bluuebunny/crossref_metadata_2025 huggingface dataset:
Tacrolimus versus mycophenolate for autoimmune hepatitis patients with incomplete response on first line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial
Authors: Stoelinga Anna , Tushuizen Maarten E , Hout Wilbert B van den , Girondo Mar DM Rodriguez , de Vries Elsemieke S , Levens Amar D , Moes Dirk-Jan AR , Gevers Tom JG , Meer Suzanne van , Brouwer Johannes T , de Jonge Hendrik JM , de Boer Ynto S , Beuers Ulrich HW , Meer Adriaan J van der , Berg Aad P van den , Guichelaar Maureen MJ , Drenth Joost PH , Hoek Bart van
Published: November 2023

• Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. Treatment goal is reaching complete biochemical response (CR), defined as normalization of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver related mortality. First-line treatment consists of the combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second line treatment for AIH.
• Methods: The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least six months of treatment with first-line therapy. Patients are randomised to TAC (0.07mg/kg/day initially and adjusted by trough levels) or MMF (max 2000mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in proportion of patients reaching CR after six months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.
• Discussion: This is the first randomised controlled trial comparing two second line therapies for AIH. Currently second line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.
• Trial registration: ClinicalTrials.gov NCT05221411.– Retrospectively registered on: 3 February 2022; EudraCT number: 2021-003420-33, Prospectively registered on 16 June 2021.
Data-Driven Robust Healthcare Network Design under Disruption Considering Conditional Value at Risk
Authors: Hasani Aliakbar , Darayi Mohamad , Haseli Gholamreza
Published: November 2023

This study proposes a distributionally robust two-stage risk-aversion model for comprehensive healthcare network design. The proposed model considers the weighted average of the expected losses to handle the disruption uncertainty affecting the network performance (i.e., service capacity, service demand, and route capacity) with conditional value-at-risk as a risk assessment measure. The proposed model is implemented in a stylized case study of healthcare network design in Iran. The results indicate the efficiency of the proposed distributionally robust optimization model compared to the traditional two-stage stochastic model. In case of a high level of uncertainty, the proposed distributionally robust network design tends to be more decentralized by establishing more new mobile facilities, selecting more backup facilities at low-risk regions, and assigning more inventory to established facilities. Results provide decision-makers with managerial insights about cost-effective decisions to handle uncertainty. Also, the sensitivity analysis shows that the type of ambiguous set and levels of confidence, risk aversion, and adjustment parameters affect the network performance.
Gender Composition in the Work Environment and Physician Income: Evidence from Longitudinal Data
Authors: Gong Qing , Hu Xiaochu
Published: November 2023

Background
Despite the rising representation of women in the physician workforce, gender-based income disparities persist. In this study, we explore the role of representation of women in the work environment in physicians’ Medicare income and the income gender gap.
Methods
Our main analytic sample is a balanced panel of 371,472 physicians over nine years, obtained from the Medicare Part B Fee-For-Service Provider Utilization and Payment Data (2012-2020) from the Centers for Medicare and Medicaid Services (CMS).
We use panel regressions with physician and year fixed effects to quantify how total Medicare income, patient volume, and per-patient income respond to gender composition changes at the specialty and practice level, controlling for other practice characteristics. We allow the gender composition to have differential impacts on women and men by interacting them with physician’s gender. In addition, we examined the subsample of physicians who have not switched specialties or practices and explored differences in the effects by practice size.
Results
Increasing women’s representation in physician work environments impacts men's and women’s income differently. We find that for women physicians, a 1% increase in the share of women in the same specialty leads to a 1.401% higher annual income, 1.284% more patients, and 0.117% more per-patient income. Conversely, these effects are reversed for men. Changes in women’s share at the practice level have qualitatively similar effects. Among physicians who have not switched specialties or practices, we still find positive effects for women but no negative effects for men. Furthermore, these effects are stronger in solo or small practices than in large practices.
Conclusions
Increasing women’s representation in the work environment helps increase income for women physicians but may reduce income for men physicians. Our findings support the efforts in increasing women’s representation in the physician workforce to mitigate gender income disparities and demonstrate the nuanced differences in its impact by gender and the size of the practice to refine policy recommendations.
Integrative Spatial Analysis of H&E and IHC Images Identifies Prognostic Immune Subtypes Correlated with Progression-Free Survival in Human Papillomavirus (HPV)-Related Oropharyngeal Squamous Cell Carcinoma
Authors: Hwang Tae Hyun , Nakkireddy Sumanth Reddy , Jang Inyeop , Kim Minji , Yin Linda X. , Rivera Michael , Garcia Joaquin , Bartemes Kathleen , Routman David , Moore Eric , Abdel-Halim Chadi , Ma Daniel , Abel Kathryn Van
Published: November 2023

