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Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop2 with an SN-38 payload recently approved for pretreated patients with locally advanced or metastatic triple-negative breast cancer (TNBC). The XenoSTART Patient-Derived Xenograft (XPDX) breast cancer platform includes over 180 models spanning all subtypes characterized with immunohistochemistry (IHC) including ER, PR, and HER2 protein levels, genomic and transcriptomic sequencing, and in vivo drug sensitivity. To better understand potential benefit of SG in breast cancers other than TNBC and further annotate our platform, Trop2 protein levels were determined in all breast models by IHC. We evaluated tumor growth inhibition by SG in 125 of our XPDX breast models and compared protein expression with agent activity. Methods: 180 breast XPDX models were evaluated for Trop2 expression (AF650, R&D Systems) and 125 were evaluated in vivo against SG; responses were grouped by ER and Trop2 status (+/-). Models were grown subcutaneously in female athymic nude mice and ER+ models supplemented with estradiol. Models were also characterized for PR, HER2, and AR protein expression by IHC and profiled using WES and RNAseq. For in vivo studies, SG was administered by intravenous injection biweekly for two cycles at 1 mg, flat; endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C< 0%) versus Day 0 tumor volume was also reported. Results: 180 breast models were examined by IHC with 75/180 (42%) classified as ER+ and 105/180 (58%) ER-. In ER+ models 38/75 (51%) were Trop2+ and 37/75 (49%) Trop2-, and in ER- models 41/105 (39%) were Trop2+ and 64/105 (61%) Trop2-. In vivo, 20% of ER+/Trop2+ models reported sensitivity to SG, most notably models from patients with acquired resistance to CDK4/6 inhibitors, including STM001 and ST4316B. Interestingly, >70% of ER+/HER2+/Trop2+ models were insensitive to SG, including ST225 and ST340. Of 41 ER-/Trop2+ models, approximately 40% reported some response to SG with 50% of these sensitive to therapy, including ST5954 established from a patient who began treatment with SG following sample collection and is currently in remission. >75% of Trop2- models were insensitive to SG regardless of ER status. Conclusion: We screened 180 models in our XPDX breast cancer platform for Trop2 expression and compared expression with in vivo SG efficacy in 125 models. Analysis is underway to correlate receptor and molecular profiles with SG sensitivity in breast models and we are expanding expression and in vivo testing to additional indications. Citation Format: Alyssa Simonson, Johnnie Flores, Ebony Anderson, Crystal Moreno, George Plasko, Kyriakos P. Papadopoulos, Amita Patnaik, Drew Rasco, Gladys Rodriguez, Amy Lang, Muralidhar Beeram, Luis Rodriguez, Ronald Drengler, Steven Abbate, Hanni Salih, Lon Smith, Maryam Elmi, Brittany DeBerry, Arthur Rosenthal, Tatiana Hernandez, Nehal Lakhani, Manish Sharma, Michael Wick. Correlation of Trop2 expression with in vivo sensitivity to sacituzumab govitecan in a panel of breast XPDX models [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-08-05.

Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) complexes, promote severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and represent host-directed therapeutic targets. The catalytic activity of SMARCA4 is required for mSWI/SNF-driven chromatin accessibility at the ACE2 locus, ACE2 expression and virus susceptibility. The transcription factors HNF1A/B interact with and recruit mSWI/SNF complexes to ACE2 enhancers, which contain high HNF1A motif density. Notably, small-molecule mSWI/SNF ATPase inhibitors or degraders abrogate angiotensin-converting enzyme 2 (ACE2) expression and confer resistance to SARS-CoV-2 variants and a remdesivir-resistant virus in three cell lines and three primary human cell types, including airway epithelial cells, by up to 5 logs. These data highlight the role of mSWI/SNF complex activities in conferring SARS-CoV-2 susceptibility and identify a potential class of broad-acting antivirals to combat emerging coronaviruses and drug-resistant variants.

