bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal planning of step‐stress accelerated degradation test based on Tweedie exponential dispersion process with random effects
Authors: He Qian , Yan Weian , Liu Weidong , Bigaud David , Xu Xiaofan , Lei Zitong
Published: April 2024

The step stress accelerated degradation test (SSADT) is an effective tool for assessing the reliability of highly reliable products. However, conducting an SSADT is expensive and time consuming, and the obtained SSADT data has an impact on the accuracy of the subsequent product reliability index estimations. Consequently, devising a cost‐constrained SSADT plan that yields high‐precision reliability estimates poses a significant challenge. This paper focuses on the optimal design of SSADT for the Tweedie exponential dispersion process with random effect (TEDR), a general degradation model capable of describing product heterogeneity. Under given budget and boundary constraints, the optimal sample size, observation frequency and observation times at each stress level are obtained by minimizing the asymptotic variance of the estimated quantile life at normal operating conditions. The sensitivity and stability of the SSADT plan are also studied, and the results indicate the robustness of the optimal plan against slight parameters fluctuations. We use the expectation maximization (EM) algorithm to estimate TEDR parameters and reliability indicators under SSADT, providing a systematic method for obtaining the optimal SSADT plan under budget constraints. The proposed framework is illustrated using the case of LED chips data, showcasing its potential for practical application.
Evaluating consistency across multiple NeoSpectra (compact Fourier transform near‐infrared) spectrometers for estimating common soil properties
Authors: Mitu Sadia M. , Smith Colleen , Sanderman Jonathan , Ferguson Richard R. , Shepherd Keith , Ge Yufeng
Published: April 2024

Rapid and cost‐effective techniques for soil analysis are essential to guide sustainable land management and production agriculture. This study aimed at evaluating the performance and consistency of portable handheld Fourier‐transform near‐infrared spectrometers and the NeoSpectra scanners in estimating 12 common soil physical and chemical properties including pH; organic carbon (OC); inorganic carbon (IC); total nitrogen (TN); cation exchange capacity (CEC); clay, silt, and sand fractions; and exchangeable potassium (K), phosphorus (P), calcium (Ca), and magnesium (Mg). A diverse set of samples (n = 600) were retrieved from a national‐scale soil archive of the Kellogg Soil Survey Laboratory of USDA‐NRCS and scanned with five NeoSpectra scanners. Predictive models for the soil properties were developed using partial least squares regression (PLSR), Cubist, and memory‐based learning (MBL). Cubist outperformed PLSR and MBL, with the best prediction performance for clay, OC, and CEC (R2 > 0.7), followed by IC, sand, silt, and Mg (R2 > 0.6), and then pH, TN, and Ca (R2 > 0.5). K and P were predicted somewhat poorly with R2 of 0.48 and 0.22. All five NeoSpectra yielded comparable near‐infrared (NIR) spectral data and the PLSR models for the soil properties (in terms of model regression coefficients). However, the consistency assessment showed that the model performance was significantly decreased when the training and testing spectra were from different NeoSpectra scanners. It is concluded that NeoSpectra scanners could be rapid and cost effective for estimating certain soil properties, and calibration transfer should be considered for applications where multiple devices are involved and high estimation accuracy from NIR data is required.
Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High‐Pressure Wound Environments
Authors: Chen Kangli , Wang Kun , Pan Yanjun , Zhang Yi , Zhang Jiajun , Ji Shizhao , Yin Meng , Liu Changsheng , Qu Xue
Published: April 2024

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high‐pressure wound environments. Traditional self‐gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self‐gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε‐polylysine (ε‐PLL) and 4‐arm polyethylene glycol succinyl succinate (4‐arm‐PEG‐NHS) forming the hydrogel framework. Na2HPO4 functions as the “H+ sucker” to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross‐linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.
The value of flexible funding for collaborative biostatistics units in universities and academic medical centres
Authors: Slade Emily , Robbins Sarah Jane K. , McQuerry Kristen J. , Mangino Anthony A.
Published: April 2024

