Functional and structural reorganization in brain tumors: a machine learning approach using desynchronized functional oscillations

Abstract

Neuroimaging studies have allowed for non-invasive mapping of brain networks in brain tumors. Although tumor core and edema are easily identifiable using standard MRI acquisitions, imaging studies often neglect signals, structures, and functions within their presence. Therefore, both functional and diffusion signals, as well as their relationship with global patterns of connectivity reorganization, are poorly understood. Here, we explore the functional activity and the structure of white matter fibers considering the contribution of the whole tumor in a surgical context. First, we find intertwined alterations in the frequency domain of local and spatially distributed resting-state functional signals, potentially arising within the tumor. Second, we propose a fiber tracking pipeline capable of using anatomical information while still reconstructing bundles in tumoral and peritumoral tissue. Finally, using machine learning and healthy anatomical information, we predict structural rearrangement after surgery given the preoperative brain network. The generative model also disentangles complex patterns of connectivity reorganization for different types of tumors. Overall, we show the importance of carefully designing studies including MR signals within damaged brain tissues, as they exhibit and relate to non-trivial patterns of both structural and functional (dis-)connections or activity.

Functional and structural reorganization in brain tumors: a machine learning approach using desynchronized functional oscillations

Abstract

Neuroimaging studies have allowed for non-invasive mapping of brain networks in brain tumors. Although tumor core and edema are easily identifiable using standard MRI acquisitions, imaging studies often neglect signals, structures, and functions within their presence. Therefore, both functional and diffusion signals, as well as their relationship with global patterns of connectivity reorganization, are poorly understood. Here, we explore the functional activity and the structure of white matter fibers considering the contribution of the whole tumor in a surgical context. First, we find intertwined alterations in the frequency domain of local and spatially distributed resting-state functional signals, potentially arising within the tumor. Second, we propose a fiber tracking pipeline capable of using anatomical information while still reconstructing bundles in tumoral and peritumoral tissue. Finally, using machine learning and healthy anatomical information, we predict structural rearrangement after surgery given the preoperative brain network. The generative model also disentangles complex patterns of connectivity reorganization for different types of tumors. Overall, we show the importance of carefully designing studies including MR signals within damaged brain tissues, as they exhibit and relate to non-trivial patterns of both structural and functional (dis-)connections or activity.

The genetic status and rescue measure for a geographically isolated population of Amur tigers

Abstract

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population’s genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

The genetic status and rescue measure for a geographically isolated population of Amur tigers

Abstract

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population’s genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia

Abstract

Background

Genomic surveillance is crucial for monitoring malaria transmission and understanding parasite adaptation to interventions. Zambia lacks prior nationwide efforts in malaria genomic surveillance among African countries.

Methods

We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241 P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection.

Results

We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. Within Zambia, identity by descent (IBD) relatedness analysis uncovers local spatial clustering and rare cases of long-distance sharing of closely related parasite pairs. Genomic regions with large shared IBD segments and strong positive selection signatures implicate genes involved in sulfadoxine-pyrimethamine and artemisinin combination therapies drug resistance, but no signature related to chloroquine resistance. Furthermore, differences in selection signatures, including drug resistance loci, are observed between eastern and western Zambian parasite populations, suggesting variable transmission intensity and ongoing drug pressure.

Conclusions

Our findings enhance our understanding of nationwide P. falciparum transmission in Zambia, establishing a baseline for analyzing parasite genetic metrics as they vary over time and space. These insights highlight the urgency of strengthening malaria control programs and surveillance of antimalarial drug resistance.

Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia

Abstract

Background

Genomic surveillance is crucial for monitoring malaria transmission and understanding parasite adaptation to interventions. Zambia lacks prior nationwide efforts in malaria genomic surveillance among African countries.

Methods

We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241 P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection.

