bluuebunny/crossref_metadata_2025 huggingface dataset:
Multistimuli responsive hydrogels with shape fix/memory capability fabricated from gold nanorod‐conjugated amino acid‐based vinyl polymer networks
Authors: Yamaguchi Yutaro , Nishimura Shin‐nosuke , Higashi Nobuyuki , Koga Tomoyuki
Published: May 2024

Fabricating robust shape‐memory hydrogels that respond to multiple external stimuli is an important challenge in facilitating gel technology for versatile applications. In this study, we report a simple approach for constructing thermo‐, redox‐, and photo‐responsive hydrogels with high mechanical strength and shape fix/memory capability. Upper critical solution temperature (UCST)‐type amino acid‐based hydrogels were facilely prepared by radical copolymerization of N‐acryloyl glycinamide (NAGAm) with cystine‐derived divinyl acrylamides (ionic cystine [NAC] or nonionic cystine‐methyl ester [NACMe]) units at different monomer concentrations (1/2 M). These hydrogels were transparent and exhibited good mechanical strength (tensile strength of 0.3–0.4 MPa and breaking elongation of 400%–700%). All hydrogels showed UCST‐type swelling‐shrinking behaviors based on thermo‐driven reversible hydrogen bonds among the PNAGAm units, and thus could be fixed into variety of shapes and recovered to the original shape by temperature manipulation. The cystine‐based crosslinkers having SS bonds served as efficient redox‐sensitive and gold‐nanorod‐(AuNR)‐adsorbing moieties; thus, AuNR could be conjugated stably and evenly into the PNAGAm/NAC hydrogel. Moreover, upon light‐irradiation, the AuNR‐conjugated hybrid hydrogel exhibited shape‐memory behavior owing to the photothermal effect of the AuNRs. These multiresponsive/functional hydrogels composed of amino acid units have considerable potential for various applications in the fields of soft actuators and biomedicines.
Enhancing photothermal depolymerization with metalloporphyrin catalyst
Authors: Ng Gervase , Prescott Stuart W. , Postma Almar , Moad Graeme , Hawker Craig J. , Anastasaki Athina , Boyer Cyrille
Published: May 2024

The ability to revert polymers to their original monomers represents a crucial chemical recycling technique, promoting sustainability and offering the chance to convert used materials into valuable products. In recent years, numerous studies have explored the use of polymers synthesized via reversible deactivation radical polymerization (RDRP) techniques to facilitate efficient depolymerization reactions. Herein, we report the use of a photocatalyst, zinc tetraphenylporphyrin (ZnTPP), along with light irradiation to accelerate depolymerization of polymers prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization. We explore various parameters affecting depolymerization efficiency, including solvents, reaction temperature (80, 100, and 120°C), the presence of photocatalysts (ZnTPP and Eosin Y), and the type of RAFT end‐groups, namely trithiocarbonate, dithiobenzoate, and 1H‐pyrazole‐1‐carbodithioate. For instance, when PMMA was diluted to 25 mM in 1,4‐dioxane and heated to 120°C under green light irradiation in the presence of ZnTPP (200 ppm), rapid depolymerization exceeding 70% occurred within 1 h. Without ZnTPP, under similar conditions, the reaction required over 8 h to achieve a slightly lower yield. Furthermore, this method confers moderate oxygen tolerance to the system, enabling depolymerization to proceed without the need of deoxygenation, albeit at a lower rate and consequently lesser monomer recovery (31%).
How do mindfulness‐based interventions promote coping and self‐efficacy in patients with cancer: A systematic review of qualitative and quantitative data
Authors: Heinen Jana Maria , Laing Ebba Magdalena , Schäffeler Norbert , Bäuerle Alexander , Krakowczyk Julia Barbara , Schug Caterina , Ziesemer Stefanie Katharina , Teufel Martin , Erim Yesim , Zipfel Stephan , Stengel Andreas , Graf Johanna
Published: May 2024

Objective

The purpose of this study was to review the existing quantitative and qualitative evidence regarding how mindfulness‐based interventions (MBIs) help cope with cancer‐related challenges and increase affected patients' perceived self‐efficacy.

Methods

A systematic literature search was conducted on PubMed, PsycInfo, PubPsych, and CINAHL. Quantitative, qualitative, and mixed methods studies were included if they (1) evaluated MBIs (2) for patients with cancer or cancer survivors (3) regarding their impact on coping with cancer and perceived self‐efficacy. The reports were screened by two independent reviewers and conflicts were resolved by a third reviewer. The review was pre‐registered on PROSPERO (CRD42022368765).

Results

Findings from 28 reports of 19 quantitative studies, six qualitative studies, and three mixed‐methods studies (total N = 1722) were extracted and integrated. The synthesis of quantitative data showed considerable heterogeneity in outcomes and measurement instruments. Most often reported were significant positive impacts of mindfulness on general coping skills, self‐regulation, and perceived efficacy in coping with cancer. Qualitative interviews with patients supported those results. The three meta‐themes identified were that MBI (1) provided patients with tools to use in stressful situations, (2) promoted a general change of mindset and (3) created a feeling of social connectedness.

