bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Progesterone Receptor Expressed by the Cortical Thymic Epithelial Cells Dictates Thymus Involution in Murine Pregnancy
Authors: Ahn Soo Hyun , Nguyen Sean L. , Kim Tae Hoon , Jeong Jae-Wook , Arora Ripla , Lydon John P. , Petroff Margaret G.
Published: April 2022

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo. Interestingly, the maternal thymus also is a known expressor ofPgr; its absence is associated with murine pregnancy complications. However, the localization of its expression and its functional importance were not known. Here, we used a transgenic dual fluorescent reporter mouse model and genetic deletion ofPgrin Foxn1+ thymic epithelial cells (TEC) to demonstrate TEC-specificPgrexpression in pregnancy, especially in the cortex where thymocyte maturation occurs. Using our TEC-specificPgrdeletion mouse model, we demonstrate that TEC-specificPgris necessary for pregnancy-induced thymic involution in pregnancy. Our investigation reveals that PGR expression is upregulated in the cortical thymic epithelial cells during pregnancy, and that PGR expression is important for thymic involution during murine pregnancy.
Identification and Validation of a Prognostic Prediction Model in Diffuse Large B-Cell Lymphoma
Authors: Yan Jiaqin , Yuan Wei , Zhang Junhui , Li Ling , Zhang Lei , Zhang Xudong , Zhang Mingzhi
Published: April 2022

Background

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group with varied pathophysiological, genetic, and clinical features, accounting for approximately one-third of all lymphoma cases worldwide. Notwithstanding that unprecedented scientific progress has been achieved over the years, the survival of DLBCL patients remains low, emphasizing the need to develop novel prognostic biomarkers for early risk stratification and treatment optimization.

Method

In this study, we screened genes related to the overall survival (OS) of DLBCL patients in datasets GSE117556, GSE10846, and GSE31312 using univariate Cox analysis. Survival-related genes among the three datasets were screened according to the criteria: hazard ratio (HR) >1 or <1 and p-value <0.01. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analysis were used to optimize and establish the final gene risk prediction model. The TCGA-NCICCR datasets and our clinical cohort were used to validate the performance of the prediction model. CIBERSORT and ssGSEA algorithms were used to estimate immune scores in the high- and low-risk groups.

Results

We constructed an eight-gene prognostic signature that could reliably predict the clinical outcome in training, testing, and validation cohorts. Our prognostic signature also performed distinguished areas under the ROC curve in each dataset, respectively. After stratification based on clinical characteristics such as cell-of-origin (COO), age, eastern cooperative oncology group (ECOG) performance status, international prognostic index (IPI), stage, and MYC/BCL2 expression, the difference in OS between the high- and low-risk groups was statistically significant. Next, univariate and multivariate analyses revealed that the risk score model had a significant prediction value. Finally, a nomogram was established to visualize the prediction model. Of note, we found that the low-risk group was enriched with immune cells.

Conclusion

In summary, we identified an eight-gene prognostic prediction model that can effectively predict survival outcomes of patients with DLBCL and built a nomogram to visualize the perdition model. We also explored immune alterations between high- and low-risk groups.
The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients
Authors: Wang Junyi , Xu Zihui , Lv Kang , Ye Yingchun , Luo Deng , Wan Li , Zhou Fen , Yu Ailin , Wang Shuo , Liu Jingcheng , Gao Ling
Published: April 2022

Background

Cardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences.

Methods

In this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN <100 ms). All patients’ clinical data were collected and the correlation of clinical variables with HRV were analyzed by correlation and logistic regression analysis. The area below the ROC curve was used to evaluate the predictive performance of serum calcium on HRV.

Results

In this study, declines in HRV were present in 37.0% of T2DM patients. Significant differences in albumin-adjusted serum calcium levels (CaA) (8.86 ± 0.27 vs. 9.13 ± 0.39 mg/dl, p <0.001) and E/A (0.78 ± 0.22 vs. 0.83 ± 0.26, p = 0.029) were observed between declined HRV and normal HRV groups. Bivariate linear correlation analysis showed that CaA and E/A were positively correlated with HRV parameters including SDNN (p < 0.001), SDNN index (p < 0.001), and Triangle index (p < 0.05). The AUC in the ROC curve for the prediction of CaA on HRV was 0.730 (95% CI (0.750–0.815), p < 0.001). The cutoff value of CaA was 8.87 mg/dl (sensitivity 0.644, specificity 0.814). The T2DM patients with CaA <8.87 mg/dl had significantly lower HRV parameters (SDNN, SDNN index, rMSSD, and triangle index) than those with CaA ≥8.87 mg/dl (p < 0.01, respectively). Multivariate logistic regression analysis showed a significantly increased risk of declined HRV in subjects with CaA level <8.87 mg/dl [OR (95% CI), 0.049 (0.024–0.099), p < 0.001].

