bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chalkiness and premature controlled by energy homeostasis in OsNAC02 Ko-mutant during vegetative endosperm development
Authors: yan mei , Jiao Gui ai , shao Gao neng , chen ying , Zhu mao di , Yang Ling wei , Xie Li hong , qing pei song , tang shao qing 
Published: October 2023

Abstract
The Ko-Osnac02mutant demonstrated an obvious early maturation stage compared to the wild type (WT) with 15 days earlier. The result showed that the mature endosperm of Ko-Osnac02 mutant exhibited chalkiness, characterized by white-core and white-belly in mature endosperm. As grain filling rate is a crucial factor in determining the yield and quality of rice (Oryza sativa, ssp. japonica), it's significant that mutant has a lower amylose content (AC) and higher soluble sugar content in the mature endosperm. Interestingly among the top DEGs in the RNA Sequencing of N2 (3DAP) and WT seeds revealed that the OsBAM2 (LOC_Os10g32810) expressed significantly high in N2 mutant, which involved in Maltose up-regulated by the starch degradation. As pro-pro interactions induced the chalky endosperm formation in N2 seeds (3 DAP), seven genes were expressed at a lower-level. this effect could be verified by a heatmap diagrams based on DEGs of N2 versus WT. The Tubulin genes controlling cell cycle are downregulated their expression together with the MCM family genes MCM4 ( ↓ ), MCM7 ( ↑ ), which may cause white-core in the early endosperm development. In conclusion, the developing period drastically decreased in the Ko-Osnac02 mutants, which might cause the chalkiness in seeds during the early endosperm development.
Immunogenic cell death related genes for predicting prognosis and drug sensitivity in gastric cancer
Authors: Wang Yujie , Hao Zhibin , Liu Jingyu , Chen Ling , Li Xiaoxiao , Li Jie , Yin Tong , Wu Meihong , Zhang Yingyi , Xu Huawei , Peng Xiaobo , Zhan Xianbao 
Published: October 2023

Abstract
Background: Immunogenic cell death (ICD), a specific type of regulated cell death, can trigger antitumor immune responses by inducing damage-associated molecular patterns. Determining the precise role of ICD in gastric cancer and how it can benefit patients in terms of predicting prognosis and efficacy could be of great value.
Methods: We used the ESTIMATE immune score combined with a weighted gene co-expression network analysis to delineate ICD-associated gene modules and developed a predictive ICD risk model applicable to patients of any age, gender, and stage of gastric cancer. The prognoses and tumor microenvironment between the two groups were then compared. Finally, we assessed the capability of our risk signature to predict responses to immune checkpoint blockades (ICBs) and commonly used drugs.
Results: In our ICD risk signature, nine ICD-related genes (PTTG1IP, TM2D1, LHX6, GLUD2, TIRAP, LIN7A, CAST, NKAPD1, and SWSAP1) were determined to be predictive markers. The risk score was calculated as follows: Risk score = (0.47124) × PTTG1IP + (-0.917) × TM2D1 + (0.67637) × LHX6 + (0.8493) × GLUD2 + (-1.1537) × TIRAP + (0.51718) × LIN7A + (0.71179) × CAST + (-0.7168) × NKAPD1 + (-0.8875) × SWSAP1.Patients with a low ICD score had longer overall survival, earlier clinical stages, lower immune cell infiltration, and less inhibitory receptor expression. Moreover, these patients responded better to ICBs and conventional chemotherapy.
Conclusions: We established an ICD risk signature that could be used to predict prognosis and treatment efficacy in patients with gastric cancer. Our findings could shed light on fundamental ICD-relevant research and contribute to the development of precision therapies for patients with gastric cancer.
Bronchitis during long-term treatment with rituximab for ANCA-associated vasculitis: a retrospective cohort study
Authors: Zonozi Reza , Jeyabalan Anushya , Efe Orhan , Sauvage Gabriel , Cosgrove Katherine , Laliberte Karen A. , Niles John L. 
Published: October 2023

