bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of contrail avoidance in a commercial flight planning system: an operational analysis
Authors: Martin Frias A , Shapiro M L , Engberg Z , Zopp R , Soler M , Stettler M E J
Published: March 2024

Aircraft condensation trails, also known as contrails, contribute a substantial portion of aviation’s overall climate footprint. Contrail impacts can be reduced through smart flight planning that avoids contrail-forming regions of the atmosphere. While previous studies have explored the operational impacts of contrail avoidance in simulated environments, this paper aims to characterize the feasibility and cost of contrail avoidance precisely within a commercial flight planning system. This study leverages the commercial Flightkeys 5D algorithm, developed by Flightkeys GmbH, with a prototypical contrail forecast model based on the Contrail Cirrus Prediction (CoCiP) model to simulate contrail avoidance on 49 411 flights during the first two weeks of June 2023, and 35 429 flights during the first two weeks of January 2024. The utilization of a commercial flight planning system enables high-accuracy estimates of additional cost and fuel investments by operators to achieve estimated reductions in contrail-energy forcing and overall flight global warming potential. The results show that navigational contrail avoidance will require minimal additional cost (0.08%) and fuel (0.11%) investments to achieve notable reductions in contrail climate forcing (−73.0%). This simulation provides evidence that contrail mitigation entails very low operational risks, even regarding fuel. This study aims to serve as an incentive for operators and air traffic controllers to initiate contrail mitigation testing as soon as possible and begin reducing aviation’s non-

CO
2

emissions.
Crossing Over
Authors: Robison Claire C
Published: March 2024

This chapter describes the process of revising religion for Indian devotees and its impacts on notions of family. It focuses on members’ narratives of joining ISKCON, which reorients their relationships to the regional and family-based forms of the Hindu and Jain traditions in which most devotees were raised. Building on Tweed’s theory of religion, I depict their processes of joining ISKCON as acts of “crossing over” to a new identity, sometimes heightened by recent geographic migrations to Mumbai. Chowpatty’s ISKCON community provides a systematic, institutionalized framework for members to be fitted into new religious lifeways. Adopting a brahmanically inflected Krishna bhakti that shifts social and familial bonds with newly forged religious networks—including their Counselling System, the brahmacari ashram, and the Marriage Board—they offer models of religious kinship in their place.
Inverse kinetic isotope effect in singlet-to-triplet intersystem crossing contributes to greater robustness of deuterated organocatalyst
Authors: Murayama Sei , Ishimoto Takayoshi , Naka Hiroshi
Published: March 2024

Precisely defined deuterium labeling of simplified Maruoka Catalyst® markedly increases its robustness under basic conditions, but the reason for this has remained unclear. Based on multicomponent density functional theory (MC_DFT) calculations, we find that an inverse kinetic isotope effect in singlet-to-triplet intersystem crossing contributes to the greater robustness of the deuterated catalyst.
Cortical thickness reveals sex differences in verbal and visuospatial memory
Authors: Sang Feng , Zhao Shaokun , Li Zilin , Yang Yiru , Chen Yaojing , Zhang Zhanjun
Published: March 2024

Although previous studies have reported the sex differences in behavior/cognition and the brain, the sex difference in the relationship between memory abilities and the underlying neural basis in the aging process remains unclear. In this study, we used a machine learning model to estimate the association between cortical thickness and verbal/visuospatial memory in females and males and then explored the sex difference of these associations based on a community-elderly cohort (n = 1153, age ranged from 50.42 to 86.67 years). We validated that females outperformed males in verbal memory, while males outperformed females in visuospatial memory. The key regions related to verbal memory in females include the medial temporal cortex, orbitofrontal cortex, and some regions around the insula. Further, those regions are more located in limbic, dorsal attention, and default-model networks, and are associated with face recognition and perception. The key regions related to visuospatial memory include the lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and were associated with object recognition. These findings imply the memory performance advantage of females and males might be related to the different memory processing tendencies and their associated network.
Reversible modulation of the local environment around metal centers bearing multifunctional carbenes
Authors: Yamauchi Yasuhiro , Ogoshi Sensuke , Uetake Yuta , Hoshimoto Yoichi
Published: March 2024

