jimnoneill/paper-to-field-training huggingface dataset:
Effect of NIR-II on cancer nanocomposite vaccines for lymph node targeted delivery and enhanced immunotherapy.

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

e20506 Background: Cancervaccines have become one of the hot areas of research in recent years. However, different types of tumors and the tumor tissue itself are heterogeneous. Some cancervaccines contain a single epitope and have weak immunogenicity. The antigen-presenting cells cannot adequately absorb and present the antigen peptide contained in the vaccine. As a result, the body fails to elicit an effective immune response, which greatly limits the therapeutic effect of the cancervaccine. In situ cancervaccines composed of antigens and adjuvants are a promising cancer treatment modality; however, convenient manufacturing of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remain a significant challenge. In this study, we outline a facile approach to simultaneously achieve in situ programming of vaccines via two synergistic nanomedicines to generate robust immune responses. Methods: We first prepared two synergistic nanocomposite systems: Gold nanorods, amphiphilic polymer polyphosphate mPEG- b-PHEP encapsulating the immune adjuvant R848, and nanoparticles doped with cationic liposomes DOTAP. Two nanomedicines were characterized and the efficacy of the nanovaccine was verified at the Cellular Experiments. At the animal level, the lymph node targeting of the nanoparticles was demonstrated through IVIS. We also constructed distant model and lung metastasis model to verify the nanovaccine's effect on enhancing systemic immunotherapy. Results: We used amphiphilic polymer polyphosphate mPEG- b-PHEP to encapsulate TLR7/8 agonist R848 to obtain VNP R848 nanoparticles. Gold nanorods (~ 100nm) can produce a strong photothermal effect mediated by NIR-II, killing tumor cells and releasing abundant antigens at the same time. The small size of VNPR848 (~ 30nm) is beneficial to the enrichment of lymph nodes. After capturing the antigens produced by photothermal, nanoparticles will be targeted and delivered to the tumor draining lymph nodes together with R848, and will be effectively absorbed by DC cells. This in situ tumor vaccine with the ability of targeted delivery of lymph nodes can trigger a strong anti-tumor immune response. This therapy can completely inhibit distant tumors in some mice and produce a long-term immune memory effect on NSCLC metastasis. Conclusions: We propose a simple personalized in situ cancervaccine strategy, which uses nanotechnology to remove tumors in situ and release antigens. Antigens and immune adjuvants are simultaneously delivered to the draining lymph nodes to initiate the antigen presentation function of DC cells, resulting in an anti-tumor immune response to inhibit tumor recurrence and metastasis. The nano-vaccine based on powerful therapeutic effect provides an attractive technology for in situ programming of personalized cancervaccine and an effective strategy for the development of cancervaccine.
The Biomedical Significance of PQQ

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

This chapter presents an overview of the biomedical significance of Pyrroloquinoline quinone (PQQ). It was first isolated from cultures of methylotrophic bacteria as an acetone adduct and its structure determined by X-ray diffraction and confirmed by organic synthesis. PQQ captures electrons from primary amines, catechols, catecholamines, ascorbic acid, and NAD(P)H to form PQQ-semiquinone and/or PQQ-hydroquinone. In a collaborative study with Dr. Manfred Karnovsky, an expert in respiratory burst biochemistry, they have recently shown that superoxide may be derived from a reaction involving the dioxygen oxidation of a reduced ortho-quinom, probably PQQ, which is present in phorbol myristate acetate-activated guinea pig peritoneal exudate neutrophils. The recent reports on the anti-inflammatory and antioxidant actions of PQQ are discussed. Rats given a variety of hepatotoxins capable of destroying the liver through the induction of oxidative stress injury are protected by PQQ in a dose-dependent manner. PQQ is a potent antioxidant and anti-inflammatory agent, which could be used pharmaceutically.
Brief Overview about Inherited Rare coagulation disorders

Field: Medicine (Health Sciences)

