Additional Sites Research Articles

Synergetic electrochemical behavior of magnesium-doped ZnO nanorods with reduced graphene oxide

In this study, we synthesized magnesium-doped ZnO (Mg-ZnO) nanorods embedded in reduced oxide graphene layers (rGO) using the simplest one-pot hydrothermal method. The composites ZnO/rGO and Mg-doped ZnO-rGO (Mg-ZnO/rGO) are polycrystalline and showed successful doping of Mg in ZnO lattice which expands the ZnO lattice structure helping lithium storage by providing more sites. Mg doping in the ZnO lattice extenuates ZnO volume contraction and expansion which promotes structural stabilization of the electrode during multiple charging-discharging cycles. In composites, ZnO and Mg-ZnO attain the shape of nanorods and tightly interleaved theirselves in the sheet of rGO. XPS showed the dominant peak of C1s of sp2 bonding supporting the formation of reduced GO along with Zn, O and Mg elements. The performance of the materials is evaluated as anode for LIB. The ZnO/rGO anode exhibits a discharge capacity of 445 mAh/g at 100 mA g−1 that was significantly enhanced to 463 mAh/g after doping ZnO with 2 % Mg. With further increasing the concentration of Mg to 4 %, the Mg-ZnO/rGO anode achieves a higher discharge capacity of 520 mAh g−1 with better rate capability than its counterpart electrodes. The synergistic effects between Mg-ZnO and carbon-based nanomaterials are ascribed to the creation of additional contact sites to penetrate electrolyte ions into the electrode, thus resulting in the fast lithium-ion diffusion rate.

Efficient catalytic oxidation of formaldehyde by defective g–C3N4–anchored single-atom Pt: A DFT study

Indoor volatile formaldehyde is a serious health hazard. The development of low-temperature and efficient nonhomogeneous oxidation catalysts is crucial for protecting human health and the environment but is also quite challenging. Single-atom catalysts (SACs) with active centers and coordination environments that are precisely tunable at the atomic level exhibit excellent catalytic activity in many catalytic fields. Among two-dimensional materials, the nonmagnetic monolayer material g-C3N4 may be a good platform for loading single atoms. In this study, the effect of nitrogen defect formation on the charge distribution of g-C3N4 is discussed in detail using density functional theory (DFT) calculations. The effect of nitrogen defects on the activated molecular oxygen of Pt/C3N4 was systematically revealed by DFT calculations in combination with molecular orbital theory. Two typical reaction mechanisms for the catalytic oxidation of formaldehyde were proposed based on the Eley-Rideal (E-R) mechanism. Pt/C3N4–V3N was more advantageous for path 1, as determined by the activation energy barrier of the rate-determining step and product desorption. Finally, the active centers and chemical structures of Pt/C3N4 and Pt/C3N4–V3N were verified to have good stability at 375 K by determination of the migration energy barriers and ab initio molecular dynamics simulations. Therefore, the formation of N defects can effectively anchor single-atom Pt and provide additional active sites, which in turn activate molecular oxygen to efficiently catalyze the oxidation of formaldehyde. This study provides a better understanding of the mechanism of formaldehyde oxidation by single-atom Pt catalysts and a new idea for the development of Pt as well as other metal-based single-atom oxidation catalysts.

Amino-terminally elongated Aβ peptides are generated by the secreted metalloprotease ADAMTS4 and deposit in a subset of Alzheimer's disease brains.