Collaborative biostatistics units within universities and academic medical centres operate under a wide range of different funding models; common to many of these models is the challenge of allocating time to activities that are not linked to a specific research project, such as professional development, mentorship and administrative tasks. The purpose of this paper is to describe a proposed model for ‘flexible funding’, that is, funding that is not linked to a specific research project, within a collaborative biostatistics unit and to detail the benefits and challenges associated with the proposed model. We present results from a qualitative study representing the perspectives of collaborative biostatisticians working under the proposed flexible funding model. In addition to providing examples of activities undertaken as part of time allocated to flexible funding, the qualitative results reveal several benefits of flexible funding both for a collaborative biostatistician (e.g., job satisfaction and professional development) and for the collaborative biostatistics unit as a whole (e.g., retention, process improvement, and leadership).
The effect of carbon nanotube on self‐healing properties of engineered cementitious composites subjected to high temperatures
Authors: Tanyıldızı Harun , Bulut Metehan
Published: April 2024

This study aims to examine the effect of carbon nanotubes (CNT) on the self‐healing performance of engineered cementitious composites (ECC) subjected to high temperatures. In ECC samples, CNT was used at 0%, 0.25%, 0.50%, and 0.75% by weight instead of cementitious materials. The cylindrical specimens containing CNT (Ø100 × 200 mm) were manufactured. The produced specimens were subjected to temperatures of 23 ± 2, 100, 200, 300, 400, 500, 600, 700, and 800°C after being cured at 23 ± 2°C for 28 days, and then, they left to cool at 23 ± 2°C for 1 day. Then, these specimens were preloaded at 70% of the ultimate splitting tensile strength to produce microcracks. Lastly, wetting–drying cycles were performed on ECCs for self‐healing. The ultrasonic pulse velocity (UPV), splitting tensile strength (fst), and rapid chloride permeability (RCPT) tests were applied to evaluate the self‐healing performance of specimens. Moreover, microstructural analyses such as scanning electron microscope (SEM), energy dispersive X‐ray spectroscopy (EDX), and X‐ray diffraction (XRD) were accomplished to identify the healing products formed in self‐healed cracks. According to the results of this study, the highest recovery rate of fst with 103.46% was attained from the ECC specimen containing 0.25% CNT exposed to 200°C.
Exploring science teachers' efforts to frame phenomena in the community
Authors: Clark Heather F. , Gyles Symone A. , Tieu Darlene , Venkatesh Shriya , Sandoval William A.
Published: April 2024

This article examines two teachers' efforts to re‐organize their science teaching around issues of environmental and food justice in the urban community where they teach through the pedagogical approach of community‐oriented framing. We introduce this approach to teachers' framing of phenomena in community as supporting students' framing of phenomena as personally and locally relevant. Drawing on classroom observations of remote learning during the COVID‐19 pandemic, we took an analytic approach that characterized features of classroom discourse to rate community‐oriented framing at the lesson level. Results show that teachers framed phenomena as both social and scientific, and as rooted in students' lived experiences, with classroom activities designed to gather localized and personalized evidence needed to explain or model phenomena. We also share examples of how Black and Latinx students took up this framing of phenomena in their classroom work. By providing a detailed description of the launch and implementation of activities, findings illustrate how community‐oriented framing supported teachers in posing local questions of equity and justice as simultaneously social and scientific, and helping students perceive science learning as meaningful to their everyday lives. Community‐oriented framing offers a practical means of designing locally and socially relevant instruction. We contribute to justice‐centered science pedagogies by conceptualizing transformative science learning environments as those in which students understand their goal in science class as understanding, and later addressing, inequities in how socioscientific issues manifest in their community.
High expression of AlkB homolog 5 suppresses the progression of non‐small cell lung cancer by facilitating ferroptosis through m6A demethylation of SLC7A11
Authors: Huang Zhangzhou , Lin Gen , Hong Yaping , Weng Lihong , Zhu Kai , Zhuang Wu
Published: April 2024

Objective

Non‐small cell lung cancer (NSCLC) is a prevailing LC characterized by poor outcomes. AlkB homolog 5 (ALKBH5) functions as a tumor suppressor in several cancers. This study delved into the role of ALKBH5 in NSCLC development.