This Highlight Review provides examples of external-stimuli-driven reversible modulations of the spatial, electronic, and magnetic environment around metal centers that bear multifunctional N-heterocyclic carbenes (NHCs). In particular, recent reports on Lewis-base- or Lewis-acid-mediated reversible molecular transformations of Ni(0) complexes that bear N-phosphine-oxide-substituted imidazolylidenes (PoxIms) and the corresponding imidazolinylidenes (SPoxIms) are spotlighted. We also discuss the utility of using X-ray absorption spectroscopy to examine the synthesized (S)PoxIm–Ni complexes to gain spectroscopic insight into the changes in the local environment and electronic state of the metal centers induced by these reversible transformations. Overall, this review highlights the multipurpose utility of multifunctional NHCs as a key to designing and reversibly modulating the local environment of metal centers, which paves the way for accomplishing hitherto challenging molecular transformations and developing unprecedented reactivity of multimetallic compounds.
Feminist Matters: The Politics of Eating in Chimamanda Ngozi Adichie’s Purple Hibiscus
Authors: Githire Njeri
Published: March 2024

Using food as a narrative device in her critically acclaimed debut novel Purple Hibiscus (2003), Adichie offers a markedly feminist critique of the legacies of neocolonialism on Africa’s ability to choose its own destiny. Indeed, Adichie’s exploration of food as the locus of hospitality and hostility and the dining table as a fraught and shifting site of power and its contestation yields a commentary on the domestic arena as a metaphor for the national sociopolitical and economic situation. More specifically, Adichie links notions of food control and tyrannical power to prevailing patriarchal systems that expose women and children to violent injustices and to material and spiritual want. She depicts colonial and fundamentalist religious institutions as inimical to women’s participation in political and economic processes.
Photoplethysmography and intracardiac pressures: early insights from a pilot study
Authors: Scholte Niels T B , van Ravensberg Annemiek E , Edgar Roos , van den Enden Antoon J M , van Mieghem Nicolas M D A , Brugts Jasper J , Bonnes Judith L , Bruining Nico , van der Boon Robert M A
Published: March 2024

Aims

Invasive haemodynamic monitoring of heart failure (HF) is used to detect deterioration in an early phase thereby preventing hospitalizations. However, this invasive approach is costly and presently lacks widespread accessibility. Hence, there is a pressing need to identify an alternative non-invasive method that is reliable and more readily available. In this pilot study, we investigated the relation between wrist-derived photoplethysmography (PPG) signals and the invasively measured pulmonary capillary wedge pressure (PCWP).

Methods and results

Fourteen patients with aortic valve stenosis who underwent transcatheter aortic valve replacement with concomitant right heart catheterization and PPG measurements were included. Six unique features of the PPG signals [heart rate, heart rate variability, systolic amplitude (SA), diastolic amplitude, crest time (CT), and large artery stiffness index (LASI)] were extracted. These features were used to estimate the continuous PCWP values and the categorized PCWP (low < 12 mmHg vs. high ≥ 12 mmHg). All PPG features resulted in regression models that showed low correlations with the invasively measured PCWP. Classification models resulted in higher performances: the model based on the SA and the model based on the LASI both resulted in an area under the curve (AUC) of 0.86 and the model based on the CT resulted in an AUC of 0.72.

Conclusion

These results demonstrate the capability to non-invasively classify patients into clinically meaningful categories of PCWP using PPG signals from a wrist-worn wearable device. To enhance and fully explore its potential, the relationship between PPG and PCWP should be further investigated in a larger cohort of HF patients.
Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study
Authors: Niu Ying-ying , Zhong Jian-feng , Wen Hui-yan , Yan Hao-yu , Diao Zhi-quan , Li Jia-xin , Bai Xue-rui , Qiu Jia-min , Xu Zhi-tong , Chen Lian-hong , Li Cheng-ping , Li Jing , Liang Xiao-feng , Liu Dan
Published: March 2024

Background

The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity.

Methods

We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia.

Results

Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5–6, patients with multimorbidity and a lifestyle score of 0–1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5–6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5–6 to 0–1. And we observed more pronounced association between them among people younger than 60 years old.

Conclusions

Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.
AI-luminating Artificial Intelligence in Inflammatory Bowel Diseases: A Narrative Review on the Role of AI in Endoscopy, Histology, and Imaging for IBD
Authors: Gu Phillip , Mendonca Oreen , Carter Dan , Dube Shishir , Wang Paul , Huang Xiuzhen , Li Debiao , Moore Jason H , McGovern Dermot P B
Published: March 2024