Conclusions

The reviewed studies suggest that MBI can promote coping and enhance the perceived self‐efficacy of patients with cancer. In the future, more research investigating the different aspects of coping and the potentially moderating role of self‐efficacy could provide further insights with respect to how coping and self‐efficacy related to MBI.
Implementation and outcomes of a quality improvement project to systematically assess the gross motor skills in school‐aged children with cystic fibrosis
Authors: Good Abby , Shannon Jackie , Brinton John T. , Hoppe Jordana E.
Published: May 2024

Introduction

Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this research project was to implement a systematic gross motor assessment in children with CF ages 4−12 years. Secondarily, we aimed to assess demographic characteristics associated with gross motor delays.

Methods

Physical therapists aimed to evaluate at least 50% of eligible children (4−12 years) at our CF Center over 1 year using the Bruininks‐Oseretsky Test of motor Proficiency, second edition (BOT‐2). Delays are defined by scores less than 18th percentile. Demographic and clinical data included body mass index, hospitalizations, genotype, and comorbidities. Basic descriptive statistics summarized patient information. Parametric and nonparametric methods compared groups of interest. Linear regression assessed associations between BOT‐2 measures and clinical characteristics.

Results

The BOT‐2 evaluation was successfully implemented with 69% of eligible patients being evaluated. Forty‐five (62.5%) scored below average. Impaired strength (22.2%) was most common, followed by impaired balance (16.7%), running speed and agility (15.3%), and bilateral coordination (8.3%). 15.5% scored below average on their total motor composite score (TMC). Increased age, comorbidities and hospitalizations were associated with a lower TMC.

Conclusions

The BOT‐2 was successfully implemented as part of routine CF care to screen for gross motor delays in children. Results suggest that a high percentage of children with CF, especially older children with comorbid conditions or a history of hospitalization, have impaired gross motor function. These findings support the need for routine gross motor evaluations and physical therapy interventions within pediatric CF clinics.
First‐Principles Study of the Al–N‐Codoped Zincblende ZnO
Authors: Xiang Yang , Tang Hao , Zhu Zihao , Pang Bo , Zhou Tingjun , Zhan Huahan , Kang Junyong , Zhou Yongliang
Published: May 2024

Electronic properties of intrinsic ZnO, N‐doped ZnO, and Al–N‐codoped ZnO of both hexagonal wurtzite (HW) and zincblende (ZB) structures are investigated by first‐principles calculations. Both N‐doped ZB‐ZnO and N‐doped HW‐ZnO achieve p‐type transition by the introduction of N‐2p states, forming shallow acceptor levels above the valence band. However, the positive impurity formation energy implies the difficulty and instability of N‐doped ZnO. In Al–N‐codoped ZnO, the Al elements compensate the p‐type doping effect, but partially enhance the solubility of N. Furthermore, the comparison of the electronic properties between HW‐ZnO and ZB‐ZnO indicates that the ZB structure favors the achieving of p‐type doping.
Graphene Plasmonic Time Crystals
Authors: Kim Kwang‐Hyon , O Kang‐Hyok
Published: May 2024

The concept of photonic crystals has recently been extended to the time domain and attracted great interest. Unfortunately, realizing photonic time crystals is a challenging task due to the practical difficulty in modulating dielectric constants with large modulation depth. This problem can be resolved using graphene, the conductivity of which is tunable with significantly large contrast. Herein, graphene plasmonic time crystals, as new kinds of photonic time crystals in atomically thin 2D material, are proposed and their optical properties are investigated. Their band structures are analytically calculated and the propagations of graphene plasmons in temporal crystalline structures are numerically evaluated. Periodically driven by temporally modulating the Fermi energy, graphene plasmons exhibit in‐gap amplification and defect‐immune topological edge states, revealing the nature as plasmonic time crystals. Graphene plasmonic time crystals are realized soon after this proposal due to the possibility of modulating its conductivity with large contrast by simple electrical gating.
Prognostic score‐based methods for estimating center effects based on survival probability: Application to post‐kidney transplant survival
Authors: Lee Youjin , Reese Peter P. , Tran Amelia H. , Schaubel Douglas E.
Published: May 2024

In evaluating the performance of different facilities or centers on survival outcomes, the standardized mortality ratio (SMR), which compares the observed to expected mortality has been widely used, particularly in the evaluation of kidney transplant centers. Despite its utility, the SMR may exaggerate center effects in settings where survival probability is relatively high. An example is one‐year graft survival among U.S. kidney transplant recipients. We propose a novel approach to estimate center effects in terms of differences in survival probability (ie, each center versus a reference population). An essential component of the method is a prognostic score weighting technique, which permits accurately evaluating centers without necessarily specifying a correct survival model. Advantages of our approach over existing facility‐profiling methods include a metric based on survival probability (greater clinical relevance than ratios of counts/rates); direct standardization (valid to compare between centers, unlike indirect standardization based methods, such as the SMR); and less reliance on correct model specification (since the assumed model is used to generate risk classes as opposed to fitted‐value based ‘expected’ counts). We establish the asymptotic properties of the proposed weighted estimator and evaluate its finite‐sample performance under a diverse set of simulation settings. The method is then applied to evaluate U.S. kidney transplant centers with respect to graft survival probability.
Aspergillus Oryzae Mediated α‐Fe2O3 Nanoparticles for Photocatalytic Remediation of Basic Fuschin Dye and Antimicrobial Activities
Authors: Kadam Avdhut D. , Sapkal Aboli C. , Survase Avinash A. , Kamble Santosh B.
Published: May 2024