Methods

TCGA database predicted ALKBH5 expression in NSCLC patients. ALKBH5 levels in NSCLC and human bronchial epithelial cells were determined. pcDNA3.1‐ALKBH5/NC, pcDNA3.1‐SLC7A11/NC, and ferrostatin‐1 were used to explore the interactions among ALKBH5, SLC7A11, and ferroptosis. SLC7A11 mRNA and its protein levels were measured by RT‐qPCR and Western blot. Cell viability, apoptosis, migration, and invasion were assessed by CCK‐8, flow cytometry, and Transwell. Total N6‐methyladenosine (m6A) quantification and its enrichment on SLC7A11 mRNA were determined, followed by the observation of Ki67, ALKBH5 and SLC7A11‐positive cell numbers. Glutathione (GSH), lipid reactive oxygen species (lipid‐ROS), malondialdehyde (MDA), and iron ion contents were determined. Animal experiments further analyzed the role of ALKBH5 in tumor development and glutathione peroxidase 4 (GPX4) expression.

Results

Bioinformatics analysis revealed the lowly‐expressed ALKBH5 in LC patients. ALKBH5 was downregulated in NSCLC cells and its upregulation repressed proliferation activity, invasion, and migration, and facilitated apoptosis. ALKBH5 upregulation decreased GSH, increased lipid‐ROS, MDA, and iron ion contents, and downregulated SLC7A11 by reducing m6A modification. SLC7A11 upregulation partly annulled the effect of ALKBH5 overexpression on cell ferroptosis and malignant behaviors. In vivo assays elucidated the suppression of ALKBH5 upregulation on tumor development and GPX4 levels.

Conclusion

ALKBH5 upregulation downregulates SLC7A11 transcription by decreasing m6A modification, thus promoting NSCLC cell ferroptosis and ultimately repressing NSCLC progression.
Preferential flow of phosphorus and nitrogen under steady‐state saturated conditions
Authors: Malhotra Kritika , Lamba Jasmeet , Way Thomas R. , Williams Colleen , Karthikeyan K. G. , Budhathoki Suman , Prasad Rishi , Srivastava Puneet , Zheng Jingyi
Published: April 2024

Repeated broiler litter application on agricultural lands can cause nutrient enrichment of subsurface effluent, especially with the existence of preferential flow through soil macropores. Previous studies quantifying soil macropores have not attempted to establish a connection of soil macropore characteristics with the subsurface nutrient (nitrogen [N] and phosphorus [P]) losses, across different topographical locations in the field. This study investigated the effect of broiler litter application and preferential flow on subsurface nutrient transport (N and P) at different topographical positions (upslope, midslope, and downslope) in a no‐till pasture field located in Alabama, USA. Twelve intact soil columns (150 mm id and 500 mm length) were used, and the nutrient leaching measurements from laboratory experiments were linked to soil macropore characteristics quantified using X‐ray computed tomography image analysis and solute transport modeling. Treatments included surface broadcast broiler litter (5 Mg ha−1, on dry basis) and unamended control. Leachates were analyzed for dissolved reactive P (DRP), total P (TP), and nitrate + nitrite‐N (NO3− + NO2−–N). The bromide breakthrough curves provided evidence of preferential flow in all columns. Litter application significantly increased leachate P concentrations, and average TP and DRP concentrations were significantly higher in the leachate from upslope columns compared to those at downslope location. The NO3−–N concentrations in leachate exceeded the US EPA drinking water standard of 10 mg L−1 in all the treatment columns. The highest flow‐weighted mean concentrations of TP and DRP, at 2.7 and 2.5 mg L−1, respectively, were recorded in the upslope columns. Soil physicochemical properties and nutrient leaching losses varied substantially across topographical positions, indicating a need for variable litter application rates to reduce P build‐up and subsequent leaching in vulnerable locations within the field. The relevance of the effect of topographic position on nutrient leaching found in this study should be further tested by investigating a wider range of slopes and soil types in pastures.
Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer
Authors: Zhu Chaojun , Teng Lan , Lai Yihong , Yao Xingxing , Fang Yuxin , Wang Zihuan , Lin Simin , Zhang Haonan , Li Qingyuan , Li Ye , Cai Jianqun , Zhang Yue , Wu Changjie , Huang Bing , Li Aimin , Liu Side , Lai Qiuhua
Published: April 2024

