Complete Tolerance Research Articles

Whey Protein Supplementation Improves the Glycemic Response and May Reduce Non-Alcoholic Fatty Liver Disease Related Biomarkers in Women with Polycystic Ovary Syndrome (PCOS).

Polycystic ovary syndrome (PCOS) increases type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) with insulin resistance. We hypothesized that a 35 g whey preload would improve insulin sensitivity and glucose handling while reducing biomarkers associated with NAFLD. Twenty-nine age-matched women (CON = 15, PCOS = 14) completed oral glycemic tolerance tests following baseline (Day 0) as well as an acute (Day 1) and short-term whey supplementation (Day 7). Whey had an interaction effect on glucose (p = 0.02) and insulin (p = 0.03), with glucose remaining stable and insulin increasing with whey supplementation. Insulin sensitivity (p < 0.01) improved with whey associated with increased glucagon secretion (p < 0.01). Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) remained unchanged, but “day” had an effect on the AST:ALT ratio (p = 0.04), whereas triglycerides and sex hormone binding globulin overall were greater in the PCOS group (p < 0.05). Total cholesterol decreased in PCOS (by 13%) and CON (by 8%) (NS). HepG2 cells treated with plasma from participants before and after whey decreased lipid accumulation in the PCOS group after whey (p < 0.05). Whey provided an insulinogenic and glycemic homeostatic effect in women with PCOS with the potential to combat NAFLD-consequences.

Performance analysis of novel fault‐tolerant multilevel inverter with a pristine methodology for fast and exhaustive real‐time failure of switches

SummaryMultilevel inverter (MLI) provides a high power density, though the number of devices increases the chances of failures increases, reducing the reliability of power converter. It is essential to detect, isolate, and reconfigure the faults which arises in MLI. The research proposed here is capable of accomplishing the complete fault tolerance against single and multiple devices for both open circuit and short circuit faults. The control algorithm for operation of single‐pole‐double‐throw (SPDT) relays. This methodology is capable of completely preserving the normal operating condition in post‐fault condition also. The output voltage waveform matches by voltage sensors connected across load, and the controllers sense the faults originated from the variation in the look‐up‐table (LUT) and also categorize the nature of the faults. Field‐programmable gate array (FPGA)‐based controller sends a command signal through SPDT to isolate the faulty switches by redundant switches. In this way, the output power across the load is preserved. This research article also covers the comparative study that is made with the existing fault‐tolerant structures. The reliability comparison shows the better performance indices over conventional cascaded H‐bridge (CHB) inverter. The simulation and experimental results validate the effectiveness of control methodology to achieve complete fault tolerance.

ДІАГНОСТИЧНІ ПРЕДИКТОРИ ФОРМУВАННЯ ТОЛЕРАНТНОСТІ ПРИ ЕЛІМІНАЦІЙНІЙ ДІЄТІ У ДІТЕЙ З АЛЕРГІЄЮ ДО БІЛКІВ КОРОВ’ЯЧОГО МОЛОКА

Background. Cow's milk protein allergy is a topical issue in pediatrics. This disease affects 2-3% of young children. Methods. The study included 30 children with a confirmed cow’s milk protein allergy and a prescribed milk elimination diet. The children were observed for 36 months. The molecular profile was evaluated by detecting the major components of milk (Bos d 8, Bos d 5, Bos d 4), minor (Bos d 6), and cross-reactive with serum albumin (Fel d 2, Can f 3). Results. The study group included 46.7% of boys. The mean age of the subjects was 14.5±3.18 months. Nine of the 25 analyzed factors were identified in the course of our work by the method of logistic regression with progressive selection, which in combined action affect the formation of tolerance to cow's milk proteins in allergic children. There are three clinical examples of calculating the prediction of the complete tolerance development in the elimination diet in children with cow's milk protein allergy. Conclusions. Independent predictors that reduce the likelihood of the tolerance development in the elimination diet, have identified: skin test to milk, Bos d 8, Bos d 5, Bos d 4, Bos d 6. Independent predictors of the tolerance development in the elimination diet are: milk-specific IgE, total IgE, Fel d 2, Can f 3. Low probability of tolerance development by elimination therapy is a recommendation for prescribing treatment to a patient by specific oral tolerance induction.

