bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a codebook to characterize barriers, enablers, and strategies for implementing learning health systems from a multilevel perspective
Authors: Shaw Louise , Perrier Meg , Tahmasebian Kasra , Wong Kimberly , Yajnik Pranjali , Zhu Zihan , Lyons Kayley
Published: October 2024

Introduction

Learning health systems (LHSs) play a crucial role in improving healthcare delivery and outcomes through continuous learning and data‐driven decision‐making. Implementation of LHSs spans individual, organization, and systemic levels of healthcare. This paper outlines a systematic approach for developing a comprehensive codebook to identify barriers, enablers, and strategies associated with the establishment and operation of LHS from a multilevel perspective.

Methods

The codebook development process was divided into two phases and employed a coding team. Phase 1 involved the synthesis of previous literature, which drove the development of initial codes. Phase 2 included the testing of the codebook with a pilot dataset to derive new codes or iterative refinement, ensuring robustness, and validity.

Results

The literature search revealed 12 papers that detailed the barriers, enablers, and strategies for LHS implementation. Micro‐level codes were derived from a mixture of existing literature and our pilot dataset. Most meso‐level codes barriers and enablers were derived from the literature, with some subcodes derived from participant interviews. All strategies for implementation at the meso‐level were identified in the literature. At the macro‐level, all codes and subcodes were from the literature.

Conclusions

The codebook contributes to the advancement of implementation science in LHS. The codebook facilitates effective analysis and understanding of the key factors influencing the success of LHS implementation, offering practical insights for policymakers, healthcare practitioners and researchers engaged in the ongoing evolution of LHS.
Single‐cell transcriptome atlas revealed bronchoalveolar immune features related to disease severity in pediatric Mycoplasma pneumoniae pneumonia
Authors: Shen Xiantao , Jin Zhengjiang , Chen Xiaomin , Wang Zhenhui , Yi Lu , Ou Yangwei , Gong Lin , Zhu Chengliang , Xu Guogang , Wang Yi
Published: October 2024

The mechanisms underlying protective immunity in mild Mycoplasma pneumoniae pneumonia (MPP) and the pathogenesis of severe MPP, characterized by dysregulated immune responses, remain unclear. Here, we performed single‐cell RNA sequencing (scRNA‐seq) to profile bronchoalveolar lavage fluid (BALF) samples from 13 healthy donors and 24 hospitalized pediatric patients with MPP, covering both mild and severe cases. Severe MPP patients exhibited high levels of exhausted T cells and M1‐like macrophages, with the exhaustion of T cells attributed to persistent type I interferon signaling and inadequate assistance from CD4+ T cells. Significant cell‐cell interactions between exhausted T cells and programmed death‐ligand 1+ (PD‐L1+) macrophages were detected in severe patients, potentially mediated through inhibitor molecules (e.g., PD1) and their receptors (e.g., PD‐L1), as well as human leukocyte antigen class I molecules and their receptors (e.g., KLRC1/D2), resulting in the dysfunction of anti‐MP immune responses. Mild MPP patients were featured by an increased abundance of neutrophils, coupled with enhanced activation, contributing to protective immunity. Together, our study provides a detailed characterization of the BALF immune landscape in MPP patients, revealing distinct immune characteristics between mild and severe cases, which offers a valuable resource for understanding MPP immunopathogenesis and formulating effective therapeutic strategies.
Antibacterial Capabilities of Metallic Nanoparticles and Influencing Factors
Authors: Girma Abayeneh , Mebratie Gedefaw , Mekuye Bawoke , Abera Birhanu , Bekele Tigabu , Alamnie Getachew
Published: October 2024

The increase of antibiotic resistance in bacteria has become a major concern for successful diagnosis and treatment of infectious diseases. Over the past few decades, significant progress has been achieved on the development of nanotechnology‐based medicines for combating multidrug resistance in microorganisms. Among these, metallic nanoparticles (MNPs) hold great promise in addressing this challenge due to their broad‐spectrum and robust antimicrobial properties. This review illustrates the antibacterial activities of MNPs and further elucidates how different factors including synthesis method, size, shape, surface charge, pH, dose, type of capping or stabilizing agents of MNPs, and Gram‐type of the bacteria, impact their antibacterial activities, which are expected to promote the future development of more potent MNP‐based antibacterial agents.
Prognostic Significance of Early Posttreatment Audiometry in Idiopathic Sudden Sensorineural Hearing Loss
Authors: Sofer Harel , Fisher Ran , Tarnovsky Yehuda , Vofo Gaelle , Kaufmann Michal , Stern Shavit Sagit
Published: October 2024

Objective

This study aimed to assess the prognostic value of early posttreatment initiation audiometry findings in patients with idiopathic sudden sensorineural hearing loss (ISSHL).

Study Design

A retrospective cohort study.

Setting

The study was conducted at a single tertiary medical center.

Methods

A review was conducted on 299 ISSHL patients treated between 2007 and 2023. Patients underwent audiometry on Days 2 to 3 and 5 to 7 posttreatment initiation. Data on demographics, medical history, audiometry results, and prognosis were collected. Prognosis was categorized based on hearing recovery at 1 year postdiagnosis.