Conclusions

Declined HRV is associated with a lower CaA level and worse cardiac function. The serum calcium level can be used for risk evaluation of declined HRV in T2DM patients even within the normocalcemic range.
Associations Between Vertebral Marrow Proton Density Fat Fraction and Risk of Prostate Cancer
Authors: Li Shaojun , Wang Bo , Liang Wenwen , Chen Qi , Wang Wei , Mei Jiangjun , Zhang He , Liu Qianqian , Yuan Mingyuan
Published: April 2022

Bone marrow adipocytes may be responsible for cancer progression. Although marrow adipogenesis is suspected to be involved in prostate carcinogenesis, an association between marrow adiposity and prostate cancer risk has not been clearly established in vivo. This work included 115 newly diagnosed cases of histologically confirmed prostate cancer (range, 48–79 years) and 87 age-matched healthy controls. Marrow proton density fat fraction (PDFF) was measured by 3.0-T MR spectroscopy at the spine lumbar. Associations between marrow PDFF and risk of prostate cancer by stage of disease and grade sub-types were performed using multivariable polytomous logistic regression. There were no significant group differences in the vertebral marrow PDFF, despite prostate cancer patients having 6.6% higher marrow PDFF compared to the healthy controls (61.7 ± 9.8% vs. 57.9 ± 6.5%; t = 1.429, p = 0.161). After adjusting for various clinical and demographic characteristics, we found that elevated marrow PDFF was related to an increased risk of high-grade prostate cancer [odds ratios (OR) = 1.31; 95% confidence interval (CI), 1.08–1.57; p = 0.003]. Likewise, increased marrow PDFF had a significantly positive correlation with aggressive prostate cancer risk (OR = 1.54; 95% CI, 1.13–1.92; p <0.001). There were no associations between marrow PDFF and low-grade (p = 0.314) or non-aggressive (p = 0.435) prostate cancer risk. The data support the hypothesis that marrow adiposity was correlated with increased risk of aggressive prostate cancer, supporting a link between adipogenesis and prostate cancer risk.
Modified Calcium Manganites for Thermochemical Energy Storage Applications
Authors: Miller James E. , Babiniec Sean M. , Coker Eric N. , Loutzenhiser Peter G. , Stechel Ellen B. , Ambrosini Andrea
Published: April 2022

CaAl0.2Mn0.8O3-δ (CAM28) and CaTi0.2Mn0.8O3-δ (CTM28) are perovskite metal oxides developed for high-temperature thermochemical energy storage (TCES) applications, e.g., in support of air Brayton power generation. Previous reports for these compounds focus on the equilibrium non-stoichiometry (δ) as a function of temperature and oxygen partial pressure (pO2) and the endotherm (or exotherm) accompanying changes in δ resulting from thermal reduction (or re-oxidation). Herein, we report results for elemental substitution and doping (Al, Co, Fe, La, Sr, Ti, Y, Zn, and Zr) of calcium manganites (CM) that establish the preference for CAM28 and CTM28. Techniques employed include conventional (screening and equilibrium) and ballistically heated multi-cycle thermogravimetric analysis (TGA), conventional and high temperature (in-situ) X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Forward-looking results for A-site Y-doped materials, e.g., Ca0.9Y0.1MnO3-δ (CYM910), establish a route to increasing the reduction enthalpy relative to CAM28 and CTM28, albeit at the expense of increased reduction temperatures and raw materials costs. A thermodynamic model presented for CAM28, but extendable to related materials, provides values for the reaction enthalpy and extent of reduction as a function of temperature and oxygen partial pressure for use in design efforts. Taken as a whole, the results support the choice of Al-doped CaMnO3-δ as a low-cost material for TCES in a high temperature air Brayton application, but point the way to achieving higher stored energy densities that could lead to overall cost savings.
Microbial Fuel Cell for Wastewater Treatment as Power Plant in Smart Grids: Utopia or Reality?
Authors: Tsekouras George J. , Deligianni Panagiota M. , Kanellos Fotis D. , Kontargyri Vassiliki T. , Kontaxis Panagiotis A. , Manousakis Nikolaos M. , Elias Charalambos N.
Published: April 2022