The aggregation and deposition of amyloid-β (Aβ) peptides in the brain is thought to be the initial driver in the pathogenesis of Alzheimer's disease (AD). Aside from full-length Aβ peptides starting with an aspartate residue in position 1, both N-terminally truncated and elongated Aβ peptides are produced by various proteases from the amyloid precursor protein (APP) and have been detected in brain tissues and body fluids. Recently, we demonstrated that the particularly abundant N-terminally truncated Aβ4-x peptides are generated by ADAMTS4, a secreted metalloprotease that is exclusively expressed in the oligodendrocyte cell population. In this study, we investigated whether ADAMTS4 might also be involved in the generation of N-terminally elongated Aβ peptides. We used cell-free and cell-based assays in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) and electrochemiluminescence sandwich immunoassays to identify and quantify N-terminally elongated Aβ peptide variants. Antibodies against these Aβ variants were characterised by peptide microarrays and employed for the immunohistochemical analyses of human brain samples. In this study, we discovered additional ADAMTS4 cleavage sites in APP. These were located N-terminal to Asp-(1) in the Aβ peptide sequence between residues Glu-(-7) and Ile-(-6) as well as Glu-(-4) and Val-(-3), resulting in the release of N-terminally elongated Aβ-6-x and Aβ-3-x peptides, of which the latter serve as a component in a promising Aβ-based plasma biomarker. Aβ-6/-3-40 peptides were detected in supernatants of various cell lines and in the cerebrospinal fluid (CSF), and ADAMTS4 enzyme activity promoted the release of Aβ-6/-3-x peptides. Furthermore, by immunohistochemistry, a subset of AD cases displayed evidence of extracellular and vascular localization of N-terminally elongated Aβ-6/-3-x peptides. The current findings implicate ADAMTS4 in both the pathological process of Aβ peptide aggregation and in the early detection of amyloid pathology in AD.

NCI MATCH (EAY131) arm Z1D: Retrospective evaluation of attributions of adverse events experienced on nivolumab in patients with MSI-high tumors.

e14711 Background: Machine learning algorithms for prediction of Adverse Events (AEs) due to immune checkpoint inhibitors (ICIs) rely on clinically annotated data to serve as gold standards. Clinical trials are the best sources of such data, but audits to assess validity are rare, compromising future machine learning efforts. We reviewed AEs reported on the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) EAY-131 Arm Z1D. Patients matched to Arm Z1D due to MSI-high status were treated with nivolumab. Routine and serious AEs were reported to NCI. Attribution data from AEs on 29 patients with tumor genomics suitable for machine learning approaches were obtained and reviewed retrospectively. Methods: Documented AEs were sorted by grade via the Common Terminology for Adverse Events (CTCAE) system and categorized as related or unrelated to ICIs. Primary source data reported to NCI were reviewed. If any ambiguity was found, trial sites were queried to provide additional information and documentation. Decisions were made by an experienced NCI medical officer with the benefit of additional data and site responses. All serious AEs and a subset of ambiguous routine AEs were assessed to determine if attribution conformed to expected attribution per the nivolumab package insert. Uncertain attribution required additional queries, including email or phone correspondence. Grade 1 or 2 events were only evaluated to determine if any attribution to ICIs was possible. If a higher grade event was attributed to ICIs, there was no further query for lower grade events on the same patient. Results: A total of 639 Grade 1, 152 Grade 2, 75 Grade 3, 10 Grade 4, and 5 Grade 5 events were reported among the 29 patients. One Grade 5 event, 5 Grade 4 events, 13 Grade 3 Events, 9 Grade 2 events, and 6 Grade 1 events were considered less likely to be attributed to ICIs compared with the initial sponsor or site investigator assessment of possibly, probably, or definitely related. Two Grade 4 events, 1 Grade 2 event, and 8 Grade 1 events were considered to be possibly, probably, or definitely due to ICIs compared with the initial sponsor or site assessment of less likely or unrelated. Site responsiveness to retrospective queries from the sponsor varied. Additional lab values, primary source documentation, and communication with site investigators were necessary to make modifications. A total of 11 AEs required additional queries to site investigators. Conclusions: Retrospective reviews of real-time site and sponsor assessments of attribution exhibit significant modification of initial attribution to ICIs in this review of 29 patients on Arm Z1D of the NCI MATCH trial. Machine learning approaches for prediction of AEs on patients treated with ICIs may require careful assessments of primary source data to develop adequate training sets, given the paucity of gold standard data available.