RETRACTED: Whey protein preload enhances the active GLP-1 response and reduces circulating glucose in women with polycystic ovarian syndrome

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The article is a duplicate of a paper that has already been published in Nutrients: (Nutrients 2021, 13(7), 2451. https://doi.org/10.3390/nu13072451. Redundant publications overweigh the relative importance of published findings and distort the academic record of the authors. One of the conditions of submission of a paper for publication is therefore that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Ancestral transoceanic colonization and recent population reduction in a nonannual killifish from the Seychelles archipelago.

Whether freshwater fish colonize remote islands following tectonic or transoceanic dispersal remains an evolutionary puzzle. Integrating dating of known tectonic events with phylogenomics and current species distribution, we find that killifish species distribution is not explained by species dispersal by tectonic drift only. Investigating the colonization of a nonannual killifish (golden panchax, Pachypanchax playfairii) on the Seychelle islands, we found genetic support for transoceanic dispersal and experimentally discovered an adaptation to complete tolerance to seawater. At the macroevolutionary scale, despite their long-lasting isolation, nonannual golden panchax show stronger genome-wide purifying selection than annual killifishes from continental Africa. However, progressive decline in effective population size over a more recent timescale has probably led to the segregation of slightly deleterious mutations across golden panchax populations, which represents a potential threat for species preservation in the long term.

Site-Selective C8-Alkylation of Quinoline N-Oxides with Maleimides under Rh(III) Catalysis.

The site-selective modification of quinolines and their analogs has emerged as a pivotal topic in medicinal chemistry and drug discovery. Herein, we describe the rhodium(III)-catalyzed C8-alkylation of quinoline N-oxides with maleimides as alkylating agents, resulting in the formation of bioactive succinimide-containing quinoline derivatives. The reaction proceeds under mild conditions with complete functional group tolerance.

Natural History of IgE-Mediated Fish Allergy in Children

Fish allergy is not uncommon, especially in countries with high fish consumption, it can frequently be severe and may affect dietetic and lifestyle choices. Nevertheless, data on its clinical course and natural history are scarce. To describe the natural history of immunoglobulin E-mediated fish allergy and the potential differential reactivity to various fish species and identify prognostic markers in children with confirmed disease. Clinical history, specific immunoglobulin E, and skin prick tests to various fish were recorded in 126 children with confirmed immunoglobulin E-mediated fish allergy. Immunoglobulin E reactivity was also evaluated by immunoblotting. Eligible participants proceeded to a series of food challenges to tuna, swordfish, and codfish. In total, 234 challenges were performed. Fifty-eight children (9.7 ± 3.9 years) were included in the analysis. Age at first reaction was 0.5 to 5 years (median, 1.3 years). Thirteen children (22%) tolerated all fish tested, including cod, 1 to 14 years (mean, 8.2 ± 4.2 years) following their first reported reaction. Complete fish tolerance increased with age, ranging from 3.4% in preschool children to over 45% in adolescents (95% confidence interval, 26.3%-79.7%). Most children were able to tolerate swordfish (94%) and tuna (95%). Prechallenge specific immunoglobulin E to cod greater than 4.87 kUA/L was the best positive predictive marker for fish allergy persistence (94%), followed by skin prick tests to sardine greater than 6.5 mm (92%). A considerable proportion of fish-allergic children develop tolerance around adolescence. Most fish-allergic children can consume tuna and swordfish, which, thus, provide safe alternatives for a balanced diet.

Integrative transcriptomic and metabolomic analyses provide insight into the long-term submergence response mechanisms of young Salix variegata stems.