Results

Older age, worse initial speech reception threshold (SRT), ischemic heart disease, cerebrovascular accidents/transient ischemic attacks, hypertension, and diabetes were associated with a poorer prognosis. Posttreatment initiation audiometry findings on Days 2 to 3 and 5 to 7 significantly correlated with prognosis. Patients with a ≥30% improvement had substantial or complete recovery in over 80% of cases, while those with <10% had <30% recovery. Multivariate analysis identified a significant improvement on days 5 to 7 as an independent predictor of complete recovery (odds ratio = 4.25 [95% confidence interval 1.96‐9.23], P = .0002).

Conclusion

Posttreatment initiation audiometry findings, particularly on Days 5 to 7, hold significant prognostic value in ISSHL patients. A substantial improvement during this timeframe is strongly associated with favorable outcomes. These findings emphasize the potential of posttreatment initiation audiometry as a valuable tool for clinicians in counseling patients with ISSHL.
Rethinking Measures and Mortality Attribution in Health Care: The ENT Example
Authors: Patel Samip , Olivero Lorenzo , Sinclair De Frias Jorge , Anderson Stephanie S. , Pollock Ben D. , Lee Marian D. , Chirila Razvan M. , Murthy Hemant S. , Guru Pramod K. , Taylor Richard , Moreno Franco Pablo , Menser Terri
Published: October 2024

National performance metrics ultimately enhance patient decision‐making and promote meaningful improvements in health care delivery, which makes having valid and reliable measures essential. This study examined US News and World Report metrics from 2019 to 2012 and used electronic health record data, combined with detailed chart review across 3 in‐system hospitals, to assess the provision of care compared to the attribution of patients assigned to the ear, nose, and throat (ENT) mortality group. Of the initial 47 ENT‐attributed deaths, 23 of those were verified, dimensioning the mortality rate from 1.7% to just 0.8%. These results underscore the necessity of rethinking measures and mortality attribution methodologies to be more accurate. Current methods use Medicare Severity Diagnosis Related Group billing coding to map the attribution. We suggest transitioning away from specialty ranking approaches and towards a procedure and condition “rating” approach to ensure that these ranking types capture data about the provision of care within a given encounter.
High‐Valence Metals Accelerate the Reaction Kinetics for Boosting Water Oxidation
Authors: Li Lun , Qiao Lulu , Liu Di , Yu Zhichao , An Keyu , Yang Jiao , Liu Chunfa , Cao Youpeng , Pan Hui
Published: October 2024

The transition metal with high valence state in oxyhydroxides can accelerate the reaction kinetics, enabling highly intrinsic OER activity. However, the formation of high‐valence transition‐metal ions is thermodynamically unfavorable in most cases. Here, a novel strategy is proposed to realize the purpose and reveal the mechanism by constructing amorphous phase and incorporating of elements with the characteristic of Lewis acid or variable charge state. A model catalyst, CeO2‐NiFeOxHy, is presented to achieve the modulation of valence state of active site (Ni2+→Ni3+→Ni4+) for improved OER, leading to dominant active sites with high valence state. The CeO2‐NiFeOxHy electrode exhibits superior OER performance with overpotential of 214 and 659 mV at 10 and 500 mA cm−2, respectively (without IR correction), and high stability, which are much better than those of NiOxHy, NiFeOxHy and CeO2‐NiOxHy. These findings provide an effective strategy to achieve the active metals with high‐valence state for highly efficient OER.
Novel 2D Material of MBenes: Structures, Synthesis, Properties, and Applications in Energy Conversion and Storage
Authors: Yang Yuquan , Wang Huichao , Wang Chenjing , Liu Jiajia , Wu Hongjing , Liu Naiyan , Wang Qian , Shang Yang , Zheng Jinlong
Published: October 2024

2D transition metal borides (MBenes) have garnered significant attention from researchers due to their exceptional electrical conductivity, strong mechanical rigidity, excellent dynamic and thermodynamic stability, which stimulates the enthusiasm of researchers for the study of MBenes. Over the past few years, extensive research efforts have been dedicated to the study of MBenes, resulting in a growing number of synthesis methods being developed. However, there remains a scarcity of comprehensive reviews on MBenes, particularly in relation to the synthesis techniques employed. To address this gap, this review aims to provide a comprehensive summary of the latest research findings on MBenes. An exhaustive exploration of the crystal structure types of MBenes is presented, highlighting the greater structural diversity compared to MXenes. Furthermore, a comprehensive review of the recent advancements in MBenes synthesis methodologies is provided. The review also delves into the physical and chemical properties of MBenes, while elucidating their applications in the realms of energy conversion and energy storage. Lastly, this review concludes by summarizing and offering insights on MBenes from three angles: synthesis, structure‐property relationships, and application prospects.
Selective Void Deposition by Continuous, Ultrathin Ag Film Enabled Stable, High‐Performance AgNWs‐Based Transparent Heaters
Authors: Thi Sanh Vo , Nguyen Thanh Tai , Patel Malkeshkumar , Bhatnagar Priyanka , Choi Chanhyuk , Lee Junghyun , Dao Vinh‐Ai , Kim Joondong
Published: October 2024