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-β1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-β signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-β1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-β signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.
Old-age support policy and fertility with strategic bequest motives
Authors: Yakita Akira
Published: April 2024

This paper presents an analysis of the effects of public old-age support on individuals’ fertility decisions and on the long-term equilibrium in an overlapping generation economy with strategic bequest motives. Parents must pay their adult children at least the reservation wage to receive informal old-age support from them (individual rationality constraint). Formal old-age support is financed through wage taxes on children. The increased present value of formal old-age support tends to increase old-age utility, thereby decreasing the family support demand and decreasing savings for the old age. The increased wage tax reduces the opportunity cost of child-rearing time, thereby increasing the fertility rate. The effects of increased formal old-age support on per-worker capital and labor are indeterminate, as is the effect on the long-term lifetime utility of individuals. A strategic bequest motive might engender a higher fertility rate than that of the social optimum.
Segmentation in Measure Spaces
Authors: Moll Salvador , Pallardó-Julià Vicent , Solera Marcos
Published: April 2024

We consider an abstract concept of perimeter measure space as a very general framework in which one can properly consider two of the most well-studied variational models in image processing: the Rudin–Osher–Fatemi model for image denoising (ROF) and the Mumford–Shah model for image segmentation (MS). We show the linkage between the ROF model and the two phases piecewise constant case of MS in perimeter measure spaces. We show applications of our results to nonlocal image segmentation, via discrete weighted graphs, and to multiclass classification on high dimensional spaces.
Pharmacokinetic study of capivasertib and the CYP3A4 substrate midazolam in patients with advanced solid tumors
Authors: Miller Claire , Sommavilla Roberto , O’Bryant Cindy L. , Barve Minal , Dowlati Afshin , Luke Jason J. , Khatun Mahmuda , Morris Thomas , Cullberg Marie
Published: April 2024

Purpose

Capivasertib, a potent, selective inhibitor of all three AKT serine/threonine kinase (AKT) isoforms, is being evaluated in phase 3 trials in advanced breast and prostate cancer. This study evaluated the drug–drug interaction risk of capivasertib with the cytochrome P450 3A substrate midazolam in previously treated adults with advanced solid tumors.

Methods

Patients received oral capivasertib 400 mg twice daily (BID) on an intermittent schedule (4 days on/3 days off) starting on day 2 of cycle 1 (29 days) and on day 1 of each 28-day cycle thereafter. In cycle 1 only, patients received oral midazolam (1 mg) on day 1 (alone), and days 8 and 12 (3rd day off and 4th day on capivasertib, respectively). Midazolam pharmacokinetics on days 8 and 12 were analyzed versus day 1. Capivasertib, with or without standard-of-care treatment, was continued in patients deemed likely to benefit. Safety and exploratory efficacy analyses were conducted.

Results

Capivasertib–midazolam coadministration increased midazolam exposure (n = 21): geometric mean ratio (90% confidence interval) AUCinf and Cmax was 1.13 (0.97–1.32) and 1.15 (0.99–1.33) for day 8 versus day 1, and 1.75 (1.50–2.05) and 1.25 (1.08–1.46) for day 12 versus day 1. The capivasertib safety profile was manageable when administered with or without midazolam. Two patients had partial responses to treatment.

Conclusion

The up to 1.75-fold increase in midazolam exposure indicates capivasertib is a weak CYP3A inhibitor at 400 mg BID on an intermittent schedule. Capivasertib was well tolerated; exploratory efficacy analysis demonstrated evidence of clinical activity in this heavily pre-treated population.