Multicenter study evaluating the utility of AI-aided HER2 scoring in the clinically relevant categories.

e15150 Background: The availability of multiple therapeutic options for breast cancer patients with varying levels of protein expression necessitates precise and standardized HER2 scoring. This study explored the clinical utility of AI-aided HER2 scoring of whole-slide digital images by pathologists in breast core needle biopsies and excisions. Methods: The study included patients (n=764) with multiple subtypes of invasive breast cancer from 3 US reference laboratories and 1 academic medical center. The non-interventional two-arm multi-reader study retrospectively compared manual digital vs. AI-aided HER2 scoring of 8 pathologists. The fully automated HER2 AI solution detects the invasive tumor area and then classifies the tumor cells based on staining pattern based and the 2023 ASCO/CAP guidelines to output slide-level HER2 score. Both study arms were compared to reference ground truth (GT) established by the consensus of two breast subspecialists, ground truthers (GTer), who reviewed the slides digitally. One site recorded the time taken for HER2 scoring of both arms to determine the efficacy of the HER2 AI solution. Results: The initial interobserver agreement among expert GT pathologists for each HER2 score, 0, 1+, 2+, 3+, were 83%, 63.8%, 46%, and 92.6, respectively. At the clinically meaningful cut-offs, the reader pathologists’ performance improved with the AI support. At the 0 vs. 1+/2+/3+ and 0/1+ vs 2+/3+ clinical cutoffs, the readers' accuracy was 86.3% vs 88.6% and 93.7%, 93.8% with and without AI support, respectively. The AI use contributed to approximately 12%-time savings for the readers at the medical center. The AI solution demonstrated high accuracy for HER2 scoring, with 89.2% agreement with GT for 0 vs 1+/2+/3+ scores and 93.1% for 0/1+ vs 2+/3+ cutoff. The results will be updated in the final submission with the additional site data. The reader feedback survey regarding the solution’s usability will also be presented. Conclusions: The pathologists demonstrated improvements in consistency, evidenced by inter-reader agreement and accuracy with the aid of the AI. The AI solution can improve efficiency toward accurate HER2 scoring. [Table: see text]

Quantifying clinical actionability of updated tumor profiling reports through electronic health record (EHR)-enabled, on-demand ordering and resulting.

e13621 Background: Next-generation sequencing reports provide matched therapies and clinical trials based on genomic alterations to drive therapeutic decisions in clinical practice. Biomarker-matched oncology drug approvals and trials have grown tremendously over the past decade. From January 2000 to October 2022 alone, a total of 573 agents were approved for various oncology indications, with nearly half being targeted therapies. While matched therapies and clinical trials are current at time of issue, updated variant classification, changes in FDA approvals, and trials available are not reflected in static reports. It is not always practical nor feasible to provide a new biopsy specimen. To address this gap in clinical care, we piloted Tempus Refresh, an on-demand informatics service that provides clinicians with refreshed therapy and trial matches from prior molecular reports directly through the EHR. Here we quantify the clinical actionability of Refresh reports. Methods: TriHealth piloted the Tempus Refresh orderable through the Epic EHR at the treating physician’s discretion. The clinical team specified prior DNA molecular reports (tissue or blood) to update. Orders were transmitted to Tempus through an HL7 interface. All alterations provided on the prior report were updated for therapeutic and trial matches through existing workflows. An updated structured report was then delivered to the TriHealth Epic EHR linked in the lab tab. Results: From 2/2023 to 11/2023, 10 TriHealth providers participated. A total of 35 unique Refresh orders were placed via custom HL7 Epic order, of which 3 were canceled due to orders outside of pilot parameters. Of the 32 Refresh reports, 34% (11/32) contained new FDA-approved therapies (OncoKB Level 1 or 2), and 78% (25/32) were annotated with new clinical trials. The average elapsed time from original date of report issuance to Refresh order delivery was 14.5 months (range 1 month to 45 months). The mean turnaround time for issuance of a Refresh report was 29 hours (range 5 hours to 53 hours). Conclusions: These results demonstrate that on-demand report updates increase the availability of tumor biomarker-matched therapies and trials. Furthermore, the study exhibits the feasibility of integrating updates directly into the standard EHR clinical workflow. This service provides visibility across teams and can support specialty pharmacists in therapy authorization. Considering the success of this pilot, future studies will assess the expansion of Tempus Refresh to additional sites.

A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.

