bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of Prehospital Care for Patients With Limited English Proficiency Among Emergency Medical Technicians and Paramedics
Authors: Stadeli Kathryn M. , Sonett Dylan , Conrick Kelsey M. , Moore Megan , Riesenberg Matthew , Bulger Eileen M. , Meischke Hendrika , Vavilala Monica S.
Published: January 2023

Importance

Patients with limited English proficiency (LEP) experience disparities in prehospital care. On-scene interactions between patients with LEP and emergency medical services (EMS) providers (ie, firefighters/emergency medical technicians [EMTs] and paramedics) are critical to high-quality care and have been minimally explored.

Objective

To identify EMS-perceived barriers and facilitators to providing high-quality prehospital care for patients with LEP.

Design, Setting, and Participants

In this qualitative study, semi-structured focus groups were conducted with firefighters/EMTs and paramedics with all levels of experience from urban areas with a high proportion of residents with LEP from July to September 2018. Data were analyzed from July 2018 to May 2019.

Exposures

Providing prehospital care for patients with LEP.

Main Outcomes and Measures

The main outcomes were barriers and facilitators to prehospital care for patients with LEP, assessed using thematic analysis. Four domains of interest were examined: (1) overall impressions of interactions with patients with LEP, (2) barriers and facilitators to communication, (3) barriers and facilitators to providing care, and (4) ideas for improving prehospital care for patients with LEP.

Results

Thirty-nine EMS providers participated in 8 focus groups: 26 firefighters/EMTs (66%) and 13 paramedics (33%). The median age of participants was 46 years (range, 23-63 years), and 35 (90%) were male. Participants described barriers to optimal care as ineffective interpretation, cultural differences, high-stress scenarios (eg, violent events), unclear acuity of patient’s condition, provider bias, and distrust of EMS. Perceived facilitators to optimal care included using an on-scene interpreter, high-acuity disease, relying on objective clinical findings, building trust and rapport, and conservative decision-making regarding treatment and transport. Providers reported transporting most patients with LEP to hospitals regardless of illness severity due to concern for miscommunication and unrecognized problems. Better speed and technology for interpretation, education for communities and EMS providers, and community-EMS interactions outside emergencies were cited as potential strategies for improvement.

Conclusions and Relevance

In this study, EMS providers described many barriers to high-quality care during prehospital emergency response for patients with LEP yet were unaware that these barriers impacted quality of care. Barriers including ineffective interpretation, provider bias, distrust of EMS, and cultural differences may contribute to outcome disparities and overutilization of resources. Future work should focus on the development of targeted interventions to improve modifiable barriers to care, such as improving interpretation and cultural humility and increasing trust.
Analysis of genomic and immune intratumor heterogeneity in linitis plastica via multiregional exome and T‐cell receptor sequencing
Authors: Huang Jin , Zhao Guofeng , Peng Qiu , Yi Xin , Ji Liyan , Li Jing , Li Pansong , Guan Yanfang , Ge Jie , Chen Ling , Chen Runzhe , Hu Xin , Lee Won‐Chul , Reuben Alexandre , Futreal P. Andrew , Xia Xuefeng , Ma Jian , Zhang Jianjun , Chen Zihua
Published: January 2023

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole‐exome sequencing (WES) and T‐cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non‐silent mutations from multi‐samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi‐cancers. IHC using antibodies against CD4, CD8, and PD‐L1 demonstrated scant T‐cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T‐cell clones shared across tumor regions in any of the patients, while over 94% of T‐cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi‐regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T‐cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.
Radiation biology workforce in the United States
Authors: Williams Jacqueline P. , Anscher Mitchell S. , Vazquez Marcelo , Kronenberg Amy , Willey Jeffrey S. , Lawrence Theodore , Woloschak Gayle E. , Marples Brian , Wong Rosemary , Howell Roger W.
Published: January 2023

In recent decades, the principal goals of participants in the field of radiation biologists have included defining dose thresholds for cancer and non‐cancer endpoints to be used by regulators, clinicians and industry, as well as informing on best practice radiation utilization and protection applications. Importantly, much of this work has required an intimate relationship between “bench” radiation biology scientists and their target audiences (such as physicists, medical practitioners and epidemiologists) in order to ensure that the requisite gaps in knowledge are adequately addressed. However, despite the growing risk for public exposure to higher‐than‐background levels of radiation, e.g. from long‐distance travel, the increasing use of ionizing radiation during medical procedures, the threat from geopolitical instability, and so forth, there has been a dramatic decline in the number of qualified radiation biologists in the U.S. Contributing factors are thought to include the loss of applicable training programs, loss of jobs, and declining opportunities for advancement. This report was undertaken in order to begin addressing this situation since inaction may threaten the viability of radiation biology as a scientific discipline.
Risk of End‐Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study
Authors: Hansen Renata Baronaite , Falasinnu Titilola , Faurschou Mikkel , Jacobsen Søren , Simard Julia F.
Published: January 2023

Objective

The risk of end‐stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients.