Background: Numerous rare congenital bleeding disorders include fibrinogen and prothrombin deficiency as well as factor (V, VII, VIII, XI, X, and XIII) deficiency. In the general population, the severe variants of these illnesses are hereditary and possess a frequency that falls somewhere between one in every two million for factor XIII and one in per half a million for factor VII. Patients who have rare congenital bleeding disorders may exhibit a broad range of symptoms, from relatively mild subcutaneous bleeding to potentially life-threatening hemorrhages for example in the central nervous system. The majority of treatment for these disorders when specific plasma-derived or recombinant products are available is to replace the missing factor. Diagnosing and treating rare congenital bleeding disorders can be challenging due to the wide variety of symptoms they manifest in patients. Patients with rare inherited bleeding diseases must be closely monitored at specialized hemophilia treatment centers once they are diagnosed, due to the unique difficulty of their therapy. More research is required to improve the worldwide care for individuals with rare inherited bleeding diseases, despite the fact that a lot has been learned about their frequency, symptoms, and genetic characteristics in the past ten years. We aimed at this review to give a brief overview about Inherited Bleeding Disorders.
Cost Drivers of Versioning: Pricing and Product Line Strategies for Information Goods

Field: Business, Management and Accounting (Social Sciences)

In this paper, we extend the understanding of versioning strategy of an information goods monopolist and provide new insights on when versioning is optimal. To do so, we derive the optimal product line or versions of an information good and the corresponding prices. By relaxing common assumptions on consumers’ usage costs, versioning costs and capital research and development costs, we provide new insights as well as reconcile extant findings on versioning. For a good with no-free-disposal (NFD), i.e., one where consumers have usage costs, our results show that a monopolist’s marginal cost and consumers’ usage costs have the same impact on its versioning strategy, and that these factors are the sole reason for optimality of versioning of information goods. By endogenizing the production of the highest-quality, we show that capital costs create a downward distortion of quality even for the highest types in the market even under full information. Presence of separate versioning costs also lowers the qualities served to the high types and reduces the segment of consumers who are served with product versions. However, versioning costs do not affect market coverage or the price-quality menu itself. Further, when some of the consumer usage costs are absorbed by the firm (as in case of cloud-based provisioning), it does not necessarily lead to market expansion. This paper was accepted by Chris Forman, information systems.
Lactate Testing in Suspected Sepsis

Field: Medicine (Health Sciences)

Serum lactate monitoring is central to risk stratification and management of sepsis and is now part of a potential quality measure. We examined 11-year trends in lactate testing and predictors of failure to measure lactates in patients with severe sepsis.Retrospective cohort study.Two U.S. academic hospitals.Adult patients admitted from 2003 to 2013.Annual rates of lactate measurement were assessed in patients who had blood cultures ordered and patients with severe sepsis, as defined by concomitant International Classification of Diseases, Ninth Revision codes for infection and organ dysfunction. The approximate time of suspected sepsis was determined by the first blood culture order with concurrent antibiotic initiation. Multivariate analysis was performed to identify predictors of failure to measure lactates in severe sepsis cases in 2013.Among hospitalizations with blood culture orders, rates of lactate measurement increased from 11% in 2003 to 48% in 2013 (p < 0.001 for linear trend). Rates of repeat lactate measurement within 6 hours after lactate levels greater than or equal to 4.0 mmol/L increased from 23% to 69% (p < 0.001). Patients were progressively less likely to be on vasopressors at the time of first lactate measurement (49% in 2003 vs 21% in 2013; p < 0.001). Despite these trends, lactates were measured at the time of suspected sepsis in only 65% of patients with severe sepsis in 2013. On multivariate analysis, hospital-onset sepsis and hospitalization on a nonmedical service were significant predictors of failure to measure lactates (adjusted odds ratio, 7.56; 95% CI, 6.31-9.06 and adjusted odds ratio, 2.08; 95% CI, 1.76-2.24, respectively).Lactate testing has increased dramatically over time and is being extended to patients without overt shock. However, rates of serial lactate testing are still suboptimal, and lactates are not being measured in many patients with severe sepsis. Hospital-onset sepsis and nonmedical units may be high-yield targets for quality improvement initiatives.
[Tenosynovitis in chronic inflammatory joint diseases and its sequelae in the area of the hand].

