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Locoregional failure (LRF) in patients with breast cancer post-surgery and post-irradiation is linked to a dismal prognosis. In a refined new model, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1/CD203a (ENPP1) to be closely associated with LRF. ENPP1hi circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of polymorphonuclear myeloid-derived suppressor cells and neutrophil extracellular trap (NET) formation. Genetic and pharmacologic ENPP1 inhibition or NET blockade extends relapse-free survival. Furthermore, in combination with fractionated irradiation, ENPP1 abrogation obliterates LRF. Mechanistically, ENPP1-generated adenosinergic metabolites enhance haptoglobin (HP) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.Significance:CTC exploit the ENPP1/HP axis to promote local recurrence post-surgery and post-irradiation by subduing myeloid suppressor cells in breast tumors. Blocking this axis impairs tumor engraftment, impedes immunosuppression, and obliterates NET formation, unveiling new opportunities for therapeutic intervention to eradicate local relapse and ameliorate patient survival.This article is highlighted in the In This Issue feature, p. 1171

Supplementary Data from Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer

Supplementary Figure from Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer

Abstract Locoregional failure (LRF) in patients with breast cancer post-surgery and post-irradiation is linked to a dismal prognosis. In a refined new model, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1/CD203a (ENPP1) to be closely associated with LRF. ENPP1hi circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of polymorphonuclear myeloid-derived suppressor cells and neutrophil extracellular trap (NET) formation. Genetic and pharmacologic ENPP1 inhibition or NET blockade extends relapse-free survival. Furthermore, in combination with fractionated irradiation, ENPP1 abrogation obliterates LRF. Mechanistically, ENPP1-generated adenosinergic metabolites enhance haptoglobin (HP) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse. Significance: CTC exploit the ENPP1/HP axis to promote local recurrence post-surgery and post-irradiation by subduing myeloid suppressor cells in breast tumors. Blocking this axis impairs tumor engraftment, impedes immunosuppression, and obliterates NET formation, unveiling new opportunities for therapeutic intervention to eradicate local relapse and ameliorate patient survival. This article is highlighted in the In This Issue feature, p. 1171

A new low-profile flexible RFID tag antenna operating in the ultra-high frequency (UHF) European band (865 MHz–868 MHz) is proposed for blood bag traceability. Its structure combines inductive and capacitive parts with nested slots allowing for the achieving of conjugate impedance matching with the IC-chip. The whole electrical parameters of the environment (substrate, bag, and blood) were considered for the design of the tag antenna. A good agreement was obtained between the measurements and electromagnetic simulations for the input impedance of the tag antenna in the UHF band. A reading range close to 2.5 m was experimentally obtained. Therefore, this tag antenna could be effective and useful in future RFID systems for blood bag monitoring, thus improving patient safety in healthcare infrastructures.

This work presents a novel low-pass filter based on using dielectric materials, in the critical areas of the structure, to prevent high-power space condition adverse effects, like multipactor breakdown. It is shown that the use of dielectric pieces in the inverters of the filter leads to increased gaps between metallic parts in the irises. In addition, by completely filling up the air space in critical gaps, the multipactor breakdown thresholds can be increased. Moreover, they also lead to a volume reduction, increasing compactness of the structure. To demonstrate the proposed concept, a prototype has been manufactured with an aluminum housing and a Teflon dielectric material, and tested for multipactor effect at ESA-VSC Laboratory. Tests confirmed that the manufactured filter has good electrical performance with cut-off frequency 13.6 GHz, insertion losses 0.32 dB, return losses better than 15 dB, and additionally does not show multipactor breakdown up to the maximum power tested in the experimental facility (5.5 kW). This research work has been financially supported by the Spanish Ministerio de Ciencia e Innovación in the frame of the project “Green an Efficient Technologies for Advanced Telecommunication Systems (GRETAS)” with Ref. TPID2019-103982RB-C42.

Compact double notch coplanar and microstrip bandstop filters are described. They are based on a version of the open interconnected split ring resonator (OISRR) integrated in microstrip or coplanar waveguides. The OISRR introduces an RLC resonator connected in parallel with the propagating microstrip line. Therefore, this resonator can be modeled as a shunt circuit to ground, with the R, L and C elements connected in series. The consequence for the frequency response of the device is a notch band at the resonant frequency of the RLC shunt circuit. The number of notch bands can be controlled by adding more OISRRs, since each pair of rings can be modeled as a shunt circuit and therefore introduces an additional notch band. In this paper, we demonstrate that these additional rings can be introduced in a concentric way in the same cell, so the size of the device does not increase and a compact multi-notch bandstop response is achieved, with the same number of notch bands as pairs of concentric rings, plus an additional spurious band at a higher frequency. The authors gratefully acknowledge financial support from Agencia Estatal de Investigación (AEI) of Spain (grant no.: PID2019-103982RB-C42/AEI/10.13039/ 501100011033).