Methods

By means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE–DM) and those without DM (SLE–non‐DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow‐up) strata. The overall hazard ratio (HR) was also adjusted for hypertension.

Results

The SLE–DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE–non‐DM group. SLE–DM patients had a 3 times higher risk of ESRD compared with SLE–non‐DM patients (multivariable‐adjusted HR 3.3 [95% confidence interval 1.8–6.1]). In stratified multivariable‐adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension.

Conclusion

Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM.
An Ultrafast, High‐Loading, and Durable Poly(p‐aminoazobenzene)/Reduced Graphene Oxide Composite Electrode for Supercapacitors
Authors: Ai Zhiting , Li Lu , Huang Muyun , Su Xiaofang , Gao Yanan , Wu Jifeng
Published: January 2023

Although challenging, the fabricated supercapacitor electrodes with excellent rate capability, long cycling stability, and high mass‐loading are crucial for practical applications. Herein, a novel 3D porous poly(p‐aminoazobenzene)/reduced graphene oxide hydrogel is designed and prepared as an ultrafast, high‐loading, and durable pseudocapacitive electrode through a facile two‐step self‐assembly approach. Owing to abundant stable redox‐active sites, fast electrolyte diffusion, and efficient charge conduction, the PRH electrode (5 mg cm−2) shows a high specific capacitance (701 F g−1 at 2 A g−1) and ultrafast rate (97% capacitance retention at 100 A g−1). Furthermore, even with a mass‐loading of 10 mg cm−2, the electrode still exhibits comparable high performance and excellent long‐term cycling life (only 6.7% capacitance loss after 10 000 cycles). This work demonstrates novel polyaniline analog composites for constructing novel electrodes, promising to open an avenue toward practical applications.
Small Changes, Big Impact: Tungsten Bronzes with Extremely Large Second Harmonic Generation Achieved by the Transition Metal Doping on the B‐Site
Authors: Pi Yejin , Kuk Yunseung , Ok Kang Min
Published: January 2023

Two novel transition metal‐doped tungsten bronze oxides, Pb2.15Li0.85Nb4.85Ti0.15O15 (PLNT) and Pb2.15Li0.55Nb4.85W0.15O15 (PLNW), are synthesized by high‐temperature solid‐state reactions. The Rietveld method using the high‐resolution synchrotron radiation indicates that PLNT and PLNW crystallize in the orthorhombic polar noncentrosymmetric space group, Pmn21 (no. 31). As a class of tungsten bronze oxide, PLNT and PLNW retain a unique rigid framework composed of d0 transition metal cation (Ti4+ or W6+)‐doped highly distorted NbO6 octahedra along with the subsequently generated Pb/LiO12 and PbO15 polyhedra. Interestingly, the d0 transition metal‐doped tungsten bronzes, PLNT and PLNW, exhibit extremely large second‐harmonic generation (SHG) responses of 56 and 67 × KH2PO4, respectively. The observed immeasurably strong SHG is mainly attributed to a net polarization originating from the alignment of highly distorted NbO6 octahedra with doped transition metals in the frameworks. It is believed that doping transition metal cations at the B‐site of the tungsten bronze structures should be an innovative strategy to develop novel high‐performance nonlinear optical materials.
Toward Electrocatalytic Methanol Oxidation Reaction: Longstanding Debates and Emerging Catalysts
Authors: Wang Jianmei , Zhang Bingxing , Guo Wei , Wang Lei , Chen Jian , Pan Hongge , Sun Wenping
Published: January 2023