Green synthetic approach for the synthesis of Iron oxide (α‐Fe2O3) nanoparticles were successfully carried out using Aspergillus oryzae culture mediated biogenic route. The synthesized nanoparticle was confirmed by structural and optical characterization with the help of hematite phase. The α‐Fe2O3 nanoparticles show antimicrobial activity against bacterial strains Staphylococcus aureus, Pseudomonas aeruginosa and fungal strain Candida albicans. Under visible light, the α‐Fe2O3 nanoparticles demonstrate remarkable antibacterial action, confirming their superior efficacy for photocatalytic remediation. The present study discloses that the α‐Fe2O3 nanoparticles are efficient photocatalysts for 96 % degradation of basic fuchsin dye and highly active antimicrobial agent.
Effective Foot‐and‐Mouth Disease Virus Control Using Silver Nanoparticles
Authors: Dung Tran Thi Ngoc , Chi Nguyen Thi Yen , Viet Quang Dang , Thanh Cong Nguyen , Lai Thi Ngoc Ha , Le Van Phan
Published: May 2024

This study investigates the antiviral efficacy of chitosan‐stabilized silver nanoparticles (AgNPs) against the Foot‐and‐Mouth Disease virus (FMDV), a highly contagious pathogen affecting cloven‐hoofed animals. In vitro experiments demonstrated that AgNPs effectively inhibited FMDV replication in a dose‐dependent manner. At a concentration of 1.56 μg/ml, AgNPs exhibited no cytotoxicity to baby hamster kidney 21 (BHK21) cells while achieving complete deactivation of FMDV at a titer of 103 TCID50 and inhibiting viral growth at a titer of 104 TCID50. These findings suggest the potential of silver nanoparticles as a novel disinfectant for controlling FMDV transmission and preventing disease outbreaks.
A Simplistic Label‐Free Electrochemical Immunosensing Approach for Rapid and Sensitive Detection of Anti‐SARS‐COV‐2 Nucleocapsid Antibodies
Authors: Kock Branham J. , Du Plooy Jarid , Cloete Rochida A. , Jahed Nazeem , Nguyen Pham‐Truong Thuan , Arendse Christopher , Pokpas Keagan
Published: May 2024

Rapid and precise detection of SARS‐CoV‐2 antibodies is paramount for effective outbreak monitoring and vaccine efficacy assessment. While existing approaches for antibody detection often rely on complex electrochemical immunosensing with nanomaterial functionalization targeting S‐protein antibodies, their limitations in sensitivity and complexity have hindered widespread application. Here, we present a simplistic immunosensing platform designed for the rapid, and precise detection of SARS‐CoV‐2 specific IgG and Nucleocapsid antibodies. Notably, this study marks only the second exploration of SARS‐CoV‐2 N‐protein antibody detection. The platform utilizes traditional self‐assembled monolayers to establish selective bio‐affinity between SARS‐CoV‐2 specific Nucleocapsid antibodies and a gold electrode functionalized with the N‐protein antigen. Interestingly, despite the absence of nanomaterial functionalization, the developed platform achieves sensitivity comparable to existing sensors across a wide detection range (0.025 to 1 ng/mL) with an impressive limit of detection (0.019 ng/mL). The simplicity of the approach, relying solely on immunocomplex reactions, underscores that effective binding efficiency may be achieved in the absence of complex functionalization and determines its affordability, specificity, and high sensitivity. By eliminating the need for additional functionalization steps, the platform offers a streamlined solution for SARS‐CoV‐2 antibody detection and demonstrates the possibility of N‐protein antibody detection as a promising avenue for widespread application in SARS‐CoV‐2 outbreak monitoring and vaccine efficacy assessment particularly in underdeveloped regions.
NLOphoric Anthraquinone Dyes – A Review
Authors: Gupta Puja O. , Sekar Nagaiyan
Published: May 2024

This review is about anthraquinone dyes. One of the advantages of organic NLOphores materials is the variety of chromophores explored for a wide range of potential applications in optoelectronics and biology. The second and third harmonic generations, as well as hyper‐Rayleigh scattering (HRS), the Z‐scan technique, degenerate four‐wave mixing (DFWM), and density functional theory (DFT), are all covered in this review. The most active sites for establishing enhanced NLO properties were found to be positions 2 and 6 of the anthraquinone core. The structural characteristics of dyes are used to divide them into subcategories. In each section, structures with a higher NLO response are highlighted. Researchers will benefit from this review when designing and synthesizing NLOphores.
Upgrading Gel Electrolytes Through Electrostatic‐Induced Dual‐Salt Paradigm for Superior Zn‐Ion Battery Performance
Authors: Wu Jianyang , Li Mengchao , Ding Xuan , Chen Zheming , Luo Jing , Zhang Qiaoli , Qiu Yanbin , Wang Qian , Liu Wen , Yang Chengkai
Published: May 2024