ClinicalTrials.gov: NCT04958226.
Low light intensity increased survival of coral spat in aquaculture
Authors: Ramsby B. D. , Emonnot F. , Flores F. , Schipper S. , Diaz-Pulido G. , Abdul Wahab M. A. , Severati A. , Negri A. P.
Published: April 2024

Coral reef ecosystems are declining and may not recover under future climate scenarios without intervention. Seeding reefs with corals bred in aquaculture is a promising restoration intervention; however, early coral recruits (spat) are vulnerable to overgrowth by benthic algae and maximizing their survival is essential for the feasibility of large-scale breeding operations. This study investigated the optimal light quality and intensity for spat survival and growth in the presence of algal communities typically used in coral aquaculture to induce larval settlement, but which might also outcompete spat and reduce survival during the grow-out period. Spat were exposed to two light spectra (blue and a full spectrum) at four light intensities (5–160 µmol m−2 s−1) over 12-week post-settlement. Survival was reduced under the highest intensity by nearly 40% compared to the lowest intensity. Light spectrum only affected survival at 60 µmol m−2 s−1—where survival was higher under blue compared to full spectrum light. Light treatments did not affect final spat size but spat were 33% smaller at the highest light intensity in weeks 6 and 8 due to overgrowth by crustose coralline algae (CCA), which was most abundant under these conditions. Low light intensity, on the other hand, favored green and brown algae, potentially due to their respective physiologies or less competition from crustose coralline algae. These results indicate that low light intensity presents several advantages for maintaining spat in coral aquaculture, including maximizing survival without significantly affecting growth, as well as minimizing husbandry and operating expenses.
The influence of Sargassum biomass and thallus density on the recruitment of coral reef fishes
Authors: Webber Kelsey , Fabricius Katharina , Wilson Shaun K. , Hoey Andrew S.
Published: April 2024

A habitat’s structural complexity is a key determinant of the recruitment and composition of associated communities. While the influence of the physical structure of corals on coral reef fish recruitment is well studied, the significance of other benthic components, like macroalgae, remains unclear. We used experimental patches of the canopy-forming macroalga Sargassum to assess the influence of macroalgal complexity, which was manipulated by altering thallus density and biomass, on coral reef fish recruitment. We established twenty-five 75 × 75 cm patches on the reef flat of Orpheus Island, (inshore, central Great Barrier Reef) during austral summer. Patches were randomly divided into five treatments of varying Sargassum thallus density (3–9 thalli) and/or biomass (177–779 g per patch) and surveyed daily for recruiting fishes for 18 d. We recorded 35 fish species recruiting to our patches, with Sargassum biomass having the greatest influence on fish recruits’ abundance and species richness. Comparisons between treatments with equal thallus density but varying biomass revealed a positive association between Sargassum biomass and fish species richness and abundance (up to ~ 2.5-fold differences). Additionally, treatments with similar total Sargassum biomass but different density revealed a negative relationship between density and fish species richness and abundance (20–30% reduction). These positive associations with Sargassum thallus biomass suggest that recruiting fishes favour the fine-scale complexity of intra-thallus spaces, rather than the larger, inter-thallus gaps. This study highlights that fine-scales of complexity within tropical macroalgal beds may influence the reef fish recruitment value of these often-underappreciated areas.
L1 slope: an overlooked spinal parameter
Authors: Iplikcioglu Ahmet Celal , Karabag Hamza
Published: April 2024

Objective

Lumbar lordosis can be divided into two parts by a horizontal line, creating the L1 slope and the sacral slope. Despite being a major spinopelvic parameter, the L1slope (L1S) is rarely reported. However, there is some evidence that L1S is a relatively constant parameter. This study aimed to analyze the L1 slope and its relationships with other spinopelvic parameters.

Methods

Standing lateral lumbosacral x-ray radiographies of 76 patients with low back pain and CT scans of 116 asymptomatic subjects were evaluated for spinal and spinopelvic parameters including L1 slope (L1S). The x-ray and CT groups were divided into subgroups according to mean sacral slope (SS) or pelvic incidence (PI) values. The mean values of the spinopelvic parameters and the correlations between them were investigated and compared.