The study of direct methanol fuel cells (DMFCs) has lasted around 70 years, since the first investigation in the early 1950s. Though enormous effort has been devoted in this field, it is still far from commercialization. The methanol oxidation reaction (MOR), as a semi‐reaction of DMFCs, is the bottleneck reaction that restricts the overall performance of DMFCs. To date, there has been intense debate on the complex six‐electron reaction, but barely any reviews have systematically discussed this topic. To this end, the controversies and progress regarding the electrocatalytic mechanisms, performance evaluations as well as the design science toward MOR electrocatalysts are summarized. This review also provides a comprehensive introduction on the recent development of emerging MOR electrocatalysts with a focus on the innovation of the alloy, core–shell structure, heterostructure, and single‐atom catalysts. Finally, perspectives on the future outlook toward study of the mechanisms and design of electrocatalysts are provided.
Controlled Distributed Ti3C2Tx Hollow Microspheres on Thermally Conductive Polyimide Composite Films for Excellent Electromagnetic Interference Shielding
Authors: Zhang Yali , Ruan Kunpeng , Zhou Kun , Gu Junwei
Published: January 2023

Flexible multifunctional polymer‐based electromagnetic interference (EMI) shielding composite films have important applications in the fields of 5G communication technology, wearable electronic devices, and artificial intelligence. Based on the design of a porous/multilayered structure and using polyimide (PI) as the matrix and polymethyl methacrylate (PMMA) microspheres as the template, flexible (Fe3O4/PI)–Ti3C2Tx–(Fe3O4/PI) composite films with controllable pore sizes and distribution of Ti3C2Tx hollow microspheres are successfully prepared by sacrificial template method. Owing to the porous/multilayered structure, when the pore size of the Ti3C2Tx hollow microspheres is 10 µm and the mass ratio of PMMA/Ti3C2Tx is 2:1, the (Fe3O4/PI)–Ti3C2Tx–(Fe3O4/PI) composite film has the most excellent EMI shielding performance, with EMI shielding effectiveness (EMI SE) of 85 dB. It is further verified by finite element simulation that the composite film has an excellent shielding effect on electromagnetic waves. In addition, the composite film has good thermal conductivity (thermal conductivity coefficient of 3.49 W (m·K)−1) and mechanical properties (tensile strength of 65.3 MPa). This flexible (Fe3O4/PI)–Ti3C2Tx–(Fe3O4/PI) composite film with excellent EMI shielding performance, thermal conductivity, and mechanical properties has demonstrated great potential for applications in EMI shielding protection for high‐power, portable, and wearable flexible electronic devices.
Humidity‐Resistant, Broad‐Range Pressure Sensors for Garment‐Integrated Health, Motion, and Grip Strength Monitoring in Natural Environments
Authors: Homayounfar S. Zohreh , Kiaghadi Ali , Ganesan Deepak , Andrew Trisha L.
Published: January 2023

Wearable electromechanical sensors are essential to improve health monitoring and off‐site point‐of‐care applications. However, their practicality is restricted by narrow ranges of detection, failure to simultaneously sense static and dynamic pressures, and low durability. Here, an all‐fabric pressure sensor with high sensitivity in a broad range of pressures, from subtle heart pulses to body posture, exceeding that of previously‐reported sensors is introduced. By taking advantage of chemical vapor deposition of p‐doped poly(3,4‐ethylenedioxythiophene) chloride (PEDOT‐Cl) on two natural textiles (cotton gauze and cotton balls), multiscale tunable pressure sensitivity with low power demand for data read‐out is obtained. To protect the sensor against humidity induced degradations, the sensor is encapsulated with a hydrophobic coating that leads to ultrastability of the sensor performance even after 1 week of exposure to 100% relative humidity and 20 laundry cycles. The sensor reveals excellent performance retention of >99% over 70 000 bending cycles under ambient conditions. The varied utility of this sensor for health monitoring is demonstrated by recording heartbeats, respiration, and joint movements. Furthermore, using this sensor, grip strength is successfully detected by 93.6% accuracy as compared to commercial dynamometer, speaking of its potential as the first fabric‐based sensor allowing for personalized real‐time grip strength analysis.
Photoinduced Synthesis of Bis‐Sulfonyl γ‐Arylated Ketones via DMAP/DDQ‐Mediated Stereogenic Conjugated Addition of α‐Sulfonyl Chalcones with Benzylic Sulfones
Authors: Hsueh Nai‐Chen , Chang Meng‐Yang
Published: January 2023

The DMAP/DDQ‐mediated stereochemical conjugated addition of sulfonyl chalcones and benzylic sulfones under photolytic irradiation produces diverse bis‐sulfonyl γ‐arylated ketones with three contiguous stereogenic centers in a yield of 79%–92%. Herein, a plausible mechanism is proposed and discussed.