Field: Medicine (Health Sciences)

The synovial lining of tendons may participate early in chronic rheumatic diseases. As a result of the inflammatory activity degenerative changes of tendons may occur. Increasing damage to tendons ends in their rupture. At 775 tenosynovectomies, 395 of them in chronic rheumatic diseases, in 68 patients (78 hands) 173 ruptures of tendons (14 flexors, 159 extensors) were found. The value of early tenosynovectomy as a preventive measure is emphasized.
Prospective Multicenter Registry to Investigate the Clinical Feasibility of Combination Workflow With 90 W/4 s and Ablation Index‐Guided 50 W Ablation (PRECISE—COMBO 90 W/50 W Study)

Field: Medicine (Health Sciences)

ABSTRACT Background High‐power short‐duration (HPSD) ablation is an established therapy for pulmonary vein (PV) isolation (PVI) in atrial fibrillation (AF), aiming to form efficient transmural lesions. Very HPSD (vHPSD) can further shorten ablation time but may increase the risk of acute PVI failure compared with HPSD. A combined HPSD and vHPSD strategy (90 W/50 W combination workflow) potentially balances efficiency and durability, though its clinical feasibility remains unknown. Therefore, this multicenter registry evaluated the acute and long‐term efficacy of a 90 W/50 W combination workflow for PVI in patients with paroxysmal AF. Methods In this prospective study, a total of 101 consecutive patients with paroxysmal AF underwent PVI using radiofrequency ablation with a 90 W/50 W combination workflow. We evaluated acute outcomes, including first‐pass isolation and acute PV reconnection, and monitored atrial tachyarrhythmia recurrences over 12 months. Results Median PVI procedure time was 35 min, with total procedure time at 105 min. First‐pass PVI was achieved in 58.4% of patients, including 74.3% in the right PV and 72.3% in the left PV. Acute PV reconnection occurred in 31.7% (32/101). In multivariate analysis, carina sites independently predicted acute PVI failure in both HPSD and vHPSD groups, while contact force also predicted failure in the HPSD group. After 1 year, 89.9% of patients remained free from documented atrial tachyarrhythmias. Conclusion The 90 W/50 W combination workflow did not notably shorten procedure time or enhance first‐pass success. More standardized strategies, particularly in carina segments with higher contact force and ablation index under HPSD, may be required to ensure optimal lesion durability and favorable outcomes.
Methamphetamine Activates Toll-Like Receptor 4 to Induce Central Immune Signaling within the Ventral Tegmental Area and Contributes to Extracellular Dopamine Increase in the Nucleus Accumbens Shell

Field: Neuroscience (Life Sciences)

Methamphetamine (METH) is a globally abused, highly addictive stimulant. While investigations of the rewarding and motivational effects of METH have focused on neuronal actions, increasing evidence suggests that METH can also target microglia, the innate immune cells of the central nervous system, causing release of proinflammatory mediators and therefore amplifying the reward changes in the neuronal activity induced by METH. However, how METH induces neuroinflammatory responses within the central nervous system (CNS) is unknown. Herein, we provide direct evidence that METH creates neuroinflammation, at least in part, via the activation of the innate immune Toll-like receptor 4 (TLR4). Biophysical studies revealed that METH bound to MD-2, the key coreceptor of TLR4. Molecular dynamics simulations showed METH binding stabilized the active heterotetramer (TLR4/MD-2)2 conformation. Classic TLR4 antagonists LPS-RS and TAK-242 attenuated METH induced NF-κB activation of microglia, whereas added MD-2 protein boosted METH-induced NF-κB activation. Systemically administered METH (1 mg/kg) was found to specifically up-regulate expression of both CD11b (microglial activation marker) and the proinflammatory cytokine interleukin 6 (IL-6) mRNAs in the ventral tegmental area (VTA), but not in either the nucleus accumbens shell (NAc) or prefrontal cortex (PFC). Systemic administration of a nonopioid, blood-brain barrier permeable TLR4 antagonist (+)-naloxone inhibited METH-induced activation of microglia and IL-6 mRNA overexpression in VTA. METH was found to increase conditioned place preference (CPP) as well as extracellular dopamine concentrations in the NAc, with both effects suppressed by the nonopioid TLR4 antagonist (+)-naloxone. Furthermore, intra-VTA injection of LPS-RS or IL-6 neutralizing antibody suppressed METH-induced elevation of extracellular NAc dopamine. Taken together, this series of studies demonstrate that METH-induced neuroinflammation is, at least in part, mediated by TLR4-IL6 signaling within the VTA, which has the downstream effect of elevating dopamine in the NAc shell. These results provide a novel understanding of the neurobiological mechanisms underlying acute METH reward that includes a critical role for central immune signaling and offers a new target for medication development for treating drug abuse.
P-15. Safety and Efficacy of a Low-Dose Estrogen Intravaginal Tablet (Vagifem) to Treat Estrogen Deficiency-Derived Atrophic Vaginitis