Endoscopy, histology, and cross-sectional imaging serve as fundamental pillars in the detection, monitoring, and prognostication of inflammatory bowel disease (IBD). However, interpretation of these studies often relies on subjective human judgment, which can lead to delays, intra- and interobserver variability, and potential diagnostic discrepancies. With the rising incidence of IBD globally coupled with the exponential digitization of these data, there is a growing demand for innovative approaches to streamline diagnosis and elevate clinical decision-making. In this context, artificial intelligence (AI) technologies emerge as a timely solution to address the evolving challenges in IBD. Early studies using deep learning and radiomics approaches for endoscopy, histology, and imaging in IBD have demonstrated promising results for using AI to detect, diagnose, characterize, phenotype, and prognosticate IBD. Nonetheless, the available literature has inherent limitations and knowledge gaps that need to be addressed before AI can transition into a mainstream clinical tool for IBD. To better understand the potential value of integrating AI in IBD, we review the available literature to summarize our current understanding and identify gaps in knowledge to inform future investigations.
Profiling Small RNA From Brain Extracellular Vesicles in Individuals With Depression
Authors: Ibrahim Pascal , Denniston Ryan , Mitsuhashi Haruka , Yang Jennie , Fiori Laura M , Żurawek Dariusz , Mechawar Naguib , Nagy Corina , Turecki Gustavo
Published: March 2024

Background

Major depressive disorder (MDD) is a leading cause of disability with significant mortality risk. Despite progress in our understanding of the etiology of MDD, the underlying molecular changes in the brain remain poorly understood. Extracellular vesicles (EVs) are lipid-bound particles that can reflect the molecular signatures of the tissue of origin. We aimed to optimize a streamlined EV isolation protocol from postmortem brain tissue and determine whether EV RNA cargo, particularly microRNAs (miRNAs), have an MDD-specific profile.

Methods

EVs were isolated from postmortem human brain tissue. Quality was assessed using western blots, transmission electron microscopy, and microfluidic resistive pulse sensing. EV RNA was extracted and sequenced on Illumina platforms. Functional follow-up was performed in silico.

Results

Quality assessment showed an enrichment of EV markers, as well as a size distribution of 30 to 200 nm in diameter, and no contamination with cellular debris. Small RNA profiling indicated the presence of several RNA biotypes, with miRNAs and transfer RNAs being the most prominent. Exploring miRNA levels between groups revealed decreased expression of miR-92a-3p and miR-129-5p, which was validated by qPCR and was specific to EVs and not seen in bulk tissue. Finally, in silico functional analyses indicate potential roles for these 2 miRNAs in neurotransmission and synaptic plasticity.

Conclusion

We provide a streamlined isolation protocol that yields EVs of high quality that are suitable for molecular follow-up. Our findings warrant future investigations into brain EV miRNA dysregulation in MDD.
Bacterial adenine cross-feeding stems from a purine salvage bottleneck
Authors: Chuang Ying-Chih , Haas Nicholas W , Pepin Robert , Behringer Megan G , Oda Yasuhiro , LaSarre Breah , Harwood Caroline S , McKinlay James B
Published: March 2024

Diverse ecosystems host microbial relationships that are stabilized by nutrient cross-feeding. Cross-feeding can involve metabolites that should hold value for the producer. Externalization of such communally valuable metabolites is often unexpected and difficult to predict. Previously, we discovered purine externalization by Rhodopseudomonas palustris by its ability to rescue an Escherichia coli purine auxotroph. Here we found that an E. coli purine auxotroph can stably coexist with R. palustris due to purine cross-feeding. We identified the cross-fed purine as adenine. Adenine was externalized by R. palustris under diverse growth conditions. Computational modeling suggested that adenine externalization occurs via diffusion across the cytoplasmic membrane. RNAseq analysis led us to hypothesize that adenine accumulation and externalization stem from a salvage pathway bottleneck at the enzyme encoded by apt. Ectopic expression of apt eliminated adenine externalization, supporting our hypothesis. A comparison of 49 R. palustris strains suggested that purine externalization is relatively common, with 16 strains exhibiting the trait. Purine externalization was correlated with the genomic orientation of apt, but apt orientation alone could not always explain purine externalization. Our results provide a mechanistic understanding of how a communally valuable metabolite can participate in cross-feeding. Our findings also highlight the challenge in identifying genetic signatures for metabolite externalization.
Personalizing renal replacement therapy initiation in the intensive care unit: a reinforcement learning-based strategy with external validation on the AKIKI randomized controlled trials
Authors: Grolleau François , Petit François , Gaudry Stéphane , Diard Élise , Quenot Jean-Pierre , Dreyfuss Didier , Tran Viet-Thi , Porcher Raphaël
Published: March 2024

Objective

The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals’ evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials.

Materials and methods

We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a “crude strategy” maximizing the population-level hospital-free days at day 60 (HFD60) and a “stringent strategy” recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60.

Results

We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI −5.3 to 35.7] and 14.9 [95% CI −3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices.

Discussion

Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many.