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Full Field Model Describing Phase Front Propagation, Transformation Strains, Chemical Partitioning, and Diffusion in Solid–Solid Phase Transformations
Authors: Pohjonen Aarne
Published: January 2023

A novel mathematical formulation is presented for describing growth of phase in solid‐to‐solid phase transformations and it is applied for describing austenite to ferrite transformation. The formulation includes the effects of transformation eigenstrains, the local strains, as well as partitioning and diffusion. In the current approach the phase front is modeled as diffuse field, and its propagation is shown to be described by the advection equation, which reduces to the level‐set equation when the transformation proceeds only to the interface normal direction. The propagation is considered as thermally activated process in the same way as in chemical reaction kinetics. In addition, connection to the Allen–Cahn equation is made. Numerical tests are conducted to check the mathematical model validity and to compare the current approach to sharp interface partitioning and diffusion model. The model operation is tested in isotropic 2D plane strain condition for austenite to ferrite transformation, where the transformation produces isotropic expansion, and also for austenite to bainite transformation, where the transformation causes invariant plane strain condition. Growth into surrounding isotropic austenite, as well as growth of the phase which has nucleated on a grain boundary are tested for both ferrite and bainite formation.
A Comprehensive Analysis of Eco‐Friendly Cs2SnI6 Based Tin Halide Perovskite Solar Cell through Device Modeling
Authors: Pal Debashish
Published: January 2023

The choice of appropriate materials is of paramount importance in realizing a high efficiency perovskite solar cell. Lead free eco‐friendly perovskite solar cell architecture is theoretically investigated using solar cell capacitance simulator (SCAPS) for device performance. Preliminary investigations on Cs2SnI6 solar cell architectures have indicated that the presence of hole transport layer is crucial in achieving an open‐circuit voltage greater than 0.6 V. The presence of a valence band offset between the Cs2SnI6 absorber and hole transport layer has a significant detrimental impact on the short‐circuit current density and fill factor of the cell. A novel device architecture employing TiO2 as an electron transport material and Cu2O as a hole transport material is proposed to overcome the limitations associated with the current designs. Theoretical investigations are carried out employing 1D SCAPS simulation program in order to optimize the structure by varying the perovskite thickness, bandgap, and defect concentration. The proposed solar cell after optimization has a practically realizable power conversion efficiency of 17.77%.
Spontaneously Right‐Side‐Out‐Orientated Coupling‐Driven ROS‐Sensitive Nanoparticles on Cell Membrane Inner Leaflet for Efficient Renovation in Vascular Endothelial Injury
Authors: Qin Xian , Zhu Li , Zhong Yuan , Wang Yi , Wu Guicheng , Qiu Juhui , Wang Guixue , Qu Kai , Zhang Kun , Wu Wei
Published: January 2023

Biomimetic cell membrane camouflaged technology has drawn extensive attention as a feasible and efficient way to realize the biological functions of nanoparticles from the parent cells. As the burgeoning nanotherapeutic, the right‐side‐out orientation self‐assembly and pathological dependent “on‐demand” cargo release of cell membrane camouflaged nanocarriers remarkably limit further development for practical applications. In the present study, a spontaneously right‐side‐out‐orientated coupling‐driven ROS‐sensitive nanotherapeutic has been constructed for target endothelial cells (ECs) repair through the synergistic effects of spontaneously right‐side‐out‐orientated camouflaging. This condition results from the specific affinity between the intracellular domain of key transmembrane receptors band 3 on cell membrane inner leaflet and the corresponding P4.2 peptide‐modified nanoparticles without the additional coextrusion. The “on‐demand” cargo release results from the pathological ROS‐cleavable prodrug. Particularly, the red blood cell camouflaged nanotherapeutics (RBC‐LVTNPs) can enhance target drug delivery through low oscillatory shear stress (LSS) blood flow in the injured ECs lesion. Both in vitro and in vivo results collectively confirm that RBC‐LVTNPs can restore the damaged ECs and function with the recovered vascular permeability and low inflammation microenvironment. The findings provide a powerful and universal approach for developing the biomimetic cell membrane camouflaged nanotechnology.
Brachistochrone Bowl‐Inspired Hybrid Nanogenerator Integrated with Physio‐Electrochemical Multisensors for Self‐Sustainable Smart Pool Monitoring Systems
Authors: Maharjan Pukar , Bhatta Trilochan , Hui Xue , Pradhan Gagan Bahadur , Song Hyesu , Shrestha Kumar , Park Jae Yeong
Published: January 2023