Field: Medicine (Health Sciences)

Dept. of Obstetrics and Gynecology, New Brunswick, New Jersey, USA; Women 's Medical and Diagnostic Center, The Climacteric Clinic, Gainesville, Florida, USA; and Novo Nordisk Pharmaceuticals Inc., Princeton, New Jersey, USA.
The Newly Sequenced Genome of Pisum sativum Is Replete with Potential G-Quadruplex-Forming Sequences—Implications for Evolution and Biological Regulation

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

G-quadruplexes (G4s) have been long considered rare and physiologically unimportant in vitro curiosities, but recent methodological advances have proved their presence and functions in vivo. Moreover, in addition to their functional relevance in bacteria and animals, including humans, their importance has been recently demonstrated in evolutionarily distinct plant species. In this study, we analyzed the genome of Pisum sativum (garden pea, or the so-called green pea), a unique member of the Fabaceae family. Our results showed that this genome contained putative G4 sequences (PQSs). Interestingly, these PQSs were located nonrandomly in the nuclear genome. We also found PQSs in mitochondrial (mt) and chloroplast (cp) DNA, and we experimentally confirmed G4 formation for sequences found in these two organelles. The frequency of PQSs for nuclear DNA was 0.42 PQSs per thousand base pairs (kbp), in the same range as for cpDNA (0.53/kbp), but significantly lower than what was found for mitochondrial DNA (1.58/kbp). In the nuclear genome, PQSs were mainly associated with regulatory regions, including 5′UTRs, and upstream of the rRNA region. In contrast to genomic DNA, PQSs were located around RNA genes in cpDNA and mtDNA. Interestingly, PQSs were also associated with specific transposable elements such as TIR and LTR and around them, pointing to their role in their spreading in nuclear DNA. The nonrandom localization of PQSs uncovered their evolutionary and functional significance in the Pisum sativum genome.
Evaluation of Marginal Accuracy and Microstructure of Heat Pressed Lithium Disilicate and Zirconia Reinforced Lithium Silicate Crowns after Thermal Tempering

Field: Dentistry (Health Sciences)

Objectives: To evaluate the effect of two thermal tempering cycles on marginal accuracy of crowns fabricated from two heat-pressed glass ceramics. Materials and methods:Twenty-eight ceramic crowns were pressed from glass ceramic materials in two groups (n=14).Group (E): Lithium disilicate IPS e.max Press, Group (C): Zirconia reinforced lithium silicate (ZLS) Celtra Press.Each group was subdivided according to tempering temperature into (T1) 9% and (T2) 5% below pressing temperature of each ceramic.A stereomicroscope was used to measure the marginal adaptation before and after tempering and microstructure was analyzed.Three-way ANOVA test was used to study the effect of ceramic type, tempering, tempering procedure and their interactions on marginal gap distance.Bonferroni's posthoc test was used for pair-wise comparisons when ANOVA test is significant.The significance level was set at P ≤ 0.05. Results:The interaction between the three variables had statistically significant effect on mean marginal gap distance (P-value <0.001).Before tempering and after (T1) tempering, there was no statistically significant difference between ceramic types (P-value = 0.577).After (T2) tempering, there was a statistically significant difference between ceramic types (P-value <0.001).Celtra showed statistically significantly higher mean marginal gap distance compared to E.max. Conclusions:Mean marginal gap distance for lithium disilicate was not affected after tempering.ZLS after -5% tempering showed the highest mean marginal gap distance.All tested groups showed clinically acceptable marginal adaptation except ZLS with -5% tempering which showed clinically unacceptable marginal adaptation >120 µm.
Investment Strategies Amongst Property and Casualty Insurance Companies