Microbial fuel cells (MFCs) have undergone great technological development in the last 20 years, but very little has been done to commercialize them. The simultaneous power production and wastewater treatment are features those greatly increase the interest in the use of MFCs. This kind of distributed power generation is renewable and friendly and can be easily integrated into a smart grid. However, there are some key issues with their commercialization: high construction costs, difficulty in developing high power structures, MFC lifespan, and maintaining a high level of efficiency. The objective of this article is to explore the possibilities of using MFCs in urban wastewater not only regarding the technical criteria of their application, but also mainly from an economic point of view, to determine the conditions through which the viability of the investment is ensured and the possibilities of their integration in a smart grid are identified. Initially, this article explores the implementation/configuration of a power plant with MFCs within an urban wastewater treatment plant on a theoretical basis. In addition, based on the corresponding physical quantities for urban wastewater treatment, the construction and operational costs are determined and the viability of the investment is examined based on classic economic criteria such as net present value, benefit–cost ratio, internal rate of return, and discounted payback period. Furthermore, sensitivity analysis is carried out, concerning both technical parameters, such as the percentage of organic matter removal, power density, sewage residence time, MFC efficiency, etc., and economical parameters, such as the reduction of construction costs due to change of materials, change of interest rate, and lifetime. The advantages and disadvantages of their use in smart grids is also analyzed. The results show that the use of MFCs for power generation cannot be utopian as long as they are integrated into the structure of a central wastewater treatment plant on the condition that the scale-up technical issues of MFCs are successfully addressed.
Eco-Physiological Responses of Native Desert Plant Species to Drought and Nutritional Levels: Case of Kuwait
Authors: Madouh Tareq A.
Published: April 2022

Drought is the most critical limiting factor affecting plant survival, development, and adaptation in the desert ecosystem. Native desert plant species are adaptable natural biomass crops of the desert’s ecosystem. These native species use water efficiently and tolerate drought and other environmental constraints. In addition, they sustain moderate nutritional values that are essential in terms of maintaining optimum vegetation, development and productivity, and tolerating natural grazing. The objective of this study was to quantify the biomass production and nutritive values of three native desert grass species as influenced by drought stress, that is, 100, 75, 50, and 25% potential evapotranspiration (ETp). Three native desert grasses, viz.,Cenchrus ciliaris,Lasiurus scindicus, andPennisetum divisumwere grown in pots, irrigated with fresh water in a greenhouse, and investigated for their drought tolerance and nutritive values. The results showed that the grasses differ in their responses to drought stress by controlling stomata conductance (gs). The gsincreased significantly (p< 0.001) with adequate irrigation (100 and 75% ETp) and decreased with 50 and 25% ETp in all species. Under moderate drought stress (75 and 50% ETp), all desert grasses used the water efficiently and produced a considerable dry matter yield and stable amounts of nutritive value. At 50% ETp, all desert species showed significant increase (p< 0.001) in root biomass than shoots that increased water absorption to survive a drought environment.L. scindicusexhibited a significantly higher increase (p< 0.001) in root formation at 25% ETp than the 100% ETp treatment. In all the grass species, the protein contents increased as drought stress increased. No significant differences in fat content were detected under all irrigation conditions, while the ash content was significantly (p< 0.001) influenced by severe drought stress. Under natural desert conditions, these adjustments may reduce transpiration demand relative to water deprivation, leading to improved species establishment and supported adaptation to severe desert environments. Understanding the physiological responses and the requirements of desert plant species can be an excellent way to restore ecological functions and biodiversity conservation in a desert environment.
Does the E-Commerce City Pilot Reduce Environmental Pollution? Evidence From 265 Cities in China
Authors: Zhang Zhixin , Sun Zhenya , Lu Hang
Published: April 2022

In order to promote the healthy and rapid development of e-commerce, China launched the construction of National E-commerce Demonstration Cities in 2009. This paper presents a feasible road to achieving sustainable development through the new urban development model. The paper employs the data of 265 cities in China from 2007 to 2016 as a research sample and uses the multiperiod difference-in-difference method to test the impact of National E-commerce Demonstration Cities pilots on urban environmental pollution. The basic result shows that urban environmental pollution is reduced by about 17.5% on average after becoming pilot cities, and the National E-commerce Demonstration Cities policy significantly reduces urban environmental pollution. We adopt a series of robustness tests, and all tests show that the basic result is still robust. Moreover, heterogeneity tests show that the pollution reduction effect of the National E-commerce Demonstration Cities policy in big cities is stronger than in small- and mid-sized cities, and there is no significant difference between the eastern cities and mid-western cities. The pollution reduction effect of the National E-commerce Demonstration Cities policy is more significant in cities with high human capital, low fiscal expenditure, and high information infrastructure. The empirical results of the spatial Dubin model show that the pilot city has no significant spatial spillover to neighboring cities. In the era of rapid development of e-commerce, this study provides a reference for developing countries to improve the urban environment and achieve sustainable development by using the new urban development model integrating e-commerce and urbanization.
Mining of the Association Rules Between Socio-Economic Development Indicators and Rural Harmless Sanitary Toilet Penetration Rate to Inform Sanitation Improvement in China
Authors: Li Yong , Cheng Shikun , Cui Jiangshui , Gao Mingjun , Li Zifu , Wang Ling , Chen Cong , Basandorj Davaa , Li Tianxin
Published: April 2022

