Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Stimulus of Work Function on Electron Transfer Process of Intermetallic Nickel-Antimonide Toward Bifunctional Electrocatalyst for Overall Water Splitting.

Engineering the intermetallic nanostructures as an effective bifunctional electrocatalyst for hydrogen and oxygen evolution reactions (HER and OER) is of great interest in green hydrogen production. However, a few non-noble metals act as bifunctional electrocatalysts, exhibiting terrific HER and OER processes reported to date. Herein the intermetallic nickel-antimonide (Ni─Sb) dendritic nanostructure via cost-effective electro-co-deposition method is designed and their bifunctional electrocatalytic property toward HER and OER is unrevealed. The designed Ni─Sb delivers a superior bifunctional activity in 1 m KOH electrolyte, with a shallow overpotential of ≈119 mV at -10 mA for HER and ≈200 mV at 50 mA for OER. The mechanism behind the excellent bifunctional property of Ni─Sb is discussed via "interfacial descriptor" with the aid of Kelvin probe force microscopy (KPFM). This study reveals the rate of electrocatalytic reaction depends on the energy required for electron and proton transfer from the catalyst's surface. It is noteworthy that the assembled Ni─Sb-90 electrolyzer requires only a minuscule cell voltage of ≈1.46 V for water splitting, which is far superior to the art of commercial catalysts.

GV1001 modulates neuroinflammation and improves memory and behavior through the activation of gonadotropin-releasing hormone receptors in a triple transgenic Alzheimer's disease mouse model.

GV1001 protects neural cells from amyloid-ß (Aß) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Aß oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro, GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Aß oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways.

Bursal acromial resurfacing improves shoulder biomechanics in a cadaveric model of massive rotator cuff tear.

PURPOSE: To investigate the effectiveness of bursal acromial resurfacing (acromiograft) on acromiohumeral distance, subacromial contact area, and pressure in a cadaveric model of massive rotator cuff tear. METHODS: Eight fresh-frozen cadaveric shoulders were tested using a customized shoulder testing system. Humeral head translation, subacromial contact pressure, and the subacromial contact area were evaluated across four conditions: (1) intact shoulder; (2) simulated massive rotator cuff tear; (3) 3-mm acromiograft condition; (4) 6-mm acromiograft condition. The acromiografts were simulated using Teflon and a reported technique. The values were measured at 0°, 20°, and 40° abduction and 0°, 30°, 60°, and 90° external rotation (ER) for each abduction status. RESULTS: Compared with a massive cuff tear, the 6-mm acromiograft significantly reduced the superior translation of the humeral head at all abduction/ER angles (P<0.05). The 3-mm acromiograft also decreased superior translation of the humeral head compared to massive cuff tear, but not all differences were significant. The 3- and 6-mm acromiografts significantly decreased the subacromial contact pressure and increased the subacromial contact area in almost all positions (P<0.05). The 3-mm acromiograft maintained biomechanical properties similar to the intact condition, whereas the 6-mm acromiograft increased the contact area. CONCLUSIONS: This biomechanical study demonstrated that both 3- and 6- mm acromiografts using Teflon in a cadaveric model of a massive cuff tear resulted in recentering of the superiorly migrated humeral head, increased the subacromial contact area, and decreased the subacromial contact pressure. The 3- mm graft was sufficient for achieving the intended therapeutic effects. CLINICAL RELEVANCE: The acromiograft can normalize altered biomechanics and may aid the treatment of massive cuff tears. As grafting the acromion's undersurface is new with limited clinical outcomes, further observation is crucial. Using Teflon instead of ADM allograft for bursal acromial resurfacing could yield different results, requiring careful interpretation.

Varus-valgus alignment of humeral short stem in reverse total shoulder arthroplasty: does it really matter?