TPS8118 Background: Each year, approximately 35,000 patients are diagnosed with stage I lung cancer in the United States. Despite early detection, the 5-year overall survival for this population remains disappointing, ranging between 73-86% with recurrence rates from 18-38%. The current standard of care for stage I NSCLC is surgery alone followed by observation as prior trials of adjuvant chemotherapy in this subgroup have failed to show benefit. More modern therapies such as programmed death-1 (PD-1) inhibitors have not been evaluated in the stage I setting but have demonstrated significant improvements in pathologic complete response, event free survival, and overall survival when added to chemotherapy for patients with fully resected stage II and III disease. The use of PD-(L)1 inhibition has also demonstrated clinically and statistically significant improvements in OS in both unresectable stage III NSCLC following chemoradiation and in the metastatic setting. Given the activity of PD-(L)1 inhibition in nearly every other subset of NSCLC patients, we aimed to evaluate this therapy following resection in stage I NSCLC patients. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial randomizes patients 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone. Patients are stratified by PD-L1 score (PD-L1 ≥50% vs. < 50%) and tumor size (1-2cm vs. > 2-4cm), and they undergo repeat CT imaging every 12 weeks. The study is being conducted through the Big Ten Cancer Research Consortium, and there are currently 11 sites open to accrual with one additional site pending activation. The primary endpoint is disease free survival with secondary endpoints including OS, DFS at multiple timepoints (1-, 2-, and 3-years), and safety. The trial initially opened to accrual at the lead site, Indiana University, in May 2020, and enrollment is currently at 95 patients with a planned enrollment of 244. (NCT04317534) Clinical trial information: NCT04317534 .

Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families

PurposeFemale CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. MethodsIncluding 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women. ResultsWe found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward. ConclusionA significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.

LiF-MS+, a revised technique for mapping peptide-protein interactions.

Short linear motifs are sequences of amino acids present in unstructured polypeptide regions that function as ligands for specific sites on folded protein domains. These interactions, which often occur with low to modest affinity, modulate dynamic biological processes such as signal transduction and membrane trafficking. We recently described Ligand Footprinting-Mass Spectrometry (LiF-MS), a technique that rapidly and precisely maps sites at which short peptide ligands bind their biologically relevant recognition sites on folded protein domains. This approach marks the binding location of a peptide ligand on a structured protein using a cleavable crosslinker appended to the ligand that leaves behind a stable chemical modification following cleavage. This modification serves as a mass tag detectable by mass spectrometry, pinpointing sites of peptide ligand binding. Here we present LiF-MS+, an improved version of the footprinting technique that replaces the butanol mass tag with 1-butylpyrrolidine, which is positively charged at neutral pH and thus aids in ionization of the crosslinked peptide for analysis by mass spectrometry. We show ligand-mediated butylpyrrolidine footprinting effectively maps the well characterized binding interaction of the p38α mitogen-activated protein kinase (MAPK) with a MKK6 D-motif short linear motif peptide ligand, uncovering additional binding site information not observed in our original experiment. LiF-MS+ is thus a straightforward improvement of our previously published methodology for mapping the binding of short linear motifs to folded protein domains.

Mo4/3B2Tx induced hierarchical structure and rapid reaction dynamics in MoS2 anode for superior sodium storage

Molybdenum sulfide (MoS2) with large layer distance and high theoretical capacity has been identified as one of the most promising anodes for sodium ion batteries, but the poor intrinsic conductivity and severe structural agglomeration restricted its diffusion kinetic and specific capacity. In this work, the synergistic effect of heterogeneous interface and Na2S adsorption/conversion active sites was employed to construct Mo4/3B2Tx-MoS2@C composites using a self-assembly and calcination strategy. Theoretical calculation and experimental results demonstrated that the charge transfer and interface between Mo4/3B2Tx and MoS2 along with the 3D hydrangea-like structure improved the intrinsic conductivity and provided fast ion diffusion channels, boosting the electrochemical kinetics; while the favorable adsorption of Na2S and weakened Na-S bond at Mo4/3B2Tx-Mo interface optimized the recombination energies of Mo-S bond, accelerating the ion diffusion and enhancing the electrochemical reversibility. In addition, the copious sulfur vacancies provided additional active sites for ion storage, ameliorating the electrochemical capacity. As expected, the novel Mo4/3B2Tx-MoS2@C electrode delivered a satisfactory rate capacity (340.6 mAh g−1 at 1 A g−1) and durable cyclic performance (267.2 mAh g−1 after 600 cycles at 2 A g−1). When paring with Na3V2(PO4)3, the Mo4/3B2Tx-MoS2@C||Na3V2(PO4)3 full cell exhibited high energy densities of 234.0 and 131.7 Wh kg−1 at 215.7 W kg−1 and 4.4 kW kg−1, respectively. The proposed synergistic strategy of heterogeneous interface and Na2S adsorption/conversion active sites provided a new guidance for the rational design of transitional metal sulfide anodes for sodium ion batteries.