The imbalance of socioeconomic development (SED) in different regions of China has resulted in the variability of rural infrastructure penetration. This study aims to improve the SED of each region in China to increase the penetration rate of rural harmless sanitary toilets (RHST). For this purpose, we used association rule mining to analyze the relationship between SED indicators and the penetration rate of RHST for proposing differentiated improvement strategies. Population urbanization rate, tertiary vs. secondary industry output ratio, nonagricultural output value ratio, nonagricultural employment ratio, per capita gross domestic product, and the proportion of added value of industry in the total added value of commodity were used to measure the SED level of 30 regions in China from 2007 to 2017. Results showed that the SED of each region has been improving, and the proportion of added value of industry in the total added value of commodity accounted for the highest proportion of SED. The penetration rate of RHST in each region increased continuously but with significant variability from 2007 to 2017. The range of six SED indicators corresponding to high and low penetration rates of RHST was determined by association rule mining analysis. On the basis of the degree of RHST penetration rate by region in China in 2017 as a reference, differentiated measures were proposed to improve the penetration of RHST in different regions.
A Spatial Empirical Examination of the Relationship Between Agglomeration and Green Total-Factor Productivity in the Context of the Carbon Emission Peak
Authors: Hao Aimin , Tan Jiayin , Ren Zhen , Zhang Zimo
Published: April 2022

We aim to explore the impact of economic agglomeration on the development of green total-factor productivity (GTFP) from both theoretical and empirical levels. We use the non-radial directional distance function method to formulate the GTFP index and further empirically study the impact of economic agglomeration on GTFP. The results indicate that: 1) there is a “U-shaped” curve relationship between economic agglomeration and GTFP, and the formation mechanism is that the economic agglomeration has a threshold effect on the agglomeration externalities such as infrastructure sharing, knowledge spillover, and labor market upgrading. 2) The mismatch of industrial structure is an important reason that the economic agglomeration in this region has not produced an obvious spatial spillover effect on other regions; relaxing restrictions on the concentration of economic activity to regional centers would contribute to the improvement of GTFP. 3) GTFP has the classic “snowball effect” in the time dimension but has the obvious “warning effect” in the space and time dimension. The conclusions of the research show that it is necessary to conform to the redistribution of economic geography, promote the rational allocation of human resources in the territorial space, and promote the coordination of economic agglomeration and green economic development goals.
Factors Controlling the Distribution of Intermediate Host Snails of Schistosoma in Crater Lakes in Uganda: A Machine Learning Approach
Authors: Tabo Zadoki , Neubauer Thomas A. , Tumwebaze Immaculate , Stelbrink Björn , Breuer Lutz , Hammoud Cyril , Albrecht Christian
Published: April 2022

Schistosomiasis affects over 700 million people globally. 90% of the infected live in sub-Saharan Africa, where the trematode species Schistosoma mansoni and S. haematobium transmitted by intermediate hosts (IH) of the gastropod genera Biomphalaria and Bulinus are the major cause of the human disease burden. Understanding the factors influencing the distribution of the IH is vital towards the control of human schistosomiasis. We explored the applicability of a machine learning algorithm, random forest, to determine significant predictors of IH distribution and their variation across different geographic scales in crater lakes in western Uganda. We found distinct variation in the potential controls of IH snail distribution among the two snail genera as well as across different geographic scales. On the larger scale, geography, diversity of the associated mollusk fauna and climate are important predictors for the presence of Biomphalaria, whereas mollusk diversity, water chemistry and geography mainly control the occurrence of Bulinus. Mollusk diversity and geography are relevant for the presence of both genera combined. On the scale of an individual crater lake field, Biomphalaria is solely controlled by geography, while mollusk diversity is most relevant for the presence of Bulinus. Our study demonstrates the importance of combining a comprehensive set of predictor variables, a method that allows for variable selection and a differentiated assessment of different host genera and geographic scale to reveal relevant predictors of distribution. The results of our study contribute to making realistic predictions of IH snail distribution and schistosomiasis prevalence and can help in supporting strategies towards controlling the disease.
Microbial Residual Nitrogen Distribution in Brown Earth’s Aggregates as Affected by Different Maize Residues and Soil Fertility Levels
Authors: Xue Pingluo , Pei Jiubo , Ma Nan , Wang Jingkuan
Published: April 2022