Gel electrolytes are gaining attention for rechargeable Zn‐ion batteries because of their high safety, high flexibility, and excellent comprehensive electrochemical performances. However, current gel electrolytes still perform at mediocre levels due to incomplete Zn salts dissociation and side reactions. Herein, an electrostatic‐induced dual‐salt strategy is proposed to upgrade gel electrolytes to tackle intrinsic issues of Zn metal anodes. The competitive coordination mechanism driven by electrostatic repulsion and steric hindrance of dual anions promotes zinc salt dissociation at low lithium salt addition levels, improving ion transport and mechanical properties of gel electrolytes. Li+ ions and gel components coordinate with H2O, reducing active H2O molecules and inhibiting associated side reactions. The dual‐salt gel electrolyte enables excellent reversibility of Zn anodes at both room and low temperatures. Zn||Polyaniline cells using the dual‐salt gel electrolyte exhibit a high discharge capacity of 180 mAh g−1 and long‐term cycling stability over 180 cycles at −20 °C. The dual‐salt strategy offers a cost‐effective approach to improving gel electrolytes for high‐performance flexible Zn‐ion batteries.
Autocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment
Authors: Ye Zhang , Sheu Wendy C. , Qu Huan , Peng Bin , Liu Jia , Zhang Li , Yuan Fanen , Wei Yuxin , Zhou Jiangbing , Chen Qianxue , Xiao Xuan , Zhang Shenqi
Published: May 2024

Glioblastoma multiforme (GBM) is a formidable cancer to treat due to the lack of effective drugs that can also efficiently cross the blood–brain barrier (BBB). Herein, a novel strategy involving the synthesis of p28 peptide‐conjugated, lexiscan (LEX)‐loaded, bardoxolone methyl (BM) self‐assembled nanoparticles, designated as p28‐LBM NPs, is introduced. These NPs are designed to overcome the dual challenges of effectively killing GBM cells and efficiently penetrating the brain. The p28 peptide is chosen for targeted delivery to brain tumors, and LEX is employed to enhance drug penetration across the BBB. The successful penetration of brain tumors by the p28‐LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28‐LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future.
Enhanced Efficiency and Stability of Wide‐Bandgap Perovskites via Br‐Rich Bulk and Surface 2D Passivation for Indoor Photovoltaics
Authors: Li Can , Liang Yu , Zhang Yicong , Du Liming , Min Jiayu , Li Zhen
Published: May 2024

Indoor photovoltaics (IPV) is a promising technology to power the rapidly developing Internet of Things (IoT) devices, offering advantages of distributed power source and reduced maintenance cost. Wide‐bandgap perovskite solar cells (PSCs), with the features of easy bandgap tuning and low‐cost solution process, hold significant potential for powering indoor IoT devices. However, the efficiency and stability of wide‐bandgap PSCs suffers from severe phase segregation and surface defects. Herein, a novel bromide‐rich 2D passivation strategy targeting both bulk and surface passivation of wide‐bandgap PSCs for IPV application is introduced. Ammonium salts with optimized alkyl chain length is confirmed to suppress the phase segregation in the bulk. Bromide‐rich 2D perovskite exhibit superior performance compared to their iodide counterparts, effectively suppressing nonradiative recombination and forming favorable energy band alignment with the electron transport layer (ETL). The wide‐bandgap PSCs achieved an impressive power conversion efficiency (PCE) up to 41.58% under 1000 lux light emitting diode (LED) illumination. Furthermore, the wide‐bandgap perovskite module efficiently powers a Bluetooth IoT sensor at 400 lux indoor illumination, which can sense and broadcast the environmental information. This work highlights the remarkable potential of wide‐bandgap PSCs for indoor IoT devices and provides valuable insights into enhancing the efficiency and stability of PSCs for future IoT applications.
Palaeoscolecids from the Ludlow Series of Leintwardine, Herefordshire (UK): the latest occurrence of palaeoscolecids in the fossil record
Authors: Howard Richard J. , Parry Luke A. , Clatworthy Innes , D'Souza Leila , Edgecombe Gregory D.
Published: May 2024

The documentation of cuticular micro‐ornament is vital for the taxonomic assignment of palaeoscolecids: vermiform lower Palaeozoic ecdysozoans interpreted as stem‐group priapulans or early diverging panarthropods. This is due to the absence of the character‐rich proboscis and tail hooks in palaeoscolecid material not from Burgess Shale‐type Konservat‐Lagerstätten. Here, the cuticular micro‐ornamentation of palaeoscolecids from the upper Silurian (Ludlow) fauna of Leintwardine (Herefordshire, England), is described using scanning electron microscopy and reflectance transformation imaging. This material is taxonomically unstable because it was included in an effective wastebasket genus (Protoscolex) long before these imaging techniques were developed. The Leintwardine material is shown to be most closely comparable to a palaeoscolecid from the Darriwilian (Middle Ordovician) of the Builth–Llandrindod inlier, Powys, Wales, and is transferred accordingly to Radnorscolex Botting et al. as Radnorscolex latus (Bather). The Leintwardine fauna represents the uppermost stratigraphic occurrence of palaeoscolecids, constrained to the Saetograptus leintwardinensis Zone (lower Ludfordian), and the comparatively sparse Silurian palaeoscolecid record is subsequently discussed. It is hypothesized that palaeoscolecids may have become extinct during the mid‐Ludfordian Lau Event, the onset of which is recorded in the biozone immediately above the Leintwardine fauna (Bohemograptus Zone). Finally, the British palaeoscolecid fauna is summarized, including a new record from the Dapingian (Middle Ordovician) of Carmarthenshire, South Wales.
Coupled Experimental Study and Thermodynamic Modeling of the Fe–Si–N System
Authors: You Zhimin , Shen Junjie , Liu Yuxin , Jung In‐Ho , Wu Zewen , Jiang Zhouhua
Published: May 2024