Results

L1S was 19.70 and 18.15 in low SS and high SS subgroups of x-ray respectively. L1S was 7.95 and 9.36 in low and high PI subgroups of CT, respectively, and the differences were insignificant statistically. L1S was the only spinal parameter that did not change as SS or PI increased in standing and supine positions. L1S was correlated with lumbar lordosis (LL) proximal lumbar lordosis (PLL) and distal lumbar lordosis (DLL) in both x-ray and CT groups. L1S was also the strongest correlated parameter with pelvic incidence lumbar lordosis mismatch (PI-LL) mismatch in supine position.

Conclusions

L1S is a relatively constant parameter and is around 16°–18° and 8°–9° in the standing and supine positions, respectively. It was significantly correlated with LL, PLL, DLL, and PI-LL. In the standing position it was nearly equal to PLL while this equality was present in low PI subgroups of CT. There is strong evidence that L1S is significantly correlated with health-related quality of life scores.
Anti-infectious and anti-inflammatory effect of amniopatch in the treatment of spontaneous previable rupture of membranes
Authors: Alföldi Martin , Ferianec Vladimír
Published: April 2024

Spontaneous previable rupture of membranes complicates approximately 0.4–0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure–volume ratios. The supposed basis of this physical–mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical–academic and publishing outputs of the authors based on their many years’ experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008–2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research–academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.
Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules
Authors: Niccolai Elena , Pedone Matteo , Martinelli Ilaria , Nannini Giulia , Baldi Simone , Simonini Cecilia , Di Gloria Leandro , Zucchi Elisabetta , Ramazzotti Matteo , Spezia Pietro Giorgio , Maggi Fabrizio , Quaranta Gianluca , Masucci Luca , Bartolucci Gianluca , Stingo Francesco Claudio , Mandrioli Jessica , Amedei Amedeo
Published: April 2024

Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons’ pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments.

Graphical abstract
Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia
Authors: Zamboni Giovanna , Maramotti Riccardo , Salemme Simone , Tondelli Manuela , Adani Giorgia , Vinceti Giulia , Carbone Chiara , Filippini Tommaso , Vinceti Marco , Pagnoni Giuseppe , Chiari Annalisa
Published: April 2024

Background

Studies have shown that the prevalence of all-variants Alzheimer’s disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way.

Methods

We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations.

Results

The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40–44 age group to 1411/1,000,000 in the 60–64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence.

Conclusions

Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.
Modelling multidecadal variability in flood frequency using the Two-Component Extreme Value distribution
Authors: Totaro Vincenzo , Gioia Andrea , Kuczera George , Iacobellis Vito
Published: April 2024

The Two-Component Extreme Value (TCEV) distribution is traditionally known as the exact distribution of extremes arising from Poissonian occurrence of a mixture of two exponential exceedances. In some regions, flood frequency is affected by low-frequency (decadal) climate fluctuations resulting in wet and dry epochs. We extend the exact distribution of extremes approach to such regions to show that the TCEV arises as the distribution of annual maximum floods for Poissonian occurrences and (at least two) exponential exceedances. A case study using coastal basins in Queensland and New South Wales (Australia) affected by low-frequency climate variability, shows that the TCEV produces good fits to the marginal distribution over the entire range of observed values without the explicit need to resort to climate covariates and removal of potentially influential low values. Moreover, the TCEV reproduces the observed dog-leg, a key signature of different flood generation processes. A literature review shows that the assumptions underpinning the TCEV are conceptually consistent with available evidence on climate and flood mechanisms in these basins. We provide an extended domain of the TCEV distribution in the L-moment ratio diagram to account for the wider range of parameter values encountered in the case study and show that for all basins, L-skew and L-kurtosis fall within the extended domain of the TCEV.
Hierarchical reinforcement Thompson composition
Authors: Tanık Güven Orkun , Ertekin Şeyda
Published: April 2024