Dengue virus exploits autophagy vesicles and secretory pathways to promote transmission by human dendritic cells.

Dengue virus (DENV), transmitted by infected mosquitoes, is a major public health concern, with approximately half the world's population at risk for infection. Recent decades have increasing incidence of dengue-associated disease alongside growing frequency of outbreaks. Although promising progress has been made in anti-DENV immunizations, post-infection treatment remains limited to non-specific supportive treatments. Development of antiviral therapeutics is thus required to limit DENV dissemination in humans and to help control the severity of outbreaks. Dendritic cells (DCs) are amongst the first cells to encounter DENV upon injection into the human skin mucosa, and thereafter promote systemic viral dissemination to additional human target cells. Autophagy is a vesicle trafficking pathway involving the formation of cytosolic autophagosomes, and recent reports have highlighted the extensive manipulation of autophagy by flaviviruses, including DENV, for viral replication. However, the temporal profiling and function of autophagy activity in DENV infection and transmission by human primary DCs remains poorly understood. Herein, we demonstrate that mechanisms of autophagosome formation and extracellular vesicle (EV) release have a pro-viral role in DC-mediated DENV transmission. We show that DENV exploits early-stage canonical autophagy to establish infection in primary human DCs. DENV replication enhanced autophagosome formation in primary human DCs, and intrinsically-heightened autophagosome biogenesis correlated with relatively higher rates of DC susceptibility to DENV. Furthermore, our data suggest that viral replication intermediates co-localize with autophagosomes, while productive DENV infection introduces a block at the late degradative stages of autophagy in infected DCs but not in uninfected bystander cells. Notably, we identify for the first time that approximately one-fourth of DC-derived CD9/CD81/CD63+ EVs co-express canonical autophagy marker LC3, and demonstrate that DC-derived EV populations are an alternative, cell-free mechanism by which DCs promote DENV transmission to additional target sites. Taken together, our study highlights intersections between autophagy and secretory pathways during viral infection, and puts forward autophagosome accumulation and viral RNA-laden EVs as host determinants of DC-mediated DENV infection in humans. Host-directed therapeutics targeting autophagy and exocytosis pathways thus have potential to enhance DC-driven resistance to DENV acquisition and thereby limit viral dissemination by initial human target cells following mosquito-to-human transmission of DENV.

Biodegradable chelator GLDA intercalated magnesium/aluminum layered double hydroxides for efficient phosphate capture and removal from wastewater

Phosphate removal and recovery from wastewater play a vital role in controlling water eutrophication and facilitating resource recycling. Adsorbents of layered double hydroxides (LDHs) exhibit promising potential in the removal of phosphate; however, the removal efficiency often suffers insufficient as easy aggregation and inevitable loss of LDHs. Herein, a novel N, N–bis (carboxymethyl)–L–glutamic acid intercalated magnesium–aluminum LDH (GLDA@MgAl–LDH) were successfully synthesized. Intercalating with GLDA spawned dual functionality, i.e., the layer spacing expansion elevated the loading of phosphate, while GLDA also acted as additional binding sites toward phosphate. A higher phosphate capture (＞90%) was obtained in pH 5.0–8.0. Phosphate uptake was predominantly observed within the first1h, reaching equilibrium in approximately 4 h. The maximum adsorption capacity of 44.17 mg g–1 was attained for GLDA@MgAl–LDH at pH 6.70, which are far higher than that of pristine MgAl–LDH. GLDA@MgAl–LDH also had the excellent stability and reusability in five adsorption/desorption experiments. The GLDA@MgAl–LDH demonstrated significant efficacy in treating actual phosphate-containing wastewater in the fixed–bed adsorption column. Spectroscopic analysis, in conjunction with density functional theory, elucidated that GLDA intercalation enhanced the adsorption efficiency of MgAl–LDH. The key mechanisms facilitating phosphate removal included electrostatic attraction, anion and ligand exchange, and surface complexation. The above results highlight that GLDA@MgAl–LDH could serve as a promising and environmentally friendly candidate for phosphate treatment from the real wastewater.