The mechanisms underlying long-term complete submergence tolerance in S. variegata involve enhanced oxidative stress responses, strengthened ethylene and ABA signaling, synthesis ofraffinose family oligosaccharides,unsaturated fatty acids, and specific stress-related amino acids. Salix variegata Franch. is a riparian shrub species that can tolerate long-term complete submergence; however, the molecular mechanisms underlying this trait remain to be elucidated. In this study, we subjected S. variegata plants to complete submergence for 60d and collected stems to perform transcriptomic and metabolomic analyses, as well as quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Results revealed that photosynthesis and the response to light stimulus were inhibited during submergence and recovered after desubmergence. Ethylene and abscisic acid (ABA) signaling could be important for the long-term submergence tolerance of S. variegata. Jasmonic acid (JA) signaling also participated in the response to submergence. Raffinose family oligosaccharides, highly unsaturated fatty acids, and specific stress-related amino acids accumulated in response to submergence, indicating that they may protect plants from submergence damage, as they do in response to other abiotic stressors. Several organic acids were produced in S. variegata plants after submergence, which may facilitate coping with the toxicity induced by submergence. After long-term submergence, cell wall reorganization and phenylpropanoid metabolic processes (the synthesis of specific phenolics and flavonoids) were activated, which may contribute to long-term S. variegata submergence tolerance; however, the detailed mechanisms require further investigation. Several transcription factors (TFs), such as MYB, continuously responded to submergence, indicating that they may play important roles in the responses and adaption to submergence. Genes related to oxidative stress tolerance were specifically expressed after desubmergence, potentially contributing to recovery of S. variegata plants within a short period of time.

Biochemical characterization and enhanced production of endoxylanase from thermophilic mould Myceliophthora thermophila.

Endoxylanase production from M. thermophila BJTLRMDU3 using rice straw was enhanced to 2.53-fold after optimization in solid state fermentation (SSF). Endoxylanase was purified to homogeneity employing ammonium sulfate precipitation followed by gel filtration chromatography and had a molecular mass of ~ 25kDa estimated by SDS-PAGE. Optimal endoxylanase activity was recorded at pH 5.0 and 60°C. Purified enzyme showed complete tolerance to n-hexane, but activity was slightly inhibited by other organic solvents. Among surfactants, Tweens (20, 60, and 80) and Triton X 100 slightly enhanced the enzyme activity. The Vmax and Km values for purified endoxylanase were 6.29µmol/min/mg protein and 5.4mg/ml, respectively. Endoxylanase released 79.08 and 42.95% higher reducing sugars and soluble proteins, respectively, which control after 48h at 60°C from poultry feed. Synergistic effect of endoxylanase (100U/g) and phytase (15U/g) on poultry feed released higher amount of reducing sugars (58.58mg/feed), soluble proteins (42.48mg/g feed), and inorganic phosphate (28.34mg/feed) in contrast to control having 23.55, 16.98, and 10.46mg/feed of reducing sugars, soluble proteins, and inorganic phosphate, respectively, at 60°C supplemented with endoxylanase only.

DETERMINATION OF FREQUENCY OF A NOVEL DIAGNOSTIC CATEGORY OF HYPERGLYCEMIA I.E. IMPAIRED RANDOM GLUCOSE IN PREVIOUSLY UNKNOWN PATIENTS OF PREDIABETES AND DIABETES MELLITUS

Objective: To determine the frequency of normoglycemia (NG), prediabetes and diabetes mellitus (DM) amongpatients having impaired random glucose (IRG) and establish the optimum cutoff of impaired random glucosefor the diagnosis of diabetes and prediabetes.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Armed Forces Institute of Pathology Rawalpindi and Combined Military HospitalQuetta, from Nov 2016 to Nov 2018.&#x0D; Methodology: Healthy individuals of both genders undergoing investigation for diabetes mellitus were enrolled through non probability consecutive sampling while patients with diabetes, pregnant, hospitalized, using concomitant medications (corticosteroids, immunosuppressive, chemotherapy) and those unable to complete oral glucose tolerance test (OGTT) were excluded. Random plasma glucose (RPG) was determined and patients having impaired random glucose underwent oral glucose tolerance test, analysis being done on ADVIA1800®using hexokinase methodology.&#x0D; Results: Among the 280 study participants, majority were female {156 (57.5%) vs 124 (44.3%) male}. Mean age in male and female patients was 33.625 ± 3.34 years vs 35.150 ± 2.79 years with p-value 0.50 while mean IRG was 7.12 ± 1.47 vs 6.90 ± 1.17 mmol/L respectively with p-value 0.16 (statistically insignificant). Oral glucose tolerance test results showed NG in 61.8% (173), prediabetes in 24.6% (69) while diabetes was found in 38 (13.6%) patients. Optimal impaired random glucose cutoff value for diagnosis of diabetes was found 7.45 mmol/L (AUC 0.956 [CI 0.927-0.984], p&lt;0.001, sensitivity 94.7%, specificity 74.4%), however, same cut-off value showed impaired random glucose as fair diagnostic test for prediabetes (AUC 0.771 [CI 0.717-0.825], p&lt;0.001, sensitivity 72.5%, specificity 77.3%).......