Maintaining clean and fresh pool water requires regular monitoring and treatment. However, the employed methods are manual, complex, and time‐consuming. Herein, a self‐sustainable autonomous smart pool monitoring system (SPMS) that can monitor various physio‐electrochemical properties of the pool water in real‐time without requiring external power is proposed. SPMS includes an electromagnetic generator inspired by the novel brachistochrone bowl which harvests energy from random motion (peak power 72 mW at 4 Hz and 0.5 g) and supplies the wireless transmission unit and the highly sensitive multifunctional sensor unit (MSU) including pH (−60.71 mV pH−1), temperature (2.5 Ω °C−1), chloride (0.355 mV ppm−1; <250 ppm), conductivity (3.25 × 10−5 µS ppm−1), and wave motion (1.27 V Hz−1). The fabricated MSU has adequate sensitivity and accuracy to detect minor variations in the water quality for indoor and outdoor environments. Finally, the smart pool monitoring application of the SPMS is demonstrated in real‐time by acquiring the sensor data and wirelessly transmitting it to the custom‐developed mobile application utilizing harvested energy. Combining energy harvesting and water quality sensing, the free‐floating completely isolated SPMS device demonstrates a portable, freestanding, wireless, autonomous, and self‐powered pool monitoring system for maintaining a hygienic and safe swimming environment.
Occupational exposure to respirable crystalline silica among US metal and nonmetal miners, 2000–2019
Authors: Misra Shilpi , Sussell Aaron L. , Wilson Samantha E. , Poplin Gerald S.
Published: January 2023

Background

In metal and nonmetal (M/NM) mines in the United States, respirable crystalline silica (RCS) exposures are a recognized health hazard and a leading indicator of respiratory disease. This study describes hazardous exposures that exceed occupational exposure limits and examines patterns of hazardous RCS exposure over time among M/NM miners to better inform the need for interventions.

Methods

Data for this study were obtained from the Mine Safety and Health Administration (MSHA) Open Government Initiative Portal for the years 2000–2019, examining respirable dust samples with MSHA‐measured quartz concentration >1%. Descriptive statistics for RCS were analyzed for M/NM miners by year, mine type, sector, commodity, occupation, and location in a mine.

Results

This study found the overall geometric mean (GM) for personal exposures to RCS was 28.9 μg/m3 (geometric standard deviation: 2.5). Exposures varied significantly by year, mine type, sector, commodity, occupation, and location in a mine. Overall, the percentages of exposures above the MSHA permissible exposure limit (PEL for respirable dust with >1% quartz, approximately 100 μg/m3 RCS) and the National Institute for Occupational Safety and Health RCS recommended exposure limit (REL, 50 μg/m3) were 11.8% and 27.3%, respectively. GM exposures to RCS in 2018 (45.9 μg/m3) and 2019 (52.9 μg/m3) were significantly higher than the GM for all years prior. The overall 95th percentile of RCS exposures from 2000 to 2019 was 148.9 μg/m3, suggesting a substantial risk of hazardous exposures above the PEL and REL during the entire period analyzed.

Conclusions

The prevalence of high exposures to RCS among M/NM miners continues in the past 20 years and may be increasing in certain settings and occupations. Further research and intervention of the highest exposures are needed to minimize the risks of acquiring silica‐induced respiratory diseases.
Refractive index as a process analytical technology to measure real time protein concentration for monitoring and control of commercial scale tangential flow filtration operations
Authors: Lam Yik , McCann Devin , Loman Abdullah , Smelko John Paul , Brinkmann Alex
Published: January 2023

Biological therapeutics are increasingly being formulated to high protein concentrations to decrease drug substance storage space and increase the flexibility of administration to patients. With the higher protein concentration targets comes added challenges to the downstream purification manufacturing process. Tangential flow filtration (TFF) operations are typically performed to reach target protein concentration. TFF operations for a given drug substance may include an Ultrafiltration and Diafiltration (UFDF) step, or a UFDF step followed by a single pass tangential flow filtration (SPTFF) step. Whether a TFF step achieves a target protein concentration is determined by at‐line protein concentration measurements performed at the completion of a process step. If the measured protein concentration is outside the specified range, the unit operation may need to be restarted, reprocessing may need to be performed, or a batch may need to be terminated. Out of specification protein concentration measurements may be a result of the TFF operation or sample measurement. Increased viscosities associated with high concentration TFF operations pose added challenges to the TFF process and sample measurement. Implementation of an inline process analytical technology (PAT) to monitor real‐time protein concentration during TFF operations has the potential to improve the accuracy of the operations in achieving target protein concentrations. This will result in improved process consistency and efficiency, increased operator confidence and decreased likelihood of batch failures. This paper studies the performance of a K‐Patents PR‐23 refractometer (Vaisala) as a PAT to monitor and control the UFDF and SPTFF unit operations of a commercial scale monoclonal antibody purification process.
Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
Authors: De Kort Anna M. , Kuiperij H. Bea , Marques Tainá M. , Jäkel Lieke , van den Berg Emma , Kersten Iris , van Berckel‐Smit Hugo E. P. , Duering Marco , Stoops Erik , Abdo Wilson F. , Rasing Ingeborg , Voigt Sabine , Koemans Emma A. , Kaushik Kanishk , Warren Andrew Davock , Greenberg Steven M. , Brinkmalm Gunnar , Terwindt Gisela M. , Wermer Marieke J. H. , Schreuder Floris H. B. M. , Klijn Catharina J. M. , Verbeek Marcel M.
Published: January 2023