In situ redox growth of Pd/CuOx for enhanced electrocatalytic degradation of organic chlorides via indirect atomic H* reduction

Efficient utilization of atomic hydrogen (H*) is crucial for electrocatalytic dechlorination. We synthesized a Pd/CuOx cathode by atomic reconstruction to boost H* utilization, creating additional active sites within a biphasic interface. This enhanced H* generation degraded 2,4-dichlorophenoxyacetic acid (2,4-D) with a 96 % removal efficiency at 4 mA cm2 and 1.96 kWh m3 energy consumption. Cyclic voltammetry (CV) showed a 0.009 μmol cm2 increase H* on the Pd/CuOx cathode compared to the pristine Cu cathode. The contribution of H* to the electrocatalytic dechlorination process was further corroborated by scavenging experiments and electron spin resonance investigation. We then evaluated the toxicity of products during the degradation process. Density functional theory calculations revealed that the coordination structure between CuOx and Pd optimized the dissociation of H2O and the free adsorption energy of hydrogen. This research introduces an effective alternative to enhance the H* production for the removal of organochlorine compounds from wastewater.

Different inhibitory mechanisms of flexible and rigid clay minerals on the transport of microplastics in marine porous media

Colloidal interactions between clay minerals and microplastics (MPs) in high salinity seawater are crucial for determining MP fate in marine environments. Montmorillonite (MMT) forms thin and pliable films that tightly cover MPs, while the thick and rigid lamellae of kaolinite (KLT) have limited contact with MPs, resulting in unstable bonding. However, a small quantity of small-sized KLT can create relatively stable heteroaggregates by embedding into the interstitial spaces of MPs. Both MMT and KLT colloids can decrease the mobility of MPs in seawater-saturated sea sand, but their breakthrough curves (BTCs) show distinct phenomena of "blocking" and "ripening", respectively. The "blocking" phenomenon occurs when flexible MMT adheres to the sand surface, depleting attachment sites quickly and inhibiting the retention of subsequent heteroaggregates of MMT-wrapped MPs. The transport of single MMT also experiences colloid competition for attachment sites, but pre-equilibration experiments reveal no competition between MMT and bare MPs for attachment sites. Instead, the attached MMT provides additional attachment sites for MPs. These results suggest that the wrapping of MPs by MMT plays a dominant role in the "blocking" of cotransport. In contrast, rigid KLT forms a three-dimensional stack on the sand surface, offering more attachment sites for subsequent MPs and heteroaggregates.

Machine learning for faster estimates of groundwater response to artificial aquifer recharge

Groundwater models are a valuable tool in optimising the decisions influencing groundwater flow. Spatially distributed models represent the groundwater level in the entire area from where essential information can be extracted, directly aiding in the decision-making process. However, these models are time-consuming, limiting the number of scenarios that can be considered. This study explores different machine learning (ML) models as faster alternatives to predict the increase in steady-state groundwater head due to artificial recharge in the unconfined aquifer while considering a wider spatial extent (832 columns x 1472 rows totalling 765 km2) than previous ML groundwater models. We trained three ML models (encoder-decoder, U-Net, and attention U-Net) with various hypothetical artificial recharge sites (100, 300, 500, and 1000 sites) in the Baakse Beek catchment (the Netherlands), using a detailed numerical groundwater model, AMIGO. The applied recharge rate along with geo-hydrological properties from the AMIGO baseline run were used as inputs to the ML models. The properties’ permutation importance indicated that all properties of the first aquifer were important to predicting the response and were included when training the ML models. All three ML models improved with additional training sites but showed limited benefits from more than 500 recharge sites. Of the three ML models, U-Net and Attention U-Net outperformed the encoder-decoder. These two models achieved Nash-Sutcliffe efficiency (NSE) of more than 0.8 when trained with 300 or more recharge sites. U-Net trained on 1000 recharge sites had the highest overall NSE of 0.95. U-Net better captures input features with highly variable spatial characteristics, such as rivers and drains which influence the maximum height of the groundwater response. The model captured the influence of the input features on the response, reproducing the response patterns across the entire catchment. Finally, we showed that the trained ML models are faster than the numerical model, predicting within 0.24 s (97th percentile), making it ideal for optimising decisions.