Brown earth is one of the typical soils in the dryland areas of Northeast China, and its degradation is closely related to food security in the local. Effectively preventing soil nitrogen (N) loss can promote the soil fertility supply. As the hub of nitrogen cycling, microorganisms play an important role in N transformation and accumulation. Soil aggregates are important in improving soil fertility and preventing soil degradation because they are an important index to maintain soil fertility. However, the allocation of microbial residual N and its contribution to total N in brown earth’s aggregates are still limited, especially the effects of different maize residue types’ return and soil fertility levels. Focusing on this, a 360-day laboratory incubation experiment at 25°C was carried out induced by adding maize roots and shoots into brown earth with low (L) and high (H) fertility, respectively. Randomized soil samples were taken on the incubation day of 0, 30, 60, 180, and 360, and then, they were divided into macroaggregates (>250 μm) and microaggregates (<250 μm) using a dry-sieved method. The relative contributions of fungal and bacterial residual N to soil total N were calculated by the amino sugar content to examine the accumulated differences of microbial residual N in brown earth’s aggregates with the addition of different parts of maize residues and fertility levels. The results showed that maize residue types had different effects on the fungal and bacterial residual N enrichment in soil aggregates. In macroaggregates, maize roots promoted the accumulation of fungal residual N. The fungal residual N contributions to total nitrogen with root treatments were 1.03 times more than those with shoot treatments. However, in microaggregates, the bacterial residual N contributions to total nitrogen with shoot treatments were 1.01 times more than those with root treatments. These indicated that maize roots should be more beneficial to the accumulation of bacterial residual N in microaggregates. Moreover, the high fertility soil could sequester more microbial residual N than the low fertility soil, showing the content of microbial residual N in high fertility was 1.12–1.18 times more than that in low fertility. Furthermore, the fungal residual N was more beneficially accumulated in low fertility soil. Regardless of the level of fertility, the proportion of N in total N with shoot treatment was higher than that with root treatment, indicating that the above ground maize residues could better promote the metabolic process of microorganisms than the below ground ones. These could provide a theoretical basis for studying the microbial transformation mechanism of nitrogen after maize straw returning to the field, which could be of great significance to main soil fertility.
Physiological Responses of Typical Wetland Plants Following Flooding Process—From an Eco-Hydrological Model Perspective
Authors: Liu Chengliang , Zeng Yijian , Su Zhongbo , Zhou Demin
Published: April 2022

Anaerobics increase resistance to gas transport and microbial activity in flooded soils. This may result in the presence of aerenchyma in the roots of some wetland plants. Increased aerenchyma airspaces enable oxygen to be transported from the above-ground plant parts to the submerged roots and rhizosphere. Nevertheless, there is still a lack of studies linking field experiments and eco-hydrological modeling to the parameterization of the physiological responses of typical wetland plant species to natural flooding events. Furthermore, from the modeling perspective, the contribution of aerenchyma was not sufficiently considered. The goal of this study was to develop and apply an eco-hydrological model capable of simulating various patterns of plant physiological responses to natural flooding events based on key processes of root oxygen diffusion and aerenchyma functioning in a variably-saturated wetland soil environment. Eco-hydrological experiments were conducted accordingly, with surface water level, root-zone soil water content, soil temperature, leaf net photosynthesis rate and root morphology monitored simultaneously in situ at a site dominated by meadow species Deyeuxia angustifolia (Kom.) Y. L. Chang and invaded shrub species Salix rosmarinifolia Linn. var. brachypoda (Trautv.et Mey.) Y.L. Chou in a typical natural floodplain wetland. The results are as follows: (1) Root oxygen respiration rates are strongly correlated with leaf net photosynthesis rates of the two plant types, particularly under flooding conditions during the growing season; (2) Meadow species with a preference for wet microhabitats has a competitive advantage over first-year invading shrub species during flooding events; and (3) an aerenchyma sub-model could improve the eco-hydrological model’s accuracy in capturing plant physiological responses. These findings have the potential to contribute to the management of wetland and its restorations.
The Effect of Manipulated Prenatal Conditions on Growth, Survival, and Reproduction Throughout the Complete Life Course of a Precocial Bird
Authors: Vedder Oscar , Bichet Coraline , Tschirren Barbara
Published: April 2022