Conclusion

We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.
Bone loss over time and risk of osteoporosis in advanced pancreatic cancer
Authors: Takeda Tsuyoshi , Sasaki Takashi , Okamoto Takeshi , Hirai Tatsuki , Ishitsuka Takahiro , Yamada Manabu , Nakagawa Hiroki , Furukawa Takaaki , Mie Takafumi , Kasuga Akiyoshi , Ozaka Masato , Sasahira Naoki
Published: March 2024

Background

Pancreatic cancer has a high risk of developing osteoporosis. However, the impact of osteoporosis has not been well-studied. This study aimed to evaluate bone loss over time and risk of osteoporosis in patients with advanced pancreatic cancer.

Methods

We retrospectively examined consecutive patients with unresectable pancreatic cancer who had evaluable computed tomography before treatment and at 1-year follow-up. Bone mineral density at the first lumbar vertebra was measured on computed tomography, and osteoporosis was defined as bone mineral density < 135 Hounsfield units. The prevalence and risk factors for osteoporosis, changes in bone mineral density over time and incidence of bone fractures were analyzed.

Results

Three hundred eighty patients were included. Osteoporosis was associated with older age, female sex, low body mass index and poor performance status at baseline. A consistent decrease in bone mineral density was observed over time regardless of age, sex or disease status, resulting in an increase in the prevalence of osteoporosis over time (47% at baseline, 79% at 1 year, 88% at 2 years, 89% at 3 years, 95% at 4 years and 100% at 5 years). Changes in bone mineral density from baseline were greater in patients with locally-advanced pancreatic cancer, in those who received modified FOLFIRINOX or S-IROX for more than 3 months, and in those who received radiation therapy. Incident fractures developed in 45 patients (12%) during follow-up.

Conclusions

Osteoporosis and osteoporotic fractures were highly prevalent in patients with advanced pancreatic cancer. This study highlights the importance of screening for osteoporosis in such patients.
Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women
Authors: Gonzalo-Encabo Paola , Vasbinder Alexi , Bea Jennifer W , Reding Kerryn W , Laddu Deepika , LaMonte Michael J , Stefanick Marcia L , Kroenke Candyce H , Jung Su Yon , Shadyab Aladdin H , Naughton Michelle J , Patel Manali I , Luo Juhua , Banack Hailey R , Sun Yangbo , Simon Michael S , Dieli-Conwright Christina M
Published: March 2024

Background

Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality.

Methods

This prospective cohort study included 8068 postmenopausal women enrolled in the Women’s Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022.

Results

Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval  [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile.

Conclusion

Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.
Cross-sectional and longitudinal changes in body composition, anxiety, and depression in a clinical sample of adolescents with anorexia nervosa
Authors: Dosal Alexis , Denhardt Brenna , Diaz Rebekah , Obleada Katrina , Feldman Marissa , Reese Jasmine , Sobalvarro Sarah
Published: March 2024

Objective

Eating disorders among children and adolescents have increased in prevalence, and mortality rates for anorexia nervosa are among the highest for any psychiatric disorder. Our current study aimed to (a) examine the cross-sectional relationship between body composition and anxiety/depressive symptoms among 97 adolescents and young adults who have been diagnosed with anorexia nervosa, (b) examine the longitudinal changes in body composition and anxiety/depressive symptoms over three months (from baseline to follow-up visit), and (c) examine the longitudinal relationship between change in body composition and change in anxiety/depression over three months.

Method

A retrospective chart review was conducted within an interdisciplinary eating disorder clinic between August 2019 and December 2021. In total, 97 adolescents aged 11–20 years old with diagnoses of anorexia nervosa were included in the analyses. Body composition data were collected at each visit along with parent- and youth-report measures of symptoms of anxiety/depression symptoms.

Results

Findings indicated adolescents demonstrated some improvement in body composition, as well as parent-reported reductions in anxiety/depression symptoms. Based on parent reports, increased BMI percentile was associated with improvements in anxiety/depression symptoms. On the other hand, youth did not report significant changes in anxiety/depressive symptoms. Additionally, there were no associated improvements with body composition measures, which may be associated with continued body dissatisfaction or symptoms of anxiety and depression predating the eating disorder.

