Mixed Blood Research Articles

Identifying effects of volatile organic compounds exposure on kidney stone prevalence in U.S. adults: a cross-sectional analysis of NHANES 2007-2020.

Our aim was to comprehensively investigate the relationship between blood volatile organic compounds (VOCs) and kidney stone prevalence for U.S. adults. In this cross-sectional study, 10,052 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariate logistic regression model was employed to investigate the association between 9 blood VOCs and kidney stones. We explored the dose-response relationship between blood VOCs and kidney stones using restricted cubic spline (RCS) analysis. Additionally, weighted quantile sum (WQS) regression model was performed to assess the overall association of 9 blood VOCs with kidney stones. Finally, subgroup analyses were conducted to identify the findings in different populations at high prevalence. Logistic regression analysis and dose-response risk curves revealed that blood benzene (aOR = 1.308, 95% CI: 1.118-1.530, P = 0.001), blood ethylbenzene (aOR = 1.280, 95% CI: 1.054-1.554, P = 0.013), blood m-/p-xylene (aOR = 1.187, 95% CI: 1.008-1.398, P = 0.040), blood 2,5-dimethylfuran (aOR = 1.319, 95% CI: 1.135-1.533, P < 0.001) and blood furan (aOR = 1.698, 95% CI: 1.305-2.209, P < 0.001) were positively associated with the prevalence of kidney stones. WQS regression analysis revealed that exposure to mixed blood VOCs was positively correlated with kidney stone prevalence (OR = 1.34, 95% CI: 1.14-1.57), with furans carrying the greatest weight. Subgroup analyses suggested that kidney stones were more susceptible to the effects of blood VOCs in young and middle-aged, female, overweight and obese, non-hypertensive, and non-diabetic populations. In this study, the results indicated that high VOC exposure was positively and independently associated with kidney stones in U.S. adults. This finding highlighted the need for public health strategies to reduce VOC exposure and its role in kidney stone prevention and treatment.

The Unique Morphofunctional Structure of the Reptilian Heart

The paper analyzes the evolution of the thermoenergetic statuses of vertebrates and the associated evolutionary development of their heart. The analysis shows that in most modern lepidosaurs and turtles, the heart is not completely, conditionally five-chambered: it has two atria and one ventricle, in which two incomplete septas divide it into three functional chambers. In some of them, these two septas were modified in evolution so that they turned into one with vertical and horizontal elements, as a result of which the heart became functionally four-chambered, with improved separation of arterial and venous blood flows. Crocodiles have a fully morphologically four-chambered heart. But the hearts of all reptiles, both recent and extinct, perform two opposite functions in parallel – the separation of arterial and venous blood flows and at the same time their regulated mixing. To do this, there are special morphological and physiological mechanisms in their hearts. Such a strange functional duality in the work of the reptilian heart aims to regulate the metabolism level by controlling the amount of carbon dioxide entering the blood flow: increasing the amount of CO2 in the blood flow reduces the metabolic rate, reducing its amount increase metabolism. Mixed blood in reptiles’ blood flow is not an immature, primitive state, but a physiological necessity. Moreover, this method of regulating of metabolic rate is most adequate to the initial, ancestral thermoenergetic state in reptiles, because basal terrestrial tetrapods and most ancient reptiles were meso- and even tachymetabolic, i.e. almost or completely warm-blooded, endothermic animals. It was just these endothermic animals that needed such type of metabolism regulation. As a result, all recent reptiles have a complex morphophysiological organization of the heart, which was functionally more suitable for their almost warm-blooded ancestors. Recent reptiles use part of their ancestral properties as an adaptation to new environmental conditions, new environmental requirements, and their new morphophysiological state. This unique organization of the heart is characteristic of all modern and extinct reptiles, and, importantly, it is characteristic exclusively for reptiles due to their original endothermic state.

Routine maternal ABO/Rhesus D blood typing can alert of massive foetomaternal haemorrhage.

Spontaneous massive foetomaternal haemorrhage (SM-FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM-FMH. Retrospective analysis of medical records from neonates born at our tertiary, university-affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM-FMH was based on neonates born with severe anaemia (haematocrit [HCT] <15%) within the first 24 h post-delivery with positive maternal Kleihauer-Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM-FMH. Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM-FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM-FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.