Altres ajuts: Red Española de Supercomputación (QHS-2022-2-0029) Electric-field-driven ion motion to tailor magnetic properties of materials (magneto-ionics) offers much promise in the pursuit of voltage-controlled magnetism for highly energy-efficient spintronic devices. Electrolyte gating is a relevant means to create intense electric fields at the interface between magneto-ionic materials and electrolytes through the so-called electric double layer (EDL). Here, improved magneto-ionic performance is achieved in electrolyte-gated cobalt oxide thin films with the addition of inorganic salts (potassium iodide, potassium chloride, and calcium tetrafluoroborate) to anhydrous propylene carbonate (PC) electrolyte. Ab initio molecular dynamics simulations of the EDL structure show that K+ is preferentially located on the cobalt oxide surface and KI (when compared to KCl) favors the accumulation of positive charge close to the surface. It is demonstrated that room temperature magneto-ionics in cobalt oxide thin films is dramatically enhanced in KI-containing PC electrolyte at an optimum concentration, leading to 11-fold increase of generated magnetization and 35-fold increase of magneto-ionic rate compared to bare PC.

Gene profiling using a customized NanoString platform can be applied to routine mycosis fungoides (MF) samples, revealing their specific molecular features. This study shows that MF samples carry a signature derived from individual molecular features found in consecutive biopsies.

Resumen Introduccion La implementacion del diagnostico en un solo paso (DUSP) de la infeccion activa por virus de la hepatitis C (VHC) conjuntamente con la incorporacion de alertas informativas ha demostrado que reduce de forma significativa, respecto al diagnostico tradicional, la cifra de pacientes que no eran remitidos para valoracion terapeutica. Metodos A partir de la implementacion en 2018 del DUSP en los servicios de microbiologia de los hospitales del Servicio Gallego de Salud (SERGAS), se identifican y caracterizan de manera retrospectiva los nuevos diagnosticos de infeccion activa por VHC. Resultados En 2018 se identificaron mediante DUSP un total de 258 pacientes con infeccion activa por VHC desconocida (70,2% hombres, mediana de edad de 52 anos) procedentes de consultas de unidades de atencion primaria y especializada en un 54,8% y 39,8%, respectivamente, asi como de otras localizaciones en un 5,4%. De los 258 pacientes, el 81,0% fueron derivados para valoracion terapeutica, con una mediana de 54 dias desde su diagnostico. En el 58,3% de los casos se determino el DUSP mediante carga viral, el genotipo predominante fue el 1a (30,7%), un 52,1% fue tratado y se observo una respuesta viral sostenida en el 93,7% de estos. Conclusion La implementacion en toda Galicia del DUSP de la hepatitis C conjuntamente con alertas informativas ha permitido obtener, en conjunto, tasas de derivacion para tratamiento similares a las obtenidas en otros estudios. Sin embargo, existe una amplia variabilidad entre los distintos centros, que exigen la incorporacion de mejoras, como la formacion o la utilizacion de medidas de rescate para su optimizacion.

The ballistocardiogram (BCG) is a graphic representation of the movements of the body associated with cardiac activity. In this article, a 10-min BCG has been captured for ten different volunteers with a polymer optical fiber (POF) specklegram sensor. This transducer, which is composed of a charge-coupled device (CCD) camera, a laser emitting diode, and two meters of POF, allows capturing the BCG by analyzing how the induced speckle pattern changes over time. These changes are related to cardiac activity. Several processing methods have been compared to determine which method achieves the best performance: complex cepstrum, power of spectral density (PSD), Pam-Tompkins algorithm, wavelet, autocorrelation, Savitzky?Golay filter, mean absolute deviation, and Hilbert transform. Accuracy and resource consumption have been characterized and compared for these methods. Hilbert, PSD, and Savitzky-Golay exhibit both small errors and computational costs. This article describes a baseline for the main frequency determination of POF-based BCG signals in real-time. This work was supported by the Project PID2019-107270RB-C21 through MCIN/ AEI /10.13039/501100011033.

