Renal impairment is prevalent in pediatric NAFLD/MASLD and associated with disease severity.

OBJECTIVES: Renal impairment is prevalent in adults with nonalcoholic fatty liver disease (NAFLD/metabolic dysfunction associated steatotic liver disease [MASLD]) and is associated with increased mortality. Pediatric data are limited. Our objective was to determine the prevalence of hyperfiltration or chronic kidney disease (CKD) in children with NAFLD/MASLD and determine links with liver disease severity. METHODS: Data from children who had previously participated in prospective, multicenter, pediatric studies by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) were collected. Renal function was determined using the calculated glomerular filtration rate (cGFR). Hyperfiltration was defined as cGFR > 135 mL/min/1.73m2, while CKD stage 2 or higher as cGFR < 90 mL/min/1.73 m2. Renal dysfunction progression was defined as transition from normal to hyperfiltration or to CKD stage ≥ 2, or change in CKD by ≥1 stage. Multinomial logistic regression models were used to determine the prevalence of CKD and independent associations between CKD and liver disease severity. RESULTS: The study included 1164 children (age 13 ± 3 years, 72% male, 71% Hispanic). The median cGFR was 121 mL/min/1.73 m2; 12% had CKD stage 2-5, while 27% had hyperfiltration. Hyperfiltration was independently associated with significant liver fibrosis (odds ratio: 1.45). Baseline renal function was not associated with progression in liver disease over a 2-year period (n = 145). Renal dysfunction worsened in 19% independently of other clinical risk factors. Progression of renal impairment was not associated with change in liver disease severity. CONCLUSIONS: Renal impairment is prevalent in children with NAFLD/MASLD and hyperfiltration is independently associated with significant liver fibrosis. Almost 1/5 children have evidence of progression in renal dysfunction over 2 years, not associated with change in liver disease severity. Future assessments including additional renal impairment biomarkers are needed.

Fracture resistance of partial and complete coverage veneers and ceramic crowns for maxillary central incisors.

STATEMENT OF PROBLEM: Minimally invasive treatments have gained popularity in recent years. However, research comparing the fracture resistance of lithium disilicate partial coverage veneer restorations with that of ceramic crowns is lacking. PURPOSE: The purpose of this in vitro study was to evaluate and compare the fracture resistance of lithium disilicate restorations fabricated for preparations of various designs. The designs included veneer preparations with finish lines in the upper, middle, and lower third of the facial surface and ceramic crown preparations with margins in the lower third of the facial surface. All restorations were designed and fabricated using a chairside digital workflow. MATERIAL AND METHODS: Four maxillary right central incisor typodont teeth were prepared for partial coverage veneer preparation with the margin in the upper middle third of the facial surface (PU1/3); partial coverage veneer preparation with margin in lower middle third of the facial surface (PL1/3); complete coverage veneer preparation (CV) with margin in the cervical region; and ceramic crown (CC) preparation. Each preparation was scanned, and 15 casts were 3D printed from each scan. A total of 60 lithium disilicate restorations were fabricated (n=15 per group) using a chairside computer-aided design and computer-aided manufacturing (CAD-CAM) system (Primescan and MCXL). The different restorations were cemented to the 3D printed testing dies with a photopolymerizable resin cement. The specimens were artificially aged with 10 000 thermal cycles between 5 and 55 °C with a dwell time of 30 seconds and were loaded to failure using a universal testing machine. The maximum load to fracture was analyzed using a 1-way ANOVA and post hoc Tukey honestly significant difference (HSD) test (α=.05). Additionally, the fracture patterns of the specimens were evaluated with a stereomicroscope for descriptive purposes. RESULTS: The mean fracture resistance of the chairside CAD-CAM lithium disilicate veneers and ceramic crowns was statistically different depending on the design of the restoration (P<.05). Group CC demonstrated the highest fracture resistance values (1440.66 N), followed by CV (929.8 N) and PU1/3 (756.13 N). The lowest value was for PL1/3 (532.4 N). CONCLUSIONS: The fracture resistance measured for the maxillary central incisor partial coverage veneers with margins in the middle third of the facial surface appear capable of resisting average occlusal forces. However, these veneers demonstrated lower fracture resistance values when compared with complete coverage veneers. Further, lithium disilicate crowns demonstrated higher fracture resistance than veneers, irrespective of their design.