BACKGROUND: The utilization of short humeral stems in reverse total shoulder arthroplasty has gained attention in recent times. However, concerns regarding the risk of misalignment during implant insertion are associated with their use. METHODS: Eight fresh-frozen cadaveric shoulders were prepared for dissection and biomechanical testing. A bespoke humeral implant was fabricated to facilitate assessment of neutral, varus, and valgus alignments using a single stem, and 10° was established as the maximum permissible angle for misalignments. Shift in humerus position and changes in deltoid length attributable to misalignments relative to the neutral position were evaluated using a Microscribe 3DLx system. The impingement-free range of motion, encompassing abduction, adduction, internal rotation, and external rotation (ER), was gauged using a digital goniometer. The capacity for abduction was evaluated at maximal abduction angles under successive loading on the middle deltoid. A specialized traction system coupled with a force transducer was employed to measure anterior dislocation forces. RESULTS: Relative to the neutral alignment, valgus alignment resulted in a more distal (10.5 ± 2.4 mm) and medial (8.3 ± 2.2 mm) translation of the humeral component, whereas the varus alignment resulted in the humerus shifting more superiorly (11.2 ± 1.3 mm) and laterally (9.9 ± 0.9 mm) at 0° abduction. The valgus alignment exhibited the highest abduction angle than neutral alignment (86.2°, P < .001). Conversely, the varus alignment demonstrated significantly higher adduction (18.4 ± 7.4°, P < .001), internal rotation (68.9 ± 15.0°, P = .014), and ER (45.2 ± 10.5°, P = .002) at 0° abduction compared to the neutral alignments. Anterior dislocation forces were considerably lower (23.8 N) in the varus group compared to the neutral group at 0°ER (P = .047). Additionally, abduction capability was markedly higher in varus alignment at low deltoid loads than the neutral alignment (5N, P = .009; 7.5 N, P = .007). CONCLUSIONS: The varus position enhances rotational range of motion (ROM) but increases instability, while the valgus position does not significantly impact ROM or instability compared to the neutral position.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

Chitosan-GSNO nanoparticles: a positive modulator of drought stress tolerance in soybean.

BACKGROUND: Chitosan biopolymer is an emerging non-toxic and biodegradable plant elicitor or bio-stimulant. Chitosan nanoparticles (CSNPs) have been used for the enhancement of plant growth and development. On the other hand, NO is an important signaling molecule that regulates several aspects of plant physiology under normal and stress conditions. Here we report the synthesis, characterization, and use of chitosan-GSNO nanoparticles for improving drought stress tolerance in soybean. RESULTS: The CSGSNONPs released NO gas for a significantly longer period and at a much lower rate as compared to free GSNO indicating that incorporation of GSNO in CSNPs can protect the NO-donor from rapid decomposition and ensure optimal NO release. CS-GSNONPs improved drought tolerance in soybean plants reflected by a significant increase in plant height, biomass, root length, root volume, root surface area, number of root tips, forks, and nodules. Further analyses indicated significantly lower electrolyte leakage, higher proline content, higher catalase, and ascorbate peroxidase activity, and reduction in MDA and H2O2 contents after treatment with 50 µM CS-GSNONPs under drought stress conditions. Quantitative real-time PCR analysis indicated that CS-GSNONPs protected against drought-induced stress by regulating the expression of drought stress-related marker genes such as GmDREB1a, GmP5CS, GmDEFENSIN, and NO-related genes GmGSNOR1 and GmNOX1. CONCLUSIONS: This study highlights the potential of nano-technology-based delivery systems for nitric oxide donors to improve plant growth, and development and protect against stresses.

GV1001 Inhibits the Severity of the Ligature-Induced Periodontitis and the Vascular Lipid Deposition Associated with the Periodontitis in Mice.

GV1001, a 16 amino acid peptide derived from the catalytic segment of human telomerase reverse transcriptase, was developed as an anti-cancer vaccine. Subsequently, it was found to exhibit anti-inflammatory and anti-Alzheimer's disease properties. Periodontitis is a risk factor for a variety of systemic diseases, including atherosclerosis, a process in which chronic systemic and vascular inflammation results in the formation of plaques containing lipids, macrophages, foam cells, and tissue debris on the vascular intima. Thus, we investigated the effect of GV1001 on the severity of ligature-induced periodontitis, vascular inflammation, and arterial lipid deposition in mice. GV1001 notably reduced the severity of ligature-induced periodontitis by inhibiting gingival and systemic inflammation, alveolar bone loss, and vascular inflammation in wild-type mice. It also significantly lowered the amount of lipid deposition in the arterial wall in ApoE-deficient mice receiving ligature placement without changing the serum lipid profile. In vitro, we found that GV1001 inhibited the Receptor Activator of NF-κB ligand (RANKL)-induced osteoclast formation and tumor necrosis factor-α (TNF-α)-induced phenotypic changes in endothelial cells. In conclusion, our study suggests that GV1001 prevents the exacerbation of periodontitis and atherosclerosis associated with periodontitis partly by inhibiting local, systemic, and vascular inflammation and phenotypic changes of vascular endothelial cells.

Electrospun Polymer-Derived Carbyne Supercapacitor for Alternating Current Line Filtering.