Although the majority of HPV (+) oropharyngeal squamous cell carcinoma (OPSCC) patients exhibit a favorable prognosis, approximately 20% face recurrent or metastatic disease, posing management challenges. Therefore, the identification of robust prognostic markers for risk stratification is essential. Our study focused on the comprehensive characterization of intratumor heterogeneity within the tumor immune microenvironment (TME) in both primary tumors and metastatic lymph nodes. Utilizing computational approaches, we integrated hematoxylin and eosin (H&E) and 11 adjacent immunohistochemistry (IHC)-stained slides to investigate the cellular composition and functional characteristics across different regions within the TME. Based on these detailed immune characteristics, we classified patients into specific immune subtypes. Our integrative TME analysis indicated that patients with high tumor-infiltrating lymphocytes (TIL), increased CD8 + levels, and reduced CD163 + cell counts within their primary tumors were likely to have a more favorable progression-free survival outcome. The integration of H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability and improves patient stratification in HPV(+) OPSCC.
Evaluation of methods for simulation of heat-affected zones in duplex stainless steels
Authors: WESTIN Elin Marianne , WESTERBERG Lars-Göran
Published: November 2023

The weldability of duplex stainless steels partly depends on the ferritization of the high temperature heat-affected zone (HT-HAZ). This area is rather narrow, and it can be challenging to visualize and determine its actual impact on the properties. To address this, various methods were applied to study the grain growth and austenite reformation in the HT-HAZ of the lean duplex grade UNS S32101. Thermo-mechanical Gleeble® simulations were conducted at 1360°C with different holding times and cooling rates. Subsequently, the grain size and ferrite content were measured on polished and etched cross-sections. Bead-on-plate welds were performed on the same heat of 6 mm plate thickness using the gas tungsten arc welding (GTAW) process. The shielding gas was Ar + 0–8% N2 to illustrate which effect nitrogen additions would have on the HT-HAZ morphology. The arc was either stationary, welding at one spot for 0.5–120 s, or travelling at different speeds to generate varying heat inputs. The thermo-mechanical simulations came closest to the results obtained by travelling arc welding and allowed for a more comprehensive investigation. Stationary arc welding was not suitable for HT-HAZ studies as it quickly caused nitrogen depletion and resulted in significantly higher ferrite contents compared to the travelling arc welds.
Pass-To-Pass Microstructural Variations in ARC Based AM Deposits in As-Built Conditions
Authors: Liu Stephen , Ream Jordan , Yu Zhenzhen
Published: November 2023

Wire arc additive manufacturing (WAAM) is a technique that involves the use of a computer numeric-controlled (CNC) arc welding torch with an integrated wire feed to deposit metal one layer at a time in the fabrication of a near-net-shape part. However, few studies have been performed to characterize the metallurgical properties of WAAM builds, particularly regarding the evolution of microstructure and mechanical properties along the entire build length. This work characterized the microstructure, composition of alloying elements, and hardness of ER70S-6 carbon steel deposits on a layer-to-layer basis to better understand how the WAAM process affects the properties of the part as a whole. The composition of alloying elements was found to increase within each layer, from bottom to top. With remelting of the top regions of each prior layer during the AM process, the richer composition near the top of the deposit would be incorporated into the subsequent layer. Arc stirring and pool mixing would uniformize the composition but partition during solidification will again create a composition gradient in this subsequent pass. This process repeats throughout the entire height of the build elevating gradually, but continuously, the concentration of the alloying elements. Between subsequent passes, volumes of the prior deposit are heat treated by the process thermal conditions to form a heat affected zone, similar to that found in weldments. For the alloy system investigated, irregular pockets of lath martensite and martensite-austenite-carbide (MAC) microconstituents were found dispersed in the HAZ along the length of the deposit and along the build direction. With subsequent deposits, however, the initially formed hard and soft regions were tempered to result in a more homogenized ferritic microstructure with lower hardness. Except for the initial and end transients, the remainder of a WAAM build would exhibit a relatively uniform microstructure and hardness.
Parental Involvement in Supporting Academic Performance of Intermediate Phase Learners in a Low Socio-economic Context
Authors: Mekgwe Tumelo , Maseko Nonhlanhla
Published: November 2023

Parental involvement is essential for realising quality school performance and good academic performance. The study explores the role of parents’ involvement in intermediate-phase learners’ academic performance in a low socio-economic context in the North West Province, South Africa. This study intended to assist schools with strategies that could be used by the schools to involve parents to enhance the academic performance of learners. The study followed a qualitative design, underpinned by the interpretivism paradigm to explore the role of parental involvement in supporting intermediate-phase learners academically. Data was gathered using semi-structured individual and focus group interviews, and document analysis. Three parents were purposively selected to participate, from each grade (Grades 4,5,6). Thus, the total number of participating parents was nine, comprising six females and three males. The article is underpinned by the Epstein (1987) model of school, family, and community partnership that encourages mutual collaboration between different stakeholders. The findings indicated that parental involvement in children’s education enhances their academic performance.
Growing crystalline artificial magnet ice in a kagome lattice
Authors: Ge Jun-Yi , Zhang Jia-Jie , Tu Li-Ming , Gladilin Vladimir
Published: November 2023