Modern real-world control problems call for continuous control domains and robust, sample efficient and explainable control frameworks. We are presenting a framework for recursively composing control skills to solve compositional and progressively complex tasks. The framework promotes reuse of skills, and as a result quick adaptability to new tasks. The decision tree can be observed, providing insight into the agents’ behavior. Furthermore, the skills can be transferred, modified or trained independently, which can simplify reward shaping and increase training speeds considerably. This paper is concerned with efficient composition of control algorithms using reinforcement learning and soft attention. Compositional and temporal abstraction is the key to improving learning and planning in reinforcement learning. Our Thompson sampling inspired soft-attention model is demonstrated to efficiently solve the composition problem.
Intramedullary versus plate fixation of both bone forearm fractures in skeletally immature patients: a systematic review and meta-analysis
Authors: Ahmed Ahmed Mohamed , Said Elsayed , Addosooki Ahmad , Attya Hossam Ahmed , Awad Ahmad Khairy , Ahmed Emad Hamdy , Tammam Hamdy
Published: April 2024

Background

Both bone forearm fractures (BBFFs) are a common injury amongst the pediatric population. The main indications of surgical fixation are open, irreducible, or unstable fractures. The two most commonly used surgical techniques are closed or open reduction with intramedullary fixation (IMF) and open reduction with plate fixation (PF). The aim of this systematic review and meta-analysis was to determine which fixation method is superior for BBFFs.

Methods

PubMed, Scopus, Web of Science, and CENTRAL were searched to identify studies comparing IMF and PF. We extracted data on union rates, complications, early hardware removal rates, reoperation rates, and radiographic, clinical, and perioperative outcomes.

Results

Sixteen studies were included in the analysis, with a total of 922 patients (539 IMF and 383 PF). Similar union rates were achieved by both fixation technique. IMF was associated with a higher incidence of symptomatic hardware, and early hardware removal. Better restoration of the radial bow was observed with the PF group, especially in older children and adolescents. The rate of excellent function was comparable between groups, whereas better cosmesis was reported with the IMF group. Despite shorter fluoroscopy time and immobilization time, PF demonstrated longer tourniquet time, operating time, and hospital stay compared to IMF.

Conclusions

We found no significant difference between IMF and PF in terms of union rates and functional outcomes taking in consideration the merits and demerits of each technique. High-quality randomized controlled trials are, therefore, necessary to determine the superiority of one fixation technique over the other.

Level of evidence

III.
Multi-omics analysis of immune-related microbiome and prognostic model in head and neck squamous cell carcinoma
Authors: Liu Yingqiao , Lin Haitao , Zhong Weijun , Zeng Yudi , Zhou Guihai , Chen Zhifeng , Huang Shi , Zhang Leitao , Liu Xiqiang
Published: April 2024

Objectives

The aim of our study is to explore the transcriptional and microbial characteristics of head and neck cancer’s immune phenotypes using a multi-omics approach.

Materials and methods

Employing TCGA data, we analyzed head and neck squamous cell carcinoma (HNSCC) immune cells with CIBERSORT and identified differentially expressed genes using DESeq2. Microbial profiles, obtained from the TCMA database, were analyzed using LEfSe algorithm to identify differential microbes in immune cell infiltration (ICI) subgroups. Random Forest algorithm and deep neural network (DNN) were employed to select microbial features and developed a prognosis model.

Results

We categorized HNSCC into three immune subtypes, finding ICI-2 with the worst prognosis and distinct microbial diversity. Our immune-related microbiome (IRM) model outperformed the TNM staging model in predicting survival, linking higher IRM model scores with poorer prognosis, and demonstrating clinical utility over TNM staging. Patients categorized as low-risk by the IRM model showed higher sensitivity to cisplatin and sorafenib treatments.

Conclusions

This study offers a comprehensive exploration of the ICI landscape in HNSCC. We provide a detailed scenario of immune regulation in HNSCC and report a correlation between differing ICI patterns, intratumor microbiome, and prognosis. This research aids in identifying prime candidates for optimizing treatment strategies in HNSCC.