En el presente artículo se aborda la exclusión en vivienda de la Población de Origen Inmigrante (POI) en España. Para ello, se presentan medidas cuantitativas, cuatro índices de segregación residencial, para los casos de Terrassa (Barcelona) y Torre-Pacheco (Murcia). También se aporta un análisis cualitativo a partir de un trabajo de campo desarrollado durante los años 2018 y 2019.Destacan unos valores de segregación residencial y espacial poco significativos, en la línea de otros estudios en el Sur de Europa; sin embargo, el trabajo de campo revela una precariedad residencial que, ante unas políticas de vivienda poco eficaces, hace depender la inclusión social de la capacidad económica del colectivo, su capital social y relacional y las posibilidades de acceso a un mercado de vivienda saturado y restringido. Además, las actitudes de rechazo de la población autóctona producen una discriminación velada sobre el colectivo en su acceso a la vivienda.

Introduction:Hyperkalemia (HK) is common and potentially a life-threatening condition. If untreated, HK can progress to ventricular arrhythmia and cardiac arrest. Early treatment reduces mortality in HK. This study evaluates a novel protocol for identification and empiric management of presumed HK in the prehospital setting.Methods:This was a retrospective, observational chart review of a single, large, suburban Emergency Medical Services (EMS) system. Patients treated for presumed HK, with both a clinical concern for HK and electrocardiogram (ECG) changes consistent with HK, from February 2018 through February 2021 were eligible for inclusion. Patients were excluded if found to be in cardiac arrest on EMS arrival. Empiric treatment of HK included administration of calcium, sodium bicarbonate, and albuterol. Post-treatment, patients were placed on cardiac monitoring and adverse events recorded enroute to receiving hospital. Protocol compliance was assessed by two independent reviewers. Serum potassium (K) level was obtained from hospital medical records.Results:A total of 582 patients were treated for HK, of which 533 patients were excluded due to cardiac arrest prior to EMS arrival. The remaining 48 patients included in the analysis had a mean age of 56 (SD = 20) years and were 60.4% (n = 29) male with 77.1% (n = 37) Caucasian, 10.4% (n = 5) African American, and 12.5% (n = 6) Hispanic. Initial blood draw at the receiving facilities showed K >5.0mEq/L in 22 (45.8%), K of 3.5-5.0mEq/L in 23 (47.9%), and K Conclusion:The study evaluated a novel protocol for detecting and managing HK in the prehospital setting. It is feasible for EMS crews to administer this protocol, although a larger study is needed to make the results generalizable.

El artículo presenta un análisis sobre el acceso a la vivienda de los inmigrantes en España desde una perspectiva de los derechos humanos. Este colectivo que reside en barrios y municipios españoles tiende a concentrarse en determinadas zonas de viviendas baratas y degradadas y que, consecuentemente, terminan siendo estigmatizadas por la población nativa. No en vano, los inmigrantes encuentran especiales dificultades para acceder a una vivienda digna por una serie de cuestiones, pero, fundamentalmente por una situación económica precaria derivada, en algunos casos, de la ausencia de políticas públicas eficaces y de las actitudes excluyentes por parte de los propietarios y arrendatarios de vivienda. Sobre este último punto, se propone un análisis a tres niveles para el estudio de la exclusión social: el Estado, el mercado y la sociedad civil, (macro, meso y micro) para observar así la influencia de estos agentes en el grado de cumplimiento del derecho humano a la vivienda que experimenta el colectivo inmigrante en España. Recibido: 02 febrero 2022Aceptado: 31 mayo 2022

Clinically and biologically, it is essential to detect rare DNA-sequence variants for early cancer diagnosis or drug-resistance mutation identification. Some of the common quantitative polymerase chain reaction (qPCR)-based variant detection methods are restricted in the limit of detection (LoD) because the DNA polymerases used for these methods have a high polymerase misincorporation rate; thus, the detection sensitivity is sometimes unsatisfactory. With the proofreading activity, high-fidelity (HiFi) DNA polymerases have a 50- to 250-fold higher fidelity. However, there are currently no proper probe-based designs functioning as the fluorescence indicator allowing multiplexed HiFi qPCR reactions, thus restricting the application of HiFi DNA polymerases like the variant detection. We presented the occlusion system, composed of a 5'-overhanged primer with a fluorophore modification and a probe with a short-stem hairpin and a 3' quencher modification. We demonstrated that the occlusion system allowed multiplexing HiFi qPCR reaction, and it was compatible with the current variant-enrichment method to improve the LoD up to 10-fold. Thus, the occlusion system satisfactorily functioned as an efficient fluorescence indicator in HiFi qPCR reactions and allowed the application of HiFi DNA polymerases in variant detection methods to improve detection sensitivity.