Effect of Model Resin and Shaft Taper on the Trueness and Fit of Additively Manufactured Removable Dies in Narrow Ridge Models.

Effect of model resin and shaft taper angle on the trueness and fit of additively manufactured removable dies in narrow ridge casts Purpose. To evaluate how model resin and shaft taper affect the trueness and fit of additively manufactured removable dies in narrow ridge casts. MATERIAL AND METHODS: A typodont model with a prepared mandibular molar was scanned to design virtual dies with different shaft tapers (0-degree (straight), 5-degree, and 10-degree tapered). Fifteen dies and one hollowed cast per taper were additively manufactured from two resins (G-PRINT 3D Model, GP and DentaMODEL, DM). Dies and casts were digitized to evaluate their trueness (root mean square (RMS)). The fit of the dies was evaluated with crown portion's RMS when seated in the cast and with distance deviations. Kruskal-Wallis and Mann-Whitney U tests were used to analyze data (α =.05). RESULTS: GP dies had lower overall, root, and base RMS, while DM dies had lower crown RMS (P≤.016). Straight dies had the highest overall, root, and base RMS within GP (P≤.030). Ten-degree dies had the lowest overall and base RMS, lower crown RMS than straight, and lower root RMS than 5-degree dies within DM (P≤.047). When the dies were seated, GP had lower crown portion RMS within 5- and 10-degree dies, and 5-degree dies had the highest RMS within DM (P≤.003). GP had lower distance deviations within 5- and 10-degree dies. Five-degree dies had the highest deviations within DM (P≤.049). CONCLUSIONS: GP dies mostly had higher trueness and better fit. Straight dies mostly had lower trueness within GP. Ten-degree taper mostly led to higher trueness within DM. The shaft taper affected DM dies' fit.

Analysis of a new negevirus-like sequence from Bemisia tabaci unveils a potential new taxon linking nelorpi- and centiviruses.

This study presents the complete genome sequence of a novel nege-like virus identified in whiteflies (Bemisia tabaci MEAM1), provisionally designated as whitefly negevirus 1 (WfNgV1). The virus possesses a single-stranded RNA genome comprising 11,848 nucleotides, organized into four open reading frames (ORFs). These ORFs encode the putative RNA-dependent-RNA-polymerase (RdRp, ORF 1), a glycoprotein (ORF 2), a structural protein with homology to those in the SP24 family, (ORF 3), and a protein of unknown function (ORF 4). Phylogenetic analysis focusing on RdRp and SP24 amino acid sequences revealed a close relationship between WfNgV1 and Bemisia tabaci negevirus 1, a negevirus sequence recently discovered in whiteflies from Israel. Both viruses form a clade sharing a most recent common ancestor with the proposed nelorpivirus and centivirus taxa. The putative glycoprotein from ORF 2 and SP24 (ORF 3) of WfNgV1 exhibit the characteristic topologies previously reported for negevirus counterparts. This marks the first reported negevirus-like sequence from whiteflies in the Americas.

Spike-wave discharges during low-current thalamic deep brain stimulation in mice.

BACKGROUND: Deep brain stimulation of central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger spike-wave discharges (SWDs). OBJECTIVES: To report the probability of inducing SWDs during CT-DBS in awake mice. METHODS: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording EEG. We titrated stimulation current by gradually increasing it at each frequency until an SWD appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused an SWD during titration. RESULTS: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused SWDs at currents lower than the titrated current, at currents as low as 20 uA. CONCLUSION: Our study found a small but significant probability of inducing SWDs even after titration and at relatively low currents. EEG should be closely monitored for SWDs when performing CT-DBS in both research and clinical settings.

Mechanical properties and degree of conversion of resin-based core build-up materials and short fiber-reinforced flowable resin-based composite.