Late Paleozoic intra-oceanic arc and its accretionary complex in East Junggar (NW China): implications for multiple arc amalgamation in the southern Altaids

The East Junggar is a key to understanding the accretionary history of the southern Altaids. However, the tectonic setting and amalgamation history of the East Junggar during the Carboniferous–Permian remain controversial. Here we report new field, geochronological and geochemical data for the Carboniferous–Permian volcanic and sedimentary rocks from the Jiangjun unit and the Hongliugou ophiolitic complex of East Junggar to constrain its tectonic evolution. Carboniferous volcanic rocks, with zircon and apatite U–Pb ages from 337 ± 2 to 303 ± 32 Ma, display arc-related geochemical characteristics. Carboniferous–Permian sedimentary rocks predominantly contain Carboniferous–Permian detrital zircons and have maximum depositional ages from 318 ± 5 to 281 ± 6 Ma. Provenance analysis indicates that the sediments from the west Jiangjun unit were sourced from the Yemaquan arc and those from the east Jiangjun unit may be sourced solely from a new intra-oceanic arc. Integrated data indicate that Carboniferous–Permian strata in the Jiangjun unit were formed in the intra-oceanic arc setting that remained until the middle Permian. These analyses suggest an amalgamation process of multiple convergence and accretion for the southern Altaids during the formation of NE Pangaea in the late Paleozoic.

Inflammation as a pathway for heavy metal-induced liver damage—Insights from a repeated-measures study in residents exposed to metals and bioinformatics analysis

BackgroundEpidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms. MethodWe conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage. ResultWe obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (β = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (β = −0.21; 95% CI: −0.39, −0.03), Mn and the annual increase rate of GLB (β = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (β = −1.15; 95% CI: −2.00, −0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways. ConclusionOur findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.

Heat transfer analysis of mixed convection boundary layer blood base nanofluids with the influence of viscous dissipation

In this research study, we delve into the analysis of two-dimensional boundary layer incompressible viscous flow of blood based nanofluids, incorporating a couple stress model. This investigation encompasses considerations of heat transmission and viscous dissipation effects. Specifically, focus on a particular type of nanoparticle, Magnesium oxide (MgO), dispersed in blood, the base fluid. By employing suitable similarity transformations, transform a set of partial differential equations (PDEs) into nonlinear ordinary differential equations (ODEs). To leverage the Homotopy Analysis Approach (HAM) to solve this system of equations. This study discerns the impacts of various factors on temperature and velocity distributions. Visualization through graphs depicting nanoparticle volume concentration, magnetic field strength, couple stress parameter, Eckert number, and Prandtl number aids in presenting our findings. These insights illuminate the intricate interplay among different parameters and offer insights for enhancing heat transfer in blood-based nanofluids. Additionally, scrutinize the thermal performance of the blood-based nanofluid, assessing the Nusselt number and local skin friction coefficient. Such analysis holds significance for ensuring patient safety and treatment efficacy, particularly in medical procedures involving blood circulation, where mixed convection plays a pivotal role. Understanding these dynamics is crucial for the design and optimization of various medical devices and therapies, ensuring optimal temperature maintenance during blood circulation-related operations.

The exposure to volatile organic compounds associate positively with overactive bladder risk in U.S. adults: a cross-sectional study of 2007-2020 NHANES.

