Investigating reindeer pastoralism and exploitation of high mountain zones in northern Mongolia through ice patch archaeology

In interior Eurasia, high mountain zones are crucial to pastoral subsistence, providing seasonally productive pastures and abundant wild resources. In some areas of northern Mongolia, mountainous tundra zones also support a low-latitude population of domestic reindeer herders–a lifestyle whose origins are poorly characterized in the archaeological record of early Mongolia. Traditionally, reindeer pastoralists make significant seasonal use of munkh mus (eternal ice) for their domestic herds, using these features to cool heat-stressed animals and provide respite from insect harassment. In recent years, many of these features have begun to melt entirely for the first time, producing urgent threats to traditional management techniques, the viability of summer pastures, and reindeer health. The melting ice is also exposing fragile organic archaeological materials that had previously been contained in the patch. We present the results of horseback survey of ice patches in Baruun Taiga special protected area, providing the first archaeological insights from the region. Results reveal new evidence of historic tool production and wild resource use for fishing or other activities, and indicate that ice patches are likely to contain one of the few material records of premodern domestic reindeer use in Mongolia and lower Central Asia. The area’s ancient ice appears to be rapidly melting due to changing climate and warming summer temperatures, putting both cultural heritage and traditional reindeer herding at extreme risk in the years to come

Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

Marina G Tarakanovskaya,1 Jigjidsuren Chinburen,2 Purev Batchuluun,2 Chogsom Munkhzaya,2 Genden Purevsuren,2 Dorjiin Dandii,3 Tsogkhuu Hulan,3 Dandii Oyungerel,4 Galyna A Kutsyna,5 Alan A Reid,6 Vika Borisova,6 Allen I Bain,7 Vichai Jirathitikal,7 Aldar S Bourinbaiar6–8 1Ekomed LLC, 2National Cancer Center, 3Monserum LLC, 4National Center for Public Health, Ulaanbaatar, Mongolia; 5Department of Infectious Diseases, Luhansk State Medical University, Luhansk, Ukraine; 6Immunitor China Ltd, Beijing, People’s Republic of China; 7Immunitor Inc, Vancouver, BC, Canada; 8Immunitor LLC, Ulaanbaatar, Mongolia Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])—an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.Methods: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7%) females and 46 (61.3%) males with a median age of 60 years (mean 61.6±8.1 years). Out of these, 23 (30.7%) had hepatitis B and 34 (45.3%) had hepatitis C infections, including 9 (12%) with dual infection, 4 (5.3%) negative for both viruses, and 5 (6.7%) without established viral diagnosis. Most patients (94.7%) had underlying liver cirrhosis of varying severity.Results: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP) (66.7%; P=0.006 by Wilcoxon signed rank test). Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2–92,407; 95% confidence interval [CI] 1,186–7,280) and post-treatment values were 102.3 IU/mL (mean 2,539; range 0.9–54,478; 95% CI 503–4,575). The decrease in AFP was correlated either with tumor clearance or regression on computed tomography scans. The median overall survival time could not be established since 68 out of 75 (90.7%) patients were still alive after median follow-up of 12 months (mean 15±9.7; range 7–59; 95% CI 12.8–17.2). The first patient in this study received immunotherapy 5 years ago and still remains in complete remission. None of the patients experienced any serious adverse effects or toxicity.Conclusion: The results indicate that hepcortespenlismut-L is a safe, effective, and fast-acting immunomodulatory intervention for HCC. The Phase III, randomized, double-blind, placebo-controlled trial is now initiated at the Mongolian National Cancer Center to confirm these promising findings. Keywords: allogeneic, inflammation, immune toleranc

SARS-CoV-2 Infection in Beaver Farm, Mongolia, 2021

We report an outbreak of COVID-19 in a beaver farm in Mongolia in 2021. Genomic characterization revealed a unique combination of mutations in the SARS-CoV-2 of the infected beavers. Based on these findings, increased surveillance of farmed beavers should be encouraged

Interim results from ongoing Phase III placebo-controlled, randomized trial of hepcortespenlisimut-L for advanced hepatocellular carcinoma indication