Comparative analysis of pulsed-field and cryoballoon ablation in octogenarians with atrial fibrillation: a multicenter study

Abstract Background The prevalence of atrial fibrillation (AF) increases with advancing age, and AF contributes to higher rates of stroke, dementia, heart failure, and mortality. Catheter ablation is recognized as an effective treatment for AF; however, data regarding its efficacy in octogenarians are limited. Cryoballoon ablation (CBA) has been reported to be safe and effective in this age group. Recently, single-shot devices using pulsed-field energy have been developed, offering a tissue-specific effect. However, data on the safety and effectiveness of this novel pulsed-field ablation (PFA) in octogenarians are still insufficient. Purpose This study aims to evaluate the procedural outcomes and complications of PFA in octogenarians with AF, in comparison to CBA, from 3 high-volume European centers. Methods We retrospectively enrolled patients who underwent PFA via the FarapulseTM system from January 2022 to June 2023, and those who underwent second-generation CBA from January 2015 to June 2023. Results A total of 176 patients (PFA group: 63, CBA group: 113) were included. The PFA group had a higher proportion of patients with persistent AF (p=0.03) and undergoing a repeat procedure (p<0.01). (Table 1) Unlike CBA, PFA procedures involved additional extrapulmonary targets, such as posterior wall and mitral isthmus. Nonetheless, procedure time was similar between groups. There were no significant differences in complications but phrenic nerve palsy was not observed in the PFA group (Table 2). Conclusions PFA for octogenarians provides the possibility to target additional extrapulmonary sites with equivalent procedural times and safety compared to CBA, without the concern of phrenic nerve palsy.Table 1Table 2

Modulating the Coordination Chemistry of Cobalt Catalytic Sites by Ruthenium Species to Accelerate the Polysulfide Conversion Kinetics in Lithium-Sulfur Batteries.

The performance of lithium-sulfur batteries is compromised by the loss of sulfur as dissolved polysulfides in the electrolyte and consequently the polysulfide redox shutting effect. Accelerating the conversion kinetics of polysulfide intermediates into sulfur or lithium sulfide through electrocatalysis has emerged as a root-cause solution. Co-N-C composite electrocatalyst is commonly used for this purpose. It is illustrated here that how the effectiveness can be improved by modulating the coordination chemistry of Co-N-C catalytic sites through introducing Ru species (RuCo-NC). The well-dispersed Ru in the Co-NC carbon matrix altered the total charge distribution over the Co-N-C catalytic sites and led to the formation of electron-rich Co-N, which is highly active for the polysulfide conversion reactions. Using Ru to modulate the electronic structure in the Co-N-C configuration and the additional catalytic sites over the Ru-Nx species can manifest optimal adsorption behavior of polysulfides. Consequently, the sulfur cathode with RuCo-NC can reduce the capacity fade rate from 0.11 % per cycle without catalyst (initial capacity of 701 mAh g-1) to 0.054 % per cycle (initial capacity of 1074 mAh g-1) over 400 cycles at 0.2 C rate. The results of this study provide the evidence for a feasible catalyst modification strategy for the polysulfide electrocatalysis.

Advancements in alveolar bone reconstruction: A systematic review of bone block utilization in dental practice.