The aim of this study was to comprehensively investigate the potential relationship between blood volatile organic compounds (VOCs) and overactive bladder (OAB) risk. A total of 11,183 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study. We used multivariate logistic regression models to investigate the relationship between nine blood VOCs and OAB risk. Restricted cubic spline (RCS) analysis was used to investigate the dose-response relationship between blood VOCs and OAB. In addition, the overall association of blood VOCs with OAB risk was assessed by weighted quantile sum (WQS) regression model. Finally, we conducted subgroup analyses to explore the findings in different high-risk populations. After adjusting for potential confounders, logistic regression analysis revealed that blood 2,5-dimethylfuran (aOR = 2.940, 95% CI: 1.096-7.890, P = 0.032), benzene (aOR = 1.460, 95% CI: 1.044-2.043, P = 0.027) and furan (aOR = 9.426, 95% CI: 1.421-62.500, P = 0.020) were positively independent associated with the risk of OAB. And dose-response risk curves indicated that 2,5-dimethylfuran, benzene and furan in the blood were linearly positive associated with OAB risk. WQS regression analysis showed that exposure to mixed blood VOCs increased the risk of OAB (OR = 1.29, 95% CI: 1.11-1.49), with furans having the greatest weight. In subgroup analyses, we found that OAB was more susceptible to blood VOCs in young and middle-aged, male, non-hypertensive, and alcohol-drinking populations. The results of this study indicate that high exposure to VOCs is independently and positively associated with OAB risk in U.S. adults, particularly 2,5-dimethylfuran, benzene, and furan. In addition, age, gender, hypertension and alcohol consumption may influence the association. Our study provided novel epidemiologic evidence to explore the potential role of environmental pollutants in OAB.

Whole-genome sequences reveal zygotic composition in chimeric twins

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

Next generation sequencing improves the resolution of detecting mixed host blood meal sources in field collected arboviral mosquito vectors.

Accurate knowledge of blood meal hosts of different mosquito species is critical for identifying potential vectors and establishing the risk of pathogen transmission. We compared the performance of Miseq next generation sequencing approach relative to conventional Sanger sequencing approach in identification of mosquito blood meals using genetic markers targeting the 12S rRNA and cytochrome oxidase I (COI) genes. We analysed the blood meals of three mosquito vector species (Aedes aegypti, Aedes simpsoni s.l. and Culex pipiens s.l.) collected outdoors, and compared the frequency of single- versus multiple-blood feeding. Single host blood meals were mostly recovered for Sanger-based sequencing of the mitochondrial 12S rRNA gene, whereas Miseq sequencing employing this marker and the COI marker detected both single and multiple blood meal hosts in individual mosquitoes. Multiple blood meals (two or more hosts) which mostly included humans were detected in 19%-22.7% of Ae. aegypti samples. Most single host blood meals for this mosquito species were from humans (47.7%-57.1%) and dogs (9.1%-19.0%), with livestock, reptile and rodent hosts collectively accounting for 4.7%-28.9% of single host blood meals. The frequency of two or more host blood meals in Ae. simpsoni s.l. was 26.3%-45.5% mostly including humans, while single host blood meals were predominantly from humans (31.8%-47.4%) with representation of rodent, reptile and livestock blood meals (18.2%-68.2%). Single host blood meals from Cx. pipiens s.l. were mostly from humans (27.0%-39.4%) and cows (11.5%-27.36%). Multiple blood meal hosts that mostly included humans occurred in 21.2%-24.4% of Cx. pipiens s.l. samples. Estimated human blood indices ranged from 53%-76% for Ae. aegypti, 32%-82% for Ae. simpsoni s.l. and 26%-61% for Cx. pipiens s.l. and were consistently lower for Sanger-based sequencing approach compared to Miseq-based sequencing approach. These findings demonstrate that Miseq sequencing approach is superior to Sanger sequencing approach as it can reliably identify mixed host blood meals in a single mosquito, improving our ability to understand the transmission dynamics of mosquito-borne pathogens.

An Entomological Investigation during a Recent Rift Valley Fever Epizootic/Epidemic Reveals New Aspects of the Vectorial Transmission of the Virus in Madagascar.