This paper presents a control of the parallel operation of diode rectifier based high-voltage direct current (DR-HVDC) and voltage source converter based HVDC (VSC-HVDC) links. The two links are connected to offshore wind farms (OWFs). The VSC-HVDC controls the voltage and frequency of the offshore AC-grid needed for the OWFs start-up. The proposed grid forming control is based on controlling the OWFs voltage by controlling the active power balance at the VSC-HVDC AC-bus. When the OWFs inject more power than a certain active power reference established for the VSC-HVDC, the OWFs voltage increases and the DR-HVDC starts conducting. Then, the offshore voltage automatically accommodates the required value for transmitting the OWFs power through the DR-HVDC link while the system frequency is controlled by the VSC-HVDC through satisfying the reactive power balance. The power transmitted through the VSC-HVDC can be set by adjusting the corresponding power command while the DR-HVDC will automatically close the power balance. The main advantage of the proposed control system is that the VSC-HVDC can be sized just to support the system energization; while once the OWFs are in operation, the DR-HVDC will be loaded automatically. Simulation results verify the proposed control system.

Alveolar Type II (AT2) epithelial cell dysfunction is a hallmark of the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF), a progressive interstitial lung disease. Mutations in the surfactant protein C (SP-C) gene (SFTPC) are a high effect size etiological cause of PF in a subset of these patients. Prior in vitro studies from our lab showed that SFTPC mutations located within the BRICHOS domain of the SP-C proprotein result in production of ER retained and aggregation prone conformers. A major aspect of the proteostasis network is the unfolded protein response (UPR), which is initiated when misfolded proteins activate one or more of 3 ER transmembrane sensing proteins (Protein kinase R-like ER kinase (PERK), the Inositol-Requiring kinase 1 (IRE1) and Activating Transcription Factor 6 (ATF6). Consistent with this, we published that clinical IPF associated BRICHOS SFTPC mutations activate all 3 arms of UPR/ER stress signaling in mice in vivo. The goal of this study was to define AT2 proteostatic responses to SFTPC expression and the contribution of ATF6 to the UPR. For this, we generated stable doxycycline-inducible Mouse Lung Epithelial (MLE-12) cell lines expressing either Wild Type (SP-CWT) or an aggregating mutant (SP-CC121G) which were interrogated using cycloheximide chase and / or treatments with activators or inhibitors of ATF6, IRE1, and PERK as well as ERAD (vp97) or autophagy. Readouts included qPCR, luciferase reporter assays, and immunoblotting to assess UPR signaling and apoptosis, coupled with fluorescence microscopy to localize SP-C expression. Using this model system we found that SP-CC121G was ER retained and activated the UPR within 8 hours of Dox induction expression as measured by BIP expression. Commensurate with this both IRE1a (as spliced XBP1 (sXBP1)) and ATF6 were activated by SP-CC121G. The clearance of both mutant SP-CC121G as well as a portion of proSP-CWT was dependent on ERAD as its disruption using the vp97 inhibitor Eeyarestatin I induced formation of higher molecular weight aggregates while bafilomycin failed to induce SP-CC121G aggregates or block their clearance. ATF6 and IRE1 activation during ERAD inhibition accelerated aggregate protein degradation. When SP-CC121G MLE12 cells were treated with either an ATF6 inhibitor or an IRE1 activator, marked increases in levels of C/EBP Homologous Protein (CHOP) occur while either ATF6 agonism or IRE1 inhibition decreased CHOP expression. Collectively, these our data demonstrate a primary role for ERAD in the proteostatic response to SP-C expression while ATF6 agonism appears to provide protection from SFTPC mutant expression in part by accelerating degradation of SP-C aggregates in the face of IRE1 UPR signaling. NIH R01 HL145408 (MFB), VA Merit Review 2I01BX001176 (MFB) and NIH F32HL160011 (LRR) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutation that led to AEC2 endoplasmic reticulum (ER) stress and spontaneous lung fibrosis, providing proof of concept for disruption to proteostasis as a proximal driver of PF. Using two clinical SP-C mutation models, we have now discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop a reprogrammed cell state that heretofore has been seen only as a response to lung injury. Using single-cell RNA sequencing in vivo and organoid-based modeling, we show that this state arises de novo from intrinsic AEC2 dysfunction. The cell-autonomous AEC2 reprogramming can be attenuated through inhibition of inositol-requiring enzyme 1 (IRE1α) signaling as the use of an IRE1α inhibitor reduced the development of the reprogrammed cell state and also diminished AEC2-driven recruitment of granulocytes, alveolitis, and lung injury. These findings identify AEC2 proteostasis, and specifically IRE1α signaling through its major product XBP-1, as a driver of a key AEC2 phenotypic change that has been identified in lung fibrosis.

