Relationship Between Climate Change and Marmot Plague of Marmota himalayana Plague Focus - the Altun Mountains of the Qinghai-Xizang Plateau, China, 2000-2022.

Introduction: Plague is a zoonotic disease that occurs naturally in specific geographic areas. Climate change can influence the populations of the plague host or vector, leading to variations in the occurrence and epidemiology of plague in animals. Methods: In this study, we collected meteorological and plague epidemiological data from the Marmota himalayana plague focus in the Altun Mountains of the Qinghai-Xizang Plateau. The data spanned from 2000 to 2022. We describe the climatic factors and plague epidemic conditions and we describe their analysis by Pearson's correlation. Results: During the period from 2000 to 2022, the isolation rates of Yersinia pestis (Y.pestis) from marmots and fleas were 9.27% (451/4,864) and 7.17% (118/1,646), respectively. Additionally, we observed a positive rate of F1 antibody of 11.25% (443/3,937) in marmots and 18.16% (142/782) in dogs. With regards to climate, there was little variation, and a decreasing trend in blowing-sand days was observed. The temperature in the previous year showed a negative correlation with the Y. pestis isolation rate in marmots (r=-0.555, P=0.011) and the positive rate of F1 antibody in marmots (r=-0.552, P=0.012) in the current year. The average annual precipitation in the previous two years showed a positive correlation with marmot density (r=0.514, P=0.024), while blowing-sand days showed a negative correlation with marmot density (r=-0.701, P=0.001). Furthermore, the average annual precipitation in the previous three years showed a positive correlation with the isolation rate of Y. pestis from marmots (r=0.666, P=0.003), and blowing-sand days showed a negative correlation with marmot density (r=-0.597, P=0.009). Conclusions: The findings of this study indicate that there is a hysteresis effect of climate change on the prevalence of plague. Therefore, monitoring climate conditions can offer significant insights for implementing timely preventive and control measures to combat plague epidemics.

Pasteurella multocida strains of a novel capsular serotype and lethal to Marmota himalayana on Qinghai-Tibet plateau in China.

Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P < 0.05). Our findings suggested P. multocida is a lethal pathogen for wildlife on Qinghai-Tibet plateau, in addition to Yersinia pestis. Individuals residing within the M. himalayana plague focus are at risk for P. multocida infection, and public health warnings are necessitated.

Nanoscale Prediction of the Thermal, Mechanical, and Transport Properties of Hydrated Clay on 106- and 1015-Fold Larger Length and Time Scales.

Coupled thermal, hydraulic, mechanical, and chemical (THMC) processes, such as desiccation-driven cracking or chemically driven fluid flow, significantly impact the performance of composite materials formed by fluid-mediated nanoparticle assembly, including energy storage materials, ordinary Portland cement, bioinorganic nanocomposites, liquid crystals, and engineered clay barriers used in the isolation of hazardous wastes. These couplings are particularly important in the isolation of high-level radioactive waste (HLRW), where heat generated by radioactive decay can drive the temperature up to at least 373 K in the engineered barrier. Here, we use large-scale all-atom molecular dynamics simulations of hydrated smectite clay nanoparticle assemblages to predict the fundamental THMC properties of hydrated compacted clay over a wide range of temperatures (up to 373 K) and dry densities relevant to HLRW management. Equilibrium simulations of clay-water mixtures at different hydration levels are analyzed to quantify material properties, including thermal conductivity, heat capacity, thermal expansion, suction, water and ion self-diffusivity, and hydraulic conductivity. Predictions are validated against experimental results for the properties of compacted bentonite clay. Our results demonstrate the feasibility of using atomistic-level simulations of assemblages of clay nanoparticles on scales of tens of nanometers and nanoseconds to infer the properties of compacted bentonite on scales of centimeters and days, a direct upscaling over 6 orders of magnitude in space and 15 orders of magnitude in time.

Case report: A case of brucellosis misdiagnosed as coronavirus disease 2019/influenza in China.

Brucellosis is an important zoonosis and a multisystem disease. The signs and symptoms of brucellosis are not specific. In the clinical, brucellosis is often ignored and misdiagnosed. We report a case of brucellosis who was misdiagnosed as coronavirus disease 2019 (COVID-19)/influenza and received delayed treatment during strict COVID-19 control. The neglect of other diseases due to COVID-19 and empirical diagnosis and treatment by medical staff are part of the reasons for misdiagnosis. Otherwise, the normal erythrocyte sedimentation rate (ESR), increased white blood cell count (WBC), and increased neutrophil count (NEUT) of this patient was also a cause of misdiagnosis, which is an important reminder for diagnosis. For patients with the unknown origin of fever and other symptoms related to brucellosis, especially those from endemic areas of brucellosis, brucellosis screening is a priority item, and grassroots doctors should be vigilant and standardize the diagnosis and treatment based on epidemiology history, clinical manifestation, and laboratory tests according to the diagnostic criteria of brucellosis.