Field: Economics, Econometrics and Finance (Social Sciences)

The purpose of this work is to take an in-depth look into the investment side of property and casualty insurance. Many P&C companies have thrived over the past century, and much of this success can be attributed to investment income. This thesis will examine how investment philosophy changes from firm to firm, while also looking at how strategies have changed over time. It will also look into the insurance “float,” and examine how investors such as Warren Buffett have utilized this instrument to their favor. Investing is a huge aspect of property and casualty insurance, and this piece will give the reader a better idea of how a firm’s investment income comes about.
Writing a Durable Mark: A Community of Isolatoes in John Marr and Other Sailors

Field: Arts and Humanities (Social Sciences)

Taking the solitude that permeates John Marr and Other Sailors (1888) as a central point of inquiry, this essay argues that the ﬁrst four poems in the collection—"John Marr," "Bridegroom Dick," Tom Deadlight," and "Jack Roy"—compose what I term "a community of isolatoes." While the poetical utterances of solitary ex-sailors in these poems seem misaddressed at ﬁrst glance, I view them as forming polyphonic voices rather than offering monologues. Furthermore, I situate these poems in a long genealogy of Melville's postal imagery that dates back to the early 1850s, especially the dead letters in "Bartleby, the Scrivener" (1853). In Melville's formulation, a dead letter refers not to a letter's death but to a suspended state where the letter fluctuates between life and death, waiting to be read and restored. By ﬁguratively construing John Marr as a dead letter partly addressed to future readers, this essay joins recent scholarly efforts to challenge the critical image of Melville in his later years as a solitary recluse.
HPLC analysis and role of the Saudi Arabian propolis in improving the pathological changes of kidney treated with monosodium glutamate

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

BACKGROUND: Monosodium glutamate is commonly used in our foods and reported many physiological effects. Propolis is a natural product widely used in folk medicine due to its bioactive compounds. It is considered one of the richest sources of phenolic acids and flavonoids.
METHODS: The phenolic acids and flavonoids content of Saudi Arabian propolis was determined by HPLC analysis. Three groups of albino rats were used in the present study for histological and histochemical studies. Group 1 (control group) received 0.9% NaCL, group 2 was given monosodium glutamate (6 mg/g bw) and group 3 received monosodium glutamate (6 mg/g body weight) and propolis (50 mg/kg body weight).
RESULTS: The HPLC analysis of the Saudi Arabian propolis revealed presence of predominant phenolic acids; trans-cinnamic, p-coumaric, caffeic, ferulic, sinapic, and flavonoids; apigenin, kaempferol, quercetin, rutin. The rats administered orally with the monosodium glutamate (6 mg/g body weight) and propolis (50 mg/kg body weight) for 8 weeks showed a significant protective effect of propolis in prevention MSG induced toxic pathological changes in kidney of the rats.
CONCLUSION: The presence of phenolic compounds in the Saudi Arabian propolis is coincided with its role in improving the histological and ultrastructural pictures of kidney treated with monosodium glutamate.
Analysis of the determinants of the sustainability of cattle marketing systems in Zambezi Region of north-eastern communal area of Namibia

Field: Agricultural and Biological Sciences (Life Sciences)

This article aims to contribute to a better understanding of variables that influence the motivation behind the preferred choice of cattle marketing channels in north eastern communal area of Namibia. The data required for the study were collected through a small-scale survey, key informants in-depth interviews and review of secondary data were analysed using Multinomial Logistical Regression. The results showed that the majority (62%) of small scale cattle farmers preferred to trade through informal marketing channel (comprising open market, private sales and butcheries). The abattoir was the single most preferred channel for 38% and the only available formal market. Four factors are identified motivating cattle farmers to choose this marketing channel namely, the gender of the household head, marketing information received, education and number of livestock sold. The results also suggest that formal marketing is relatively relevant to farmers with large cattle numbers and meet the required standards from abattoirs. The study recommended that in order to increase the number of cattle marketed through the formal channels, there is need to improve overall herd size, as well as setting attractive prices coupled with reduced delays in making payments to the farmers for their livestock sold. Key words: Formal market, informal market, factors, sales, agriculture, livestock.