Abstract
Background
Pulmonary complications from B cell depletion with rituximab remain with limited description in the literature. Our objective is to describe the frequency and risk factors for development of bronchitis in patients receiving prolonged rituximab.
Methods
We conducted a single-center retrospective cohort study of 113 consecutive adult patients with ANCA-associated vasculitis (AAV) who had continuous B cell depletion with rituximab for greater than 24 months. The primary outcome was an episode of cough measured with an ordinal scale as follows: 0 = no cough; 1 = daily cough, non-productive; 2 = cough with sputum production once daily; 3 = cough with sputum production twice or more daily. Secondary outcome measures included serum immunoglobulin G (IgG) level, sputum culture, and antibiotic use. Logistic regression analysis was used to assess the odds ratio of developing cough with smoking status, nadir IgG level, length of time on continuous B cell depletion, and lung involvement of AAV as independent variables.
Results
The median (IQR) follow-up (i.e., duration of continuous B cell depletion) was 3.4 years (IQR, 2.7–5.2). Five patients (4.5%) and 43 patients (38.4%) were current and former smokers, respectively. A non-productive cough was identified in 4.2% of patients (n = 5). Throughout follow-up, a daily cough with sputum production once daily was identified in 6.2% of patients (n = 7), and a daily cough with sputum production twice or more daily was identified in 11.5% of patients (n = 13). A specimen for sputum culture was obtained in 25 patients, 12 (48%) of which were positive for a bacterial organism. The most common was Haemophilus influenzae (n = 2). Antibiotics for suspected bacterial bronchitis were used in 19.5% of patients (n = 22). The median (IQR) nadir IgG level was 675 mg/dL (521–798). No patient received intravenous IgG supplementation. In univariate and multivariate logistic regression models, the smoking status, nadir IgG level, length of time on continuous B cell depletion, and lung involvement of AAV were not associated with an increased odds of developing a cough.
Conclusions
Bronchitis was seen in approximately one-fifth of patients with AAV on prolonged B cell depletion with rituximab.
The Multistep Process for Amyotrophic Lateral Sclerosis: A Study in the Province of Palermo, Northern Sicily
Authors: D'Amico Anna , Bella Vincenzo La , Spataro Rossella 
Published: October 2023

Abstract

Objective: Recent studies have suggested that the clinical onset of Amyotrophic Lateral Sclerosis (ALS) is the final expression of a multistep process. We evaluated the conformity of the hypothesis in a relatively small yet well-defined ALS population in the Province of Palermo, Sicily Island, almost entirely followed by the local tertiary ALS Clinical Center.
Methods: Incident data were extracted from the patients’ database of the ALS Center (years 2014-2020). We examined both sporadic and familial forms of the disease. To evaluate the multistep process in our population, we regressed the natural log of age-specific incidence against the natural log of age of the patients.
Results: We identified 175 ALS patients. We obtained a slope of 4.69 (r2 = 0.986); the CI95% stands at 3.86-5.53 values, remaining relatively large due to the small sample share and with a p-value=0.00038. The slope estimate was consistent with a 6-step process.
Conclusions. In the ALS population of the Province of Palermo, Sicily, the multistep analysis confirms a process consistent with a 6-step model. This data, obtained in a relatively homogeneous population, further highlights the probability of strict interaction between environmental and genetic variables in the disease. Our data offer insights into the complexity of the mechanisms involved in the pathogenesis of the disease, particularly during its asymptomatic phase. This study supports the hypothesis that a single therapeutic silver bullet would probably be insufficient to arrest or slow the disease’s progression.
Pretrained transformers applied to clinical studies improve predictions of treatment efficacy and associated biomarkers
Authors: Jacob Etai , Arango Gustavo , Kipkogei Elly , Stewart Ross , Patra Arijit , Kagiampakis Ioannis 
Published: October 2023