A Rift Valley fever (RVF) outbreak occurred in at least five regions of Madagascar in 2021. The aim of this study was to provide an overview of the richness, abundance, ecology, and trophic preferences of mosquitoes in the Mananjary district and to investigate the distribution of mosquitoes that were RT-PCR-positive for RVFV. Three localities were prospected from 26 April to 4 May 2021, using light traps, BG-Sentinel traps baited with an artificial human odor, Muirhead-Thomson pit traps, and indoor pyrethroid spray catches. A total of 2806 mosquitoes belonging to at least 26 species were collected. Of 512 monospecific pools of mosquitoes tested with real-time RT-PCR, RVFV was detected in 37 pools representing 10 mosquito species. The RVFV-positive species were as follows: Aedes albopictus, Ae. argenteopunctatus, Anopheles coustani, An. gambiae s.l., An. mascarensis, An. squamosus/cydippis, Culex antennatus, Cx. decens, Cx. Tritaeniorhynchus, and Uranotaenia spp. Of the 450 tested engorged females, 78.7% had taken a blood meal on humans, 92.9% on cattle, and 71.6% had taken mixed (human-cattle) blood meals. This investigation suggests the potential role of mosquitoes in RVFV transmission within this epizootic/epidemic context and that the human populations at the three study sites were highly exposed to mosquitoes. Therefore, the use of impregnated mosquito nets as an appropriate prevention method is recommended.

The Predictive Role of Lactate in the Emergency Department in Patients with Severe Dyspnea.

An accurate identification of patients at the need for prioritized diagnostics and care are crucial in the emergency department (ED). Blood gas (BG) analysis is a widely available laboratory test, which allows to measure vital parameters, including markers of ventilation and perfusion. The aim of our analysis was to assess whether blood gas parameters in patients with dyspnea at an increased risk of respiratory failure admitted to the ED can predict short-term outcomes. The study group eventually consisted of 108 patients, with available BG analysis. The clinical and laboratory parameters were retrospectively evaluated, and three groups were distinguished-arterial blood gas (ABG), venous blood gas (VBG), and mixed blood gas. The primary endpoint was short-term, all-cause mortality during the follow-up of median (quartile 1-quartile 3) 2 (1-4) months. The independent risk factors for mortality that could be obtained from blood gas sampling were evaluated. The short-term mortality was 35.2% (38/108). Patients who died were more frequently initially assigned to the red triage risk group, more burdened with comorbidities, and the median SpO2 on admission was significantly lower than in patients who survived the follow-up period. In the multivariable analysis, lactate was the strongest independent predictor of death, with 1 mmol/L increasing all-cause mortality by 58% in ABG (95% CI: 1.01-2.47), by 80% in VBG (95% CI: 1.13-2.88), and by 68% in the mixed blood gas analysis (95% CI: 1.22-2.31), what remained significant in VBG and mixed group after correction for base excess. In each group, pH, pO2, and pCO2 did not predict short-term mortality. In patients admitted to the ED due to dyspnea, at risk of respiratory failure, lactate levels in arterial, venous, and mixed blood samples are independent predictors of short-term mortality.

Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration.

The Bacillus Calmette Guerin (BCG) vaccine has been shown to induce non-specific protection against diseases other than tuberculosis in vaccinated individuals, attributed to the induction of trained immunity. We have previously demonstrated that BCG administration induces innate immune training in mixed peripheral blood mononuclear cells and monocytes in calves. Gamma Delta (γδ) T cells are non-conventional T cells that exhibit innate and adaptive immune system features. They are in higher proportion in the peripheral blood of cattle than humans or rodents and play an essential role in bovine immune response to pathogens. In the current study, we determined if BCG administration induced innate immune training in bovine γδ T cells. A group of 16 pre-weaned Holstein calves (2-4 d age) were enrolled in the study and randomly assigned to vaccine and control groups (n=8/group). The vaccine group received two doses of 106 colony forming units (CFU) BCG Danish strain subcutaneously, separated by 2 weeks. The control group remained unvaccinated. Gamma delta T cells were purified from peripheral blood using magnetic cell sorting three weeks after receiving the 1st BCG dose. We observed functional changes in the γδ T cells from BCG-treated calves shown by increased IL-6 and TNF-α cytokine production in response to in vitro stimulation with Escherichia coli LPS and PAM3CSK4. ATAC-Seq analysis of 78,278 regions of open chromatin (peaks) revealed that γδ T cells from BCG-treated calves had an altered epigenetic status compared to cells from the control calves. Differentially accessible peaks (DAP) found near the promoters of innate immunity-related genes like Siglec14, Irf4, Ifna2, Lrrfip1, and Tnfrsf10d were 1 to 4-fold more accessible in cells from BCG-treated calves. MOTIF enrichment analysis of the sequences within DAPs, which explores transcription factor binding motifs (TFBM) upstream of regulatory elements, revealed TFBM for Eomes and IRF-5 were among the most enriched transcription factors. GO enrichment analysis of genes proximal to the DAPs showed enrichment of pathways such as regulation of IL-2 production, T-cell receptor signaling pathway, and other immune regulatory pathways. In conclusion, our study shows that subcutaneous BCG administration in pre-weaned calves can induce innate immune memory in the form of trained immunity in γδ T cells. This memory is associated with increased chromatin accessibility of innate immune response-related genes, thereby inducing a functional trained immune response evidenced by increased IL-6 and TNF-α cytokine production.