Some key experiments are carried out to determine the solubility of N in Fe–Si liquid solutions at various compositions, temperatures, and N2 pressures using the sampling method. The Fe–Si–N system is thermodynamically modeled using the CALculation of PHAse Diagrams (CALPHAD) approach for the first time based on critical evaluation of all available experimental data. In the present thermodynamic modeling, the liquid and solid solutions of the Fe–Si–N system are described using the modified quasichemical model and compound energy formalism, respectively. In particular, the Gibbs energies of liquid, FCC_A1, and BCC_A2 solutions are carefully determined to resolve the discrepancies among existing experimental data. The solubility product of β‐Si3N4(s) in Si steels and ferrosilicon alloys, activity coefficients, and interaction parameters of N in liquid and solid Fe–Si–N solutions are determined over a wide temperature range. As an application of the database, the N solubility in Si steels and phase constitution of nitrided ferrosilicon alloys in a wide composition, temperature, and N2 pressure ranges are predicted.
Experimental and numerical investigation of the bending, shear, and punching shear behavior of recycled aggregate concrete precast/prestressed hollow core slabs
Authors: McGinnis Michael J. , Gangone Michael V. , Nogales Alejandro , Gomez‐Santana Lizeth Marisol , Weldon Brad , Reihl Adam , Tošić Nikola , Kurama Yahya
Published: May 2024

Although it has been shown that using recycled concrete aggregate in new structural concrete is economical and sustainable, the use of this material for such applications is still not widespread. One of the reasons is that manufacturers, designers, engineers, owners, and other market players are not familiar with specifying and utilizing this material—although standards are starting to incorporate provisions for recycled aggregate concrete, successful, practical example projects are needed. The current paper describes the results of a partnership between universities and a precast concrete manufacturer of hollow core slabs. Seven hollow core slabs with volumetric replacement ratios of natural aggregate with recycled aggregate from 0% to 60% were tested to failure in both bending and shear, and then undamaged portions of the slabs were subjected to punching shear until failure. The results showed only mild differences in strength, with different replacement percentages of recycled aggregate under the various loading scenarios. Numerical simulations performed in Abaqus demonstrated the feasibility of analyzing recycled aggregate concrete structural elements and provided important insights into their behavior.
Evaluation of residual sodium carbonate (RSC) and sodium adsorption ratio (SAR) in fresh water and laundry grey water for irrigation usage
Authors: Khapra Rajat , Singh Nirankar
Published: May 2024

The current study was carried out to assess the suitability of laundry grey water (LGW) for reuse in irrigation so that it can help in the reduction of freshwater stress in irrigation sector. To address this objective, concentration of sodium (Na+), calcium (Ca2+), magnesium (Mg2+), carbonate (CO32−), bicarbonate (HCO3−), and phosphate (PO43−) were tested in fresh water (FW) collected before laundry washing and LGW generated after laundry washing from different households. The suitability of LGW for irrigation purpose was determined by using water quality indices such as Sodium adsorption ratio (SAR) and Residual Sodium Carbonate (RSC). The SAR values of FW at the rural and urban area sites varied from 0.84 to 1.10 and 0.82 to 4.30 respectively and remained in the excellent category for irrigation purpose. The SAR values of LGW at the rural and urban sites varied from 10.06 to 13.01 and 6.26 to 9.68, respectively. In contrast to the SAR values of the LGW at rural site, which remained under good quality category, SAR values remained under excellent category for irrigation purpose at urban sites. RSC values of FW and LGW were below 3.97 showing low or medium hazards associated with it for irrigation.
Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure
Authors: Panés Julian , D’Haens Geert R. , Sands Bruce E. , Ng Siew C. , Lawendy Nervin , Kulisek Nicole , Guo Xiang , Wu Joseph , Vranic Ivana , Panaccione Remo , Vermeire Séverine
Published: May 2024

Background and Aims

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report an integrated summary of tofacitinib safety from the completed global UC clinical program (9.2 years maximum tofacitinib exposure).

Methods

This analysis included patients receiving tofacitinib 5 or 10 mg twice daily (b.i.d.) from completed phase 2/3 placebo‐controlled studies, an open‐label, long‐term extension study and a randomized phase 3b/4 study. Proportions and incidence rates (IRs; unique patients with events/100 patient‐years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest (AESI).