The filtering device is a vital component of electronic goods that rectifies ripples which occur upon converting alternating current (AC) to direct current (DC) and attenuates high-frequency noise during switching or voltage declines. Classical filtering devices suffer from low performance metrics and are bulky, limiting their use in modern electronic devices. The fabrication process of electrode materials for high-frequency symmetric supercapacitor (HFSSC) is complicated, hindering commercialization. Herein, for the first time, the design of a high-performance stand-alone carbyne film comprised of sp/sp2 -hybridized carbon as an electrode for AC filtering under a wide frequency range is reported. The carbyne film as HFSSC shows the ideal capacitive behavior at ultrahigh scan rate of 10 000 V s-1 with excellent linearity which is top among the reported AC line filter capacitor. The carbyne HFSSC exhibits a high energy density of 703.25 µF V2  cm-2 at 120 Hz, which is superior to that of current commercial electrolytic filters and many reported AC line supercapacitors. As a proof of concept, a carbyne device is implemented in a real time AC to DC adaptor that demonstrates excellent filtering performance at high frequencies.

Regulation of Charge Carrier Dynamics in ZnO Microarchitecture-Based UV/Visible Photodetector via Photonic-Strain Induced Effects.

A feasible, morphological influence on photoresponse behavior of ZnO microarchitectures such as microwire (MW), coral-like microstrip (CMS), fibril-like clustered microwire (F-MW) grown by one-step carrier gas/metal catalyst "free" vapor transport technique is reported. Among them, ZnO F-MW exhibits higher photocurrent (IPh ) response, i.e., IPh/ZnO F-MW > IPh/ZnO CMS > IPh/ZnO MW . The unique structural alignment of ZnO F-MW has enhanced the IPh from 14.2 to 186, 221, 290 µA upon various light intensities such as 0 to 6, 11, 17 mW cm-2 at λ405 nm . Herein, the nature of the as-fabricated ZnO photodetector (PD) is also demonstrated modulated by tuning the inner crystals piezoelectric potential through the piezo-phototronic effect. The IPh response of PD decreases monotonically by introducing compressive strain along the length of the device, which is due to the synergistic effect between the induced piezoelectric polarization and photogenerated charge carriers across the metal-semiconductor interface. The current behavior observed at the two interfaces acting as the source (S) and drain (D) is carefully investigated by analyzing the Schottky barrier heights (ΦSB ). This work can pave the way for the development of geometrically modified strain induced performances of PD to promote next generation self-powered optoelectronic integrated devices and switches.

Influence of Morphology and Common Oxidants on the Photocatalytic Property of ß-SnWO4 Nanoparticles.

In this paper, we report a simple, cost effective and surfactant-free method for synthesizing different morphology of ß-SnWO4 with irregular, spherical, flake-like and leaf-like structures by using sonochemical method followed by calcination. A well dispersed and highly crystalline ß-SnWO4 crystallites with various sizes have been prepared. The samples were characterized by using X-ray diffraction (XRD), scanning electron microscope (SEM), UV-vis spectroscopy, particle size and Zeta potential analyser. The SEM images reveal the successful preparation of an irregular, spherical, flake-like and leaf-like structure of ß-SnWO4. The absorption maximum of as-prepared different structures of ß-SnWO4 was observed in visible region. The degradation efficiency was found to be increased in leaf-like structures compared to irregular, spherical and flake-like structures of ß-SnWO4. Further, an enhanced photocatalytic effect was observed in leaf-like ß-SnWO4 nanoparticles while the common oxidants such as peroxomonosulphate (PMS), peroxodisulphate (PDS) and hydrogen peroxide (H2O2) were added. The degradation efficiency of these oxidants was found in the order of PMS > H2O2 > PDS. Generally these oxidants act as electron scavengers. From our experimental results, it is found that maximum efficiency of 93% was achieved when PMS was added. This shows the vital role of common oxidants in photocatalytic characteristics and their future applications in waste-water treatment.

Unravelling the Bi-Functional Electrocatalytic Properties of {Mo72Fe30} Polyoxometalate Nanostructures for Overall Water Splitting Using Scanning Electrochemical Microscope and Electrochemical Gating Methods.