Background Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. Methods Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. Results We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074–2.005; p = 0.048). Conclusion In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

A full-wave design technique of n-order Chebyshev stepped impedance band-pass filters in substrate integrated waveguide (SIW) is presented for the first time. The structure of the filter is based on including elliptic patterns etched on the SIW top surface to synthesize Chebyshev transfer functions. The band-pass response is obtained from the high-pass characteristic of the SIW line together with the behavior of the elliptic patterns, which implement the impedance inverters needed to control an upper cut-off frequency in the response of the filter. The synthesis technique is applied to the design of a sixth-order Chebyshev stepped impedance band-pass SIW filter. It is shown that the use of elliptic patterns instead of circular patterns can increase the spurious free range of the filter. In addition, when exponential microstrip-to-SIW transitions are integrated into the design process, a reduction in size and improvement in return loss are achieved, as compared to a base-line filter (sixth-order Chebyshev stepped impedance band-pass filter) designed with transitions separately. Electromagnetic (EM) simulation and measurements results have shown the effectiveness of the proposed design technique to carry out high-performance band-pass filters in SIW technology.

A shunt RLC resonant circuit obtained from a broadside-coupled open split ring resonator (BC-OSRR) is proposed. This BC-OSRR cell allows a parallel connection with planar waveguides. Hence, it has been applied to a half-mode substrate integrated waveguide (HMSIW) section. The analysis of the frequency response and electromagnetic field distribution of the HMSIW structure loaded with an appropriate BC-OSRR cell have shown two main behaviors. The first characteristic is a high-pass frequency response inherent to the HMSIW and the second is a transmission zero in the passband of the HMSIW, which is due to the resonance of the BC-OSRR cell. The First- and second-order prototypes have been designed and fabricated. The measured bandstop HMSIW filters using BC-OSRR achieve a 3-dB stopband bandwidth around 10% with more than 21-dB insertion loss. This BC-OSRR cell with low undesired radiation loss can be a new alternative for the implementation of compact bandstop filters in the planar technology.

Background The neurosurgical boot camp has been fully incorporated into U.S. postgraduate education. This is the first implementation of the neurosurgical boot in a developing country. To advance neurosurgical education, we developed a similar boot camp program, in collaboration with Bolivian neurosurgeons, to determine its feasibility and effectiveness in an international setting. Methods In a collective effort, the Bolivian Society for Neurosurgery, Foundation for International Education in Neurological Surgery, Solidarity Bridge, and University of Massachusetts organized and executed the first South American neurosurgical boot camp in Bolivia in 2015. Both U.S. and Bolivian faculty led didactic lectures followed by a practicum day using mannequins and simulators. South American residents and faculty were surveyed after the course to determine levels of enthusiasm and their perceived improvement in fund of knowledge and course effectiveness. Results Twenty-four neurosurgery residents from 5 South American countries participated. Average survey scores ranged between 4.2 and 4.9 out of 5. Five Bolivian neurosurgeons completed the survey with average scores of 4.5–5. This event allowed for Bolivian leaders in the field to unify around education, resulting in the formation of an institute to continue similar initiatives. Total cost was estimated at $40 000 USD; however, significant faculty, industry, and donor support helped offset this amount. Conclusion The first South American neurosurgical boot camp had significant value and was well received in Bolivia. This humanitarian model provides a sustainable solution to education needs and should be expanded to other regions as a means for standardizing the core competencies in neurosurgery.

We present a method for the teaching of Electronics, defined as the scientific discipline that studies the movement and behavior of electrons in semiconductor materials and in vacuum. Electronics can be considered as a science with a solid physical foundation. Within the field of Electronics there are different disciplines, some of them can be considered as pure science, while some others are more oriented to applications. Our methodology has been applied to the wide range of courses that develop the different approaches to Electronics, from the physics of semiconductors or the physics of microelectronic devices, generally taught at physics faculties, to microelectronic fabrication technology or microelectronic design, subjects that typically have a more application-oriented character. To ensure an effective learning of these subjects, a teaching-learning model has been established. This model involves the criteria for developing the programs and defining objectives according to the curricular competences, as well as the development of a series of activities in which the methods, techniques, forms of presentation and didactic resources most useful to achieve the proposed objectives will be used. An evaluation system that assesses the effectiveness of the educational process and detects its anomalies is also included. The impact of this method on the effectiveness of the teaching-learning process was evaluated by a comparative analysis of the results of the surveys distributed by the university to the students for the assessment of quality, together with surveys to the lecturers of the subjects of Electronics