Results

Overall, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg b.i.d.; 938 (81.1%) were in the predominant dose tofacitinib 10 mg b.i.d. group; 552 (47.7%) received tofacitinib for ≥2 years; total exposure: 3202.0 PY; 994 (85.9%) experienced AEs; 254 (22.0%) experienced serious AEs. Median treatment duration: 1.7 (range 0.0–9.2) years. IRs (95% CI) for combined tofacitinib doses: deaths 0.24 (0.10–0.48); serious infections (SIs) 1.80 (1.37–2.32); herpes zoster (HZ; non‐serious and serious) 3.24 (2.63–3.94); serious HZ 0.24 (0.10–0.48); opportunistic infections 0.96 (0.65–1.36); malignancies (excluding non‐melanoma skin cancer [NMSC]) 0.88 (0.59–1.26); NMSC 0.71 (0.45–1.07); major adverse cardiovascular events 0.27 (0.12–0.52); deep vein thrombosis 0.06 (0.01–0.22); pulmonary embolism 0.18 (0.07–0.40); and gastrointestinal perforations 0.09 (0.02–0.27).

Conclusions

Except for HZ and SIs, IRs for AESI were <1 case/100 PY. Safety was consistent with previous analyses of shorter exposure and tofacitinib's known safety profile, including real‐world data.

ClinicalTrials.gov

NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT03281304.
Water scarcity in the fast‐growing megacity of Lagos, Nigeria and opportunities for managed aquifer recharge
Authors: Olabode Oluwaseun Franklin , Comte Jean‐Christophe
Published: May 2024

In the last three decades, the world has experienced a rapid emergence of megacities. The increasing demographics, urbanization, and water demand brought severe and undesired effects on the quantity and quality of their water resources. A prime example is Lagos (Nigeria, West Africa), which is projected to become the world's largest city by 2100, and faces water scarcity challenges common to other megacities of developing countries. A literature review reveals the vast gap between water demand and regulated supply, inadequate knowledge and information on the current state of water (re)sources, and major, yet unregulated, use of groundwater. It further highlights the impacts of uncontrolled wastewater discharge into surface waters and aquifers, the role of increasing paved surfaces and blocked drainages on flooding, the inadequate supply of potable water, and the unsustainable abstraction of groundwater. Here, we examine the potential of managed aquifer recharge (MAR) to address these recurrent challenges across the megacity. The analysis reveals the opportunities and potential risks associated with the capture of wastewater, storm water, and brackish surface water for MAR. These waters, after appropriate treatment and subsurface storage may bridge the growing water supply–demand gap and mitigate the effects of groundwater (over)exploitation, including aquifer depletion, saltwater intrusion and land subsidence. Immediate efforts should focus on improving the conceptual and quantitative knowledge of Lagos' hydrogeology and groundwater resources through comprehensive spatial–temporal groundwater monitoring and socio‐economic studies of groundwater access and use. The insights provided may inform other fast‐growing coastal megacities in Africa and the wider developing world.

This article is categorized under:

Science of Water > Water and Environmental Change

Engineering Water > Water, Health, and Sanitation

Human Water > Value of Water

Science of Water > Hydrological Processes
Grid Search Optimization of Novel SNN-ESN Classifier on a Supercomputer Platform
Authors: Penkov Dimitar , Koprinkova-Hristova Petia , Kasabov Nikola , Nedelcheva Simona , Ivanovska Sofiya , Yordanov Svetlozar
Published: May 2024

This work is demonstrating the use of a supercomputer platform to optimise hyper-parameters of a proposed by the team novel SNN-ESN computational model, that combines a brain template of spiking neurons in a spiking neural network (SNN) for feature extraction and an Echo State Network (ESN) for dynamic data series classification. A case study problem and data are used to illustrate the functionalities of the SNN-ESN. The overall SNN-ESN classifier has several hyper-parameters that are subject to refinement, such as: spiking threshold, duration of the refractory period and STDP learning rate for the SNN part; reservoir size, spectral radius of the connectivity matrix and leaking rate for the ESN part. In order to find the optimal hyper-parameter values exhaustive search over all possible combinations within reasonable intervals was performed using supercomputer Avitohol. The resulted optimal parameters led to improved classification accuracy. This work demonstrates the importance of model parameter optimisation using a supercomputer platform, which improves the usability of the proposed SNN-ESN for real-time applications on complex spatio-temporal data.
Ethical Judgment of What (Not) to Be Disclosed
Authors: Ghaly Mohammed
Published: May 2024

Chapter three provides an in-depth ethical analysis of what types of incidental findings (IFs) from genomic research or clinical testing should or should not be disclosed to individuals. It begins by providing a lucid definition of IFs and delineating the scope under consideration. The chapter then examines two categories where disclosure is judged as obligatory: firstly, informing potential recipients about the likelihood of IFs arising, and secondly, disclosing life-saving IFs associated with actionable genetic conditions. A key focus is the controversial issue of misattributed paternity IFs, which reveal that the assumed father is not the biological father. Two contrasting perspectives are presented: one prohibiting disclosure to the assumed father based on Islamic jurisprudential principles and societal ethical concerns, while another minority viewpoint asserts the obligation to disclose, with supporting arguments outlined, and accompanied with critical commentary. Subsequently, the chapter goes on to analyze IFs recommended (praiseworthy but not obligatory) for disclosure, employing the theoretical framing of the Islamic ethical concepts around seeking/providing medical care, with the American College of Medical Genetics (ACMG) list serving as an applied example. Additionally, a category of IFs judged as reprehensible (blameworthy but not prohibited) to disclose is examined through the lens of distant lineage and demonstrated through the applied case of genetic ancestry findings.
Subsystem complexity and measurements in holography
Authors: Jian Shao-Kai , Zhang Yuzhen
Published: May 2024