This study reports the use of Keplerate-type {Mo72Fe30} polyoxometalate (POMs) nanostructures as a bi-functional-electrocatalyst for HER and OER in an alkaline medium with a lower overpotential (135 mV for HER and 264 mV for OER), and excellent electrochemical stability. The bi-functional catalytic properties of {Mo72Fe30} POM are studied using a scanning electrochemical microscope (SECM) via current mapping using substrate generation and tip collection mode. Furthermore, the bipolar nature of the {Mo72Fe30} POM nano-electrocatalysts is studied using the electrochemical gating via simultaneous monitoring of the electrochemical (cell) and electrical ({Mo72Fe30} POM) signals. Next, a prototype water electrolyzer fabricated using {Mo72Fe30} POM electrocatalysts showed they can drive 10 mA cm-2 with a low cell voltage of 1.62 V in lab-scale test conditions. Notably, the {Mo72Fe30} POM electrolyzers' performance assessment based on recommended conditions for industrial aspects shows that they require a very low overpotential of 1.89 V to drive 500 mA cm-2, highlighting their promising candidature toward clean-hydrogen production.

GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.

GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aß) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. This study aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer's disease (3xTg-AD) mice. GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aß1-42), phosphorylated tau, volume of dentate gyrus, ß-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aß1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated ß-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.

Investigation of transfer characteristics of high performance graphene flakes.

In this article, we attempted a study on field effect transport characteristics of graphene flakes. These graphene flakes were exfoliated by mechanical peeling-off technique and the electrical contacts were patterned by photo-lithographic method. Graphene devices have shown better transfer characteristics which was obtained even in low-voltage (< 5 V). Back-gated graphene transistors were patterned on oxidized silicon wafers. A clear n-type to p-type transition at Dirac point and higher electron drain-current modulation in positive back-gate field with current minimum (the Dirac point) were observed at V(GS) = -1.7 V. The carrier mobility was determined from the measured transconductance. The transconductance of the graphene transistors was observed as high as 18.6 microS with a channel length of 68 microm. A maximum electron mobility of 1870 +/- 143 cm2/V x s and hole mobility of 1050 +/- 35 cm2/V x s were achieved at a drain bias 2.1 V which are comparatively higher values among reported for mechanically exfoliated graphene using lithographic method. The fabricated devices also sustained with high-current density for 40 hr in continuous operation without any change in device resistance, which could be applied for robust wiring applications.

ZnO piezoelectric fine wire gated graphene oxide field effect transistor.

Here we report the fabrication and characteristics of graphene oxide (GO) field effect transistor gated with piezopotential of ZnO fine wires on a flexible substrate. The FET device consists of GO thin film on the bottom and ZnO piezoelectric fine wire (PFW) on the top. In the FET device the GO serves as a carrier transport channel and ZnO PFW acts as a gate. When the substrate is bent, a piezopotential is generated in the ZnO PFW. The piezopotential created by the strain in the ZnO PFW was used to control the carrier transport in the GO channel. This device demonstrates the application of piezoelectric ZnO PFW for creating the gating effect on the semiconducting performance of GO film.

Untethered Magnetic Soft Robot with Ultra-Flexible Wirelessly Rechargeable Micro-Supercapacitor as an Onboard Power Source.

Soft robotics has developed rapidly in recent years as an emergent research topic, offering new avenues for various industrial and biomedical settings. Despite these advancements, its applicability is limited to locomotion and actuation due to the lack of an adequate charge storage system that can support the robot's sensory system in challenging conditions. Herein, an ultra-flexible, lightweight (≈50 milligrams), and wirelessly rechargeable micro-supercapacitor as an onboard power source for miniaturized soft robots, capable of powering a range of sensory is proposed. The simple and scalable direct laser combustion technique is utilized to fabricate the robust graphene-like carbon micro-supercapacitor (GLC-MSC) electrode. The GLC-MSC demonstrates superior areal capacitance (8.76 mF cm-2 ), and maintains its original capacitance even under extreme actuation frequency (1-30 Hz). As proof of conceptthe authors fabricate a fully integrated magnetic-soft robot that shows outstanding locomotion aptitude and charged wirelessly (up to 2.4 V within 25s), making it an ideal onboard power source for soft robotics.

Topochemically prepared tungsten disulfide nanostructures as a novel pseudocapacitive electrode for high performance supercapacitor.