Alveolar reconstructive surgery employs a variety of surgical techniques and biomaterials, with a particular focus on bone blocks as a crucial methodology for restoring and augmenting deficient bone structures. Bone blocks are often employed to support periodontal health or as a foundation for future prosthetic rehabilitation with dental implants. This systematic review investigated recent advances in bone blocks for alveolar bone reconstruction, comparing autologous, allogeneic and xenogeneic types. A search of PubMed identified 56 records, of which 21 were included in the qualitative analysis. The studies involved 685 patients in total. Bone blocks are pivotal for three-dimensional bone regeneration, providing a stable scaffold for achieving the desired bone volume during healing. Autologous bone, harvested from the patient, boasts high biocompatibility, excellent osteogenic properties and minimal immunologic risks. However, its drawbacks include the need for an additional surgical site and extended procedural times. Allogeneic bone blocks involve transferring bone between individuals, offering increased graft availability and customization options without requiring a second surgical site. However, they exhibit moderate resorption rates and carry a heightened risk of immunologic reactions and disease transmission. Innovative techniques, such as tunneling, laser osteotomy, graft customization, and platelet-rich fibrin (PRF) application on wound during surgical treatment show promise in enhancing alveolar bone reconstruction efficacy. In conclusion, despite the traditional preference for autologous bone, the review suggests that alternative materials, particularly individualized allogeneic bone blocks, coupled with modern techniques, could emerge as a standard procedure for regenerating alveolar bone defects due to their satisfactory results and potential advantages.

Rapid antibody conjugation strategy via instant charge inversion of AuNBPs toward ultrasensitive SERS-LFIA detection of AFP

Alpha-fetoprotein (AFP) is widely utilized as the primary serum marker for diagnosing Hepatocellular carcinoma. Integrating surface-enhanced Raman scattering (SERS) with lateral flow immunoassays (LFIA) displays significant promise for the rapid quantification of AFP. Gold nanobipyramids (AuNBPs) is a kind of SERS probe with high activity showing strong application potential in SERS-LFIA. However, the drastic electrostatic interaction between negative charged antibodies and positive charged AuNBPs will result in uncontrollable aggregation, which poses a challenge for antibody binding and limits its application in SERS-LFIA. Hence, we propose a rapid antibody conjugation strategy with the aid of instant charge inversion of AuNBPs, which enables efficient and expedited antibody coupling onto AuNBPs. The thiol-free fish sperm (FSDNA) was employed to adsorb on the cetyltrimethylammonium bromide (CTAB) coated AuNBPs for immediate charge inversion. The adsorption of FSDNA will cause partial stripping of CTAB from the AuNBPs surface to provide additional active sites for antibodies binding. In this study, approximately average 37 AFP-antibodies were verified bonding on one charge inverted AuNBPs by direct incubation for 30 min. The antibodies modified AuNBPs were further incubated with 4-nitrothiophenol for preparing SERS immune probes, which display excellent colloid stability and specificity. The probes were used to construct SERS-LFIA strips for AFP detection, enabling highly sensitive detection of AFP with the limit of detection (LOD) as low as 0.72 pg·mL−1. The developed SERS-LFIA strip demonstrates excellent stability and accuracy in detecting serum samples, with a recovery rate ranging from 84 % to 114 %. This rapid antibody coupling strategy is applicable to a wide range of positively charged nanoparticles, effectively addressing the challenging issue of utilizing such nanomaterials in LFIA.

Synergistic Enhancement of Supercapacitors with Cobalt–Copper Bimetal–Organic Framework

Metal–organic frameworks (MOFs), as high‐potential electrode materials for applications in supercapacitors, have received significant attention recently. Unfortunately, MOF materials still suffer from unsatisfactory specific capacitances due to poor conductivity and limited redox active sites. Herein, a novel cobalt–copper‐based bimetal–organic framework (CoCu‐MOF) is synthesized by a bottom‐up synthesis strategy, the material properties systematically characterized, and finally investigated as a supercapacitor electrode material. The synthesized CoCu‐MOF presents a high specific surface area of 62.4 m2 g−1, and 83% of the copper ions attains the +1 oxidation state contributing to the formation of additional redox active sites and leading to the formation of dual‐redox sites. The CoCu‐MOF displays an excellent specific capacitance of 618 F g−1 at a current density of 1 A g−1, which is more than twice that of Co‐MOF and four times that of Cu‐MOF. The CoCu‐MOF retains 75% of its original capacitance after 3000 charge–discharge cycles at the current density of 1 A g−1. Overall, this work demonstrates how the bimetallic synergistic strategy can effectively enhance the electrochemical properties of MOFs by providing a higher specific surface area and by the introduction of dual redox sites.