To evaluate the degree of conversion (DC), surface hardness (SH), and flexural strength (FS) of resin-based core build-up materials. Core build-up materials used were: MultiCore Flow (MCF); Activa (ACT); Core-X Flow (CXF); and everX flow (EVX), and DC, SH and FS were measured. An increase of DC was identified for all materials post-cure, except for EVX. The DC change percentage ranged from 5%-33%, and EVX was displayed the greatest DC rate. All materials displayed an SH increase after 30 days and the greatest increase was observed in ACT. At 1 h, the SH of EVX and CXF was different from the other materials. At 30 days, MCF displayed the greatest SH. All materials displayed an increase in their FS after 30 days except for EVX, and ranging 3%-36% were noticed. Differences observed between materials, thus clinician should be acquainted mechanical properties of these materials to ensure the success of the restorations.

The 3D-printed shell complete denture technique: Simplifying prosthodontic diagnosis prior to implant planning.

Traditionally, artificial teeth arrangements or the definitive complete dentures are used to establish important prosthodontic parameters such as the occlusal plane orientation, vertical dimension, and the incisal edge position. The relationship of these elements with the underlying bony structures is commonly evaluated using advanced planning protocols such as the dual scan technique. This technique article presents an uncomplicated alternative approach to establish these parameters intraorally using a 3D-printed shell complete denture generated from a 3D scan of the patient's existing complete denture.

Review of Explosive Contamination and Bioremediation: Insights from Microbial and Bio-Omic Approaches.

Soil pollution by TNT(2,4,6-trinitrotoluene), RDX(hexahydro-1,3,5-trinitro-1,3,5-triazacyclohexane), and HMX(octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), resulting from the use of explosives, poses significant challenges, leading to adverse effects such as toxicity and alteration of microbial communities. Consequently, there is a growing need for effective bioremediation strategies to mitigate this damage. This review focuses on Microbial and Bio-omics perspectives within the realm of soil pollution caused by explosive compounds. A comprehensive analysis was conducted, reviewing 79 articles meeting bibliometric criteria from the Web of Science and Scopus databases from 2013 to 2023. Additionally, relevant patents were scrutinized to establish a comprehensive research database. The synthesis of these findings serves as a critical resource, enhancing our understanding of challenges such as toxicity, soil alterations, and microbial stress, as well as exploring bio-omics techniques like metagenomics, transcriptomics, and proteomics in the context of environmental remediation. The review underscores the importance of exploring various remediation approaches, including mycorrhiza remediation, phytoremediation, bioaugmentation, and biostimulation. Moreover, an examination of patented technologies reveals refined and efficient processes that integrate microorganisms and environmental engineering. Notably, China and the United States are pioneers in this field, based on previous successful bioremediation endeavors. This review underscores research's vital role in soil pollution via innovative, sustainable bioremediation for explosives.

Verifying the seating of a 3D-printed removable die using elastomeric matrices: A dental technique.

Computer-aided design and computer-aided manufacturing systems enable digital designing and 3-dimensional (3D) printing of definitive casts with removable dies. However, the fit of the removable dies should be without interferences for their accurate positioning in the cast. Given that the accuracy of additive manufacturing depends on design- and manufacturing-related factors, verifying the accuracy of the position of 3D-printed removable dies in their cast is essential to fabricate positionally accurate definitive prostheses, which would enable minimal or no laboratory and clinical adjustments. This dental technique article presents a straightforward approach to verify the seating of a 3D-printed removable die by using verification matrices made of a polyvinylsiloxane interocclusal registration material.

The association between county-level mental health provider shortage areas and suicide rates in the United States during the COVID-19 pandemic.

OBJECTIVE: Prior literature has shown that mental health provider Health Professional Shortage Areas (MHPSAs) experienced a greater increase in suicide rates compared to non-shortage areas from 2010 to 2018. Although suicide rates have been on the rise, rates have slightly decreased during the COVID-19 pandemic. This study sought to characterize the differences in suicide rate trends during the pandemic by MHPSA status. METHOD: We used generalized estimating equation regression to test the associations between MHPSA status and suicide rates from 2018 to 2021. Suicide deaths were obtained from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research. RESULTS: MHPSA status was associated with higher suicide rates (adjusted IRR:1.088 [95% CI, 1.024-1.156]). Furthermore, there was a significant interaction between MHPSA status and year (adjusted IRR:1.056 [95% CI, 1.022-1.091]), such that suicide rates did not significantly change among MHPSAs but slightly decreased among non-MHPSAs from 2018 to 2021. CONCLUSIONS: During the COVID-19 pandemic, there was a slight decrease in suicide rates among non-MHPSAs, while those with shortages experienced no significant changes in suicide rates. It will be important to closely monitor MHPSAs as continued at-risk regions for suicide as trendlines return to their pre-pandemic patterns.