Metallic nanowire‐based transparent conductors (MNTCs) are essential to various technologies, including displays, heat‐regulating windows, and photo‐communication. Hybrid configurations are primarily adopted to design stable, high‐functioning MNTCs. Although hybrid MNTCs enhance electrical performance, they often suffer from optical degradation due to losses associated with the hybrid layers. Highly conductive hybrid MNTCs with minimal reduction in transparency are achieved with AgNWs/Ag(O)/Al‐doped ZnO (AZO) design. The design provides a high visible light transmittance of 95.1%, representing a minimized optical loss of 3% compared to pristine AgNWs by optimizing optical interference between the AZO and Ag(O) layers. Furthermore, it allows for enhanced mobility of metallic nanowires by controlling the selective formation of conductive layers in the voids of the nanowire networks. The oxygen additive enables a continuous Ag ultrathin film of 6 nm in the macro‐voids of AgNWs system, corresponding to 25 times higher mobility for AgNWs/Ag(O)/AZO than that of sole AgNWs. The significant enhancement in the mobility of AgNWs/Ag(O)/AZO induces a reduction of sheet resistance of MNTCs by 73%. The AgNWs/Ag(O)/AZO, with an optimized sheet resistance of 24 Ω sq−1, is explored for transparent heater applications, demonstrating a fast thermal response with reliable stability, as evidenced by consistent high‐temperature profiles during prolonged operation.
Waste to Wealth: One‐Step Exfoliating of Spent Graphite to Build a Low‐Cost Cathode for Lithium–Sulfur Batteries
Authors: Zhang Qiongfang , Hu Le , Ren Yibin , Li Jianbo , Kong Yuelin , Li Zhen , Huang Yunhui
Published: October 2024

With the booming development of Li‐ion batteries (LIBs), the recycling and reusing of spent graphite (SG) from LIBs is becoming increasingly crucial. Meanwhile, developing low‐cost and efficient carbon hosts for lithium–sulfur (Li–S) batteries has gained widespread attention in the past decade. Nevertheless, the processing of carbon materials as sulfur hosts is often energy‐consuming and complex. Herein, a simple and environmental‐friendly strategy is proposed to reuse the SG to prepare graphene/sulfur composite cathode for Li–S batteries. Due to expanded layer spacing and defects of SG, sulfur molecules can strip it into a graphene‐type host via ball milling. By optimizing the S/SG ratio and ball milling time, the as‐prepared graphene/sulfur composite cathode with 70 wt.% sulfur content exhibits a high capacity of 1000 mAh g−1. With a high sulfur loading of 4.68 mg cm−2, the graphene/sulfur cathode can maintain 526 mAh g−1 after 400 cycles. This work provides a novel waste‐to‐wealth perspective for recycling spent graphite from LIBs to reuse in Li–S batteries.
2D Microporous Polymers/Reduced Graphene Oxide with Built‐In Lithiophilic Sites for Uniform Lithium Deposition in Lithium Metal Anode
Authors: Ghazi Zahid Ali , Yin Lichang , Sun Zhenhua , Sun Chengguo , Shi Yin , Shi Huifa , Li Feng
Published: October 2024

Lithium (Li) metal is an attractive anode material for use in high‐energy lithium‐sulfur and lithium‐air batteries. However, its practical application is severely impeded by excessive dendrite growth, huge volume changes, and severe side reactions. Herein, a novel Li metal anode composed of lithiophilic two dimensional (2D) conjugated microporous polymer (Li‐CMP) and reduced graphene oxide (rGO) sandwiches (Li‐CMP@rGO) for Li metal batteries (LiMBs) is reported. In the Li‐CMP@rGO anode, the conductive rGO facilitates the charge transfer while the functionalized‐CMP provides Li nucleation sites within the micropores, thereby preventing dendrite growth. As a result, the Li‐CMP@rGO anode can be cycled smoothly at 6 mA cm−2 of current density with a platting capacity of 2 mAh cm−2 for 1000 h. A Coulombic efficiency of 98.4% is achieved over 350 cycles with a low overpotential of 28 mV. In a full cell with LiFePO4 cathode, the Li‐CMP@rGO anode also exhibited good cycling stability compared to CMP@rGO and CMP/Super‐P. As expected, the simulation results reveal that Li‐CMP@rGO has a strong affinity for Li ions compared to CMP@rGO. The strategies adopted in this work can open new avenues for designing hybrid porous host materials for developing safe and stable Li metal anodes.
Subtraction‐based DNA Origami Cryptography by using Structural Defects for Information Encryption
Authors: Jiang Chu , Tan Ruihao , Li Weiying , Zhang Yinan , Liu Huajie
Published: October 2024

Conventional cryptographic methods rely on increased computational complexity to counteract the threat posed by growing computing power for sustainable protection. DNA cryptography circumvents this threat by leveraging complex DNA recognition to maintain information security. Specifically, DNA origami has been repurposed for cryptography, using programmable folding of the long scaffold strand carrying additional tagged strands for information encryption. Herein, a subtraction‐based cryptographic strategy is presented that uses structural defects on DNA origami to contain encrypted information. Designated staple strands are removed from the staple pool with “hook” strands to create active defect sites on DNA origami for information encryption. These defects can be filled by incubating the structures with the intact pool of biotinylated staple strands, resulting in biotin patterns that can be used for protein‐binding steganography. The yields of individual protein pixels reached over 91%, and self‐correction codes are implemented to aid the information recovery. Furthermore, the encrypted organization of defective DNA origami structures is investigated to explore the potential of this method for scalable information storage. This method uses DNA origami to encrypt information in hidden structural features, utilizing subtraction for robust cryptography while ensuring the safety and recovery of data.
Hydrogen‐Bonded Organic Framework Enhanced Antifouling Property for Efficient In Situ Electrochemical Assay of Cerebral Ascorbic Acid
Authors: Zheng Zhiyuan , Liu Ningxuan , Lu Jiajia , Zhou Xiang , Song Zibin , An Yida , Lu Ling , Zhao Peng , Tao Jia
Published: October 2024