Geometric frustration has been the focus of studying complex many-body interactions where exotic phenomena are widely observed. Among all systems possessing geometric frustration, artificial ice based on nanomagnets and interactive particles allows imaging individual interaction units and designing exotic frustrated lattices, which are difficult to access in traditional ice systems such as water ice and pyrochlore spin ice. However, the relatively weak interaction between nanomagnets and commonly existing quenched disorder hamper the observation of truly long-range ordered (LRO) crystalline state as well as the experimental investigation of the underlying physics. Here we report a totally new design of artificial ice based on macromagnets arranged in a geometrically frustrated kagome lattice. The unique advantage of our design is that the frustrated crystalline lattice is grown by adding the magnets into the system one by one, thus facilitating the minimization of both local and global interaction energy. As a result, an LRO ferromagnetic phase (FM-I) with charge order, as has been predicted for artificial colloidal ice, can be easily realized even in a sample with weak interactions. We also develop a magnetic comb to locally write and erase the FM-I phase at will. Moreover, a totally new ordered ferromagnetic phase (FM-II) emerges following the breakdown of FM-I phase under strong enough interactions. Our results provide unique testbed to probe the up to now elusive states in artificial ice systems.
Modelling Patches Number of Residential Areas in Relation to Some Environmental Characteristics (Case Study: Tehran City)
Authors: Majd Golazin Radyn , Jozi Seyed Ali , Hejazi Rokhshad , Amiri Mohammad Javad , Ghaffarzadeh Hamidreza
Published: November 2023

With human intervention, the face of the land is divided into smaller spots and after a while many problems will arise. If the number of patches is less and the land uses are more uniform, the appearance of the land will be less damaged. Therefore, the landscape metrics are indicators of environmental sensitivity. Today, Tehran, as a metropolis, is facing many problems that does not have the physical, spatial and functional structure appropriate to its needs and it has a long distance with sustainability indicators and biological standards. The present study considers the spatial modelling patches number of residential areas in relation to some environmental characteristics as a research necessity for the Tehran city and addressed it. In order to conduct research, some of the most important environmental factors influencing the creation and development of residential areas in Tehran were considered. These factors include: elevation, slope, vegetation, density of rivers, of ground water depth, wind speed and precipitation in the region. Then, a raster layer was prepared for each of the factors in Arc map software. Landsat 8 satellite images were used to prepare the layer of residential areas. In the next step, a grid with 20 rows and columns was placed on Tehran, and the entire area was covered by 238 pixels. For modeling, patches number of residential areas were considered as the response variable and other factors were considered as independent variables. In order to perform negative binomial model, the collected data were analyzed by RStudio software. The results showed that the elevation, vegetation and slope respectively have a positive, positive and negative effect at the 99% confidence level on the response variable (patches number of residential areas) they have. Mapping the patches number of residential areas based on modeling results showed that the number of patches is more in the northeast part of Tehran. This result shows that the continuity of ecological zones is low in these parts. The correlation between the raster layer of the number of real patches and the modeling was 0.856, which shows that the modeling is very accurate and can be used in urban planning.
The Formation of Unsaturated IrOx in SrIrO3-based Perovskites by Cobalt-doping for Efficient Acidic Oxygen Evolution Reaction
Authors: Li Gao-Ren , Zhao Jia-Wei , Yue Kaihang , Zhang Hong , Wei Shu-Yin , Zhu Jiawei , Wang Dongdong
Published: November 2023

Electrocatalytic water splitting is a promising route for sustainable hydrogen production. However, the high overpotential of the anodic oxygen evolution reaction (OER) poses significant challenge. SrIrO3-based perovskite-type catalysts have shown great potential for OER in acidic medium, but the origins of their high activity are still unclear. Herein, we develop a Co-doped SrIrO3 system to enhance OER activity and elucidate the origin of catalytic activity. In-situ experiments reveal Co activates surface oxygen, rapidly exposing IrOx active sites, while bulk Co doping optimizes the adsorbate binding energy of IrOx. The Co-doped SrIrO3 demonstrates excellent OER electrocatalytic activity, markedly surpassing the commercial IrO2 catalysts in both conventional electrolyzer and proton exchange membrane water electrolyzer. The insights significantly advance the understanding of how SrIrO3-based perovskites achieve high acidic OER catalytic performance. The findings also provide guidance for designing efficient acidic OER electrocatalysts toward green hydrogen production.
Electrospun PAN-based Carbon Nanofibers for Aqueous Boron Recovery
Authors: Park Ji Wan , Kim Su Young , Jeong Tae Uk , Han Do Young , Kim Da Eun , Huh Seong , Won Yong Sun
Published: November 2023