The topochemical preparation of nanostructured materials (NMs) has received significant attention in recent years due to the exceptional electrochemical properties exhibited by the resulting NMs. This work focuses on the preparation of two-dimensional tungsten di-sulfide (WS2) nanostructures through the topochemical conversion of tungsten trioxide (WO3) nanostructures and also evaluates their potential applications as electrode materials for supercapacitors (SCs). The X-ray diffraction and photoelectron studies conducted in this research reveal the conversion of hexagonal WO3 into hexagonal WS2 nanosheets, accompanied by changes in oxidation states. The FE-SEM and HR-TEM studies confirm the formation of WS2 in the sheet-like morphologies with lateral dimensions of 100 × 100 nm. The electrochemical investigation, using techniques such as CV, galvanostatic CD, and EIS, confirmed the presence of intercalation pseudocapacitance in the WS2 electrode, with a higher electrode-specific-capacitance (260 F g-1) than that of WO3 electrode. The WS2 symmetric SC delivered high device capacitance (59.17 F g-1), energy density (8.21 Wh kg-1) and power density (3,750 W kg-1) with better cyclic stability over 5000 cycles. These experimental findings show that the topochemically synthesized WS2as novel supercapacitor electrodes might be useful for the advancement of future-generation energy storage devices.

Retrospective Analysis of the Clinical Characteristics of Patients with Breast Cancer Treated with Telomerase Peptide Immunotherapy Combined with Cytotoxic Chemotherapy.

Purpose: Telomerase activation, a critical step in cancer progression, occurs in approximately 95% of breast cancer cases. Telomerase is an attractive therapeutic target for breast cancer owing to its unique expression pattern. GV1001, a telomerase-derived peptide, is loaded onto human leukocyte antigen (HLA) class II antigen-presenting cells and binds to CD4+ T cell activating immune responses. This study aimed to evaluate the effectiveness and safety of co-administration of GV1001 and cytotoxic chemotherapy in patients with heavily-treated metastatic breast cancer. Patients and methods: We analyzed 63 patients with breast cancer who received both GV1001 and cytotoxic chemotherapy. The GV 1001 administration methods involves 0.56 mg intradermal injection three times during the first week, one time at weeks 2, 3, 4, and 6, and then once every 28 days. The primary endpoint of this study was quality of life according to EORTC QLO-C30 and EQ-5D, while the secondary endpoint was the antitumor response according to RECIST 1.1, progression-free survival, overall survival, and toxicity profile. Results: In 34 patients with HR+ breast cancer evaluable for tumor response, the disease control rate (DCR) and overall response rate (ORR) were 58.8% and 26.4%, respectively. The DCR and ORR were 66.6% and 28.5% in 21 patients with HER-2+ and 50% and 25% in patients with triple-negative breast cancer (TNBC), respectively. The median progression free survival was 10.4, 8.7, and 5.6 months in HR+, HER-2+, TNBC, respectively. The overall survival was 19.7, 13.2, and 9.4 months for patients with HR+, HER-2+, and TNBC, respectively. Most patients had an improved quality of life with statistically significant differences in some variables. The patients in this study experienced no additional toxicities other than the cytotoxic chemotherapy-associated side effects. Conclusion: GV1001 is a relatively safe anticancer vaccine for patients with heavily-treated breast cancer and can to improve the quality of life.

Effects of GV1001 on Language Dysfunction in Patients With Moderate-to-Severe Alzheimer's Disease: Post Hoc Analysis of Severe Impairment Battery Subscales.

Background and Purpose: The efficacy and safety of GV1001 have been demonstrated in patients with moderate-to-severe Alzheimer's disease (AD). In this study, we aimed to further demonstrate the effectiveness of GV1001 using subscales of the Severe Impairment Battery (SIB), which is a validated measure to assess cognitive function in patients with moderate-to-severe AD. Methods: We performed a post hoc analysis of data from a 6 month, multicenter, phase 2, randomized, double-blind, placebo-controlled trial with GV1001 (ClinicalTrials.gov, NCT03184467). Patients were randomized to receive either GV1001 or a placebo for 24 weeks. In the current study, nine subscales of SIB-social interaction, memory, orientation, language, attention, praxis, visuospatial ability, construction, and orientation to name- were compared between the treatment (GV1001 1.12 mg) and placebo groups at weeks 12 and 24. The safety endpoints for these patients were also determined based on adverse events. Results: In addition to the considerable beneficial effect of GV1001 on the SIB total score, GV1001 1.12 mg showed the most significant effect on language function at 24 weeks compared to placebo in both the full analysis set (FAS) and per-protocol set (PPS) (p=0.017 and p=0.011, respectively). The rate of adverse events did not differ significantly between the 2 groups. Conclusions: Patients with moderate-to-severe AD receiving GV1001 had greater language benefits than those receiving placebo, as measured using the SIB language subscale.