Early Detection and Diagnostic Approach Through Automated Hematological Analysis for Plasma Cell Leukemia.

Plasma cell leukemia (PCL) is a clinically aggressive variant of multiple myeloma, characterized by a high burden of circulating plasma cells, necessitating swift and accurate diagnosis due to its poor prognosis. The conventional diagnostic criteria, including the recent recommendation by the International Myeloma Working Group (IMWG) of > 5% circulating plasma cells as positive, have evolved over time. In this context, we present a detailed case report that underscores the pivotal role of the ADVIA 2120 automated hematology counter in detecting plasma cells through cytogram analysis, along with the significance of routine peripheral blood smear analysis and the utility of a large unstained cells (LUCs) threshold of > 4.5% as an indicator for PCL. The case involves a 64-year-old patient with relapsed multiple myeloma and stable paraprotein levels who experienced sudden renal impairment. In this case report, we highlight how ADVIA analysis and cytochemistry assisted in the diagnosis, and further explore ADVIA's utility in this challenging leukemia.

Impact of selenization with NaCl treatment on the physical properties and solar cell performance of crack-free Cu(In,Ga)Se2 microcrystal absorbers.

In this study, we developed an ink using hexanethiol and Cu(In,Ga)Se2 microcrystals (CIGSe MCs) to make thin films via doctor blade coating. Besides, crack-free thin films were obtained by optimizing CIGSe MC powder concentration and annealing temperature. Subsequently, single-step selenization was performed with and without sodium chloride (NaCl) surface treatment by carefully tuning the temperature. A crack-free surface with densely packed grains was obtained at 500 °C after NaCl treatment. Moreover, the structural parameters of the thin film (annealed at 350 °C) were significantly modified via selenization with NaCl at 500 °C. For instance, the FWHM of the prominent (112) plane reduced from 1.44° to 0.47°, the dislocation density minimized from 13.10 to 1.40 × 1015 lines per m2, and the microstrain decreased from 4.14 to 1.35 × 10-3. Remarkably, these thin films exhibited a high mobility of 26.7 cm2 V-1 s-1 and a low resistivity of 0.03 Ω cm. As a proof of concept, solar cells were engineered with a device structure of SLG/Mo/CIGSe/CdS/i-ZnO/Al-ZnO/Ag, wherein a power conversion efficiency (PCE) of 5.74% was achieved with exceptional reproducibility. Consequently, the outcomes of this investigation revealed the impact of selenization temperature and NaCl treatment on the physical properties and PCE of hexanethiol-based crack-free CIGSe MC ink-coated absorbers, providing new insights into the groundwork of cost-effective solar cells.

Expediting the Rehabilitation of Severely Resorbed Ridges Using a Combination of CAD-CAM and Analog Techniques: A Case Report.

With the life expectancy increasing, there is a growing need for prosthetic dental treatments to restore the oral health, function, and quality of life of edentulous patients. Presently, only a few articles are available describing the oral rehabilitation of patients with severely resorbed ridges with milled complete dentures. This clinical case report provides a straightforward protocol consisting of a combination of analog and digital techniques for the rehabilitation of edentulous patients with severely resorbed ridges with milled fixed and removable complete dentures. This technique permits the minimization of the number of appointments, improves patient comfort, allows for the digital archiving of important clinical data, and permits the manufacture of prostheses with improved mechanical properties. These favorable outcomes were achieved by using the patient's existing PMMA complete denture as a custom tray for a final impression with light-bodied Polyvinylsiloxane. Subsequently, the resulting models were digitized, and a digital complete denture was designed and manufactured in an expedited manner using CAD-CAM techniques. Therefore, this case report highlights the potential of CAD/CAM technology to predictably restabilize oral functions and improve patients' quality of life.

Solar photovoltaic panel production in Mexico: A novel machine learning approach.