Conclusions

These results suggest the importance of including interventions addressing depression, anxiety, and body image as part of treatment.
Primary mature teratoma of the left adrenal gland: a case report
Authors: Li Shangjian , Guo Xudong , Wang Hanbo , Suo Ni , Jiang Shaobo
Published: March 2024

Teratoma are germ cell tumors, most frequently arising in the gonads and retroperitoneal teratomas are rare, especially adrenal teratomas. Only a few case reports have been documented in the literature so far. We report the case of a 52-year-old asymptomatic male patient who had an incidental finding of a left adrenal teratoma during an abdominal computed tomography scan; due to the large size of the tumor, he underwent laparoscopic left adrenalectomy, and histopathological examination revealed a mature teratoma of the left adrenal gland, Patient recovering well after surgery and had no recurrence after 6 months of postoperative follow-up. The preoperative diagnosis of adrenal teratoma is challenging because imaging features are usually non-specific. Minimally invasive surgical resection is the best option for diagnosis and treatment of adrenal teratoma.
Miscellaneous disorders of the bowel
Authors: Gimson Alexander
Published: March 2024

A wide range of miscellaneous disorders can affect the bowel. Those discussed in this chapter include cystic disorders (colitis cystica profunda and pneumatosis cystoides intestinalis), protein-losing enteropathy, vascular disorders of the intestine (spontaneous intramural haemorrhage and ortoenteric fistulas), intestinal pseudo-obstruction (acute colonic pseudo-obstruction, chronic intestinal pseudo-obstruction), various disorders of the colon and rectum (including immune checkpoint inhibitor (ICI) colitis, microscopic (collagenous and lymphocytic) colitis, malakoplakia, solitary rectal ulcer syndrome, and stercoral ulcers), complications of parenteral nutrition and intestinal failure, peritoneal disorders, and endometriosis.
Identification of G-quadruplex-interacting proteins in living cells using an artificial G4-targeting biotin ligase
Authors: Lu Ziang , Xie Shengjie , Su Haomiao , Han Shaoqing , Huang Haiyan , Zhou Xiang
Published: March 2024

G-quadruplexes (G4s) are noncanonical nucleic acid structures pivotal to cellular processes and disease pathways. Deciphering G4-interacting proteins is imperative for unraveling G4’s biological significance. In this study, we developed a G4-targeting biotin ligase named G4PID, meticulously assessing its binding affinity and specificity both in vitro and in vivo. Capitalizing on G4PID, we devised a tailored approach termed G-quadruplex-interacting proteins specific biotin-ligation procedure (PLGPB) to precisely profile G4-interacting proteins. Implementing this innovative strategy in live cells, we unveiled a cohort of 149 potential G4-interacting proteins, which exhibiting multifaceted functionalities. We then substantiate the directly binding affinity of 7 candidate G4-interacting-proteins (SF3B4, FBL, PP1G, BCL7C, NDUV1, ILF3, GAR1) in vitro. Remarkably, we verified that splicing factor 3B subunit 4 (SF3B4) binds preferentially to the G4-rich 3′ splice site and the corresponding splicing sites are modulated by the G4 stabilizer PDS, indicating the regulating role of G4s in mRNA splicing procedure. The PLGPB strategy could biotinylate multiple proteins simultaneously, which providing an opportunity to map G4-interacting proteins network in living cells.
WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination
Authors: Zhang Jie , Yu Yuanyuan , Zou Xiuqun , Du Yaning , Liang Qiankun , Gong Mengyao , He Yurong , Luo Junqi , Wu Dandan , Jiang Xiaoli , Sinclair Matt , Tajkhorshid Emad , Chen Hong-Zhuan , Hou Zhaoyuan , Zheng Yuejuan , Chen Lin-Feng , Yang Xiao-Dong
Published: March 2024

Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2’s ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.
Exploring the traditional Chinese diet and its association with health status—a systematic review
Authors: Niu Jizhao , Li Bai , Zhang Qing , Chen Ge , Papadaki Angeliki
Published: March 2024

Context

Increased adherence to a traditional Chinese diet (TCD) could reduce the increasing prevalence of noncommunicable diseases. Currently, there is no consistent definition of the TCD in the literature, and its associations with health outcomes have not yet been identified.

Objective

This systematic review aimed to assess the definition of the TCD, in the literature, and to evaluate whether the TCD, as described, is associated with health outcomes.

Data sources

Fourteen databases were searched up to April 25, 2022.

Data extraction

Three reviewers (in pairs) independently screened and extracted data. A modified risk-of-bias tool was used to assess the quality of the studies assessing the TCD definition; the Newcastle–Ottawa Scale and the Cochrane Risk-of-Bias tool were used to assess the quality of the observational studies and randomized controlled trials assessing associations between the TCD and health outcomes.