Glyphosate effects on tree species natives from Cerrado and Caatinga Brazilian biome: Assessing sensitivity to two ways of contamination

Glyphosate is applied for dissection in no-till and post-emergence management in transgenic crops in agricultural fields near the Cerrado and Caatinga biomes. These biomes together represent 33.8% of the Brazilian territory, contributing to the maintenance of great world diversity in flora and fauna. Despite actions to protect them, the proximity with agricultural areas and intense use of glyphosate puts at risk the preservation of native vegetation due to the contamination via herbicide transport processes. Our objectives were: i) to determine the sensitivity of native species from the Cerrado and Caatinga to glyphosate contamination via drift and groundwater; ii) evaluate the level of sensitivity to glyphosate among the different organs of plants. The highest intoxications (upper 80%) were observed for Bauhinia cheilantha, Mimosa caesalpiniaefolia, Mimosa tenuiflora and Amburana cearensis due to drift simullation. The species with 90% of total dry matter reduction were Bauhinia cheilantha, Enterolobium contortisiliquum, Mimosa caesalpiniaefolia, Mimosa tenuiflora, Tabebuia aurea. B. cheilantha and M. tenuiflora are most affected by exposure to glyphosate drift, with 50% of total dry matter reduction when exposed to doses below 444,0 g ha−1. Leaf growth is more sensitive to glyphosate for drift exposure for most species. Hymenaea courbaril is an exception, with greater sensitivity to root growth (50% dry matter reduction at doses below 666,0 g ha−1). B. cheilantha is the species most sensitive to drift exposure; however, it showed complete tolerance to contamination in subsurface waters. Other species such as Anadenanthera macrocarpa and M. caesalpiniifolia are also sensitive to drift, but without reach 90% of total dry matter reduction. A. macrocarpa, M. caesalpiniifolia and T. aurea were tolerant to contamination by subsurface water. The differential tolerance of trees confirms glyphosate's potential as a species selection agent in the Cerrado and Caatinga biomes.

Health and growth indices in children with cow’s milk protein allergy depending on oral tolerance development

Relevance. Dairy-free diet is the basis of cow’s milk allergy (CMA) patient’s management. Duration of the diet is individual, but some children don’t develop tolerance.The aim of the study was to investigate health and growth indices in children with CMA depending on tolerance development by the age of five. Materials and methods. 153 children from 1 to 18 months with diagnosed CMA were included in the prospective study (76.5% with IgE-mediated form). The tolerance was determined after 6–12 months of a milk-free diet and at the age of 5 using an open challenge test. Anthropometry indices (Anthro Plus), levels of specific IgE (Immuno CAP 250) and IgG4 (ELISA) to dietary proteins and the presence of allergic diseases in children also were assessed.Results. 50.3% of children developed tolerance to cow’s milk protein after 6–12 months of a milk-free diet. By the age of 5 63.3% of patients had complete tolerance of dairy products. Partially formed tolerance was observed in 22.9%. 13.8% of patients still had clinical reactions to cow’s milk proteins. Patients with persistent CMA typically had IgE-mediated form, lower growth indices and multiple allergic pathology.Conclusion. The consideration of tolerance development predictors can allow to personalize the management of CMA. Additional researches are needed to clarify the causes of growth indices decline in children with persistent CMA.