Accurate determination of cerebral ascorbic acid (AA) is crucial for understanding ischemic stroke (IS) related pathological events. Carbon fiber microelectrodes (CFEs) have proven to be robust tools with high sensitivity toward AA, however, they face ongoing challenges for in situ measurement due to the non‐specific adsorption of proteins in brain tissue. In this study, the hydrogen‐bonded organic framework PFC‐71 is synthesized and modified on CFEs through π‐π stacking interactions with carboxylated carbon nanotubes (CNT‐COOH). It is found that the gating effect and hydrophilicity of PFC‐71 provided the CFE with excellent antibiofouling properties. As a result, AA exhibited a low oxidation potential of −30 mV on the CFE/CNT‐COOH/PFC‐71, even in the presence of 20 mg mL−1 bovine serum albumin. Given the structural advantages of CFE/CNT‐COOH/PFC‐71, a ratiometric electrochemical strategy for AA is established, enabling the in situ assay of cerebral AA in a middle cerebral artery occlusion (MCAO) model with high accuracy and stability.
Sustainable Sulfur‐Carbon Hybrids for Efficient Sulfur Redox Conversions in Nanoconfined Spaces
Authors: Senokos Evgeny , Au Heather , Eren Enis Oğuzhan , Horner Tim , Song Zihan , Tarakina Nadezda V. , Yılmaz Elif Begüm , Vasileiadis Alexandros , Zschiesche Hannes , Antonietti Markus , Giusto Paolo
Published: October 2024

Nanoconfinement is a promising strategy in chemistry enabling increased reaction rates, enhanced selectivity, and stabilized reactive species. Sulfur's abundance and highly reversible two‐electron transfer mechanism have fueled research on sulfur‐based electrochemical energy storage. However, the formation of soluble polysulfides, poor reaction kinetics, and low sulfur utilization are current bottlenecks for broader practical application. Herein, a novel strategy is proposed to confine sulfur species in a nanostructured hybrid sulfur‐carbon material. A microporous sulfur‐rich carbon is produced from sustainable natural precursors via inverse vulcanization and condensation. The material exhibits a unique structure with sulfur anchored to the conductive carbon matrix and physically confined in ultra‐micropores. The structure promotes Na+ ion transport through micropores and electron transport through the carbon matrix, while effectively immobilizing sulfur species in the nanoconfined environment, fostering a quasi‐solid‐state redox reaction with sodium. This translates to ≈99% utilization of the 2e− reduction of sulfur and the highest reported capacity for a room temperature Na−S electrochemical system, with high rate capability, coulombic efficiency, and long‐term stability. This study offers an innovative approach toward understanding the key physicochemical properties of sulfurcarbon nanohybrid materials, enabling the development of high‐performance cathode materials for room‐temperature Na‐S batteries with efficient sulfur utilization.
Exploring the interplay between zinc‐induced protein dyshomeostasis and mitochondrial dysfunction using viscosity‐sensitive sensor
Authors: He Xuan , Li Jiaqi , He Wenye , Zhai Jia , Wei Yu , Zhang Xin , Shen Baoxing , Huang He
Published: October 2024

Mitochondria are crucial sites for protein quality control within cells. When mitochondrial stress is triggered by protein misfolding, it can accelerate abnormal protein aggregation, potentially inducing various diseases. This study developed a cascade‐responsive sensor, named AggHX, to monitor the microenvironment of protein aggregation induced by zinc (II) ions and the accompanying mitochondrial dysfunction. The AggHX consists of two key components: (1) A Zn2+ recognition group for triggering a fluorescent enhance response, and (2) a near‐infrared BODIPY scaffold that detects viscosity changes in cell aggregation via HaloTag. This sensor's mechanism of action is elucidated through photochemical and biochemical characterizations. To further investigate the relationship between protein aggregation and mitochondrial homeostasis, we employ fluorescence lifetime imaging microscopy to assess viscosity changes in protein aggregates under intracellular Zn2+ stress. This research provides insights into the dynamic behavior and spatial distribution of protein aggregates and mitochondria, contributing to a deeper understanding of their physiological roles in cellular processes and potential implications in disease pathology.
GIS‐based surface irrigation potential assessment of Gololcha River Watershed, Awash Basin, Ethiopia
Authors: Abagissa Wudad Yazid , Geremew Getachew Bereta , Ayana Melkamu Teshome , Ayele Elias Gebeyehu , Tilahun Alemayehu Kasaye
Published: October 2024