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Purpose: Mesothelin (MSLN) is a tumor-associated antigen, being investigated as a biomarker and therapeutic target in malignant pleural mesothelioma (MPM). The biologic function of MSLN overexpression in MPM is unknown. We hypothesized that MSLN may promote tumor invasion in MPM, a tumor characterized primarily by regional aggressiveness and rare distant metastases.Experimental Design: Human and murine MPM cells with MSLN forced expression and short hairpin RNA knockdown were examined for proliferation, invasion, and matrix metalloproteinase (MMP) secretion. The influence of MSLN overexpression on MPM cell invasion was assessed in an orthotopic mouse model and in patient samples.Results: MSLN expression promotes MPM cell invasion and MMP secretion in both human and murine MPM cells. In an orthotopic MPM mouse model characterized by our laboratory, MPM cells with MSLN overexpression preferentially localized to the tumor invading edge, colocalized with MMP-9 expression, and promoted decreased survival without an increase in tumor burden progression. In a tissue microarray from epithelioid MPM patients (n = 139, 729 cores), MSLN overexpression correlated with higher MMP-9 expression at individual core level. Among stage III MPM patients (n = 72), high MSLN expression was observed in 26% of T2 tumors and 51% of T3 tumors.Conclusions: Our data provide evidence elucidating a biologic role for MSLN as a factor promoting tumor invasion and MMP-9 expression in MSLN expressing MPM. As regional invasion is the characteristic feature in MSLN expressing solid cancers (MPM, pancreas, and ovarian), our observations add rationale to studies investigating MSLN as a therapeutic target. Clin Cancer Res; 18(9); 2478–89. ©2012 AACR.

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Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the website of the journal Current Stem Cell Research & Therapy. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

We report the use of topical cidofovir to treat patients with human monkeypox. We found that lesions on the trunk and limbs responded better than facial lesions, while anogenital lesions were affected by local irritation, leading to eventual discontinuation of treatment.

Why did Latin American states exclude a prohibition on maritime nuclear transit from their regional nuclear weapon-free zone (NWFZ)? Latin American countries and nuclear powers shared common anxieties about the dangers of the nuclear arms race in the early 1960s. Thus, they decided to craft a regional nuclear non-proliferation mechanism. Latin American states favoured limiting maritime nuclear transit as part of the Treaty for the Prohibition of Nuclear Weapons in Latin America and the Caribbean, known as the Treaty of Tlatelolco. However, they disagreed on defining transit and the zone of application of a ban, and they faced US opposition. This article identifies issue bracketing as a negotiating tactic Latin America used to ensure a successful treaty codification. It argues that Latin American states bracketed the maritime nuclear transit issue out of the NWFZ discussions and onto the agenda of the negotiations establishing ocean governance rules in the 1970s. The Latin American construction of a NWFZ questions assumptions in international law and nuclear politics studies about the agency of the global South in the global nuclear order. Latin American concessions in Tlatelolco were not impositions from nuclear powers. Their compromises were strategic decisions that helped them promote their governance preferences.

