surprisingly, interfaces formed between vibrationally similar and dissimilar materials are similarly conductive. Thus, vibrational similarity between two materials is not a necessary requirement for high G. Instead, the time-domain thermoreflectance experiment (TDTR) data, an analysis of bulk vibrational properties, and transmission electron microscopy (TEM) suggest that G depends on two other material properties, namely, the bulk phonon properties of the vibrationally softer of the two materials and the interfacial structure. To determine how G depends on interfacial structure, TDTR and TEM measurements were conducted on a series of TiN/AlN samples prepared in different ways. Interfacial disorder at a TiN/AlN interface adds a thermal resistance equivalent to ∼1 nm of amorphous material. Our findings improve fundamental understanding of what material properties are most important for thermally conductive interfaces. They also provide benchmarks for the thermal conductance of interfaces with wide band gap semiconductors.

Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test.

Background: Detecting cancer at early stages significantly increases patient survival rates. Because lethal solid tumors often produce few symptoms before progressing to advanced, metastatic disease, diagnosis frequently occurs when surgical resection is no longer curative. One promising approach to detect early-stage, curable cancers uses biomarkers present in circulating extracellular vesicles (EVs). To explore the feasibility of this approach, we developed an EV-based blood biomarker classifier from EV protein profiles to detect stages I and II pancreatic, ovarian, and bladder cancer. Methods: Utilizing an alternating current electrokinetics (ACE) platform to purify EVs from plasma, we use multi-marker EV-protein measurements to develop a machine learning algorithm that can discriminate cancer cases from controls. The ACE isolation method requires small sample volumes, and the streamlined process permits integration into high-throughput workflows. Results: In this case-control pilot study, comparison of 139 pathologically confirmed stage I and II cancer cases representing pancreatic, ovarian, or bladder patients against 184 control subjects yields an area under the curve (AUC) of 0.95 (95% CI: 0.92 to 0.97), with sensitivity of 71.2% (95% CI: 63.2 to 78.1) at 99.5% (97.0 to 99.9) specificity. Sensitivity is similar at both early stages [stage I: 70.5% (60.2 to 79.0) and stage II: 72.5% (59.1 to 82.9)]. Detection of stage I cancer reaches 95.5% in pancreatic, 74.4% in ovarian (73.1% in Stage IA) and 43.8% in bladder cancer. Conclusions: This work demonstrates that an EV-based, multi-cancer test has potential clinical value for early cancer detection and warrants future expanded studies involving prospective cohorts with multi-year follow-up.