Abstract
Cancer treatment has made significant advancements in recent decades, leading to improved outcomes and quality of life for many patients. Despite the array of available therapies, including targeted, hormone, and checkpoint blockade immunotherapy, many patients experience treatment failure or eventual resistance. Attempts to predict the efficacy of therapies, particularly immuno-oncology therapies, have suffered from limited accuracy and difficulties in identifying molecular and other determinants of response. Improving treatment prediction alone is insufficient to create clinically meaningful research tools; additional prerequisites for this goal involve accommodating small data sets, effectively handling sparse features, integrating diverse clinical data, addressing missing measurements, ensuring interpretability, and extracting valuable biological insights for both clinical context and further research. Multimodal deep-learning models offer a promising avenue to surmount these challenges by leveraging their capacity and flexibility to learn from expansive and varied clinical and molecular data sets. Similar to their application in natural language and other domains, deep-learning models can uncover complex relationships within data that are pertinent to survival and treatment response. In this study, we introduce an explainable transformer-based deep-learning framework that addresses these challenges. This framework yields predictions of survival outcomes, as quantified by concordance index, that surpass the performance of state-of-the-art methods such as Cox proportional hazards, survival random forest, and tumor mutation burden, across diverse independent data sets. We developed the clinical transformer, a deep neural-network survival prediction framework that capitalizes on the flexibility of the deep-learning model, including training strategies like gradual and transfer learning, to maximize the use of available data to enhance survival predictions and generate actionable biological insights. Finally, we illustrate the future potential of the clinical transformer’s generative capability in early-stage clinical studies. By perturbing molecular features associated with immune checkpoint inhibition treatment in immunotherapy-naive patient profiles, we identified a subset of patients who may benefit from immunotherapy. These findings were subsequently validated across three independent immunotherapy treatment cohorts. We anticipate that this research will empower the scientific community to further harness data for the benefit of patients.
FAM3A plays a key role in protecting against tubular cell pyroptosis and acute kidney injury
Authors: Zhou Lili , Li Xiaolong , Yuan Feifei , Tang Ying , Ai Jun , Miao Jinhua , Ye Wenting , Zhou Shan , Wu Qinyu , Wang Xiaoxu , Xu Dan , Li Jiemei , Huang Jiewu , Chen Qiurong , Shen Weiwei , Liu Youhua , Hou Fan Fan 
Published: October 2023

Abstract
Acute kidney injury (AKI) is in high prevalence worldwide, but with no therapeutic strategies. Targeting programmed cell death in tubular epithelial cells has been reported to improve a variety of AKI, but the main pathways and mechanisms of programmed cell death are controversial. In further analysis of previous single-cell RNA-seq data, we identified that pyroptosis was primarily responsible to AKI progression, highly relating with ATP depletion. Herein, we found that FAM3A, a mitochondrial protein responsible for ATP synthesis, was decreased and negatively correlated with tubular injury and pyroptosis in both mice and patients with AKI. Knockout of FAM3A further worsened tubular damage and renal function deterioration, increased macrophage and neutrophil infiltration, and facilitated tubular cell pyroptosis in ischemia/reperfusion injury (IRI) model. Conversely, FAM3A overexpression improved kidney injury and alleviated pyroptosis in IRI or cisplatin AKI. Mechanistically, FAM3A depletion suppressed PI3K/AKT/NRF2 signaling, thus leading to mitochondrial dysfunction and mt-ROS accumulation. NLRP3 inflammasome sensed the overloaded mt-ROS and activated Caspase-1. The activated Caspase-1 then cleaved GSDMD, pro-IL-1β, and pro-IL-18 into their mature forms to mediate pyroptosis. The pro-pyroptotic effects of FAM3A depletion were alleviated after treatment whit NRF2 activator, while the anti-pyroptotic function of FAM3A was blocked by deletion of NRF2. Hence, our study provides new mechanisms for AKI progression and demonstrated that FAM3A is a potential therapeutic target for treating AKI.
Impact of hepatitis B surface and core antibody levels on hepatitis B virus reactivation
Authors: Ohkubo Maki , Seo Emiko , Doki Kosuke , Suzuki Yoshiharu , Sekine Ikuo , Homma Masato 
Published: October 2023