Designed for the recovery of aqueous boron, a critical element with various industrial applications, the use of carbon fibers as an effective adsorbent for boron in aqueous solutions were explored, and the changes in carbon fibers were investigated during repeated boron adsorption and desorption. In this research, prepared PAN fibers by electrospinning were carbonized into nitrogen-doped carbon fibers. The resulting fiber mats undergo boron adsorption in boric acid solution and subsequent regeneration in HCl solution, and these processes repeat multiple times to assess the reusability of carbon fibers. SEM analysis confirmed the successful electrospinning of PAN fibers and their carbonized ones, while EDS and XPS analyses determined the presence of doped nitrogen on the graphene-like surface and the consequential effective boron adsorption. Then, ICP-OES showed that the boron adsorption was completed within ~ 1 hr to an equilibrium capacity even at room temperature, and the capacity increased with the regeneration of fibers, also confirmed by SEM and BET analyses in that the specific surface area increased along with the physical breakage and shattering of fibers during regeneration. In conclusion, the carbon fibers proposed in this study are applicable for aqueous boron recovery with their operative reusability.
SAFMem: Accelerating Transformer Self-Attention Functionality via Memristor-Based Hardware
Authors: Bettayeb Meriem , Halawani Yasmin , Khan Muhammad Umair , Saleh Hani , Mohammad Baker
Published: November 2023

The adoption of transformer networks has experienced a notable surge in various AI applications. However, the increasedcomputational complexity, stemming primarily from the self-attention mechanism, parallels the manner in which convolutionoperations constrain the capabilities and speed of Convolutional Neural Networks (CNNs). The self-attention algorithm,specifically the Matrix-matrix Multiplication (MatMul) operations, demands a substantial amount of memory and computationalcomplexity, thereby restricting the overall performance of the transformer. This paper introduces an efficient hardwareaccelerator for the transformer network, leveraging memristor-based in-memory computing. The design targets the memorybottleneck associated with MatMul operations in the self-attention process, utilizing approximate analog computation andthe highly parallel computations facilitated by the memristor crossbar architecture. Remarkably, this approach resulted in areduction of approximately 10 times in the number of Multiply-Accumulate (MAC) operations in transformer networks, whilemaintaining 93.37% accuracy for the MNIST dataset, as validated by a comprehensive circuit simulator employing NeuroSim3.0. Simulation outcomes indicate an area utilization of 6895.7 μm2, a latency of 15.52 seconds, an energy consumption of3 mJ, and a leakage power of 59.55 μW . The methodology outlined in this paper represents a substantial stride towards ahardware-friendly transformer architecture for edge device, poised to achieve real-time performance.
Spatial variability in herbaceous plant phenology is mostly explained by variability in temperature but also by photoperiod and functional traits
Authors: Rauschkolb Robert , Bucher Solveig Franziska , Hensen Isabell , Ahrends Antje , Fernández-Pascual Eduardo , Heubach Katja , Jakubka Desiree , Jiménez-Alfaro Borja , König Andreas , Koubek Tomáš , Kehl Alexandra , Khuroo Anzar , Lindstädter Anja , Shafee Faizan , Mašková Tereza , Platonova Elena , Panico Patrizia , Plos Carolin , Primack Richard , Rosche Christoph , Shah Manzoor A , Sporbert Maria , Stevens Albert-Dieter , Tarquini Flavio , Tielbörger Katja , Träger Sabrina , Vange Vibekke , Weigelt Patrick , Bonn Aletta , Freiberg Martin , Knickmann Barbara , Nordt Birgit , Wirth Christian , Römermann Christine
Published: November 2023

Whereas temporal variability of plant phenology in response to climate change has already been well studied, the spatial variability of phenology is not well understood. Given that phenological shifts may affect the magnitude of biotic interactions, there is a need to investigate how the variability in environmental factors relates to the spatial variability in herbaceous species’ phenology by at the same time considering their functional traits to predict their general and species-specific responses to future climate change. In this project, we analysed phenology records of 148 herbaceous species, which were observed for a single year by the PhenObs network in 15 botanical gardens. For each species, we characterised the spatial variability in six different phenological stages across gardens. We used boosted regression trees to link these variabilities in phenology to the variability in environmental parameters (temperature, latitude, and local habitat conditions) as well as species traits (seed mass, vegetative height, specific leaf area, and temporal niche) hypothesised to be related to phenology variability.
We found that spatial variability in the phenology of herbaceous species was mainly driven by the variability in temperature but also photoperiod was an important driving factor for some phenological stages. In addition, we found that early-flowering and less competitive species indicated by small specific leaf area and vegetative height were more variable in their phenology. Our findings contribute to the field of phenology by showing that besides temperature, photoperiod and functional traits are important to be included when spatial variability of herbaceous species is investigated.
Genome Sequence of Microbulbifer thermotolerans HB226069 Reveals Its Versatility to Degrade Multiple Polysaccharides and Determination of the Alginate Lyases
Authors: Li Xue , Yang Miao , Mo Kunlian , Hu Yonghua , Gu Hanjie , Sun Dongmei , Bao Shixiang , Huang Huiqin
Published: November 2023