Cover Feature: Site‐Selective C–H Amidation of 2‐Aryl Quinazolinones Using Nitrene Surrogates (Eur. J. Org. Chem. 46/2020)

The Cover Feature shows the rhodium(III) and iridium(III)-catalyzed C–H amidation reaction of 2-aryl quinazolin-4(3H)-ones with a range of nitrene surrogates including dioxazolones dioxazolones, organic azides, and N-methoxyamides through N-assisted C–H activation. Complete site-selectivity and functional group tolerance are observed. Notably, the large-scale reaction and late-stage functionalization highlight the synthetic potential of the developed protocol. This work is dedicated to Prof. Pierre H. Dixneuf for his outstanding contribution to organometallic chemistry and catalysis. More information can be found in the Full Paper by S. Hong, I. S. Kim et al.

A No-Sweat Strategy for Graphene-Macrocycle Co-assembled Electrocatalyst toward Oxygen Reduction and Ambient Ammonia Synthesis.

Toward the realm of sustainable energy, the development of efficient methods to enhance the performance of electrocatalysts with molecular level perception has gained immense attention. Inspite of untiring attempts, the production cost and scaling-up issues have been a step back toward the commercialization of the electrocatalysts. Herein, we report a one-pot electrophoretic exfoliation technique with minimum time and power input to synthesize iron phthalocyanine functionalized high-quality graphene sheets (G-FePc). The π-stacked co-assembly excels in oxygen reduction performance (major criterion for fuel cells) with a high positive E1/2 of 0.91 V (vs RHE) and a reproducible reduction peak potential of 0.90 V (vs RHE). An overpotential as low as 29 mV dec-1 and complete tolerance toward the methanol crossover effect confirm the authentication of the catalytic performance of our designed catalyst G-FePc. The catalyst simultaneously exhibits hydrogen storage efficacy by means of nitrogen fixation, yielding 27.74 μg h-1 mgcat-1 NH3 at a potential of -0.3 V (vs RHE) in an acidic electrolyte. The structure-function relationship of the catalyst is revealed via molecular orbital chemistry for the bonding of the Fe(II) active center with O2 and N2 during catalysis.

A Next-Generation Air-Stable Palladium(I) Dimer Enables Olefin Migration and Selective C-C Coupling in Air.

We report a new air‐stable PdI dimer, [Pd(μ‐I)(PCy2 tBu)]2, which triggers E‐selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C−C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C−Br, C−OTf/OFs, and C−Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous PdI dimer generations for substrates that bear substituents ortho to C−OTf.

A Next‐Generation Air‐Stable Palladium(I) Dimer Enables Olefin Migration and Selective C−C Coupling in Air

AbstractWe report a new air‐stable PdIdimer, [Pd(μ‐I)(PCy2tBu)]2, which triggersE‐selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C−C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C−Br, C−OTf/OFs, and C−Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous PdIdimer generations for substrates that bear substituentsorthoto C−OTf.

Combined metabolome and transcriptome analysis reveals key components of complete desiccation tolerance in an anhydrobiotic insect

Some organisms have evolved a survival strategy to withstand severe dehydration in an ametabolic state, called anhydrobiosis. The only known example of anhydrobiosis among insects is observed in larvae of the chironomid Polypedilum vanderplanki Recent studies have led to a better understanding of the molecular mechanisms underlying anhydrobiosis and the action of specific protective proteins. However, gene regulation alone cannot explain the rapid biochemical reactions and independent metabolic changes that are expected to sustain anhydrobiosis. For this reason, we conducted a comprehensive comparative metabolome-transcriptome analysis in the larvae. We showed that anhydrobiotic larvae adopt a unique metabolic strategy to cope with complete desiccation and, in particular, to allow recovery after rehydration. We argue that trehalose, previously known for its anhydroprotective properties, plays additional vital roles, providing both the principal source of energy and also the restoration of antioxidant potential via the pentose phosphate pathway during the early stages of rehydration. Thus, larval viability might be directly dependent on the total amount of carbohydrate (glycogen and trehalose). Furthermore, in the anhydrobiotic state, energy is stored as accumulated citrate and adenosine monophosphate, allowing rapid reactivation of the citric acid cycle and mitochondrial activity immediately after rehydration, before glycolysis is fully functional. Other specific adaptations to desiccation include potential antioxidants (e.g., ophthalmic acid) and measures to avoid the accumulation of toxic waste metabolites by converting these to stable and inert counterparts (e.g., xanthurenic acid and allantoin). Finally, we confirmed that these metabolic adaptations correlate with unique organization and expression of the corresponding enzyme genes.