Clinical relevance

This study revealed the microbial signatures associated with immunophenotyping of HNSCC and further found the microbial signatures associated with prognosis. The prognostic model based on IRM microbes is helpful for early prediction of patient prognosis and assisting clinical decision-making.
Rare association between spinocerebellar ataxia and amyotrophic lateral sclerosis: a case series
Authors: Ferrari Valerio , Conti Matteo , Bovenzi Roberta , Cerroni Rocco , Pierantozzi Mariangela , Mercuri Nicola B. , Stefani Alessandro
Published: April 2024

Introduction

In this work, we describe a new case of association between SCA2 and MND.

Case Report

A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made.

Discussion

Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP.

Conclusion

CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.
Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice
Authors: van Kooten Job P. , Dietz Michelle V. , Dubbink Hendrikus Jan , Verhoef Cornelis , Aerts Joachim G. J. V. , Madsen Eva V. E. , von der Thüsen Jan H.
Published: April 2024

Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.
Effects of moisture and aging upon decomposition of methyl iodide by reduced silver mordenite
Authors: Goettsche Heinrik , Raja Krishnan , Sabbarwall Piyush , Utgikar Vivek
Published: April 2024

Reduced silver mordenite has been considered as a sorbent for the capture of organic iodides, especially methyl iodide, from off-gases produced by aqueous used nuclear fuel reprocessing operations. The adsorption capacity of this material has been unpredictable especially when NOx and water are present. Previous work has found that a catalytic decomposition reaction is occurring on the surface but few determinations have been made of the kinetics of this reaction. The work presented tested the adsorption behavior and apparent catalytic reaction rate in humid conditions and compared those to dry conditions testing. Both experiments observed a first order reaction with rate constants of 0.0847 L/g sorbent/s and 0.1202 L/g sorbent/s respectively. Such a reduction in apparent rate constant is possibly due to either water obstructing methyl iodide adsorption or product desorption limitation. Changes in the adsorption profile were also apparent between these two, with the humid conditions experiment reaching saturation sooner than the dry conditions experiment. Additionally, an experiment into the effects of sorbent storage in a controlled laboratory environment was performed. The performance of the sorbent materials that were stored with silver in the zerovalent state was slightly inferior to those materials that were stored in ionic form (Ag+) and reduced to zerovalent silver immediately prior to subjecting them to sorption test. The materials stored with silver in the ionic form (and reduced just prior to application) behaved essentially similarly to the freshly synthesized (and reduced) sorbents in the sorption tests. This suggests that zerovalent silver experiences some oxidation resulting in deactivation of some sites.
Evaluation of markers of immunity in different metastatic immune microenvironments suggests more suppression within breast to liver metastases in breast cancer
Authors: Hsu Robert , Al-zubeidy Batul , Flores Daniel , Nazarian Ari , Baugh Aaron , Gonzalez Edgar , Castanon Sofi , Xiu Joanne , Kang Irene , Spicer Darcy , Lenz Heinz Josef , Dara Lily , Ademuyiwa Foluso O. , Korn W. Michael , Irshad Sheeba , Chan Isaac S. , Roussos Torres Evanthia T.
Published: April 2024

Purpose

Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease.

Methods

3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell fraction within the TME was calculated by QuantiSeq and MCP-counter.

Results

Compared to BrT, more LvM samples had a high TMB (≥ 10 mutations/Mb) and fewer LvM samples had PD-L1+ expression. Evaluation of the TME revealed that LvM sites harbored lower infiltration of adaptive immune cells, such as CD4+, CD8+, and regulatory T-cells compared with the BrT foci. We saw differences in innate immune cell infiltration in LvM compared to BrT, including neutrophils and NK cells.

Conclusions

LvMs are less likely to express PD-L1+ tumor cells but more likely to harbor high TMB as compared to BrTs. Unlike AxMs, LvMs represent a more immunosuppressed TME and demonstrate lower gene expression associated with adaptive immunity compared to BrTs. These findings suggest biopsy site be considered when interpreting results that influence ICI use for treatment and further investigation of immune composition and biomarkers expression by metastatic site.