Abstract

Hepatitis B virus reactivation (HBV-R) is a serious concern during cancer chemotherapy in patients with resolved HBV infection. We examined the levels of HBV surface (HBsAb) and core antibodies (HBcAb) to assess the incidence of HBV-R in patients with solid and hematopoietic cancers. Retrospective cohort study was conducted in 590 patients with resolved HBV infection. The patients consisted of solid (n = 466) and hematopoietic cancers (n = 124), including lymphoma receiving rituximab-containing chemotherapy. The incidenceof HBV-R was evaluated 761.5 (range, 4–3,898) days after the start of chemotherapy. Of 590 patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All HBV-R patients exhibited a lower HBsAb (<100 mIU/mL) at baseline. A higher HBcAb (≥100 C.O.I.) was identified as a risk factor for HBV-R,with an incidence of 9.6%. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab-containing chemotherapy had a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results indicate that baseline levels of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I are risk factors for HBV-R, except for the patients receiving chemotherapy containing rituximab.
Polymersomes Based on a Fumaric Copolymer as a Novel Drug Nanocarrier
Authors: Bada Romina , Molinuevo M. Silvina , Azcárate Julio C. , Cortizo M. Susana , Peruzzo Pablo 
Published: October 2023

Abstract

There is great interest in the development of nanoparticles as new platforms for the transport and release of drugs that present drawbacks for their direct administration into the body. In this work we developed a platform for bisphosphonates encapsulation based on polymersomes. Polymersomes were obtained by self-assembly of a new triblock amphiphilic copolymer based on polyethylene glycol (PEG) as hydrophilic block, and a statistical copolymer of vinyl benzoate (VB) and diisopropyl fumarate (DIPF) as hydrophobic block. The copolymer was synthesized by reversible addition fragmentation chain transfer polymerization (RAFT). The obtained amphiphilic polymer presented a weight fraction of hydrophilic block (f) of 30, appropriate for the formation of vesicles by self-assembly. Using the solvent injection method, we obtained vesicles of around 54 nm with a Z-average hydrodynamic diameter of 163 nm. The nanoparticles were smaller and with narrow size distribution than particles formed by the counterpart copolymer without DIPF. In order to evaluate the potential of these copolymers as a vehicle for bisphosphonates, risedronate loaded polymersomes were prepared. The obtained particles showed a similar size to their uncharged analogues, with a content of 12 ± 2 mg of risedronate per g of polymer, determined by HPLC. Cell viability and cytotoxicity were evaluated using murine monocyte-macrophage RAW264.7 cells. The empty or risedronate-loaded nanoparticles did not affect cell proliferation, viability and nitric oxide production at the tested concentrations.
Impact of Power Outages Depends on Who Loses It: Equity-Informed Grid Resilience Planning
Authors: Tutay Gizem Toplu , Kutanoglu Erhan , Hasenbein John 
Published: October 2023

Abstract
This research presents a novel approach for enhancing power grid resilience with a focus on social equity in light of increasing natural disasters. Utilizing a two-stage stochastic optimization model for flood mitigation investments, we optimize substation hardening and power flow decisions to minimize the weighted combination of expected load shed and expected equity metric. Our method uniquely approximates community power outages stemming from transmission grid disruptions, sidestepping the complexities of the distribution grid, and it incorporates two equity metrics (affected population and duration of loss) to address the uneven postdisaster well-being loss across communities. Our approach's novelty lies in integrating this equity-informed resilience model with realistic flood scenario generation and utilizing a large-scale synthetic but a realistic power grid of Texas. The findings highlight the importance of the composite objective function in altering power flow decisions to prioritize electricity provision and save communities in disadvantaged areas even without investing in substation hardening. The results also quantify the equity and load shed benefits of substation hardening as a function of the investment budget with a parameterized analysis. With an attention to equity, power outages increase in nonvulnerable communities — a trade-off made to mitigate well-being loss in the most vulnerable areas. We further explore a justice model inspired by the government's Justice40 initiative but find it less effective than our equity-informed models at preventing well-being loss. Our research, enriched by a comprehensive sensitivity analysis, offers valuable insights for policymakers, grid operators, and utilities aiming for a more resilient and equitable power grid.
Effects of rooftop solar on household energy burden in the United States
Authors: Forrester Sydney , Montañes Cristina Crespo , O’Shaughnessy Eric , Barbose Galen 
Published: October 2023