The quality of the environment individuals experience during development is commonly regarded as very influential on performance in later life. However, studies that have experimentally manipulated the early-life environment and subsequently measured individual performance in all components of fitness over the complete life course are scarce. In this study, we incubated fertile eggs of Japanese quail (Coturnix japonica) at substandard and standard incubation temperature, and monitored growth, survival, and reproduction throughout the complete life course. While embryonic development was slower and hatching success tended to be lower under substandard incubation temperature, the prenatal treatment had no effect on post-hatching growth, survival to sexual maturity, or age at first reproduction. In adulthood, body mass and investment in individual egg mass peaked at middle age, irrespective of the prenatal treatment. Individual reproduction rate declined soon after its onset, and was higher in females that lived longer. Yet, reproduction, and its senescence, were independent of the prenatal treatment. Similarly, adult survival over the complete lifespan was not affected. Hence, we did not find evidence for effects on performance beyond the developmental period that was manipulated. Our results suggest that effects of unfavorable developmental conditions on individual performance later in life could be negligible in some circumstances.
Biophysical Properties of Inner Bark and Sapwood in Tree Species From Forests With Contrasting Precipitation in Subtropical South America
Authors: Carrasco Laureano Oliva , Bucci Sandra J. , Scholz Fabian G. , Loto Dante , Gasparri Ignacio , Goldstein Guillermo , Campanello Paula I.
Published: April 2022

Stem capacitance and water storage are known to play an important role in the water economy of trees by acting as an intermediate water source for transpiring leaves. The bark, in addition to be involved in protection and mechanical support of the trees, can also serve as a water reservoir. We examined the relationship between inner bark and sapwood biophysical properties in tree species occurring in forests at the opposite ends of a moisture gradient in subtropical South America. We also assessed the relationships between wood density, growth rate and the magnitude of the water reservoir. The inner bark thickness varied between 1.89 and 0.50 cm across species and sites and there were not significant differences between forests. Inner bark capacitance of species from the dry forest was higher than sapwood capacitance, and the opposite was found in the moist forest. Sapwood capacitance (262 ± 80.8 Kg m−3 MPa−1) was significantly higher in the moist forest compared to the dry forest (41.9 ± 4.5 Kg m−3 MPa−1), while the opposite was found for inner bark (50.7 ± 8.4 and 83.1 ± 11.4 Kg m−3 MPa−1, respectively). Inner bark capacitance and density were linear and positively correlated across species, while for sapwood the relationship was well-described by a negative exponential function. In species with higher percentage of inner bark, the time lags in the daily contractions of bark and sapwood tissues were lower. Relative growth rate was negatively correlated with inner bark and sapwood density and positively with daily stored water used and percentage of inner bark across species and sites. Our results suggest that sapwood is a relevant water storage tissue in the trees of the moist forest while inner bark is important for tree functioning in the dry forest. High stem capacitance and water storage are needed to cope with short dry spells or seasonal periods of water deficit, and for maintaining growth rates. These stem properties will be more relevant under climatic scenarios with more frequent extreme drought events or seasonal reduction in precipitation in these forest ecosystems.
Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review
Authors: Zhu Jun , Wan Shuisen , Zhao Xueqi , Zhu Binlu , Lv Yuan , Jiang Hongkun
Published: April 2022

Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.

Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved.

Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA.

Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.
The More You Know, the Less You Stress: Menstrual Health Literacy in Schools Reduces Menstruation-Related Stress and Increases Self-Efficacy for Very Young Adolescent Girls in Mexico
Authors: Long Jeanne L. , Haver Jacquelyn , Mendoza Pamela , Vargas Kotasek Selvia M.
Published: April 2022

Improving the menstrual health literacy of girls and boys is a key strategy within a holistic framework of Save the Children's school health and comprehensive sexuality education programming. As menstrual health is an emerging area of study and programming, Save the Children continues to learn and adjust its interventions using program evaluations and rigorous monitoring. This paper will examine program-monitoring data from three cohorts, representing 47 public schools in Mexico City, Puebla, and Mérida, Mexico. The study focuses on female students in 5th and 6th grade who participated in We See Equal, a school-based program centered on gender equality and puberty education, between September 2018 and December 2019. This study used a cross-sectional quantitative cohort approach to document changes in girls' experiences and perceptions around managing menstruation in school. The analysis compares girls' knowledge and experiences before and after participation in We See Equal to understand how knowledge changes over the program and how those changes may contribute to menstruation-related school engagement, stress, and self-efficacy (MENSES) outcomes. Multivariate regression models explored relationships between MENSES outcomes, knowledge and socioeconomic status (SES). Overall, results show that the more knowledge girls acquired, the higher their self-efficacy score and the lower their stress score, however, certain MHH knowledge was more predictive of MENSES outcomes and varied by SES. Among girls from lower SES, we observed significant relationships between knowing what their period was prior to menarche and the three MENSES outcomes. Decreases in menstruation-related stress were driven by items related to the practical knowledge of how to dispose of sanitary pads and reduced feelings of nervousness on days they had their period at school. Increases in self-efficacy were primarily driven by girls' confidence in their ability to track their period from month to month, feelings that they could still do well on an exam if they had their period at school, and security that they could ask a friend to lend them a pad if they needed one. Implications for future menstrual health literacy programming and targeting populations for menstrual health education, as well as priorities for future research will be discussed.
Understanding Severe Exploitation Requires a Human Rights and Gender-Sensitive Intersectional Approach
Authors: Giammarinaro Maria Grazia
Published: April 2022