The Gololcha River Watershed is lacking comprehensive assessment of land suitability for surface irrigation, available water potential, and prioritized irrigable areas. This study aims to evaluate the potential of land and water resources for surface irrigation in the Gololcha River Watershed. The study employed a multi‐criteria analysis approach using the analytical hierarchy process (AHP) and ArcGIS to assess land suitability, considering factors like slope, land use/cover, soil characteristics, and proximity to water sources. The observed mean monthly water flow potential for each sub‐watershed was statistically evaluated, and the area ratio approach was used to transfer discharges from gauged sites to the site of interest. Irrigation water requirements for three major crops in the study area were calculated using the CROPWAT8.0 model. The findings revealed an average water availability for irrigation of 2.70 m3/s/month, 1.10 m3/s/month, and 1.03 m3/s/month for the Kurkura, Midagdu, and Wefi sub‐watersheds, respectively, with a total annual river flow of 161 m3/s. Based on the suitability analysis, 2508 ha (7.27%) of the watershed area was classified as highly suitable for surface irrigation, 16,420 ha (47.565%) as moderately suitable, 1502 ha (4.35%) as marginally suitable, and 14,029 ha (40.71%) as unsuitable. The overall surface irrigation potential, aligned with available water, was estimated at 4872.58 ha. However, due to water limitations, only 14.15% of the total suitable land can be irrigated using existing flows. The study highlights the significant potential for expanding surface irrigation in the Gololcha River Watershed, particularly during the rainy seasons when substantial water flows are available. The findings provide valuable insights for developing sustainable irrigation strategies, enhancing agricultural productivity, and contributing to food security in the region.
Analogical elucidation of dusty‐hybrid nanofluid flow through the microchannel: An unsteady case
Authors: Almeida Felicita , Keerthi Maasthi Lohitkumar , Venkatesh Puttaswamy , Gireesha Bijjanal Jayanna , Nagaraja Basavarajappa , Kumar Pradeep
Published: October 2024

This work is the exploration of unsteady flow of dusty fluid in the horizontal microchannel when the channel plates are susceptible to linear radiation. The flow of the dusty fluid is in the existence of magnetic field. Along with dusty fluid, there are immersions of two different types of nanoparticles namely ferrous oxide and silver . The study gives the comparison of nanofluid phase with dusty fluid phase; hybrid nanofluid phase with dusty fluid phase separately. The modeled partial differential equations are non‐dimensionalized and pdsolve command of Maple software tackles these formed partial differential equations directly. Comparative study of nanofluid‐dusty fluid and hybrid nanofluid‐dusty fluid for the flow in microchannel is to elucidate the fact of heat transfer enhancement upon appropriate insertion of nanoparticles in the base fluid; especially the nanoparticles possessing paramagnetic effect for the better performance on the application of the magnetic field. Results deduce that the fluid flow and heat transmission are known to progress with time. Also, the fluid phase is known to reach the steady state earlier than the dust phase. The nanoparticle volume fraction is known to deplete the temperature in both the hybrid fluid phase and nanofluid phase. The particle concentration parameter diminishes the velocity profile, both for fluid phase and dust phase.
On the inverse problem of parameter identification in the steady Oseen model with unilateral and frictional‐type boundary conditions
Authors: Cen Jinxia , Khan Akhtar A. , Yao Jen‐Chih , Zeng Shengda
Published: October 2024

Recently, Migórski‐Dudek  investigated a steady Oseen flow for a generalized Newtonian incompressible fluid with unilateral and frictional‐type boundary conditions. They established an existence theorem for the steady Oseen model when the divergence‐free convection field and acting volume force are known. However, prior knowledge of and is often impossible in practical engineering applications. This leads to the question of whether the divergence‐free convection field and acting volume force can be determined. The main objective of this paper is to provide a positive response to this challenging and intriguing question. Specifically, we aim to formulate an inverse problem for identifying and , characterized by a nonlinear and nonsmooth regularized optimization problem. Initially, we introduce a variational selection mapping for the steady Oseen model. We then establish the boundedness and generalized continuity of this variational selection. Finally, by leveraging optimization theory, convex analysis, and nonsmooth analysis, we develop an abstract regularization framework for the considered inverse problem and establish the existence of a solution.
Quantification of deoxythioguanosine in human DNA with LC-MS/MS, a marker for thiopurine therapy optimisation
Authors: Carlsson Björn , Karlsson Louise , Ärlemalm Andreas , Sund Sophie , Appell Malin Lindqvist
Published: October 2024

In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into the competing antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA. The current therapeutic drug monitoring (TDM) method measures the sum of the formed metabolites in the sample, after acidic hydrolysis at high temperature. In this work, the goal is to measure these drugs closer to their pharmacological endpoints, once incorporated into DNA. After extracting DNA from whole blood, followed by DNA hydrolysis, 2′-deoxythioguanosine (dTG) and the complementary natural nucleobase 2′-deoxycytidine (dC) were measured. Chromatographic separation on a HSS T3 column followed by mass spectrometric detection was performed in multi-reaction monitoring (MRM) mode on a Xevo TQ-XS with ESI in positive mode, within 5 min. The concentration range for dTG was 0.04–5 nmol/L, and for dC, 0.1–12.5 µmol/L. The lower limit of detection was determined to a concentration of 0.003 nmol/L for dTG and 0.019 µmol/L for dC. The intra- and inter-assay imprecision for the quality controls ranged between 3.0 and 5.1% and between 8.4 and 10.9%, respectively. Sample stability for up to 4 years is shown. In summary, a sensitive method to quantify the thiopurines incorporated into DNA as dTG has been developed and will be used in further clinical studies for a better understanding of the mode of action of the thiopurines and the use of this method in TDM.
Prognostic impact of microscopic residual disease after neoadjuvant chemotherapy in patients undergoing interval debulking surgery for advanced ovarian cancer
Authors: Di Donato Violante , Caruso Giuseppe , Golia D’Augè Tullio , Perniola Giorgia , Palaia Innocenza , Tomao Federica , Muzii Ludovico , Pernazza Angelina , Della Rocca Carlo , Bogani Giorgio , Benedetti Panici Pierluigi , Giannini Andrea
Published: October 2024

Purpose

To determine the prognostic impact of microscopic residual disease after neoadjuvant chemotherapy (NACT) in patients undergoing interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC).