The complex genomic diversity of Yersinia pestis on the long-term plague foci in Qinghai-Tibet plateau.

Plague is a typical natural focus disease that circulates in different ecology of vectors and reservoir hosts. We conducted genomic population and phylogenetic analyses of the Yersinia pestis collected from the 12 natural plague foci in China with more than 20 kinds of hosts and vectors. Different ecological landscapes with specific hosts, vectors, and habitat which shape various niches for Y. pestis. The phylogeographic diversity of Y. pestis in different kinds plague foci in China showed host niches adaptation. Most natural plague foci strains are region-and focus-specific, with one predominant subpopulation; but the isolates from the Qinghai-Tibet plateau harbor a higher genetic diversity than other foci. The Y. pestis from Marmota himalayana plague foci are defined as the ancestors of different populations at the root of the evolutionary tree, suggesting several different evolutionary paths to other foci. It has the largest pan-genome and widest SNP distances with most accessory genes enriched in mobilome functions (prophages, transposons). Geological barriers play an important role in the maintenance of local Y. pestis species and block the introduction of non-native strains. This study provides new insights into the control of plague outbreaks and epidemics, deepened the understanding of the evolutionary history of MHPF (M. himalayana plague focus) in China. The population structure and identify clades among different natural foci of China renewed the space cognition of the plague.

Identification of Novel Bartonella washoensis Sequence Type 22 in Marmota himalayana - Jiuquan City, Gansu Province, China, 2021-2022.

What is already known about this topic?: The prevalence of rodent-adapted Bartonella species has been increasing significantly. However, the specific Bartonella species carried by Marmota himalayana (M. himalayana), a large rodent species, and the potential risk it poses to human populations remain unknown. What is added by this report?: Bartonella washoensis (B. washoensis), associated with human endocarditis, was initially identified in M. himalayana, exhibiting a detection rate of approximately one-third and demonstrating a predilection for the heart and lungs. The discovery of the novel Sequence Type 22 has expanded both the isolation source and genetic lineage of B. washoensis. What are the implications for public health practice?: Individuals residing within the M. himalayana plague focus are at an elevated risk for B. washoensis infection. Consequently, there is a pressing need for public health warnings and efficient clinical case identification in this population.

Case Report: Screening and Analysis for Brucellosis in Akesai Kazak Autonomous County, China.

Brucellosis is a common zoonotic disease. For this study, the residents of Akesai Kazak Autonomous County, located in the high altitude of the Altun Mountains region of Gansu Province, were selected. These people rely on traditional animal husbandry for their main income. The prevalence of brucellosis and the change of antibody titer in this high-risk population were analyzed, and information on the epidemic in animals in the county was obtained from data records. One hundred ninety-nine persons were screened and 240 serum samples were collected. Eight persons and 27 serum samples were positive based on the rose bengal plate test, and seven persons were confirmed positive by standard agglutination test; 16,000 sheep were tested, of which 130 from nine different households were serum antibody positive. The results indicate that brucellosis seroprevalence increased among sheep and high-risk populations, and the occurrence of cases corresponded to the epidemic among animals. The incidence of human brucellosis was closely related to occupation, and the cases were mainly distributed among herdsmen and butchers. Most cases were asymptomatic or mild, and the serum antibody titers showed a high initial titer but a rapid decline in young cases, whereas those in older cases were relatively low but showed a slow decline.

Serological investigation of plague and brucellosis infection in Marmota himalayana plague foci in the Altun Mountains on the Qinghai-Tibet Plateau.

The Altun Mountains are among the most active regions of Marmota himalayana plague foci of the Qinghai-Tibet Plateau where animal plague is prevalent, whereas only three human cases have been found since 1960. Animal husbandry is the main income for the local economy; brucellosis appears sometimes in animals and less often in humans. In this study, a retrospective investigation of plague and brucellosis seroprevalence among humans and animals was conducted to improve prevention and control measures for the two diseases. Animal and human sera were collected for routine surveillance from 2018 to 2021 and screened for plague and brucellosis. Yersinia pestis F1 antibody was preliminarily screened by the colloidal gold method at the monitoring site to identify previous infections with positive serology. Previous plague infection was found in 3.2% (14/432) of the studied human population having close contact with livestock, which indicates evidence of exposure to the Yersinia antigen (dead or live pathogenic materials) in the Altun Mountains. Seroprevalence of brucellosis was higher in camels (6.2%) and sheepdogs (1.8%) than in other livestock such as cattle and sheep, suggesting a possible transmission route from secondary host animals to humans.