Blood meal metabarcoding of the argasid tick (Ornithodoros turicata Dugès) reveals extensive vector‐host associations

AbstractMolecular methods to understand host feeding patterns of arthropod vectors are critical to assess exposure risk to vector‐borne disease and unveil complex ecological interactions. We build on our prior work discovering the utility of PCR‐Sanger sequencing blood meal analysis that work well for soft ticks (Acari: Argasidae), unlike for hard ticks (Acari: Ixodidae), thanks to their unique physiology that retains prior blood meals for years. Here, we apply blood meal metabarcoding using amplicon deep sequencing to identify multiple host species in individual Ornithodoros turicata soft ticks collected from two natural areas in Texas, United States. Of 788 collected O. turicata, 394 were evaluated for blood meal source via metabarcoding, revealing 27 different vertebrate hosts (17 mammals, five birds, one reptile, and four amphibians) fed upon by 274 soft ticks. Information on multiple hosts was derived from 167 individual O. turicata (61%). Metabarcoding revealed mixed vertebrate blood meals in O. turicata while same specimens yielded only one vertebrate species using Sanger sequencing. These data reveal wide host range of O. turicata and demonstrate the value of blood meal metabarcoding for understanding the ecology for known and potential tick‐borne pathogens circulating among humans, domestic animals, and wildlife such as relapsing fever caused by Borrelia turicatae. Our results also document evidence of prior feeding on wild pig from an off‐host soft tick for the first time in North America; a critical observation in the context of enzootic transmission of African swine fever virus if it were introduced to the US. This research enhances our understanding of vector‐host associations and offers a promising perspective for biodiversity monitoring and disease control strategies.

Botanical dispersal pathways into Malesia: The Philippines – Southeast Asian connection

The Malay Archipelago, also known as Malesia, the triangle Malay Peninsula–Philippines–New Guinea, encompassing Indonesia, is tectonically one of the world’s most active areas with an intricate history of amalgamation of terranes. For plants it means that ancestral species must have dispersed to the area, which presently holds about 70 % of endemic species with an estimated total of up to 45 000 species. One of the possible dispersal routes mentioned runs from the SE Asian mainland via the Philippines. This was considered likely for montane species and for species that prefer a yearly dry monsoon period. However, comparisons of numbers of species, dated phylogenies with a clade on the mainland and another in the Philippines and Species Distribution Modelling all show that most likely only few species dispersed via this northern route. Chance long distance dispersal, especially for montane species, is always possible, but for the dry monsoon preferring species, for which the Philippine connection was mentioned once as a pathway, the savannah corridor during glacial periods, running from the Malay Peninsula to Java, was likely a far more important dispersal route.

Study on detection of intracerebral hemorrhage based on frequency difference of permittivity