Trilayer polymer tubes were manufactured through an extrusion process using Pebax 6333 and high density polyethylene (HDPE) as outer and inner layer, respectively. A maleic grafted linear low-density polyethylene (LLDPE) was used as the bonding layer or tie-layer. Three types of multilayer tubes were produced: (1) outer layer (Pebax) at 70% of the total wall thickness (WT), (2) outer layer at 90% of WT, and (3) outer layer at 20% of WT. The analysis of mechanical properties showed that the inner layer contributes to strength and rigidity of the tube while the outer layer provides flexibility. Melt rheology behavior for HDPE and Pebax were studied, and HDPE showed a more pronounced shear thinning behavior compared to Pebax. Orientations of the tubes were assessed using Fourier transform infrared spectroscopy (FTIR) and it was found that HDPE layer is more sensitive to molecular orientation when extruded compared to Pebax material. Melting behavior for the tubes was investigated using dynamic scanning calorimetry (DSC). The tubes showed two melting temperatures: one associated with HDPE and one with Pebax. The HDPE peak showed a specific shift to a higher melting point for tubes as a result of molecular orientation during processing. Burst and compression testing were performed on the tubes and results demonstrated that the HDPE-rich extrusion showed the highest burst pressure and compression resistance.

This case presentation focuses on an athletic female soccer player who is seen following previous surgeries for removal of ganglion cyst with complications of hypertrophic scarring and recurrent cyst formation. The patient developed several lobular mass tracking from the ankle joint within a hypertrophic scar on the lateral aspect of her right ankle. Ganglion cyst is the most common soft tissue mass in the foot and has a relatively thin wall with gelatinous fluid inside. It is most common in the dorsum of the hand and wrist, whereas 11% of all ganglia around the body occur in the foot and ankle areas. In this case, due to the athlete’s high physical activity level, the ganglion cysts frequently recurred and limited her performance on the field. The patient underwent a series of ganglion cyst aspirations, intermittent injection of corticosteroid and application of Cordran Tape as a topical corticosteroid. After a period of conservative care and continued regrowth the patient opted for surgical intervention with removal of recurrent ganglion cysts.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease (ILD). A barrier to developing more effective therapies for IPF is the dearth of preclinical models that recapitulate the early pathobiology of this disease. Intratracheal bleomycin, the conventional preclinical murine model of IPF, fails to reproduce the intrinsic dysfunction to the alveolar epithelial type 2 cell (AEC2) that is thought to be a proximal event in the pathogenesis of IPF. Murine fibrosis models based on Surfactant Protein C gene (

In recent years, the Industry 4.0 paradigm has gained special relevance, focused on the integration of smart structures to increase the efficiency of processes. Photonics, with laser advanced manufacture and light-based sensors, can offer great possibilities in this field. Within advanced manufacturing, femtosecond lasers allow inscribing different optical structures. Waveguides are one of the most widely used structures in photonic sensors. This work proposes the design, simulation and manufacture of symmetric cladding waveguides in optical fibers using the slit beam shaping technique. Cladding waveguides characterized by their low losses (0.21 dB/cm), quasi?step-index refractive index profile, and circular cross-section are used to couple evanescent light from the core of a single-mode fiber to each of the four cores of a multicore fiber. This work has been supported by the Ministerio de Ciencia, Innovación y Universidades and Agencia Estatal de Investigación (PID2019-107270RB- C21), the Ministerio de Educación, Cultura y Deporte of Spain (PhD grant FPU2018/02797), and FEDER funds.