Abstract

Policymakers at the federal and state level have begun to incorporate energy burden into equity goals and program evaluations, aiming to reduce energy burden below a “high” level of 6% for lower income households. Pairing an empirical household-level dataset spanning U.S. geographies together with modeled hourly energy demand curves, we show that rooftop solar reduces energy burden across a majority of adopters from a median of 3.3–2.7%. For low- and moderate-income adopters, solar reduced median energy burden from 7.7–6.4%, and from 4.1–3.4%, respectively. Importantly, solar reduced the rate of high or severe energy burden from 67% of all low-income households before adoption to 54% of households following adoption, and correspondingly from 21–14% for moderate-income households. Overall, rooftop solar can support state and federal goals to reduce energy burden along with other strategies such as weatherization and bill assistance.
Effect of Glucose Variability on the Mortality of the Very Old People During the First Year of the COVID-19 Pandemic
Authors: Salinero-Fort Miguel A. , Andres-Rebollo F. Javier Sam , Cárdenas-Valladolid Juan , Mostaza José , Lahoz Carlos , Rodriguez-Artalejo Fernando , Gómez-Campelo Paloma , Vich-Pérez Pilar , Jiménez-García Rodrigo , Miguel-Yanes José M. , Maroto-Rodríguez J , Iriarte-Campo Víctor 
Published: October 2023

Abstract
Background
To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures.
Methods
This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 75 years and older; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015–2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality.
Results
During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p < 0.001). The fully adjusted model, including basal FPG, showed an odds ratio for mortality that ranged from 2.48 to 2.88 according to different sensitivity analyses.
Conclusions
GV has clear implications for clinical practice, as its assessment as a risk prediction tool should be included in the routine follow-up of the elderly and in a comprehensive geriatric assessment. Electronic health records can incorporate tools that allow its calculation, and with this information, clinicians will have a broader view of the medium- and long-term prognosis of their patients.
Experimental and numerical simulation of catalyst deactivation caused by transient turbulence in gradient flow field
Authors: Li Yaode , Qiao Mingshuai , Zhang Zhiguo 
Published: October 2023

Abstract
In SCR system, the velocity of flue gas field varies with the load, forming a gradient flow field. The characteristics of gradient flow field have important influence on the physical deactivation of catalyst. Through CFD simulation in this paper, it was found that the relative standard coefficients of flow field with characteristic flow velocity were 10.03%, 12.48% and 14.37% respectively. The uniformity of flow field deteriorated with the increase of flow velocity, and the alternating flow field was more likely to scour, wear and block the catalyst channel, leading to its inactivation. This conclusion is also confirmed by the test data obtained from the measuring points installed in various parts of the system. Through LES simulation, it is found that alternating flow field will generate transient turbulent vortices in the system, and with the increase of velocity, the number and distribution range of transient turbulent vortices increase rapidly. In the low-speed flow field, the flow field at the inlet Angle of the flue is disordered, and the velocity varies from 2.42m /s to 8.14m /s. At the corner of flue gas outlet, the flow velocity also varies between 4.86 m/s and 9.03 m/s, but there is laminar flow near the wall. The transient vortices are triggered by the laminar stripping mechanism near the wall. In high velocity flow field, the number of turbulent vortices increases sharply, especially on the surface of the first layer catalyst, which has a great influence on its activity. The triggering mechanism of turbulent vortices also changes. At this time, with the increase of the shear force of the flue gas jet, the turbulent vortex is mainly triggered in the shear jet.