Objective

Vascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch‐type CAA (D‐CAA), and Alzheimer disease (AD).

Methods

Aβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D‐CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).

Results

We found decreased levels of all Aβ peptides in sCAA patients and D‐CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82–0.99; for validation: 0.94, 95% CI = 0.89–0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88–1.00; for validation: 0.91, 95% CI = 0.83–1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71–0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80–0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66–0.92).

Interpretation

A combined biomarker panel of CSF Aβ38, Aβ40, Aβ42, and Aβ43 has potential to differentiate sCAA from AD and controls, and D‐CAA from controls. ANN NEUROL 2023;93:1173–1186
Stereospecific Oxycyanation of Alkenes with Sulfonyl Cyanide
Authors: Kiyokawa Kensuke , Ishizuka Miu , Minakata Satoshi
Published: January 2023

Oxycyanation of alkenes would allow the direct construction of useful β‐hydroxy nitrile scaffolds. However, only limited examples of such reactions have been reported, and some problems including limited substrate scope and the lack of diastereocontrol in the case of the oxycyanation of internal alkenes have arisen. We herein report on the intermolecular oxycyanation of alkenes using p‐toluenesulfonyl cyanide (TsCN) in the presence of tris(pentafluorophenyl)borane (B(C6F5)3) as a catalyst, affording products that contain a sulfinyloxy group and a cyano group at the vicinal position. The reaction features a stereospecific syn‐addition. The reaction also shows a broad substrate scope with good functional group tolerance. Mechanistic investigations by experimental studies and density functional theory (DFT) calculations revealed that the reaction proceeds via an unprecedented stereospecific mechanism through the electrophilic cyanation of alkenes, in which B(C6F5)3 efficiently activates TsCN through the coordination of the cyano group to the boron center.
Fluctuation of Anti–Domain 1 and Anti–β2‐Glycoprotein I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies
Authors: Chighizola Cecilia B. , Pregnolato Francesca , Andrade Danieli , Tektonidou Maria , Pengo Vittorio , Ruiz‐Irastorza Guillermo , Belmont H. Michael , Gerosa Maria , Fortin Paul , Branch D. Ware , Andreoli Laura , Petri Michelle A. , Cervera Ricard , Knight Jason S. , Willis Rohan , Efthymiou Maria , Cohen Hannah , Erkan Doruk , Bertolaccini Maria Laura ,   Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION)
Published: January 2023

Objective

The present study was undertaken to longitudinally evaluate titers of antibodies against β2‐glycoprotein I (anti‐β2GPI) and domain 1 (anti‐D1), to identify predictors of variations in anti‐β2GPI and anti‐D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry.

Methods

Patients with available blood samples from at least 4 time points (at baseline [year 1] and at years 2–4 of follow‐up) were included. Detection of anti‐β2GPI and anti‐D1 IgG antibodies was performed using chemiluminescence (BIO‐FLASH; INOVA Diagnostics).

Results

Among 230 patients in the study cohort, anti‐D1 and anti‐β2GPI titers decreased significantly over time (P < 0.0001 and P = 0.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti‐D1 and anti‐β2GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3‐fold and 1.4‐fold decreases in anti‐D1 and anti‐β2GPI titers, respectively. Incident vascular events were associated with 1.9‐fold and 2.1‐fold increases in anti‐D1 and anti‐β2GPI titers, respectively. Anti‐D1 and anti‐β2GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6‐fold decrease in anti‐D1 titers and a 2‐fold decrease in anti‐β2GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval [95% CI] 0.62–59.3) and 9.4 (95% CI 1.1–80.2), respectively.