Low-cost and flexible radio frequency identification (RFID) tag for automatic identification, tracking, and monitoring of blood products is in great demand by the healthcare industry. A robust performance to meet security and traceability requirements in the different blood sample collection and analysis centers is also required. In this paper, a novel low-cost and flexible passive RFID tag is presented for blood sample collection tubes. The tag antenna is based on two compact symmetrical capacitive structures and works at the ultra-high frequency (UHF) European band (865 MHz&ndash, 868 MHz). The tag antenna is designed considering the whole dielectric parameters such as the blood, substrate and tube. In this way, it operates efficiently in the presence of blood, which has high dielectric permittivity and loss. Measurement results of the proposed tag have confirmed simulation results. The measured performance of the tag shows good matching in the desired frequency band, leading to reading ranges up to 2.2 m, which is 4.4 times higher than typical commercial tags. The potential of this tag as a sensor to monitor the amount of blood contained in clinic tubes is also demonstrated. It is expected that the proposed tag can be useful and effective in future RFID systems to introduce security and traceability in different blood sample collection and analysis centers.

In this contribution, we describe the design of bandpass filters using evanescent mode waveguides and dielectric resonators implemented with additive manufacturing techniques. Two C-band Chebyshev evanescent mode waveguide filters of order five have been designed using a low cost commercial dielectric material (ABSplus), widely used by Fused Deposition Modeling (FDM) 3D printers. The housings of the filters have been manufactured using traditional computer numerical control (CNC) machining techniques. Practical manufacturing considerations are also discussed, including the integration of dielectric and metallic parts. We first discuss two breadboards using two different resonator geometries. We then demonstrate how different transfer functions can be easily implemented by changing the 3D printed parts in the same metallic housing. Breadboards show fractional bandwidths between 3% and 4.6% with return losses better than RL=18dB, and spurious free ranges of SFR=1GHz. Insertion losses are better than IL=4.3dB. Even though dielectric losses from the plastic material are shown to be high, the measured results are quite satisfactory, thereby clearly showing that this strategy maybe useful for the fast production of low cost microwave filters implementing complex geometries., 9 pages, 15 figures

In this paper, a rigorous method for the design of high-performance n-order Chebyshev low-pass filters based on electromagnetic bandgap (EBG) stepped impedances in microstrip and coplanar (CPW) technologies is proposed. Fifth-order low-pass filters implemented by means of circular patterns etched in the ground plane of microstrip and CPW lines have been designed, simulated and measured on an RO3010 substrate ( ∊ r = 10.2, tanδ = 0.0023 at 10 GHz, substrate thickness h = 0.635 mm and copper thickness t = 0.018 mm). The designed filters have shown a good agreement between EM simulation and measurement results. The proposed EBG-based low pass filters, with six etched circles and a size of 42 × 20 mm2, achieve a passband with a cut-off frequency fc = 6 GHz measured at |S11| = −20 dB, return loss RL = 20 dB, 5 reflection zeros in the frequency axis, a ripple lower than 1.1 dB, and a stopband greater than 5 GHz with a rejection level higher than 30 dB. Therefore, the designed low-pass filters have an ultra-wide passband with high return loss, low insertion losses and a low ripple. In addition, they exhibit a large stopband with high rejection level compared to other reported wide stop-band low-pass filters based on EBG, defected ground structures (DGS), or modified complementary split ring resonators (CSRR). This technique can be used to design high-performance Chebyshev EBG-based low-pass filters with a high degree of control over the characteristics of their frequency responses. This allows to replace the EBG-, DGS- and CSRR-based wide stop-band low-pass filters in microwave circuit and antenna applications, with filter structures exhibiting high return loss, equiripple responses in the passband, and high rejection level in the stopband.

Background Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). Objective: We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. Design We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as > 30 days. Key results Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5 days to an average LOS of 9.8 days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96–0.98) and male gender (OR 0.88 IC95% 0.87–0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39–2.58), surgery (OR: 6.9 95% CI: 6.8–7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86–2.95). Conclusions Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home.

This study presents electromagnetic bandgap (EBG) structures in microstrip technology based on one-dimensional Koch fractal patterns (Koch fractal EBG (KFEBG)). This fractal geometry allows to adjust the radius r and distance a between patterns so that a low-pass filter response is obtained when the ratio r/a is higher than 0.5. However, in such case undesired strong ripples appear in the low bandpass region. We demonstrate that the performance in the passband of this filter can be improved by applying a tapering function to the Koch fractal dimensions and to the width of the microstrip line, while simultaneously chirping (modulating) the Koch fractal periodic pattern distance (a) so as to maintain a constant r/a ratio. Several tapering functions scaled by a factor K are presented, and the results of their application to the KFEBG microstrip structure are compared by means of relevant characteristic parameters. Optimal performance has been obtained for the Kaiser and Cauchy distributions applied to the Koch fractal pattern, combined with a rectangular and Cauchy distribution applied to the microstrip width, respectively.