A series of SARS-CoV-2 variants of concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic and genomic analyses during infection to understand the molecular responses driving VOC evolution. We discovered VOC-specific differences in viral RNA and protein expression levels, including for N, Orf6, and Orf9b, and pinpointed several viral mutations responsible. An analysis of the host response to VOC infection and comprehensive interrogation of altered virus-host protein-protein interactions revealed conserved and divergent regulation of biological pathways. For example, regulation of host translation was highly conserved, consistent with suppression of VOC replication in mice using the translation inhibitor plitidepsin. Conversely, modulation of the host inflammatory response was most divergent, where we found Alpha and Beta, but not Omicron BA.1, antagonized interferon stimulated genes (ISGs), a phenotype that correlated with differing levels of Orf6. Additionally, Delta more strongly upregulated proinflammatory genes compared to other VOCs. Systematic comparison of Omicron subvariants revealed BA.5 to have evolved enhanced ISG and proinflammatory gene suppression that similarly correlated with Orf6 expression, effects not seen in BA.4 due to a mutation that disrupts the Orf6-nuclear pore interaction. Our findings describe how VOCs have evolved to fine-tune viral protein expression and protein-protein interactions to evade both innate and adaptive immune responses, offering a likely explanation for increased transmission in humans.One sentence summarySystematic proteomic and genomic analyses of SARS-CoV-2 variants of concern reveal how variant-specific mutations alter viral gene expression, virus-host protein complexes, and the host response to infection with applications to therapy and future pandemic preparedness.

Most of the mature South American oil and natural gas fields are represented by formations with moderate porosity, low resistivity, heavy oil, and general anisotropic behavior of other petrophysical properties. This leads to complex decision making when attempting to identify zones of interest with good reservoir qualities in addition to hydrocarbon saturation. These mature fields offer a unique challenge in that the petrophysical analysis needs to rely on data from newly drilled cased hole wellbores, necessitating numerous corrections. In this challenging environment, very few technologies can provide the data required for a precise petrophysical assessment. For this reason, a geochemical spectroscopy tool was employed with measurements that included elemental concentrations, the sigma formation cross section, and a direct measurement of the carbon concentration in the surrounding formation. The resulting data and innovative interpretation provided an accurate assessment of formation mineralogy including clay types, porosity, and hydrocarbon saturation. These reservoirs, which have been in production for decades, contain relatively fresh water (approximately 2-5 kppm NaCl), moderate porosities (9 to 20 p.u.), and lithologies dominated by sand or sand/shale. The primary objective of the logging program was to incorporate nuclear spectroscopy applications to evaluate and characterize the zones of interest aligned with historical production data. In addition to the geochemical spectroscopy tool, the logging program also included gamma ray, spectral gamma ray, neutron porosity, and density. This suite of tools supplied the measurements required to characterize the formation through the determination of mineralogy, porosity, and hydrocarbon saturation. The mineralogical model was based upon quartz, feldspar, pyrite, a highly conductive mineral, and numerous clays including illite, kaolinite, chlorite, and smectite. Open hole information from nearby wells was also incorporated into the petrophysical interpretation using normalization procedures and prediction analytics. Since this was a cased hole logging program, and calcium was a significant component of the cement, a cement-mimicking mineral was constructed based upon calcium oxide. This provided important quality control information regarding the condition of the borehole and cement placement, as very little calcite was present in the subsurface formations of the field. Once the formation mineralogy, porosity, and matrix density were computed, the hydrocarbon saturation was calculated using two approaches: excess carbon and the ratio of carbon to oxygen elemental yields. The final interpretation provided key information, not only for the drilling campaign, but also for the workover planning and quantification of OOIP (original oil in place). Field examples are provided to demonstrate the complete workflow from the design of the logging program to the specialized interpretation methods and final deliverables.

We report a noteworthy case of a 10-year-old girl who presented with papular and nodular lesions on the skin that were clinically and histologically mistaken for progressive nodular histiocytosis. During the clinical management of the patient, the high lipid levels raised the suspicion of lipid metabolism disease and helped us to make the correct diagnosis of sitosterolemia. In sitosterolemia, proper management such as restriction of plant sterol intake and administration of cholesterol absorption inhibitor can improve prognosis.