This study examines the potential for widespread solar photovoltaic panel production in Mexico and emphasizes the country's unique qualities that position it as a strong manufacturing candidate in this field. An advanced model based on artificial neural networks has been developed to predict solar photovoltaic panel plant metrics. This model integrates a state-of-the-art non-linear programming framework using Pyomo as well as an innovative optimization and machine learning toolkit library. This approach creates surrogate models for individual photovoltaic plants including production timelines. While this research, conducted through extensive simulations and meticulous computations, unveiled that Latin America has been significantly underrepresented in the production of silicon, wafers, cells, and modules within the global market; it also demonstrates the substantial potential of scaling up photovoltaic panel production in Mexico, leading to significant economic, social, and environmental benefits. By hyperparameter optimization, an outstanding and competitive artificial neural network model has been developed with a coefficient of determination values above 0.99 for all output variables. It has been found that water and energy consumption during PV panel production is remarkable. However, water consumption (33.16 × 10-4 m3/kWh) and the emissions generated (1.12 × 10-6 TonCO2/kWh) during energy production are significantly lower than those of conventional power plants. Notably, the results highlight a positive economic trend, with module production plants generating the highest profits (35.7%) among all production stages, while polycrystalline silicon production plants yield comparatively lower earnings (13.0%). Furthermore, this study underscores a critical factor in the photovoltaic panel production process which is that cell production plants contribute the most to energy consumption (39.7%) due to their intricate multi-stage processes. The blending of Machine Learning and optimization models heralds a new era in resource allocation for a more sustainable renewable energy sector, offering a brighter, greener future.

Enhancing Prostate Tumor Biobanking Reliability with Improved Sampling Technique and Histological Characterization.

Acquiring fresh and well-characterized tumor tissue samples is critical for conducting high-quality "omics" studies. However, it can be particularly challenging in the context of prostate cancer (PC) due to the unique nature of this organ and the high heterogeneity associated with this tumor. On the other hand, histopathologically characterizing samples before their storage without causing significant tissue alterations is also an intriguing challenge. In this context, we present a new method for acquiring, mapping, characterizing, and micro-dissecting resected prostate tissue based on anatomopathological criteria. Unlike previously published protocols, this method reduces the time required for histopathological analysis of the prostate specimen without compromising its structure, which is crucial for assessing surgical margins. Furthermore, it enables the delineation and micro-macro dissection of fresh prostate tissue samples, with a focus on histological tumor areas defined by pathological criteria such as Gleason score, precursor lesions (high-grade prostatic intraepithelial neoplasia - PIN), and inflammatory lesions (prostatitis). These samples are then stored in a Biobank for subsequent research analyses.

First report of Pectobacterium brasiliense causing banana soft rot in Ecuador.