This paper discusses the notion of severe exploitation in relation to production and social reproduction, and argues that the existence of huge “edge populations” subject to severe exploitation, mainly involving migrants, is a structural component of global economies, and thus requires primarily not a criminal law but rather a human rights and social justice response. “Edge populations” are targeted for severe exploitation because of intersectional vulnerabilities. A gender perspective implies an analysis of how intersectional factors impact differently women's, men's and LGBTIQ+ lives; this study is however mostly based on women's experiences of severe exploitation and related vulnerabilities. Three sectors prone to severe exploitation have been analyzed, in which weak regulations, and deprivation of rights expose migrants, especially migrants in irregular situations including migrant women, to various forms of severe exploitation. Through an analysis of domestic work, agriculture and the sex industry, this paper highlights that, although in different degrees, a combination of vulnerability and agency, of coercion and negotiation, exists in most cases of severe exploitation. The study suggests that a notion of “gender intersectional exploitation” should be further explored.
Lymphoplasma Exchange Improves Myasthenia Gravis Exacerbations: A Retrospective Study in a Chinese Center
Authors: Ouyang Song , Yin Weifan , Zeng Qiuming , Li Bijuan , Zhang Jian , Duan Weiwei , Li Yi , Liang Yong , Wang Jiaqi , Tan Hong , Yang Huan
Published: April 2022

Background

Lymphoplasma exchange (LPE), a technique combining plasma exchange with leukapheresis, is emerging as promising treatment for autoimmune diseases. Data on the efficacy and safety of LPE in myasthenia gravis (MG) therapy are scarce. In this study, we aimed to comprehensively review the clinical efficacy, safety, and immunological characteristics of LPE therapy in MG patients.

Study Design and Methods

A Chinese cohort of 276 generalized MG patients in state of exacerbation, including impeding crisis, myasthenia crisis, and preparation for thoracic exsection between January 2014 and December 2020, were evaluated in this study.

Results

A total of 276 patients with a median age of 45.5 ± 16.7 years underwent a total of 635 LPE sessions. Clinical scales of Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Specific Manual Muscle Testing (MMT) scores, activities of daily living (ADL) scores, and quality of life (QOL) scores were improved during 4 weeks’ follow-up. Adverse effects occurred in 20 out of 276 patients, with 14 patients having one adverse event each. Independent predictive factors for good response to LPE therapy were symptom onset before LPE therapy ≤3 days and age on LPE therapy <50 years of age. LPE decreased the serum levels of antibodies, immunoglobulins, and complements 4 weeks after the first replacement, with decreased levels of interleukin (IL)-17A and interferon (IFN)-γ and increased level of IL-10.

Conclusion

LPE is an effective treatment for MG patients in state of exacerbation and preparation for thymectomy. Early use of LPE on early-onset MG may have good therapeutic effects. The potential mechanism for LPE is the polarization of cytokines from IL-17A, IFN-γ, into IL-10.
CyTOF® for the Masses
Authors: Iyer Akshay , Hamers Anouk A. J. , Pillai Asha B.
Published: April 2022