Area-Efficient Differential Fault Tolerance Encoding for Finite State Machines

A differential fault tolerance encoding is presented for finite state machines (FSMs) to improve their area efficiency. As the manufacturing technology for semiconductors continues to scale down, the probability of the occurrence of unexpected faults in integrated circuits has been increasing. Because an FSM controls an entire digital circuit, the faults in FSMs should be carefully addressed. Whereas the previous encoding applies a fault tolerance scheme to all the states in an FSM, the proposed encoding applies a fault tolerance scheme to only specific states depending on their importance. Compared with the previous complete fault tolerance encoding, the proposed encoding provides a comparable failure probability with a small hardware by applying the fault tolerance scheme differently to each state. The proposed method improves the area efficiency by 36.1%, 43.8%, 49.2%, and 74.6% compared with that by the non-fault tolerance, previous hardware redundancy, information redundancy, and time redundancy methods, respectively. Consequently, the proposed method can provide a flexible solution by applying the fault tolerance differently depending on the importance of the states.

Impact of smoking on gestational diabetes mellitus and offspring birthweight in primiparous women

Smoking has been shown to affect glucose homeostasis and increase the risk for type 2 diabetes mellitus. Further, gestational diabetes mellitus (GDM) and smoking are known to influence offspring birthweight. The effect of smoking on glucose homeostasis in pregnancy is less studied and the findings are inconsistent. The aim of this study was to evaluate the effect of smoking on risk for GDM and to evaluate the impact of smoking and GDM on offspring birthweight. This is an observational cohort study encompassing 4111 Finnish primiparous women from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data were obtained from Finnish national registers. Study participants had complete oral glucose tolerance test results and were divided into three groups according to smoking status: non-smokers (I), smokers who quit during first trimester (II), and smokers who continued after first trimester (III). Prevalence of GDM was 19.8%, 24.3%, and 26.6% in non-smokers, those who quit, and those who continued after the first trimester, respectively (P=.004 for differences between groups). The odds ratio for GDM in smokers who continued after the first trimester compared with non-smokers was 1.65 (95% CI 1.09-2.57) after adjustments for age, prepregnancy body mass index, education, and cohabitation. In women without GDM, offspring birthweight was lowest in those who continued smoking after the first trimester (P=.010 for differences between groups). In women with GDM, smoking status did not influence offspring birthweight. Smoking during pregnancy is associated with an increased risk for GDM. Offspring birthweight is lowest in women who continue smoking after the first trimester. If pregnancy is complicated by GDM, offspring birthweight is not influenced by smoking.

Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C), and paricalcitol (P)neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC).

4631 Background: Localized PDAC management has recently evolved. Due to concerns over micro metastases at diagnosis the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapies with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A), has shown promising clinical data in a previously reported study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. We conducted a prospective, phase 2 clinical trial of patients with resectable (R), BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 µg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2 year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date 24 of the planned 24 patients have been enrolled. 13 male, 11 female; age range 49 to 84 yo. Patient classifications is 8 R; 7 BR; 9 LAPC. Median baseline CA 19-9 156 (range 45-3674). Most common drug related grade (gr) 3-4 adverse events (AEs) are: thrombocytopenia gr 3 29%, gr 4 25%, anemia gr 3 45.8%, gr 4 4.2%, and hypophosphatemia gr 3 8.3%. CA 19-9 normalization occurred in 50% (12/24) who have completed at least 1 cycle of treatment. To date, 14 individuals went to surgery, with 13/14 achieving R0, (1 pCR). Overall response rate in measurable patients is 38% (1 CR, 8 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with non-metastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 50% of individuals. The study is ongoing and OS data is maturing. Clinical trial information: NCT03138720 .