Polysaccharide-degrading bacteria are key participants in the global carbon cycle and algal biomass recycling. Herein, a polysaccharide lyase-producing strain HB226069 was isolated from Sargassum sp. from QingGe Port, Hainan, China. Results of the phylogenetic of 16S rRNA gene and genotypic analysis clearly indicate that the isolate should be classified as Microbulbifer thermotolerans. The whole genome is a 4,021,337 bp circular chromosome with the G + C content of 56.5%. Analysis of the predicted genes indicates that strain HB226069 encodes 161 CAZymes, and abundant putative enzymes involved in polysaccharide degradation were predicted, including alginate lyase, fucosidase, agarase, xylanase, cellulase, pectate lyase, amylase, and chitinase. Three of the putative polysaccharide lyases from PL7 and PL17 families were involved in alginate degradation. The alginate lyases of strain HB226069 showed the maximum activity 117.4 U/mL at 50°C, pH 7.0 and 0.05 M FeCl3, while exhibited the best stability at 30°C and pH 7.0. The thin layer chromatography (TLC) and Electrospray Ionization Mass Spectrometry (ESI-MS) analysis indicated that the alginate oligosaccharide degraded by the partially purified alginate lyases contained oligosaccharides of DP2-DP5 and monosaccharide while reacting for 36 h. The complete genome of M. thermotolerans HB226069 enriches our understanding of the mechanism of polysaccharide lyase production and provides support for its potential application in polysaccharide degradation.
CVRmap - A Complete Cerebrovascular Reactivity Mapping Post-Processing BIDS Toolbox
Authors: Rovai Antonin , Lolli Valentina , Trotta Nicola , Goldman Serge , De Tiège Xavier
Published: November 2023

Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards.
Do corticosteroids affect immunotherapy efficacy in malignancy? – A systematic review
Authors: Byron Yoni , Yegorova-Lee Sonya , Tio Martin
Published: November 2023

Background: Early studies indicated that corticosteroids may limit the survival benefit from immunotherapy. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy in patients with malignancy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications.
Methods: 3 electronic databases (PubMed, Embase, and Medline) were searched on 1st of February 2023. Studies that measured response or survival to immunotherapy in people receiving corticosteroids for non-cancer indications compared to either no corticosteroids or corticosteroids for cancer-related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune-related adverse events (irAE) were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model.
Results: 8426 titles were identified on our search. 8 studies met our inclusion criteria for meta-analysis. Administration of corticosteroids does not have a statistically significant effect on survival and response to immunotherapy when administered for non-cancer related indications, with a pooled odds ratio for overall response rate 0.92 (95% CI 0.58-1.44); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68-1.12); and pooled HR for overall survival 0.79 (95% CI 0.59-1.05).
Conclusion: This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. These results are limited by the retrospective nature of the studies included, small sample sizes, lack of information about corticosteroid dosing the inclusion of irAE in 2 of the studies which could bias the results.
Targeting MTAP creates a therapeutic vulnerability to PARP inhibition in brain metastatic TNBC by disrupting MAT2A mediated methionine metabolism
Authors: Lou Zhenkun , Zeng Xiangyu , Zhao Fei , Zhang Lingxin , Weinshilboum Richard M , Tao Kaixiong
Published: November 2023

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited therapeutic strategy and unfavorable prognosis, especially for patients bearing brain metastasis. Here, we demonstrate that MTAP gene deletion or MTAP inhibition by MTAP inhibitor, MTDIA, sensitizes breast cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi). Mechanistically, PARPi suppresses the expression of methionine adenosyltransferase 2A (MAT2A) by inducing METTL16 auto-inhibition mediated intron retention. Given that MAT2A and MTAP are key enzymes in methionine metabolism, the dual inhibition of MAT2A and MTAP disrupts methionine metabolism and leads to reduced s-adenosylmethionine. Dietary methionine restriction further boosts the combined anti-tumor efficacy of MTAP depletion/inhibition and PARPi. Most importantly, in brain metastatic TNBC, due to the natural low methionine environment in the brain, the combination of MTAP depletion/inhibition and PARPi confers significant therapeutic efficacy. Therefore, our findings provide a promising strategy for inhibiting primary or brain metastatic TNBC.
BAP regulates lateral bud outgrowth to promote tillering in Paphiopedilum callosum (Orchidaceae)
Authors: Yin Yuying , Zhong Ronghui , Li Yefei , Guo Beiyi , Li Lin , Ma Guohua , Wu Kunlin , Fang Lin , Zeng Songjun
Published: November 2023