Mass cytometry has revolutionized immunophenotyping, particularly in exploratory settings where simultaneous breadth and depth of characterization of immune populations is needed with limited samples such as in preclinical and clinical tumor immunotherapy. Mass cytometry is also a powerful tool for single-cell immunological assays, especially for complex and simultaneous characterization of diverse intratumoral immune subsets or immunotherapeutic cell populations. Through the elimination of spectral overlap seen in optical flow cytometry by replacement of fluorescent labels with metal isotopes, mass cytometry allows, on average, robust analysis of 60 individual parameters simultaneously. This is, however, associated with significantly increased complexity in the design, execution, and interpretation of mass cytometry experiments. To address the key pitfalls associated with the fragmentation, complexity, and analysis of data in mass cytometry for immunologists who are novices to these techniques, we have developed a comprehensive resource guide. Included in this review are experiment and panel design, antibody conjugations, sample staining, sample acquisition, and data pre-processing and analysis. Where feasible multiple resources for the same process are compared, allowing researchers experienced in flow cytometry but with minimal mass cytometry expertise to develop a data-driven and streamlined project workflow. It is our hope that this manuscript will prove a useful resource for both beginning and advanced users of mass cytometry.
Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine
Authors: Feola Sara , Russo Salvatore , Martins Beatriz , Lopes Alessandra , Vandermeulen Gaëlle , Fluhler Vinciane , De Giorgi Camilla , Fusciello Manlio , Pesonen Sari , Ylösmäki Erkko , Antignani Gabriella , Chiaro Jacopo , Hamdan Firas , Feodoroff Michaela , Grönholm Mikaela , Cerullo Vincenzo
Published: April 2022

Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as in situ cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response. However, this mechanism in some cases fails in eliciting a strong specific T cell response. One way to overcome this problem and enhance the priming efficiency is the production of genetically modified oncolytic viruses encoding one or more tumor antigens. To avoid the long and expensive process related to the engineering of the OVs, we have exploited an approach based on coating OVs (adenovirus and vaccinia virus) with tumor antigens. In this work, oncolytic viruses encoding tumor antigens and tumor antigen decorated adenoviral platform (PeptiCRAd) have been used as cancer vaccines and evaluated both for their prophylactic and therapeutic efficacy. We have first tested the oncolytic vaccines by exploiting the OVA model, moving then to TRP2, a more clinically relevant tumor antigen. Finally, both approaches have been investigated in tumor neo-antigens settings. Interestingly, both genetically modified oncolytic adenovirus and PeptiCRAd elicited T cells-specific anti-tumor responses. However, in vitro cross-representation experiments, showed an advantage of PeptiCRAd as regards the fast presentation of the model epitope SIINFEKL from OVA in an immunogenic rather than tolerogenic fashion. Here two approaches used as cancer oncolytic vaccines have been explored and characterized for their efficacy. Although the generation of specific anti-tumor T cells was elicited in both approaches, PeptiCRAd retains the advantage of being rapidly adaptable by coating the adenovirus with a different set of tumor antigens, which is crucial in personalized cancer vaccines clinical setting.
Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review
Authors: Cabezas Lara , Jouve Thomas , Malvezzi Paolo , Janbon Benedicte , Giovannini Diane , Rostaing Lionel , Noble Johan
Published: April 2022

Introduction

Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.

Materials and Methods

We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.

Results

Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.

Conclusion

TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors
Authors: Harding James J. , Garrido-Laguna Ignacio , Chen Xiaoying , Basu Cynthia , Dowlati Afshin , Forgie Alison , Hooper Andrea T. , Kamperschroer Cris , Max Steven I. , Moreau Allison , Shannon Megan , Wong Gilbert Y. , Hong David S.
Published: April 2022

P-cadherin is a cell-cell adhesion molecule that is overexpressed in several solid tumors. PF-06671008 is a T-cell–redirecting bispecific antibody that engages both P-cadherin on tumors and CD3ϵ on T cells and induces antitumor activity in preclinical models. We conducted a phase 1, open-label, first-in-human, dose-escalation study to characterize the safety and tolerability of PF-06671008, towards determining the recommended phase 2 dose. Adult patients with treatment-refractory solid tumors received PF-06671008 (1.5–400 ng/kg) as a weekly intravenous (IV) infusion on a 21-day/3-week cycle. Parallel cohorts evaluated dosing via subcutaneous injection (SC) or an IV-prime dose. Of the 27 patients enrolled in the study, 24 received PF-06671008 IV in escalating doses, two received SC, and one IV-prime. A dose-limiting toxicity of cytokine release syndrome (CRS) occurred in the 400-ng/kg IV group, prompting evaluation of SC and IV-prime schedules. In all, 25/27 patients who received PF-06671008 reported at least one treatment-related adverse event (TRAE); the most common were CRS (21/27), decreased lymphocyte count (9/27), and hypophosphatemia (8/27). Seven patients permanently discontinued treatment due to adverse events and no treatment-related deaths occurred. Cytokine peak concentrations and CRS grade appeared to positively correlate with Cmax. Although the study was terminated due to limited antitumor activity, it provides important insights into understanding and managing immune-related adverse events resulting from this class of molecules.

Clinical Trial Registration

URL: https://clinicaltrials.gov/ct2/show/NCT02659631, ClinicalTrials.gov Identifier: NCT02659631.