Conclusion

Treatment with HCQ and incident vascular events in aPL‐positive patients predicted significant anti‐D1 and anti‐β2GPI titer fluctuations over time. Both anti‐D1 and anti‐β2GPI titers decreased around the time of thrombosis, with potential clinical relevance.
Povetacicept, an Enhanced DualAPRIL/BAFFAntagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell–Related Autoimmune Diseases
Authors: Evans Lawrence S. , Lewis Katherine E. , DeMonte Daniel , Bhandari Janhavi G. , Garrett Logan B. , Kuijper Joseph L. , Ardourel Daniel , Wolfson Martin F. , Debrot Susan , Mudri Sherri , Kleist Kayla , Griffin Luana L. , Hebb LuAnne , Sanderson Russell J. , Wang NingXin , Seaberg Michelle , Chunyk Allison G. , Yang Jing , Hong Youji , Maria Zahra , Messenheimer David J. , Holland Pamela M. , Peng Stanford L. , Rixon Mark W. , Dillon Stacey R.
Published: January 2023

Objective

Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high‐affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.

Methods

A variant of TACI‐Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN‐303). Povetacicept was compared to wild‐type (WT) TACI‐Fc and related molecules in vitro and in vivo.

Results

Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI‐Fc and selective APRIL and BAFF inhibitors in cell‐based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody‐secreting cells more effectively than anti‐CD20 monoclonal antibodies, WT TACI‐Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti–double‐stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non‐human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose.

Conclusion

Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI‐Fc and CD20‐, APRIL‐, or BAFF‐selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody‐related autoimmune diseases.

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Digitaler Zwilling Brücke im Betrieb – Mögliche Anwendungsfälle
Authors: Nieborowski Sonja , Windmann Sarah , Bednorz Jennifer , Hindersmann Iris , Zinke Tim
Published: January 2023

Der Digitale Zwilling Brücke leistet einen wichtigen Beitrag auf dem Weg zum prädiktiven Lebenszyklusmanagement. In der Lebenszyklusphase „Betrieb“ kann der Digitale Zwilling Brücke als effizientes Werkzeug in Bezug auf Analysieren, Vorhersagen, Steuern und Überwachen dienen. Ziel ist eine optimierte Erhaltung, deren Bedeutung angesichts der aktuellen Herausforderungen für Ingenieurbauwerke weiter steigt. Relevante Stakeholder mit ihren Bedarfen und Anforderungen müssen frühzeitig in die Konzeption des Digitalen Zwillings Brücke eingebunden werden. Dieser Weg wird durch die Bundesanstalt für Straßenwesen (BASt) in vielfältigen Forschungsprojekten verfolgt und auch in einem laufenden Projekt zur Entwicklung einer Gesamtkonzeption des Digitalen Zwillings Brücke fortgeführt. Mögliche Anwendungsfälle wurden gesammelt und den Themenbereichen „Betriebsprozesse“, „Erhaltungsplanung und ‐durchführung“ sowie „Strategisches Lebenszyklusmanagement“ zugeordnet. Im Rahmen eines Workshops dienten die Anwendungsfälle der Diskussion und zur initialen Priorisierung mit Stakeholdern. Die Ergebnisse bilden eine wichtige Grundlage für die Ausarbeitung des modularen Gesamtkonzepts Digitaler Zwilling Brücke und den Weg in die Praxis.
Ermittlung thermischer Untergrundeigenschaften zur Optimierung der Kabeldimensionierung
Authors: Roller Fabian , Kleiber Stephanie , Drefke Christoph , Stegner Johannes , Meier Claas
Published: January 2023

Die Dimensionierung von Höchstspannungs‐Gleichstrom‐Übertragungsleitungen (HGÜ) basiert auf detaillierten Kenntnissen des Baugrunds im Hinblick auf die Wärmeleitfähigkeit. Aufgrund dessen wurde für die Realisierung der Windstromleitung SuedLink mit einer Trassenlänge von ca. 700 km ein Messprogramm entwickelt, das eine sehr große Anzahl an reproduzierbaren Wärmeleitfähigkeitsuntersuchungen ermöglicht. Mithilfe eines hocheffizienten Versuchsstands können damit vom gesättigten bis zum ofentrockenen Zustand einer Bodenprobe die korrespondierenden Wärmeleitfähigkeitswerte ermittelt werden. Die Auswertung der Wärmeleitfähigkeits‐Wassergehalts‐Beziehung wurde maßgeblich weiterentwickelt, wobei die Steinanteile des Bodens und die Grundwasserverhältnisse Berücksichtigung finden. Die daraus gewonnenen Erkenntnisse fließen in die Planung der Kabeldimensionierung zur Optimierung von Kabelachsabständen ein und tragen somit zur Minimierung der Projektkosten und der Eingriffe in die Natur bei. Darüber hinaus dienen die zahlreichen Messergebnisse der Erweiterung bestehender Datenbanken für Wärmeleitfähigkeitswerte, um für zukünftige Erdkabelprojekte über sog. Pedotransferfunktionen die Anzahl der benötigten Messungen zu verringern.
Metabolic engineering of betacyanin in vegetables for anti‐inflammatory therapy
Authors: Saito Shiori , Nishihara Masahiro , Kohakura Masato , Kimura Kosuke , Yashiro Takuya , Takasawa Seidai , Arimura Gen‐ichiro
Published: January 2023