Methods

Patients affected by FIGO stage IIIC–IV ovarian cancer undergoing IDS between October 2010 and April 2016 were selected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier analysis.

Results

In total, 98 patients were identified. Four patients (4.1%) were considered inoperable. Overall, 67 patients (out of 94; 71.3%) had macroscopic disease, equating Chemotherapy Response Score (CRS) 1 and 2, 7 (7.4%) had microscopic residuals, equating CRS3, rare CRS2, while 20 (21.3%) had both microscopic and macroscopic disease. Median OS and PFS were, respectively, 44 and 14 months in patients with no macroscopic residual disease (RD = 0) compared to 25 and 6 months, in patients with RD > 0 (OS: p = 0.001; PFS: p = 0.002). The median PFS was 9 months compared to 14 months for patients with more or less than 3 areas of microscopic disease at final pathologic evaluation (p = 0.04). The serum Ca125 dosage after NACT was higher in patients with RD > 0 compared to those without residue (986.31 ± 2240.7 µg/mL vs 215.72 ± 349.5 µg/mL; p = 0.01).

Conclusion

Even in the absence of macroscopic disease after NACT, the persistence of microscopic residuals predicts a poorer prognosis among AEOC patients undergoing IDS, with a trend towards worse PFS for patients with more than three affected areas. Removing all fibrotic residuals eventually hiding microscopic disease during IDS represents the key to improving the prognosis of these patients.
Father–Child Relationship Quality and Social Functioning Among Children at Risk for Child Maltreatment
Authors: Yoon Susan , Yoon Dalhee , Wernekinck Uwe , Lee Seungjin , Nho Choong Rai , Chung Ick-Joong
Published: October 2024

Despite the considerable growth and advancement in fatherhood research, relatively little is known about the effects of father–child relationship quality on social functioning among children who experience child maltreatment. Applying the strengths-based perspective, the current study sought to examine the association between father–child relationship quality and social functioning (social competence and positive peer relationships) among at-risk children, and to determine whether these associations are moderated by perpetrator type. This study included a sample of 681 US children (age 12 years) drawn from the Longitudinal Studies of Child Abuse and Neglect. We conducted a series of ordinary least squares multiple regression analyses. Higher-quality father–child relationships were associated with higher levels of social competence (B = 0.19, SE = 0.06, p = .002) and positive peer relationships (B = 0.05, SE = 0.02, p = .005). Significant interaction effects were found. The positive association between father–child relationships and peer relationships was significantly stronger among children with a history of maltreatment perpetrated by fathers with or without mothers (B = 0.16, SE = 0.05, p = .002). Findings highlight the importance of positive father–child relationships in building social resilience among children who experience maltreatment. Practitioners working with youth who are at risk for maltreatment should consider engaging fathers in services to support the development of strong father–child relationships.
Environmental and Welfare Effects of Large-Scale Integration of Renewables in the Electricity Sector
Authors: Davi-Arderius Daniel , Jamasb Tooraj , Rosellon Juan
Published: October 2024

The 2022 energy crisis highlighted the dependence of the Europe electricity sector on imported natural gas and the need to accelerate the adoption of renewables to the power system. However, operating a reliable power system with high share of renewables might require curtailing some renewables and activating conventional generators not scheduled in the day-ahead markets to ensure system reliability. These actions can result in environmental impacts, higher system costs and welfare impacts for customers. We use a novel high-granularity data from the Spanish power system for the period 2019–2022 to estimate the effects of these actions and forecast future impact of implementing ambitious targets of the European Gas Reduction Plan. We show that reliance on conventional generators will sharply increase with the addition of renewables. However, higher electricity consumption reduces the negative welfare impacts of integrating renewables. Until renewables and storage technologies advance further, conventional generators are needed for reliable operation of the systems.
Knowledge graph-enhanced multi-agent reinforcement learning for adaptive scheduling in smart manufacturing
Authors: Qin Zhaojun , Lu Yuqian
Published: October 2024

Self-organizing manufacturing network has emerged as a viable solution for adaptive manufacturing control within the mass personalization paradigm. This approach involves three critical elements: system modeling and control architecture, interoperable communication, and adaptive manufacturing control. However, current research often separates interoperable communication from adaptive manufacturing control as isolated areas of study. To address this gap, this paper introduces Knowledge Graph-enhanced Multi-Agent Reinforcement Learning (MARL) method that integrates interoperable communication via Knowledge Graphs with adaptive manufacturing control through Reinforcement Learning. We hypothesize that implicit domain knowledge obtained from historical production job allocation records can guide each agent to learn more effective scheduling policies with accelerated learning rates. This is based on the premise that machine assignment preferences effectively could reduce the Reinforcement Learning search space. Specifically, we redesign machine agents with new observation, action, reward, and cooperation mechanisms considering the preference of machines, building upon our previous MARL base model. The scheduling policies are trained under extensive simulation experiments that consider manufacturing requirements. During the training process, our approach demonstrates improved training speed compared with individual Reinforcement Learning methods under the same training hyperparameters. The obtained scheduling policies generated by our Knowledge Graph-enhanced MARL also outperform both individual Reinforcement Learning methods and heuristic rules under dynamic manufacturing settings.
Romanian Adaptation and Psychometric Validation of the Behavioral Emotion Regulation Questionnaire (BERQ-RO)
Authors: Ursu Andreea , Priego-Ojeda María , Opariuc-Dan Cristian
Published: October 2024

