Science Groove (Japan)

Liver transplantation is almost the only way to save patients with end-stage liver disease. Particularly, living donor liver transplantation (LDLT) has gained importance in recent years thanks to the shorter waiting times and better graft quality than with deceased donor liver transplantation (DDLT). However, some patients experience graft loss due to unexpected infections, sepsis, or immune-mediated rejection of the transplanted organ. An urgent need exists to clarify which patients experience graft loss. Several models have been proposed, but most analyze the classic DDLT, and knowledge about LDLT is lacking. In this study, we retrospectively analyzed clinical data from 748 patients who underwent LDLT. By adapting machine learning methods, we predicted early graft loss (within 180 days postoperatively) with better performance than conventional models. The model enabled us to stratify a highly heterogeneous sample of patients into five groups. By focusing on survival time, we next categorized the patients into three groups with early, intermediate, and late or no graft loss. Notably, we identified the intermediate-loss group as a distinct population similar to the early-loss population but with different survival times. Additionally, by proposing a hierarchical prediction method, we developed an approach to distinguish these populations using data up to 30 days postoperatively. Our findings will enable the early identification of individuals at risk of graft loss, particularly those in the early- and intermediate-loss groups. This will allow for appropriate patient care, such as switching to DDLT, identifying other living donors for LDLT, or preparing for re-transplantation, leading to a bottom-up improvement in transplant success rates.

Abstract Alternative tactics refer to the discontinuous patterns of phenotypic variation, often expressed as an association of several phenotypes. These tactics are widely observed in several taxa, with individuals in a population choosing a phenotype from multiple options depending on their status. In salmonids, alternative migratory tactics‐where some individuals undergo feeding migration to the ocean and others remain in their natal streams are associated with exaggerated phenotypic variations. Such discrete alternative phenotypes can have complex impacts on ecological and evolutionary processes (e.g., reproduction and the trait changes due to natural selection) owing to the large differences in demographic rates between tactics. In this study, to explore the eco‐evolutionary consequences of alternative migratory tactics in salmonid fishes, we constructed an age‐stage structured population model focusing on females. As individuals choose a tactic based on their own status, we incorporated the size structure of juveniles into the population dynamics and explored the evolution of the threshold trait. At the evolutionary endpoint, the threshold trait maximized the population size. Furthermore, the coexistence of resident and migrant tactics within a population occurred when the river environment was relatively poor and/or the ocean environment was rich; otherwise, all individuals adopted the resident tactic. This model provides several insights into the eco‐evolutionary response of the population to environmental change. For example, the increase in survivorship during migration increased the population size and the fraction of migrants as an ecological and evolutionary response, respectively.

In 2016, «Guidelines for the organization of medical care for patients with hereditary atherogenic disorders of lipid metabolism in the constituent entities of the Russian Federation» were published, defining the stages of medical care for patients with inherited dyslipidemias: screening, diagnosis, treatment, and follow-up. Objective. To determine the proportion of patients of the lipid center subject to follow-up; to regulate the referrals for follow-up and develop its algorithm; to propose measures to improve the follow-up quality. Material and methods. The main clinical characteristics of 1.233 patients of the lipid center of the Republic of Tatarstan were studied. Descriptive statistics methods were used for the statistical processing of the study data. Results. In 2018, the Republic of Tatarstan initiated the program «Early detection of familial hypercholesterolemia in working-age people and their families to reduce mortality from cardiovascular diseases» and established centers for adult and children’s lipidology. Out-patient clinics and hospitals of the republic participate in the screening of patients. Lipid centers provide diagnosis and therapy. 52 (4.22%) patients at extremely high risk of cardiovascular events, 293 (23.76%) at very high risk, 847 (68.69%) at high risk, 26 (2.11%) at moderate risk, and 15 (1.22%) at low risk were identified. Thus, 1.192 (96.67%) patients at high and very high risk were identified. An algorithm for monitoring patients with lipid metabolism disorders, including telecommunication technologies, has been developed for follow-up in a community healthcare organization. Conclusion. Establishing follow-up offices for patients with lipid metabolism disorders increases the availability of highly qualified specialized care for such patients. To implement high-quality and effective follow-up, we recommend using the proposed algorithm, telecommunication technologies, establishing patient schools, and training specialists to review the most challenging clinical cases.

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence’s impact on choosing optimal drug treatment.