Introduction: Current detection of intracerebral hemorrhage (ICH), whether employing Electrical Capacitance Tomography (ECT) or other electrical imaging techniques, rely on time-difference measurements. The time-difference methods necessitate baseline measurements from the patient in a non-hemorrhagic state, which is impractical to obtain, rendering rapid detection of ICH unfeasible.Methods: This study introduces a novel approach that capitalizes on the distinct dispersion characteristics of the permittivity in brain tissue and the spectral variance of the permittivity between blood and other brain components. Specifically, the frequency-dependent variations in the permittivity are employed to achieve absolute detection of ICH, thereby eliminating the need for non-hemorrhagic baseline data. The methodology entails identification of two frequency points that the frequency-dependent variation in the permittivity at these two frequency points manifest the maximal difference between blood and other brain tissues. Subsequently, this permittivity differential at the two identified frequency points is utilized for hemorrhage detection. Experimental measurements were conducted using an impedance analyzer and a parallel plate capacitor to capture the capacitance in four single-component substances—distilled water, sheep blood, isolated pig fat, and isolated pig brain—as well as three mixed blood compounds—distilled water enveloping sheep blood, pig fat encapsulating sheep blood, and pig brain surrounding sheep blood—across a frequency range of 10 kHz to 20 MHz.Results: The results show that in different frequency bands, it is indeed possible to distinguish single-component substances from mixed substances by the frequency difference of capacitance variation. Comparative analysis reveals that the 1 MHz to 5 MHz frequency range is most effective for detecting blood in distilled water. For blood detection in pig fat, a 10 kHz to 1 MHz frequency range is identified as optimal, while a 10 kHz to 0.5 MHz frequency range is advantageous for blood detection in pig brain tissue.Discussion: The findings confirm that absolute detection of ICH is achievable through frequency-dependent variations in the permittivity. However, this necessitates the identification of the frequency band manifesting the largest difference of frequency-dependent variation between single-component and mixed substances. The study acknowledges limitations primarily due to the use of anticoagulant-altered sheep blood, which exhibits permittivity divergent from those of natural blood. Additionally, the in vitro pig fat and pig brain samples, having been subjected to freeze-thaw cycles, also demonstrate permittivity unrepresentative of in vivo tissue.

The Effects of The Changing Locus on Lasi’s Hibridity in The Red Bekisar by Ahmad Tohari

This paper deals with Ahmad Tohari’s English-translated novel entitled The Red Bekisar. The focus is on the effects of the changing locus on the female protagonist’s hybridity. To support the analysis, several concepts are used, namely, the concepts of hybridity, mimicry, and cultural identity in postcolonial literature. Using feminist literary criticism as the frame of analysis, the general research method used is qualitative research, supported by library research. For the literary analysis, the contextual research method is applied, in which, by considering the character, conflict, and setting, the focus is on the female protagonist’s hybridity and how her hybridity is regarded by people from different loci. The results show that the female character, Lasi, has a different life because of her Javanese-Japanese mixed blood. In the remote village of Karangsoga, her hybridity is scorned, but in the big city of Jakarta, her hybridity is highly appreciated. However, she is treated like an object, a valuable doll that can be transferred to different owners. Her resistance indicates that her agency as a human being emerges when she is cornered.

Whole-Genome Sequencing Identifies Structural Variation As a Key Driver of Disease Relapse and Aggressive Clinical Behavior in Multiple Myeloma