Banana (Musa spp.) is the most economically important crop in Ecuador, with exports representing 35% of the agricultural GDP of the country. It covers 230,000 hectares, mostly concentrated in three coastal provinces, Guayas, Los Ríos, and El Oro. Between July and September 2022, disease symptomatic banana cv. Williams plants were observed in commercial plantations located in two parishes in the province of Guayas (Naranjito and Lorenzo de Garaicoa) and one parish in the province of Santo Domingo de los Tsáchilas (La Concordia), with an incidence that ranged from 5% to 15%. Symptoms included soft rot of the pseudostem and rhizome decay, characterized by a fetid odor. Three symptomatic pseudostems from each location were collected, washed with running water to remove any debris, and dried with absorbent paper. From the lesion of each pseudostem, seven pieces of 2 cm² were taken, surface-sterilized, and macerated in 9 ml of sterile peptone water (0.1% w/v). The macerate was diluted three fold in sterile water, plated on nutrient agar, and incubated at 30°C for 24 h. Eight randomly picked colonies, with convex elevation and creamy white color, were isolated on nutrient agar. Each of the bacterial isolates was biochemically profiled by the Biolog system (Biolog Inc., USA) and identified as Pectobacterium. Three isolates, one from each parish (FP220416, FP220694, and FP220904), were selected for testing Koch's postulates and further identification. Sequences from fragments of the 16S, dnaA, gapA and gyrB genes were obtained from these isolates, following the protocols used by Dobhal et al. (2020) and Boluk et al. (2020), showing 98.1-99.0%, 98.2%, 99.7-99.8%, and 98.4-98.9% identitity, respectively, with sequences from the P. brasiliense type strain LMG_21371 (Acc. number JQOE00000000). The obtained sequences were deposited in GenBank with the following accession numbers: OR392417, OR371545,OR371546, OR727281, OR727282, and OR739074-OR739080. Using BEAST v.1.10.4 (Suchard et al.,2018), a bayesian multilocus phylogenetic tree was built with multiple sequence alignments of dnaA, gapA, ang gyrB from 22 P. brasiliense isolates and 2 P. aquaticum isolates used as outgroup. The phylogenetic analysis showed that the Ecuadorian isolates cluster with P. brasiliense BF20, isolated from Opuntia ficus-indica in México and are closely related with the type strain. Pathogenicity tests were conducted through syringe infiltration with 1 ml of 1 × 10^8 CFU ml-1 bacterial suspensions. Each of the three characterized isolates were inoculated into the pseudostems of five healthy 4-month-old banana plants of the Williams cultivar. Negative control plants were infiltrated with sterile distilled water. The plants were incubated at 25°C and 74% relative humidity. Black lesions started to appear 11 days after inoculation and 5 weeks after inoculation plants showed clear symptoms of soft rot of the pseudostem, including fetid odor associated with plant tissue decomposition. Control plants remained symptom-free. Bacteria were re-isolated only from symptomatic pseudostems and identified as P. brasiliense with specific primers Pb1F and Pb1R. Soft rot of banana caused by different enterobacteria including Dickeya zeae, Erwinia carotovora, and Erwinia chrysanthemi hasve been previously reported (Jingxin et al. 2022, Arun et al. 2012, Loganathan, et al. 2019). This is the first report of P. brasiliense causing soft rot of banana in Ecuador, the biggest exporter of the fruit in the world.

Positional trueness of three removable die designs with different root geometries manufactured using stereolithographic 3D printing.

STATEMENT OF PROBLEM: Three-dimensional (3D) printed casts are a suitable alternative to dental stone casts. Contemporary dental design computer programs permit designing definitive casts with removable dies with different root geometries and retention mechanisms. Studies on the positional trueness of 3D-printed removable dies with different root geometries are lacking. PURPOSE: The purpose of this in vitro study was to investigate the 3D displacements of three 3D-printed removable die designs with different root geometries. MATERIAL AND METHODS: The digital file of a dental stone alveolar cast with root-form removable dies (MOD UJ IV Fixed Prosthetics; Ivoclar AG) was used as a reference to create 3 removable die and alveolar cast designs (Root Form, RF; Conical, CON; Cylindric, CYL) with different root geometries in 2 dental design computer programs (DentalCAD 3.1 Rijeka; exocad; GmbH; InLab CAD 22.0; Dentsply Sirona). 3 equidistant Ø1-mm spheres (C, Cervical; M, Middle; O, Occlusal) were designed on the buccal surface of the coronal portion of the removable die to evaluate their displacement. A total of 45 alveolar casts with 45 removable dies were fabricated using a stereolithographic 3D printer (Form 3; Formlabs); each die group consisted of 15 specimens. After fabrication and postprocessing, the specimens were scanned, and their digital files were analyzed in a metrology-grade computer program to evaluate the displacement of the removable dies with respect to the position of the die in the master reference file. Subsequently, the data were analyzed using a 3-way analysis of variance (ANOVA) followed by step-down Bonferroni-corrected pairwise comparisons (α=.05). RESULTS: Two statistically significant 2-way interactions were detected between the independent variables, die design and direction (P<.001), and location and direction (P<.001). The post hoc analysis identified significant differences between the displacement values of RF and CYL (P<.001) and RF and the CON (P<.001) designs on the Y axis. The measured displacements were statistically different between the C and O locations on the Y axis (P=.001) and the M and O locations on the Z axis (P=.006). CONCLUSIONS: The root geometry of a 3D-printed removable die and alveolar cast can affect seating, and variable degrees of tipping of the removable die can be seen. The seating and congruence of the removable die with the interocclusal space and relationships observed intraorally should be confirmed before adjusting indirect restorations.

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model.

Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.