Aim: We aimed to further investigate the role of hepcortespenlisimut-L (Hepko-V5 or V5), a new oral immunotherapy developed by us, for hepatocellular carcinoma (HCC) indication.Methods: The interim data from ongoing Phase III placebo-controlled, randomized trial were evaluated on the initial group of patients in advanced stage of HCC with emphasis on liver function and tumor marker alpha-fetoprotein levels. Additionally, an in vitro study was undertaken to elucidate the mechanism of action of V5 by measuring with flow cytometry the expression of cytokines such as IL-2, INF-γ, and TNF-α and cell activation markers CD69 and Ki67 on CD4- and CD8-positive lymphocytes isolated from peripheral blood of healthy volunteers.Results: As early as one month after treatment initiation, there was a clear improvement in alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin levels among HCC patients who received daily dose of V5, but not in the placebo group. Additionally, alpha-fetoprotein (AFP) levels among V5 recipients decreased, while in the placebo group they rose. Clinical results are in line with in vitro observations indicating immune activation, as evidenced by many-fold enhancement of CD69, Ki67, and INF-γ expression and at the same time marked anti-inflammatory effect resulting in 10-fold decrease in TNF-α output and lack of influence on IL-2 production.Conclusion: Hepcortespenlisimut-L, a tableted oral formulation derived from heat-inactivated pooled blood of patients with HCC and viral hepatitis shows beneficial clinical effect, as demonstrated by improvement in liver function and reduction of tumor marker AFP levels. These correlate with in vitro observations showing potent activation of the immune response and pronounced oral tolerance effect

Macrophage AMPK β1 activation by PF-06409577 reduces the inflammatory response, cholesterol synthesis, and atherosclerosis in mice

Summary: Atherosclerotic cardiovascular disease is characterized by both chronic low-grade inflammation and dyslipidemia. The AMP-activated protein kinase (AMPK) inhibits cholesterol synthesis and dampens inflammation but whether pharmacological activation reduces atherosclerosis is equivocal. In the current study, we found that the orally bioavailable and highly selective activator of AMPKβ1 complexes, PF-06409577, reduced atherosclerosis in two mouse models in a myeloid-derived AMPKβ1 dependent manner, suggesting a critical role for macrophages. In bone marrow-derived macrophages (BMDMs), PF-06409577 dose dependently activated AMPK as indicated by increased phosphorylation of downstream substrates ULK1 and acetyl-CoA carboxylase (ACC), which are important for autophagy and fatty acid oxidation/de novo lipogenesis, respectively. Treatment of BMDMs with PF-06409577 suppressed fatty acid and cholesterol synthesis and transcripts related to the inflammatory response while increasing transcripts important for autophagy through AMPKβ1. These data indicate that pharmacologically targeting macrophage AMPKβ1 may be a promising strategy for reducing atherosclerosis

Human action recognition using deep rule-based classifier

In recent years, numerous techniques have been proposed for human activity recognition (HAR) from images and videos. These techniques can be divided into two major categories: handcrafted and deep learning. Deep Learning-based models have produced remarkable results for HAR. However, these models have several shortcomings, such as the requirement for a massive amount of training data, lack of transparency, offline nature, and poor interpretability of their internal parameters. In this paper, a new approach for HAR is proposed, which consists of an interpretable, self-evolving, and self-organizing set of 0-order If...THEN rules. This approach is entirely data-driven, and non-parametric; thus, prototypes are identified automatically during the training process. To demonstrate the effectiveness of the proposed method, a set of high-level features is obtained using a pre-trained deep convolution neural network model, and a recently introduced deep rule-based classifier is applied for classification. Experiments are performed on a challenging benchmark dataset UCF50; results confirmed that the proposed approach outperforms state-of-the-art methods. In addition to this, an ablation study is conducted to demonstrate the efficacy of the proposed approach by comparing the performance of our DRB classifier with four state-of-the-art classifiers. This analysis revealed that the DRB classifier could perform better than state-of-the-art classifiers, even with limited training samples