Background:
Paphiopedilum orchids have a high ornamental value, and flower abundance is a key horticultural trait. Most Paphiopedilum plants exhibit weak tillering ability, with their tiller buds often entering a dormant state post-formation. Tiller production plays a crucial role in enhancing flower abundance and is potentially regulated by plant hormones. However, the effect of hormones on tillering in Paphiopedilumplants is still unclear.
Results:
In this study, we investigated the promotion of tillering in P. callosum through exogenous root irrigation of benzylaminopurine(BAP). We observed a dose-dependent promotion of tiller production by BAP, with the strongest effect observed at a concentration of 400mg/L. By comparing the expression of key genes in P. ‘SCBG Yingchun’ (with strong tiller ability) and P callosum (with weak tiller ability), we found that BAP promotes tillering by interacting with abscisic acid (ABA). This interaction involves down-regulation of the ABA degradation gene PcCYP707A, leading to a reduction in ABA content, and the subsequent down-regulation of dormancy-associated genes (PcDRMH1, PcSVP) to release bud dormancy. Additionally, BAP promotes sustained outgrowth of tiller buds by increasing the level of indole-3-acetic acid (IAA) through up-regulation of the IAA synthesis gene PcYUC2 and the transport gene PcPINIC. These findings provide insights into the regulatory mechanisms of BAP in tiller bud outgrowth in P. callosum.
Conclusions:
Our results indicated that the application of BAP promotes lateral bud outgrowth and increases tiller production in P. callosum. HPLC results showed exogenous BAP affects the levels of endogenous hormones, including IAA, CTKs, and ABA. Transcriptomic data combined with qPCR analyses suggest that the genes PcCYP707, PcYUC2, PcPINIC PcDRMH1, PcSVPmay play key roles in regulating tiller bud outgrowth. This study presents the first comprehensive report of BAP-promoted tillering in P. callosum, which should provide a foundational basis for further mechanistic studies on tiller development in Paphiopedilum species and other non-model plants.
Pseudo-static Solution of Active Earth Pressure Against Relief Shelf Retaining Wall Rotating Around Heel Under Seismic Load
Authors: Que Yun , Zhang Jisong , Chen Fuquan , Long Chengcheng
Published: November 2023

In practical engineering, the design process of most retaining walls must take into account earthquake resistance. It is crucial to prevent the overturning of retaining walls, particularly when the foundation's bearing capacity is weak. In this paper, the seismic active earth pressure (ES) of a relieving retaining wall in RB displacement mode is taken as the research object. By observing shear dissipation graphs across various operating conditions, the distribution law of each sliding surface is summarized, and three typical failure modes are obtained. The corresponding calculation model was established, and the earth pressure in each region was derived by the inclined strip method combined with the limit equilibrium method. Then the resultant force and its action point were obtained. By comparing the theoretical and numerical solutions with the previous studies, the correctness of the derived formula is proved, and it is found that the formula can be applied to static conditions. The variation of earth pressure distribution and resultant force under seismic acceleration are studied. The unloading plate’s position, the wall heel’s length, and seismic acceleration will weaken the unloading effect. On the contrary, the length of the unloading plate and the friction angle of filling will strengthen the unloading effect.
Stress-based topology optimization using BESO method with incremental structural nonlinear analysis
Authors: Zhang Hu-zhi , He Qing-chao , Chen Zhan-dong , Feng Fei-fan , Yin Bin
Published: November 2023

To enhance the applicability of optimization methods in civil engineering, particularly for structural members utilizing cement-based materials like concrete, this study introduces a stress-based topology optimization approach employing the Bi-directional Evolutionary Structural Optimization (BESO) method in conjunction with incremental structural nonlinear analysis. The primary objective of this method is to minimize the peak equivalent stress experienced by the structural components. It relies on the utilization of the p-norm condensation function to approximate the peak equivalent stress, alongside the establishment of sensitivity through the adjoint method. This method has demonstrated its aptness in optimizing structures containing highly nonlinear material constituents. By configuring the p-value within a specified range of 4–6 during the optimization process, consistent achievement of solutions aligned with the predefined objectives, based on element sensitivity, is feasible. This sensitivity is derived by applying a filter to the initial sensitivity calculated from the stress outcomes of the incremental structural nonlinear analysis. Subsequently, the data is meticulously filtered to procure a more robust and dependable solution that aligns more closely with the overarching optimization objective.
Dynamic Organelle Changes and Autophagic Processes in Lily Pollen Germination
Authors: Yen Chih-Chung , Hsu Chia-Mei , Jiang Pei-Luen , Jauh Guang-Yuh
Published: November 2023