INTRODUCTION: Many key genomic events leading to relapse in multiple myeloma (MM) occur outside of coding regions and can only be identified using whole-genome sequencing (WGS). Studies of MM progression examining single nucleotide variants (SNVs) and insertions/deletions (InDels) have identified a distinct pattern of mutations associated with resistance, however these do not fully account for drivers of progression. Studies of relapsed patients provide hints about the molecular mechanisms driving progression based on identification of homozygous loss of tumor suppressor genes, aberrant copy-number variants (CNVs), and rare examples of complex structural variants (SV). We have analyzed a set of presentation and relapsed MM samples, including paired data, derived from WGS of plasma cells and focused on SVs as key drivers of progression. METHODS: WGS was performed on 338 MM patient samples using CD138-sorted plasma cells, among which 237 samples were paired including 101 patients (30%) at presentation and at relapse, 35 of whom had more than one sample at relapse. A bioinformatics pipeline employing a consensus mechanism for determining the final set of somatic events was used based on Mutect2, Strelka2, and VarScan2 for SNVs; Mutect2, Strelka2, VarScan2, and SvABA for InDels; Battenberg and FACETS for CNVs; Manta, SvABA, DELLY2, and IgCaller for SVs. Additionally, an admixture workflow was used to estimate each individual's ancestral lineage using continentally-distinct references, comprising 23 regional populations within 5 super-populations from the 1000 Genomes Project (https://github.com/pblaney/mgp1000). Complex rearranged genomes were reconstructed using the graph-based R package JaBbA (https://github.com/mskilab-org/JaBbA). Additionally, the python package Pairtree (https://github.com/morrislab/pairtree) was used to describe the evolutionary history of acquired mutations in these patients. RESULTS: Themedian age of the cases studied was 67, and 42% were female. Racial admixture correlated with self-identification, including 74% of European ancestry with the remainder being predominantly of African ancestry. High-risk cytogenetic features were found in 10% and 13% at diagnosis and relapse, respectively. As expected, the tumor mutational burden of the relapse cases was higher than that at presentation. The patterns of SNV mutational drivers were similar at relapse in comparison to presentation with again evidence for a role of biallelic tumor suppressor gene inactivation as being a key mechanism. We also found that the number of SVs increased at relapse. Complex SVs including templated insertions, chromoplexy, and chromothripsis were detected and occurred exclusively at relapse in some cases as well as earlier in the natural history in others, suggesting they can occur as both early and late driver events. Characterizing complex SVs, further we identified them at lower levels in cases at presentation compared to relapse, consistent with these being at a higher clonal fraction and providing further evidence for their role as driver events. We did not see the emergence of additional rearrangements at relapse in either the templated insertions or chromoplexy events, suggesting that these occur at a single timepoint and remain structurally stable overtime. CONCLUSIONS: Complex SVs provide a novel mechanism driving relapse in MM which can deregulate multiple genes simultaneously providing new potential markers of aggressive disease behavior and disease evolution.

A novel three-step DNA extraction method for mixed bloodstains.

Mixed DNA samples from at least two contributors can be present at a crime scene, which could be the most crucial piece of genetic evidence. The mixed stains in sexual assault cases are typically separated using differential lysis procedures (a two-step method). Blood mixed stains, however, are usually difficult to separate. In this work, we propose that a mixed stain comprises three layers, that is, (1) the upper layer which is primarily made up of cells from one contributor; (2) the middle layer which is a similar mixture from two contributors; and (3) the lower layer which primarily comprises cells from the other contributor. Based on this concept, a novel three-step DNA extraction method was proposed to solve the challenge involving bloodstains from two contributors. In the experiment, we extracted three layers DNA from mixed bloodstains using three steps. As a result, single-source DNA and approximate single-source DNA were detected from steps 1 and 3, respectively. This study demonstrates that the DNA from some mixed blood stains could be effectively separated following an appropriate extraction strategy, providing valuable insights, and serving as a reference for future examination of blood mixtures.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (p = 4.1 × 10-4) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p = 0.039). A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..

TREATMENT OF UROLITHIASIS WITH TEMPUYUNG LEAF IN LOCAL CAT

Urolithiasis is a condition of calculi formation as a result of urine supersaturation, consisting of one or several type of mineral such as calcium oxalate, and phosphate that can move down along the ureters, bladder, and urethra. Urolithiasis is one of the most common diseases in animal. as many as 50 of 385 cats experienced urolithiasis. Tempuyung (Sonchus arvensis L.) is one of the medicinal plants that was efficacious as a kidney stone breaker and urine streamer. organic compounds such as flavonoids efficacious break the kidney stone and treat inflammation of the urinary tract. This reported case occurred in a local cat, male, 4.5 years old, 3.6 kg, who came to the Teaching Veterinary Hospital, Faculty of Veterinary Medicine, Udayana University, with difficulty urinating for a few days and when the urine came out it looked mixed blood. Physical examination showed cat was dehydrated. Supportive examinations were carried out in the form of hematological examination, ultrasonography (USG), and urine sedimentation. The result of the hematological examination showed that the animal had hypochromic microcytic anemia, ultrasound result showed calculi in the urinary bladder. The animal was diagnosed with urolithiasis with a dubius-fausta prognosis. The therapy that has given was fluid therapy, injection therapy with amoxicillin (antibiotic), and herbal medicine tempuyung leaves (oral). The cat's condition improved after therapy, characterized by urination without hematuria and no pain during urination, and it is recommended that the feed pattern be changed to wet feed.