Data analysis

Ninety-nine studies were identified that assessed the TCD definition. In at least 75% of the studies, rice and leafy vegetables were consistently reported as food groups that characterize the TCD; the most frequently cited food items were white rice, spinach, bokchoy, and cabbage. Fish and seafood, pork, and pork products were consistently reported in studies exclusively referring to the TCD consumed in southern China (n = 21 studies), whereas wheat and wheat products were commonly reported in studies focusing on northern China (n = 14 studies). Fifteen studies reported on the quantities of food groups that are characteristic of the TCD, but their findings were inconsistent. Of the 99 studies, 54 assessed associations with health outcomes. The TCD was overall inversely associated with obesity risk and weight gain, while relationships between the TCD and other health outcomes were inconsistent.

Conclusion

Further studies are needed to determine the quantities of foods consumed in the TCD and to establish a consistent definition for further exploration of the TCD’s potential role in preventing non-communicable diseases.
The Dignity of Legal Subjects
Authors: Huq Aziz Z
Published: March 2024

The dignitary account of the rule of law proposes that values of human dignity and agency are appropriately recognised through legal rules and institutions that create opportunities for legal subjects to engage in deliberation and the exercise of practical reason. In a collection of essays published over a period of almost two decades, Thoughtfulness and the Rule of Law, Jeremy Waldron offers a comprehensive account of the grounds and institutional implications of taking dignity so understood as a core rule-of-law desideratum. The ensuing account is novel, stimulating and distinct. There is, however, a chasm between the platforms identified by Waldron and his ambition of advancing dignity. Further, a dignity norm cannot supply a plausible evaluative benchmark under all (or most) plausible circumstances. Its domain might in consequence be more circumscribed than Waldron intimates.
From Surveying to Surveillance: Maritime Cartography and Naval (Self-)Tracking in the Long Nineteenth Century
Authors: Caputo Sara
Published: March 2024

In the eighteenth century, ‘ship tracks’, lines recording vessels’ movements on charts, facilitated wayfinding, hydrographical surveys and territorial claims. During the long nineteenth century, however, their main function shifted from surveying of the marine environment to surveillance of officers’ movements and actions. Using textual and cartographical sources produced by British naval officers, this article argues that geosurveillance and the continuous visual tracking of individuals with reference to mapping systems were developed at sea, long before the aerial and digital revolutions, and independently of panoptical models. In the nineteenth century, most cartographical tracking was disciplined self-tracking, actively performed by the surveilled themselves. This required their employers (notably the state) to emphasize honour, training, conscientiousness and procedure. The Admiralty used tracks for testing performance, verifying accounts, establishing responsibilities and co-ordinating movement. Monitoring individuals through their record was the natural inverse of a pattern discussed by historians of science: data verification through authorial ‘credibility’. The two-way bond between the surveilled and their track was eventually broken in the twentieth century by technological innovations that allowed external and non-consensual geo-tracking. This changed the import of surveillance, discipline and the sea itself, no longer a space where human movement would be inevitably lost from sight.
Small extracellular vesicle microRNAs in pediatric myasthenia gravis plasma and skeletal muscle
Authors: Zhu Mengying , Wang Yilong , Xu Xuebin , Guo Xiaotong , Mao Yuchen , Gao Feng
Published: March 2024

Background

The diagnosis of myasthenia gravis (MG) in children remains difficult. Circulating small extracellular vesicle (sEV)-derived miRNAs (sEV-miRNAs) have been recognized as biomarkers of various diseases and can be excreted by different cell types. These biomarker candidates also play a vital role in autoimmune diseases via intercellular communication.

Methods

In the present study, we used sEV isolation and purification methods to extract the plasma-derived sEV-miRNAs from children with MG and healthy controls. A small RNA sequencing analysis confirmed the miRNA expression features in plasma-derived sEVs from MG patients. The miRNA expression analysis in vitro was determined using microarray analysis. The enrichment and network analyses of altered sEV-miRNAs were performed using miRNA databases and Database for Annotation, Visualization, and Integrated Discovery website. Quantitative real-time polymerase chain reaction was performed for validation of sEV-miRNA. The diagnostic power of altered sEV-miRNAs was evaluated using receiver operating characteristic curve analyses.

Results

Twenty-four sEV-miRNAs with altered expression level were identified between groups by DESeq2 method. The miRNAs were extracted from the sEVs, which were isolated from human primary skeletal muscle cell culture treated with mAb198. The target genes and enriched pathways of sEV-miRNAs partially overlapped between cell supernatant and plasma samples. The significantly downregulated miR-143-3p was validated in quantitative real-time polymerase chain reaction analysis.

Conclusions

For the first time, we report that plasma-derived sEV-miRNAs may act as novel circulating biomarkers and therapeutic targets in pediatric MG.
Health literacy and gout characteristics in a primary care cohort
Authors: Watson Lorraine , Protheroe Joanne , Mallen Christian D , Muller Sara , Roddy Edward
Published: March 2024

Objectives

To examine the cross-sectional association between health literacy and gout characteristics.