Pollen germination is a crucial process in the life cycle of flowering plants, signifying the transition of quiescent pollen grains into active growth. This study delves into the dynamic changes within organelles and the pivotal role of autophagy during lily pollen germination—initially, mature pollen grains harbor undifferentiated organelles, including amyloplasts, mitochondria, and the Golgi apparatus. However, germination unveils remarkable transformations, such as the redifferentiation of amyloplasts accompanied by starch granule accumulation. We investigate the self-sustained nature of amylogenesis during germination, shedding light on its association with osmotic pressure. Employing BODIPY 493/503 staining, we tracked lipid body distribution throughout pollen germination, both with or without autophagy inhibitors (3-MA, NEM). Typically, lipid bodies undergo polarized movement from pollen grains into elongating pollen tubes, which is crucial for directional growth. Inhibiting autophagy disrupted this essential lipid body redistribution, underscoring the interaction between autophagy and lipid body dynamics. Notably, tubular endoplasmic reticulum (ER)-like structure their participation in autophagy. Starch granules, lipid bodies, and membrane remnants observed within vacuoles further reinforce the involvement of autophagic processes. The autophagy inhibitors, particularly BFA, significantly impede germination and growth, affecting Golgi morphology. Immunogold labeling substantiates the pivotal role of the ER in forming autophagosome-like compartments and protein localization. Our proposed speculative model of pollen germination encompasses proplastid differentiation and autophagosome formation. This study advances our understanding of organelle dynamics and autophagy during pollen germination, providing valuable insights into plant reproductive physiology.
Carbonation and modeling study for process liquor in batch mode using flue gas in the mining and mineral processing industry
Authors: SHARMA VIPIN KUMAR , Thamida Sunil Kumar , Reddy B. Naveen Kumar
Published: November 2023

​The mining and mineral processing industry generates significant amounts of process liquor containing sufficient concentrations of sodium hydroxide (NaOH). This abstract presents a technical overview of the carbonation process applied to process liquor using boiler flue gas as a source of carbon dioxide (CO2). The carbonation of process liquor using boiler flue gas offers several advantages. Firstly, it provides a sustainable solution for CO2 capture and storage, reducing the environmental impact of the mining and mineral processing industry. Secondly, the carbonation process results in the production of stable carbonate or bicarbonate compounds that can be used as valuable byproducts or raw materials in other industrial processes. Furthermore, the carbonation of process liquor can lead to improved process efficiency and reduced operational costs by facilitating the removal of impurities and the recovery of valuable metals or minerals. Factors such as temperature, pressure, pH, CO2 concentration, and reaction time must be carefully controlled to ensure efficient carbonation and maximize CO2 utilization. Trials were conducted for the effective carbonation of process liquor generated in the mineral processing industry, which contains caustic lye. This technical paper discusses successful experiments conducted for the carbonation of process liquor and further modelling and implementation of this study.
Comparative Effect of Ketogenic and Chitosan-Based Diets on Submandibular Salivary Gland Morphology in Rats: A Histological and Immuno-Histochemical Analysis
Authors: Aboulfotoh Mahmoud
Published: November 2023

Objective: This study was carried out in the submandibular salivary glands (SSGs) of rats to demonstrate the effect of a ketogenic diet (KD) in comparison with dietary chitosan supplementation.
Method: Eighteen albino rats were randomly divided into three equal groups. Rats in Group I were fed a balanced diet and considered controls. Meanwhile, those of Groups II and III were fed a KD, a balanced diet with high molecular weight chitosan, respectively. After 45 days, rats were euthanized, and the SSGs were dissected carefully for staining with hematoxylin and eosin (H&E), alpha-smooth muscle actin (α-SMA) immunohistochemical staining, and Congo red special stain. Quantitative data from α-SMA staining and Congo red staining were statistically analyzed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test.
Results: Regarding Congo red and α-SMA staining, one-way ANOVA revealed a significant difference between the three groups. For α-SMA staining and Congo red staining, Group II had the highest mean values of 91.41 ± 3.30 and 68.10 ± 5.04, respectively, while Group I had the lowest values of 56.13 ± 3.96 and 16.87 ± 2.19, respectively. Group III had mean values of 60.70 ± 3.55 for α-SMA and 19.50 ± 1.78 for Congo red. Tukey's multiple comparisons post hoc test revealed significant differences between groups I & II and between groups II & III (P ˂ 0.05). Meanwhile, there was a nonsignificant difference between groups I and III (P ˃ 0.05).
Conclusion: A KD has a deleterious effect on rats' SSG, and dietary chitosan supplementation ameliorates these damaging effects.
Taxonomic implications of the leaf anatomy of twelve species of Senna ser. Bacillares (Leguminosae) from northeastern Brazil
Authors: Souto Flávio Sousa , Silva Anauara Lima e , Santos Edinalva Alves Vital dos , Agra Maria de Fátima
Published: November 2023