Design an Effective Blood Distribution Network with Minimal Impacts on the Environment and Blood Supply Assurance.

As the world's population grows, resulting in the aggravating trend of aging population, it brings with it an increase in the demand for blood. Nowadays, in most cities, the blood distribution network is based on a single distribution centre pattern, with the blood centre acting as distribution centre for one-to-one distribution. However, despite its convenience, this pattern has a high frequency of delivery, increased risk of blood shortage, and generates high carbon emissions. This paper aims to understand the real-life problems of the current blood distribution network and to design a more rational blood distribution network by taking the characteristics of the blood supply chain into account. Two blood distribution network patterns are considered, the current single distribution centre pattern and the proposed multiple distribution centre pattern. In order to minimise environmental impacts, we introduce open vehicle routing problem for blood delivery routes planning, using mixed integer programming for modelling, to compare the carbon emissions between the two blood distribution network patterns. Numerical experimental results demonstrate that applying the proposed BDN can reduce carbon emissions by an average of 25.84% and up to 29.59%, and the delivery time in emergency situations is significantly reduced by an average of 33.15%. Such studies are essential for both reducing carbon emissions and safeguarding patients' lives.

Plague Outbreak of a Marmota himalayana Family Emerging from Hibernation.

In April 2021, a plague outbreak was identified within one Marmota himalayana family shortly after emerging from hibernation, during plague surveillance in the M. himalayana plague foci of the Qinghai-Tibet Plateau. A total of five marmots were found dead of Yersinia pestis near the same burrow; one live marmot was positive of Y. pestis fraction 1 (F1) antibody. Comparative genome analysis shows that few single nucleotide polymorphisms were detected among the nine strains, indicating the same origin of the outbreak. The survived marmot shows a high titer of F1 antibody, higher than the mean titer of all marmots during the 2021 monitoring period (W = 391.00, Z = 2.81, p < 0.01). Marmots live with Y. pestis during hibernation when the pathogen is inhibited by hypothermia. But they wake up during or just after hibernation with body temperature rising to 37°C, when Y. pestis goes through optimal growth temperature, increases virulence, and causes death in marmots. A previous report has shown human plague cases caused by excavating marmots during winter; combined, this study shows the high risk of hibernation marmot carrying Y. pestis. This analysis provides new insights into the transmission of the highly virulent Y. pestis in M. himalayana plague foci and drives further effort upon plague control during hibernation.

The contributing factors for lateral neck lymph node metastasis in papillary thyroid microcarcinoma (PTMC).

PURPOSE: Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis due to its indolent features. Only few studies have assessed the clinical factors that can predict lateral neck lymph node metastasis (LLNM) in patients with PTMC. This study aimed to examine the clinicopathological factors associated with LLNM in patients with PTMC. METHODS: We reviewed medical records of 3578 patients with PTMC that was ≤1 cm in diameter on final pathology at Yonsei University Hospital between January 2015 and December 2017. The patients were divided into two groups (metastasis group [n = 157] and no metastasis group [n = 3421]). RESULTS: The proportion of patients with multifocality, extrathyroidal extension (ETE), and central node metastasis was significantly higher in metastasis group (p < 0.001, p < 0.001 and p < 0.001, respectively), and the mean tumor size was relatively larger in metastasis group than in no metastasis group (0.7 ± 0.2 vs. 0.6 ± 0.2 cm, p < 0.001). However, no statistically significant differences were observed in the tumors harboring BRAF mutation between the two groups (84.8% vs. 80.6%, p = 0.199). Multivariate analysis indicated that the significant risk factors of LLNM include ETE (odds ratio [OR]: 1.904, 95% confidence interval [CI]: 1.267-2.861), multifocality (OR: 2.255, 95% CI: 1.544-3.293), and central node metastasis (OR: 7.768, 95% CI: 4.869-12.395), but not BRAF mutation (OR: 0.542, 95% CI: 0.337-0.874). CONCLUSION: Approximately 4.4% of patients with PTMC presented with LLNM at the time of diagnosis. Moreover, the significant risk factors of LLNM include central node metastasis, ETE, and multifocal disease but not BRAF mutation.