\n Dentre as principais doenças do tomateiro, as de etiologia viral apresentam um papel central no manejo fitossanitário da cultura, principalmente os chamados orthotospovirus, que são coloquialmente conhecidos no Brasil como \\"vira-cabeça\\", que incluem quatro diferentes espécies de vírus do gênero Orthotospovirus, denominadas de Tomato spotted wilt virus (TSWV), Tomato chlorotic spot virus (TCSV), Groundnut ringspot virus (GRSV) e Chrysanthemum stem necrosis virus (CSNV). Este assim denominado \\"complexo do vira-cabeça\\" é transmitido de maneira persistente propagativa por diferentes espécies de Thysanoptera, sendo particularmente importante por apresentar um modelo epidemiológico de doença policíclica com disseminação primária contínua, em que o vetor e as hospedeiras alternativas dos vírus conferem uma relevância mais ampla, exigindo, mais do que um manejo local, um manejo regional. Para contornar essa particularidade, a resistência genética se mostra primordial para um manejo sustentável. No caso do tomate, a utilização de cultivares que carregam o gene Sw-5, que confere resistência de amplo espectro às principais espécies de orthotospovirus, é bastante utilizada, constituindo-se uma característica básica na tomaticultura moderna. Todavia, é cada vez mais comum a ocorrência de sintomas de orthotospoviroses em campos comerciais de tomates portadores do gene Sw-5. O presente trabalho teve por objetivo estudar a prevalência das diferentes espécies de orthotospovirus em campos comerciais de tomate de mesa em diferentes regiões produtoras, a partir de levantamentos em parcelas demarcadas de 1 mil plantas. Adicionalmente, estudou-se o efeito da coinfecção com o crinivírus ToCV e o efeito do híbrido em homozigose na infectividade das espécies encontradas. Concluiu-se que a incidência de viroses em campos comerciais de cultivo de tomate portadores do gene Sw-5 nas safras de 2017 e 2018 com sintomas associados ao complexo do \\"vira-cabeça\\" foram baixas, variando entre 0,1 a 3,6%. Das amostras sintomáticas coletadas no campo, 71,5% foram positivas a orthotospovirus. Resultados de sequenciamento de isolados selecionados destas amostras sintomáticas mostraram que 70,5% pertenciam à espécie GRSV e 29,5% à TCSV ao analisar a identidade dos segmentos L e S do mesmo isolado. No caso do segmento M destes mesmos isolados, o alinhamento de todas as sequências mostrou identidade com o acesso HQ644141.1 de orthotospovirus do GeneBank, que apresenta rearranjo de genoma. As espécies CSNV e TSWV não foram detectadas. Os resultados positivos para o crinivírus ToCV corresponderam a uma incidência baixa de apenas 5,0 %, de maneira que o presente trabalho não possibilitou avaliar o efeito do crinivírus na infecção com orthotospoviroses em cultivares que carregam o gene Sw-5, evidenciando, todavia, que a suscetibilidade ao GRSV e/ou ao TCSV das cultivares que carregam o gene Sw-5 não está necessariamente relacionada com coinfecções com o ToCV. Quando transmitidos por inoculação mecânica, isolados de GRSV e TCSV provenientes de plantas resistentes sintomáticas no campo manifestaram incidência de plantas infectadas semelhantes nos genótipos homozigóticos e heterozigóticos ao gene de resistência e no controle suscetível, demonstrando que condição Sw5/ Sw5 não se mostra vantajosa.\n

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2–3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.

In Nigeria, most welding activities are carried out by road side welders, majority of this welders are ignorant of weld residual stress and its adverse effect on weldment. Residual stress (RS) measuring device is vital in the measurement of inherent stresses in material. The aim of this research was to employ proof of principle in analyzing the weld residual stresses in a material. This was achieved by measuring samples with magnetic residual stress device and then subjecting the weld samples to mechanical tensile test with hope that materials with more residual stresses fail first. Finally the result from both procedures was compared to establish a relationship. Four (4) pieces of mild steel coupons measuring 100 × 40 × 3 mm were welded, producing two specimens, A11 and B11 of 200 × 40 × 3 mm, respectively. The specimens were measured using the Magnetic device developed and 37 signals were obtained per specimen, thereafter, the welded specimens were subjected to tensile testing and results analyzed. From the results obtained, Specimen A11 was observed to have the highest signal peak at the weld zone with RS signal of 20.3983 mV compared to B11 with 19.358 mV. While under tensile loading, it took 1.63 kN to cause failure to specimen A11 and 8.65 kN for specimen B11. From this simple experiment, it implies that the Magnetic RS device was able to mimic the behavior of residual stress and also predicted that A11 would fail first.

Abstract Smith's Comment on our functional analysis of grinding stone fragments from Pleistocene contexts at Lake Mungo (Fullagar et al. 2015) draws attention to the low frequency of implements, uncertainties about functional interpretations and archaeological implications. He argues that Pleistocene seed exploitation at Lake Mungo was limited and probably not indicative of a seed grinding economy. We suggest that it is premature to speculate about the scale of seed grinding at Lake Mungo. We also use new data to address concerns raised about our methodology.

Projekte haben sich in den letzten Jahrzehnten zu einer Standard-Arbeitsform in praktisch allen Unternehmen entwickelt. Sie sind uns dadurch so vertraut geworden, dass wir uns haufig gar keine Gedanken mehr daruber machen, wie man ein Projekt – abhangig von der jeweiligen Projektart – denn am besten durchfuhren und steuern sollte.