The leaf anatomy of twelve species of Senna ser. Bacillares (Leguminosae) from northeastern Brazil was examined to provide taxonomic support for the group. Forty-three specimens were analyzed using light microscopy, following the usual techniques in plant anatomy. Four different petiole profiles were observed: circular, semicircular, hexagonal, and pentagonal; most petioles showed adaxial projections, those being strongly prominent in S. chrysocarpa and S. quinquangulata. Six different leaf rachis profiles were observed: pentagonal, elliptic, obovate, circular, semicircular, and irregularly triangular. The vascular systems of the petioles and leaf rachisies showed similar patterns, forming 4-7 central bundles and two accessory bundles. The midrib was plane-convex in all species, with an arched vascular bundle surrounded by sclerenchyma. The dorsiventral mesophyll has a uniseriate palisade, with 4-7-seriate spongy parenchyma. Five different leaflet edge outlines were observed: rounded, recurved, acute, acuminate, and truncate; the truncate type was exclusive to S. angulate, while S. gardneriwas acuminate. Idioblasts of druses and prismatic crystals were observed in the petioles, leaf rachises, and midribs of all species; crystalline sand was observed in the petioles and leaf rachises of S. angulata and S. pluribracteata, in the petiole of S. gardneri, and in the rachis of S. splendida. The sets of different anatomical characters of the petioles, leaf rachises, and leaflet edges of all of the species studied provided additional support to the taxonomy of Sennaser. Bacillares and reinforced the importance of anatomical studies to the taxonomy and systematics of this group.
Dl-3-n-Butylphthalide attenuates early brain injury and delayed neurological dysfunction by regulating NLRP3 inflammasome after subarachnoid hemorrhage
Authors: Gao Fangfang , Zeng Shujin , Chao Dachong , Wu Liangmiao
Published: November 2023

Background
Subarachnoid hemorrhage (SAH) is a severe neurological event lacking of effective therapy. Early brain injury (EBI) and delayed neurological dysfunction are important cause in the poor prognosis of patients with SAH. NLRP3 inflammasome activation has been implicated in many inflammatory lesion pathogenesis including SAH. Dl-3-n-butylphthalide (NBP) has been reported to possess substantial anti-inflammatory properties, which is beneficial for various neurodegenerative diseases. However, the effect and molecular mechanisms of NBP on SAH have not been clearly identified. We designed this study to investigate the effect of NBP against EBI and delayed neurological dysfunction after SAH and to reveal the possible underlying mechanism.
Methods
The adult mice were subjected to endovascular perforation SAH model or sham operation. Mice were randomized to sham group, SAH group, or SAH + NBP group. The EBI (short-term study) was studied at 48 h post-SAH and delayed neurological dysfunction (long-term study) at 21 days post-SAH
Results
The results suggested that NBP evidently alleviated the EBI in mice at 48 h post-SAH, as shown by elevating neurological score, reducing brain edema, blood–brain barrier disruption, neuronal loss, and astrocyte aggregation, as well as ameliorating cerebral vasospasm. Moreover, NBP was able to improve long-term neurobehavioral functions and decrease neuronal apoptosis at 21 days after SAH. Significantly, NBP treatment also inhibited the expressions of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in both EBI and delayed neurological dysfunction indued by SAH
Conclusions
Our findings suggested that NBP treatment exerts a profound neuroprotective effect against early brain injury and delayed neurological dysfunction induced by SAH, at least partially through regulating NLRP3 inflammasome signaling pathway.
multi-working condition joint topology optimization design of an electric truck aluminum alloy frame based on subjective and objective interactive weights
Authors: Zhang Zifeng , Wang Dengfeng , Chen Hongli , Zhang Shang , Chen Jing
Published: November 2023

The traditional cross-section form of the current electric truck frame impedes the further exploration and lightweight potential of the frame's overall mechanical performance. This paper introduces a method that integrates the Analytic Hierarchy Process (AHP) with the Criteria Importance Through Intercriteria Correlation (CRITIC) to establish interactive weights for multi-objective joint topology decision-making in frame design. It involves devising a novel, extrusion-compatible structural design for the frame's longitudinal and cross beams using aluminum alloy 6061T6 material. In comparison with a steel frame of an electric truck, this novel aluminum alloy frame, designed using the multi-objective joint topology optimization method combined with dimensional optimization, not only enhances the overall mechanical performance but also achieves a weight reduction of 36%. The interactive decision-making method, a fusion of AHP and CRITIC proposed in this study, can offer valuable guidance for the lightweight design of complex mechanical structures.