The aim of the present study was to adapt the Behavioral Emotion Regulation Questionnaire to the Romanian population and assess its psychometric proprieties. Participants included 399 adults, aged between 18 and 67 years old (M = 25.30, SD = 9.20; 83% females). Related to reliability and construct validity, results showed good indices. Additionally, results replicated the original five-factor structure, including seeking distraction, withdrawal, actively approaching, seeking social support and ignoring. These subscales showed good criterion validity, having significant associations with cognitive emotion regulation strategies, stress, anxiety and depression, and positive and negative affectivity. Furthermore, in terms of predictive validity, seeking distraction and actively approaching negatively predicted six months later symptoms of depression, withdrawal positively predicted six months later symptoms of depression and anxiety, while actively approaching negatively predicted six months later stress. These findings highlight that the Romanian version of the BERQ could be a helpful tool to assess emotion regulation strategies among adults.
New approximations for monotone submodular maximization with knapsack constraint
Authors: Du Hongmin W. , Li Xiang , Wang Guanghua
Published: October 2024

Given a monotone submodular set function with a knapsack constraint, its maximization problem has two types of approximation algorithms with running time $$O(n^2)$$

O
(

n
2

)

and $$O(n^5)$$

O
(

n
5

)

, respectively. With running time $$O(n^5)$$

O
(

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, the best performance ratio is $$1-1/e$$

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. With running time $$O(n^2)$$

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, the well-known performance ratio is $$(1-1/e)/2$$

(
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and an improved one is claimed to be $$(1-1/e^2)/2$$

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recently. In this paper, we design an algorithm with running $$O(n^2)$$

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and performance ratio $$1-1/e^{2/3}$$

1
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, and an algorithm with running time $$O(n^3)$$

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and performance ratio 1/2.
The Different Faces of Religion in Therapy: An Exploratory Qualitative Study of a Religion-Based Therapeutic Community for Addiction Recovery in Israel
Authors: Pagis Michal , Elbaz Ayala , Ben Yair Yitzhak
Published: October 2024

This article examines the impact of the integration of religion and psychological treatment in a religion-based therapeutic community for persons in recovery from addiction in Israel. Based on an exploratory qualitative study that includes participant observation in a Jewish forgiveness therapy training course and in-depth interviews with counselors working in the community, we identify three themes that characterize the therapeutic process. First, religion emerges as a challenge in therapy, one that should be addressed with sensitivity. Second, religion can be turned into a spiritual and cultural resource in the recovery process, with a cautious and sensitive approach. Third, religion can offer a remedial experience, without necessarily involving an intensification of faith. We offer principles that can help guide decisions regarding the integration of religion into therapy, with a focus on addiction treatment oriented to clients with a religious background.
Minimizing the earliness–tardiness for the customer order scheduling problem in a dedicated machine environment
Authors: Hoffmann Julius , Neufeld Janis S. , Buscher Udo
Published: October 2024

The customer order scheduling problem has garnered considerable attention in the recent scheduling literature. It is assumed that each of several customer orders consists of several jobs, and each customer order is completed only if each job of the order is completed. In this paper, we consider the customer order scheduling problem in a machine environment where each customer places exactly one job on each machine. The objective is to minimize the earliness–tardiness, where tardiness is defined as the time an order is finished past its due date, and earliness is the time a job is finished before its due date or the completion time of the corresponding order, whichever is later. Even though the earliness–tardiness criterion is an important objective for just-in-time production, this problem has not been studied in the context of the customer order scheduling problem. We provide a mixed-integer linear programming (MILP) formulation for this problem and derive multiple problem properties. Furthermore, we develop six different heuristics for this problem configuration. They follow the structure of the iterated greedy algorithm and additionally use a refinement function in which they differ. In a computational experiment, the algorithms were compared with each other and outperformed a solver solution of the MILP, which proves their ability to efficiently solve the problem configuration.
EMBL-MCF 2.0: an LC-MS/MS method and corresponding library for high-confidence targeted and untargeted metabolomics using low-adsorption HILIC chromatography
Authors: Dekina Svitlana , Alexandrov Theodore , Drotleff Bernhard
Published: October 2024

Introduction

Over the past two decades, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics has experienced significant growth, playing a crucial role in various scientific disciplines. However, despite these advance-ments, metabolite identification (MetID) remains a significant challenge. To address this, stringent MetID requirements were established, emphasizing the necessity of aligning experimental data with authentic reference standards using multiple criteria. Establishing dependable methods and corresponding libraries is crucial for instilling confidence in MetID and driving further progress in metabolomics.