Methods

In a primary care cohort of adults living with gout, the prevalence of poor health literacy was defined using the Single-Item Literacy Screener (SILS). Multiple logistic regression was used to obtain adjusted odds ratios (ORs) for the cross-sectional associations between health literacy and individual gout characteristics (frequency of flares, age at gout onset, history of oligo-/polyarticular flares, allopurinol use, allopurinol dose and serum urate level) with 95% CIs and adjustment for age, sex, deprivation and further education.

Results

Of 551 participants [mean age 54.4 years (s.d. 11.2), 498 (90.4%) male], 163 (30.1%) reported two or more flares in the previous 12 months. Fifty-one (9.4%) had poor health literacy. Poor health literacy was associated with having two or more flares in the preceding 12 months [adjusted OR 4.10 (95% CI 2.04, 8.19)] and a history of oligo-/polyarticular flares [OR 1.93 (95% CI 1.06, 3.55)]. No associations were identified between health literacy and age at gout onset [OR 0.99 (95% CI 0.96, 1.01)], allopurinol use [OR 0.88 (95% CI 0.46, 1.65)] or dose [OR 1.00 OR (95% CI 1.00, 1.00)] or serum urate [most recent serum urate OR 1.0 (95% CI 1.00, 1.00)].

Conclusions

Frequent flares and a history of oligo-/polyarticular flares were associated with poor health literacy. Since health literacy is an important determinant of health outcomes, it is important to consider health literacy when providing information and education to people with gout.
Digital Payments and Consumption: Evidence from the 2016 Demonetization in India
Authors: Agarwal Sumit , Ghosh Pulak , Li Jing , Ruan Tianyue
Published: March 2024

We study how consumer spending responds to digital payments, using the differential switch to digital payments across consumers induced by the sudden 2016 Indian Demonetization for identification. Digital payment use rose by 2.94 percentage points and monthly spending increased by 2.38% for an additional 10 percentage points in prior cash dependence. Spending remained elevated even when cash availability recovered. Robustness analyses show that the spending response is not driven by purchase substitution, income shocks, credit supply, or price changes. We provide causal evidence that digital payments increase consumer spending due to subdued endowment effects.
Cancer risk with tocilizumab/sarilumab, abatacept and rituximab treatment in patients with rheumatoid arthritis: a Danish cohort study
Authors: Westermann Rasmus , Cordtz René Lindholm , Duch Kirsten , Mellemkjaer Lene , Hetland Merete Lund , Magnussen Bergur , Dreyer Lene
Published: March 2024

Objectives

To investigate cancer risk in RA patients treated with tocilizumab/sarilumab, abatacept or rituximab compared with those who received TNF inhibitors (TNFi) and compared with biological DMARDs (bDMARD)-naïve RA patients.

Methods

Nationwide registry-based cohort study of RA patients who initiated bDMARD treatment with tocilizumab/sarilumab, abatacept, rituximab, and TNFi, as well as bDMARD-naive patients who initiated their second type of conventional synthetic DMARD. Patients were identified in the Danish Rheumatology Quality Register (DANBIO) and followed for cancer from 2006 to 2020. Patients could contribute multiple treatments, with person years, deaths and cancers allocated to each treatment group in a ‘latest type of treatment’ manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept and rituximab group compared with TNFi-treated and bDMARD-naïve groups, respectively.

Results

In total, 21 982 treatment initiations, 96 475 person years and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept or rituximab treatment groups (HRs ranged from 0.7 to 1.1). More than 5 years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% CI 0.74–2.71). For haematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi-treated (HR 0.09; 95% CI 0.00–2.06) and bDMARD-naïve (HR 0.13; 95% CI 0.00–1.89).

Conclusion

Treatment with tocilizumab/sarilumab, abatacept or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.
Researchers engaging with society: who does what?
Authors: Borlaug Siri Brorstad , Karaulova Maria , Svartefoss Silje Marie , Sivertsen Gunnar , Meijer Ingeborg , van Leeuwen Thed , Hessels Laurens K
Published: March 2024

Distinguishing between research collaboration, consultancy, dissemination, and commercialization of research results, this paper analyses the determinants of researchers’ societal engagement. The analytical framework integrates societal engagement as part of the credibility cycle. Several variables extend previous findings on determinants and mechanisms—herein scientific recognition and funding sources. A novel method to investigate the relationship between scientific recognition and societal engagement is explored. Drawing on a large-scale survey of European-based researchers in physics, cardiology, and economics, we find that several factors are associated with different modes of societal engagement in complex and intersecting ways. Scientific recognition is positively associated with research collaboration and dissemination, while organizational seniority is associated with all modes except for research collaboration with non-scientific actors. Female gender is positively associated with dissemination and external funding sources are positively associated will all. The findings intersect with differences in the three research fields.
Persistent or temporary? Effects of social assistance benefit sanctions on employment quality
Authors: Wolf Markus A
Published: March 2024