Background The aim of the present study was to assess the association of obesity with the mortality of hospitalized patients with acute stroke and the risk of readmission in less than 30 days. Methods A retrospective chart review of a cohort of consecutive patients admitted with stroke as the primary reason for discharge in Spain between January 1, 2005, and December 31, 2011, was performed. Patients with a diagnosis of obesity were identified. The mortality and readmittance indexes of obese patients were compared against the subpopulation without theses diagnosis. Results A total of 201,272 stroke admittances were analyzed, and 14,047 (7.0%) diagnosis of obesity were identified. In-hospital global mortality reached 14.9%, and readmittance risk was 5.9%. Obese patients showed a lower in-hospital mortality risk (odds ratio [OR], .71; 95% confidence interval [CI], .67-.76) and early readmittance risk (OR, .89; 95% CI, .82-.96) than the nonobese even after adjusting for possible confounding factors. Conclusions Obesity in those hospitalized for stroke is associated with reduced in-hospital mortality risk and early readmittance.

Ferroelectrics are interesting materials for the design of new microwave devices. The potential of ferroelectrics and other high-permittivity (high-k) dielectrics for such high-frequency devices is due to the field-dependent permittivity of these materials, which can be of application to frequency agile devices whose operation frequency can be tuned by a control signal. In this way, the same circuit can be reconfigured or adapted to operate at different frequencies. This offers considerable advantages for the design of reconfigurable passive and active devices, especially in terms of reduction of size, complexity, and cost of systems with multiband operation capabilities.

An open ring resonator (ORR) loaded with a varactor diode is designed and implemented in order to achieve high-performance tunable band-stop filters in planar technology with a compact size. This varactor-loaded ORR (VLORR) is versatile. It allows a shunt connection with different planar waveguide sections. In this paper, it has been connected to a coplanar waveguide (CPW) and a half-mode substrate integrated waveguide (HMSIW). As a reverse bias voltage is applied to the VLORR, a continuous tuning over the resulting stop-band can be achieved. To illustrate the possibilities of the VLORR, three prototypes have been designed, fabricated, and characterized. The three prototypes show an outstanding performance, with a rejection level at the resonant frequency and a tuning range greater than 12 dB and 85%, respectively. This VLORR has high potential value in microwave communication systems to eliminate unwanted signals. This work was supported by Ministerio de Economía y Competitividad, Fundación Séneca (Murcia) of Spain and European Regional Development Funds under grants TEC2016-75934-C04-4-R, 19494/PI/14 and 20147/EE/17.

An open ring resonator (ORR) is applied to a half mode substrate integrated waveguide (HMSIW) for the design of notch filters. This ORR cell is connected in parallel with a HMSIW section. The measured ORR-loaded HMSIW has the same behavior as a shunt series LC resonant circuit with a 3 dB stop-band bandwidth lower than 5 % and insertion loss above 15 dB. This ORR cell can be useful for the design of higher-order band-stop filters and reconfigurable HMSIW band-stop filters by placing a varactor diode connected to the open ring resonator.

A compact microstrip bandstop filter (BSF) with a wide electronically tunable frequency range and a constant absolute bandwidth is presented. It consists of an open ring resonator (ORR) loaded with a varactor diode and connected to a section of a microstrip transmission line. As a reverse bias is applied to the proposed varactor-loaded ORR (VLORR), the value of the resulting capacitor is controlled and the resonant frequency can be varied to the desired position. The measured tunable BSF achieves 92.6 $$\,\%$$ tuning range with a constant 15 dB absolute bandwidth of 0.27 GHz and a minimum rejection level of 37 dB. This reconfigurable microstrip BSF can be useful in microwave communication systems.

This paper describes a design tool of high-order three dimensional (3-D) filters by means of 2-D and 3-D electromagnetic (EM) softwares and two space mappings. The first space mapping aligns the 3-D EM response with the 2-D EM response of a low-order 3-D filter. The second mapping performs a calibration of the first mapping. The high-order filter is optimized using the fast 2-D EM software. The design parameters of the high-order 3-D filter are directly obtained by means of the calibration equations. This design tool is applied to 3-D bandpass filters with increasing order in evanescent rectangular waveguide.