Results

We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. Within Zambia, identity by descent (IBD) relatedness analysis uncovers local spatial clustering and rare cases of long-distance sharing of closely related parasite pairs. Genomic regions with large shared IBD segments and strong positive selection signatures implicate genes involved in sulfadoxine-pyrimethamine and artemisinin combination therapies drug resistance, but no signature related to chloroquine resistance. Furthermore, differences in selection signatures, including drug resistance loci, are observed between eastern and western Zambian parasite populations, suggesting variable transmission intensity and ongoing drug pressure.

Conclusions

Our findings enhance our understanding of nationwide P. falciparum transmission in Zambia, establishing a baseline for analyzing parasite genetic metrics as they vary over time and space. These insights highlight the urgency of strengthening malaria control programs and surveillance of antimalarial drug resistance.

Physicochemical characteristics of lakes along the southern Baltic Sea coast

Abstract

We present a unique data set of selected physicochemical parameters characterizing the environment of the Baltic coastal lakes within Polish borders. The peculiarity of the system derives principally from the interaction of the lakes with a sea of relatively low salinity. In contrast to our best understanding of the state of biological knowledge, the abiotic parameters of coastal lakes along the southern Baltic Sea have never previously been so comprehensively supplemented. The database consists of physicochemical properties of 13 coastal lakes based on the analytical assessment of 419 water samples collected seasonally between 2014 and 2019. Water properties were analyzed according to the connection of the lakes to the Baltic Sea using a total of 23 predictors. The lakes were classified as closed, intermittently connected, or open. Based on the physicochemical data, a relationship between the hydrological connection between the lakes and the sea was determined. The data collected could be used to monitor ongoing global climate change at the biosphere level.

How business environment of countries along the Belt and Road impacts China’s OFDI efficiency: a stochastic frontier gravity model approach

Abstract

The Belt and Road Initiative (BRI) provides a new opportunity for the continued deepening of economic and trade cooperation between China and countries along the BRI route. However, different business environments among countries have led to the problem of a low and uneven distribution of China’s overall trade and investment efficiency in the countries along the route. Using the stochastic frontier gravity model, this study evaluates the efficiency of China’s outward foreign direct investment (OFDI) based on the data of 47 countries along the Belt and Road route from 2013 to 2019. The empirical results indicate that the efficiency level of China’s OFDI in countries located along the Belt and Road route is 43.39%, which suggests a regional imbalance. In terms of business environment factors, regulatory governance, civic discourse, government accountability, and regulatory quality in host countries have a positive impact on China’s OFDI. The positive effects of the BRI have enabled Chinese enterprises to better face factors such as political instability, corruption and imperfections in the legal system when investing abroad. The findings and suggestions could help the governments and enterprises of the countries along the route improve the business environment in a more targeted manner, enhance the space for economic and trade cooperation, and promote the common development of the countries along the route.

A review of the COVID-19 pandemic’s effects and challenges on worldwide waste management for sustainable development

Abstract

Through an extensive literature review, this study determines the COVID-19 pandemic's impacts and challenges on worldwide waste management for sustainable development. The coronavirus 2019 (COVID-19) pandemic has adversely and harshly affected almost every element of global social, economic, and environmental systems over the past few years. The widespread use of disposables and personal protective equipment (PPE) for infested and healthy people and frontier employees caused unprecedented miscellaneous garbage. Increasing waste volumes caused a problem for standard waste disposal facilities, which harmed the global waste management sector and resulted in a vital global scenario. Since waste management in developing countries is still in its infancy, the pandemic has broken many regions of the globe. The complete assessment gives a synopsis of COVID-19's impacts and difficulties on waste management. This study reviews the COVID-19 pandemic's effects and challenges on worldwide waste management for sustainable development to fill this gap. This analysis refers to the quantitative research method used to analyze bibliographic content. It provides a general overview of a research topic that may be further broken down into publications, authors, and journals. With a few notable exceptions, the results obtained align with accepted wisdom. In this study, we used the VOSviewer software. This study showed that most countries, essential to managing the increased waste, have seen an increase due to the COVID-19 pandemic. Nonetheless, a complete bibliometric examination of the issue still needs to be completed.

In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study

Abstract

Background

A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.

Results

Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®.

Conclusions

Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs.

Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018.