This article analyzes the effects of sanctions for unemployed recipients of the social assistance benefit in Germany. I conduct an analysis using administrative data from 2012 to 2018, applying a dynamic entropy balancing approach. In contrast to most previous analyses of benefit sanction effects, I analyse outcomes over a longer period and assess effects on various dimensions of employment quality, including education (mis)match. The results show, in line with previous research, that benefit sanctions increase the employment probability in the first months after treatment. In the long run, the employment probability and employment quality of sanctioned benefit recipients are lower than those for the comparison group of non-sanctioned benefit recipients, indicating long-lasting negative effects. The negative consequences of benefit sanctions for employment quality are hence not temporary, but persistent.
Utilization of a Novel Soil-Isolated Strain Devosia insulae FS10-7 for Deoxynivalenol Degradation and Biocontrol of Fusarium Crown Rot in Wheat
Authors: He Weijie , Zhang Tiantian , Zheng Mengru , Tabl Karim M. , Huang Tao , Liao Yucai , Wu Aibo , Zhang Jingbo
Published: March 2024

Deoxynivalenol (DON) is the most widespread mycotoxin contaminant hazardous to human and animal health globally. It acts as a crucial virulence factor to stimulate the spread of pathogenic Fusarium within wheat plants. Control of DON and Fusarium disease contributes enormously to food safety, which relies on chemical fungicides. Here, we report the biodegradation of DON using a novel soil bacterium, Devosia insulae FS10-7, and its biocontrol effect against Fusarium crown rot. We demonstrated that strain FS10-7 degraded DON to 3-epi-DON by forming a 3-keto-DON intermediate. Such degradation activity can be maintained at a wide range of pH (4 to 10) and temperature (16 to 42°C) values under aerobic conditions. Notably, strain FS10-7 exhibited practical inhibitory effects on Fusarium crown rot disease caused by F. graminearum and F. pseudograminearum in the in vitro Petri dish test under laboratory conditions and the pot experiment under greenhouse conditions. The mechanisms underlying the biocontrol ability of strain FS10-7 were preliminarily investigated to be associated with its high DON-degrading activity rather than direct antagonism. These results establish the foundation to develop further bioagents capable of biodegrading mycotoxins in cereals and derived products and, accordingly, biocontrol plant diseases caused by DON-producing pathogens.
mTORC2‐AKT signaling to PFKFB2 activates glycolysis that enhances stemness and tumorigenicity of intestinal epithelial cells
Authors: Li Mengzhen , Wu Xi , Pan Yuwei , Song Manyu , Yang Xu , Xu Jiuzhi , Plikus Maksim V. , Lv Cong , Yu Lu , Yu Zhengquan
Published: March 2024

Although elevated glycolysis has been widely recognized as a hallmark for highly proliferating cells like stem cells and cancer, its regulatory mechanisms are still being updated. Here, we found a previously unappreciated mechanism of mammalian target of rapamycin complex 2 (mTORC2) in regulating glycolysis in intestinal stem cell maintenance and cancer progression. mTORC2 key subunits expression levels and its kinase activity were specifically upregulated in intestinal stem cells, mouse intestinal tumors, and human colorectal cancer (CRC) tissues. Genetic ablation of its key scaffolding protein Rictor in both mouse models and cell lines revealed that mTORC2 played an important role in promoting intestinal stem cell proliferation and self‐renewal. Moreover, utilizing mouse models and organoid culture, mTORC2 loss of function was shown to impair growth of gut adenoma and tumor organoids. Based on these findings, we performed RNA‐seq and noticed significant metabolic reprogramming in Rictor conditional knockout mice. Among all the pathways, carbohydrate metabolism was most profoundly altered, and further studies demonstrated that mTORC2 promoted glycolysis in intestinal epithelial cells. Most importantly, we showed that a rate‐limiting enzyme in regulating glycolysis, 6‐phosphofructo‐2‐kinase (PFKFB2), was a direct target for the mTORC2‐AKT signaling. PFKFB2 was phosphorylated upon mTORC2 activation, but not mTORC1, and this process was AKT‐dependent. Together, this study has identified a novel mechanism underlying mTORC2 activated glycolysis, offering potential therapeutic targets for treating CRC.