Abstract

We investigate the impact of measuring one subsystem on the holographic complexity of another. While a naive expectation might suggest a reduction in complexity due to the collapse of the state to a trivial product state during quantum measurements, our findings reveal a counterintuitive result: in numerous scenarios, measurements on one subsystem can amplify the complexity of another. We first present a counting argument elucidating this complexity transition in random states. Then, employing the subregion “complexity=volume” (CV) proposal, we identify a complexity phase transition induced by projective measurements in various holographic CFT setups, including CFT vacuum states, thermofield double states, and the joint system of a black hole coupled to a bath. According to the AdS/BCFT correspondence, the post-measurement dual geometry involves an end-of-the-world brane created by the projective measurement. The complexity phase transition corresponds to the transition of the entanglement wedge to the one connected to the brane. In the context of the thermofield double setup, complete projection on one side can transform the other side into a boundary state black hole with higher complexity or a pure AdS with lower complexity. In the joint system of a black hole coupled to a nongraviting bath, where (a part of) the radiation is measured, the BCFT features two boundaries: one for the black hole and the other for the measurement. We construct the bulk dual involving intersecting or non-intersecting branes, and investigate the complexity transition induced by the projective measurement. Notably, for a subsystem that contains the black hole brane, its RT surface may undergo a transition, giving rise to a complexity jump.
Semi-chiral operators in 4d $$ \mathcal{N} $$ = 1 gauge theories
Authors: Budzik Kasia , Gaiotto Davide , Kulp Justin , Williams Brian R. , Wu Jingxiang , Yu Matthew
Published: May 2024

Abstract

We discuss the properties of quarter-BPS local operators in four-dimensional $$ \mathcal{N} $$
N
= 1 supersymmetric Yang-Mills theory using the formalism of holomorphic twists. We study loop corrections both to the space of local operators and to algebraic operations which endow the twisted theory with an infinite symmetry algebra. We classify all single-trace quarter-BPS operators in the planar approximation for SU(N) gauge theory and propose a holographic dual description for the twisted theory. We classify perturbative quarter-BPS operators in SU(2) and SU(3) gauge theories with sufficiently small quantum numbers and discuss possible non-perturbative corrections to the answer. We set up analogous calculations for some theories with matter.
Counting atypical black hole microstates from entanglement wedges
Authors: Wei Zixia , Yoneta Yasushi
Published: May 2024

Abstract

Disentangled black hole microstates are atypical states in holographic CFTs whose gravity duals do not have smooth horizons. If there exist sufficiently many disentangled microstates to account for the entire black hole entropy, then any black hole microstate can be written as a superposition of states without smooth horizons. We show that there exist sufficiently many disentangled microstates to account for almost the entire black hole entropy of a large AdS black hole at the semiclassical limit GN → 0. In addition, we also argue that in generic quantum many-body systems with short-ranged interactions, there exist sufficiently many area law states in the microcanonical subspace to account for almost the entire thermodynamic entropy in the standard thermodynamic limit. Area law states are atypical since a typical state should contain volume law entanglement. Furthermore, we also present an explicit way to construct such a set of area law states, and argue that the same construction may also be used to construct disentangled states.
Holographic torus correlators in AdS3 gravity coupled to scalar field
Authors: He Song , Li Yun-Ze , Zhang Yunda
Published: May 2024

Abstract

This paper investigates holographic torus correlators of generic operators at conformal infinity and a finite cutoff within AdS3 gravity coupled with a free scalar field. Using a near-boundary analysis and solving the gravitational boundary value problem, we solve Einstein’s equation and calculate mixed correlators for massless and massive coupled scalar fields. The conformal Ward identity on the torus has been reproduced holographically, which can be regarded as a consistency check. Further, recurrence relations for a specific class of higher-point correlators are derived, validating AdS3/CFT2 with non-trivial boundary topology. While the two-point scalar correlator is accurately computed on the thermal AdS3 saddle, the higher-point correlators associated with scalar and stress tensor operators are explored.
Advanced tools for basis decompositions of genus-one string integrals
Authors: Zhang Yong
Published: May 2024

Abstract

In string theories, one-loop scattering amplitudes are characterized by integrals over genus-one surfaces using the Kronecker-Eisenstein series. A recent methodology proposed a genus-one basis formed from products of these series of chain topologies. A prior work further deconstructed cyclic products of the Kronecker-Eisenstein series on this basis. Building on it, our study further employs advanced and comprehensive combinatorial techniques to decompose more general genus-one integrands including a product of an arbitrary number of cyclic products of Kronecker-Eisenstein series, supplemented by Mathematica codes. Our insights enhance the understanding of multiparticle amplitudes across various string theories and illuminate loop-level parallels with string tree-level amplitudes.
Magnetic charges for the graviton
Authors: Hull C. M.
Published: May 2024