Objective

The EMBL-MCF 2.0 LC-MS/MS method and public library was designed to facilitate both targeted and untargeted metabolomics with exclusive focus on endogenous, polar metabolites, which are known to be challenging to analyze due to their hydrophilic nature. By accompanying spectral data with robust retention times obtained from authentic standards and low-adsorption chromatography, high confidence MetID is achieved and accessible to the metabolomics community.

Methods

The library is built on hydrophilic interaction liquid chromatography (HILIC) and state-of-the-art low adsorption LC hardware. Both high-resolution tandem mass spectra and manually optimized multiple reaction monitoring (MRM) transitions were acquired on an Orbitrap Exploris 240 and a QTRAP 6500+, respectively.

Results

Implementation of biocompatible HILIC has facilitated the separation of isomeric metabolites with significant enhancements in both selectivity and sensitivity. The resulting library comprises a diverse collection of more than 250 biologically relevant metabolites. The methodology was successfully applied to investigate a variety of biological matrices, with exemplary findings showcased using murine plasma samples.

Conclusions

Our work has resulted in the development of the EMBL-MCF 2.0 library, a powerful resource for sensitive metabolomics analyses and high-confidence MetID. The library is freely accessible and available in the universal .msp file format under the CC-BY 4.0 license: mona.fiehnlab.ucdavis.edu https://mona.fiehnlab.ucdavis.edu/spectra/browse?query=exists(tags.text:%27EMBL-MCF_2.0_HRMS_Library%27), EMBL-MCF 2.0 HRMS https://www.embl.org/groups/metabolomics/instrumentation-and-software/#MCF-library.
Dopaminergic neuron metabolism: relevance for understanding Parkinson’s disease
Authors: Flores-Ponce Xóchitl , Velasco Iván
Published: October 2024

Background

Dopaminergic neurons from the substantia nigra pars compacta (SNc) have a higher susceptibility to aging-related degeneration, compared to midbrain dopaminergic cells present in the ventral tegmental area (VTA); the death of dopamine neurons in the SNc results in Parkinson´s disease (PD). In addition to increased loss by aging, dopaminergic neurons from the SNc are more prone to cell death when exposed to genetic or environmental factors, that either interfere with mitochondrial function, or cause an increase of oxidative stress. The oxidation of dopamine is a contributing source of reactive oxygen species (ROS), but this production is not enough to explain the differences in susceptibility to degeneration between SNc and VTA neurons.

Aim of review

In this review we aim to highlight the intrinsic differences between SNc and VTA dopamine neurons, in terms of gene expression, calcium oscillations, bioenergetics, and ROS responses. Also, to describe the changes in the pentose phosphate pathway and the induction of apoptosis in SNc neurons during aging, as related to the development of PD.

Key scientific concepts of review

Recent work showed that neurons from the SNc possess intrinsic characteristics that result in metabolic differences, related to their intricate morphology, that render them more susceptible to degeneration. In particular, these neurons have an elevated basal energy metabolism, that is required to fulfill the demands of the constant firing of action potentials, but at the same time, is associated to higher ROS production, compared to VTA cells. Finally, we discuss how mutations related to PD affect metabolic pathways, and the related mechanisms, as revealed by metabolomics.
Assessment of Gastric Remnant Activity, Symptoms, and Quality of Life Following Gastric Bypass
Authors: Wang Tim Hsu-Han , Varghese Chris , Calder Stefan , Gharibans Armen A. , Evennett Nicholas , Beban Grant , Schamberg Gabriel , O’Grady Greg
Published: October 2024

Introduction

While most gastric bypass patients recover well, some experience long-term complications, including nausea, abdominal pain, food intolerance, and dumping. This study aimed to evaluate symptoms and quality of life (QoL) in association with the residual activity of the remnant stomach.

Methods

Patients undergoing gastric bypass and conversion-to-bypass were recruited. The Gastric Alimetry® System (Auckland, NZ) was employed, comprising a high-resolution electrode array, wearable reader, and validated symptom logging app. The protocol comprised 30-min fasting baseline, a 218-kCal meal stimulus, and 4-h of post-prandial recordings. Symptoms and QoL were evaluated using validated questionnaires. Remnant gastric electrophysiology evaluation included frequency, BMI-adjusted amplitude, and Gastric Alimetry Rhythm Index (GA-RI, reflecting pacemaker stability), with comparison to validated reference intervals and matched controls.

Results

Thirty-eight participants were recruited with mean time from bypass 46.8 ± 28.6 months. One-third of patients showed moderate to severe post-prandial symptoms, with patients’ median PAGI-SYM 28 ± 19 vs controls 9 ± 17 (p < 0.01); PAGI-QOL 37 ± 31 vs 135 ± 22 (p < 0.0001). Remnant gastric function was markedly degraded shown by undetectable frequencies in 84% (vs 0% in controls) and low GA-RI (0.18 ± 0.08 vs 0.51 ± 0.22 in controls; p < 0.0001; reference range > 0.25). Impaired GA-RI and amplitude were correlated with worse PAGI-SYM and PAGI-QOL scores.

Conclusion

One-third of post-bypass patients suffered significant upper GI symptoms with reduced QoL. The bypassed remnant stomach shows highly deranged electrophysiology in-situ, reflecting disuse degeneration. These derangements correlated with QoL; however, causality is not implied by the present study.