Abstract

Symmetries and conserved charges are investigated for linearised gravity and its dual formulation in terms of the dual graviton field. Conserved charges are constructed for the dual graviton theory that are associated with invariances of the dual graviton theory. These invariances arise for gauge parameters that are certain generalised Killing tensors. These electric-type charges for the dual graviton are then shown to give magnetic-type charges for the graviton. One of the magnetic-type gravitational charges obtained in this way is the linearisation of the gravitational charge in d ≥ 5 dimensions that arises as a central charge in the supersymmetry algebra and is carried by Kaluza-Klein monopoles. Solutions of linearised gravity carrying the magnetic gravitational charges are discussed. The application of the approach used here to other gauge theories is discussed.
Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson’s disease
Authors: Ding Liuyan , Lu Lin , Zheng Shaohui , Zhang Zhiling , Huang Xingting , Ma Runfang , Zhang Mengran , Xu Zongtang , Chen Minshan , Guo Zhimei , Zhu Si , Gong Junwei , Mao Hengxu , Zhang Wenlong , Xu Pingyi
Published: May 2024

Ubiquitin-proteasome system dysfunction triggers α-synuclein aggregation, a hallmark of neurodegenerative diseases, such as Parkinson’s disease (PD). However, the crosstalk between deubiquitinating enzyme (DUBs) and α-synuclein pathology remains unclear. In this study, we observed a decrease in the level of ubiquitin-specific protease 14 (USP14), a DUB, in the cerebrospinal fluid (CSF) of PD patients, particularly females. Moreover, CSF USP14 exhibited a dual correlation with α-synuclein in male and female PD patients. To investigate the impact of USP14 deficiency, we crossed USP14 heterozygous mouse (USP14+/−) with transgenic A53T PD mouse (A53T-Tg) or injected adeno-associated virus (AAV) carrying human α-synuclein (AAV-hα-Syn) in USP14+/− mice. We found that Usp14 deficiency improved the behavioral abnormities and pathological α-synuclein deposition in female A53T-Tg or AAV-hα-Syn mice. Additionally, Usp14 inactivation attenuates the pro-inflammatory response in female AAV-hα-Syn mice, whereas Usp14 inactivation demonstrated opposite effects in male AAV-hα-Syn mice. Mechanistically, the heterodimeric protein S100A8/A9 may be the downstream target of Usp14 deficiency in female mouse models of α-synucleinopathies. Furthermore, upregulated S100A8/A9 was responsible for α-synuclein degradation by autophagy and the suppression of the pro-inflammatory response in microglia after Usp14 knockdown. Consequently, our study suggests that USP14 could serve as a novel therapeutic target in PD.
The evolutionary novelty of insect defensins: from bacterial killing to toxin neutralization
Authors: Gao Bin , Zhu Shunyi
Published: May 2024

Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis, which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed DvirARP) with differences from its parent gene in its pattern of expression, structure and function. DvirARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 310 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. DvirARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. DvirARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the DvirARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that DvirARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection.
Sphingosine is involved in PAPTP-induced death of pancreas cancer cells by interfering with mitochondrial functions
Authors: Patel Sameer H. , Wilson Gregory C. , Wu Yuqing , Keitsch Simone , Wilker Barbara , Mattarei Andrea , Ahmad Syed A. , Szabo Ildiko , Gulbins Erich
Published: May 2024

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer.

Key messages

Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis.

The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine.

Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization.

Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase.

Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo.
Polyandry may mitigate the negative impact of reproductive interference among bumblebees in Japan
Authors: Inokuchi Fumina , Inoue Maki N. , Kanbe Yuya , Ito Masaaki , Takahashi Jun-ichi , Nomura Tetsuro , Goka Koichi , Tsuchida Koji
Published: May 2024

In social hymenopterans, monandry of the queen is an ancestral trait, and polyandry is a derived trait. Polyandry of the queen is the norm in a limited number of lineages, such as honeybees, leaf-cutting ants, Pogonomyrmex ants, and Vespula wasps, which presumably provide fitness advantages for the whole colony. The queen of the introduced bumblebee, Bombus terrestris, is polyandrous in Japan, whereas it is monandrous in native regions. We hypothesize that polyandry can evolve in a process that avoids the negative impacts of reproductive interference caused by interspecific mating and conducted genetic studies of the invasive species B. terrestris and two native subspecies, Bombus hypocrita sapporoensis and Bombus hypocrita hypocrita, in Japan. Our results revealed that although the native queens of B. hypocrita hypocrita allopatric with B. terrestris were strictly monandrous, the native queens of B. hypocrita sapporoensis sympatric with B. terrestris were polyandrous. These results suggested that the queens of native B. hypocrita sapporoensis do not experience negative impacts on interspecific mating from the invasive B. terrestris. We discuss the possibility that reproductive interference is a driving force in selection for multiple mating through an arms race between sympatric species.