Betalains, which consist of the subgroups betaxanthins and betacyanins, are hydrophilic pigments that have classically been used for food colorants. Owing to their strong antioxidant property, their usefulness for application for therapeutic use is also expected. In addition, as betalains are mainly naturally available from plants of the order Caryophyllales, including beet (Beta vulgaris), metabolic engineering for betalain production in crops such as vegetables, fruits and cereals may provide new food resources useful for healthcare. Here we conducted metabolic engineering of betacyanins in tomato fruits and potato tubers. The transgenic tomato fruits and potato tubers with coexpression of betacyanin biosynthesis genes, CYP76AD1 from B. vulgaris, DOD (DOPA 4,5‐dioxygenase) and 5GT (cyclo‐DOPA 5‐O‐glucosyltransferase) from Mirabilis jalapa, under control of suitable specific promoters, possessed dark red tissues with enriched accumulation of betacyanins (betanin and isobetanin). The anti‐inflammatory activity of transgenic tomato fruit extract was superior to that of wild‐type fruit extract on macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS), as a result of decreased LPS‐stimulated transcript levels of proinflammatory genes. These findings were in accord with the observation that administration of the transgenic tomato fruits ameliorated dextran sulfate sodium (DSS)‐induced colitis as well as body weight loss and disease activity index in mice, via suppression of DSS‐stimulated transcript levels of pro‐inflammatory genes, including Tnf (encoding TNF‐alpha), Il6, and Ptgs2 (encoding cyclooxygenae 2). Intriguingly, given the fact that the transgenic potato tuber extract failed to enrich the anti‐inflammatory activity of macrophage cells, it is likely that metabolic engineering of betacyanins will be a powerful way of increasing the anti‐inflammatory property of ordinary foods such as tomato.
Functional near‐infrared spectroscopy measures of neural activity in children with and without developmental language disorder during a working memory task
Authors: Hancock Allison S. , Warren Christopher M. , Barrett Tyson S. , Bolton David A. E. , Gillam Ronald B.
Published: January 2023

Introduction

Children with developmental language disorder (DLD) exhibit cognitive deficits that interfere with their ability to learn language. Little is known about the functional neuroanatomical differences between children developing typically (TD) and children with DLD.

Methods

Using functional near‐infrared spectroscopy, we recorded oxygenated hemoglobin (O2hb) concentration values associated with neural activity in children with and without DLD during an auditory N‐back task that included 0‐back, 1‐back, and 2‐back conditions. Analyses focused on the left dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL). Multilevel models were constructed with accuracy, response time, and O2hb as outcome measures, with 0‐back outcomes as fixed effects to control for sustained attention.

Results

Children with DLD were significantly less accurate than their TD peers at both the 1‐back and 2‐back tasks, and they demonstrated slower response times during 2‐back. In addition, children in the TD group demonstrated significantly greater sensitivity to increased task difficulty, showing increased O2hb to the IPL during 1‐back and to the DLPFC during the 2‐back, whereas the DLD group did not. A secondary analysis revealed that higher O2hb in the DLPFC predicted better task accuracy across groups.

Conclusion

When task difficulty increased, children with DLD failed to recruit the DLPFC for monitoring information and the IPL for processing information. Reduced memory capacity and reduced engagement likely contribute to the language learning difficulties of children with DLD.
Strategic outcome of competitive advantage from corporate sustainability practices: Institutional theory perspective from an emerging economy
Authors: Bhuiyan Faruk , Rana Tarek , Baird Kevin , Munir Rahat
Published: January 2023

This study examined the use and effectiveness of corporate sustainability practices (CSP) and the subsequent effect on a strategic outcome, competitive advantage. The new institutional sociology (NIS) theoretical framework was applied, informed by three different dimensions of institutional pressures (coercive, mimetic and normative). The study used a survey method and developed a seven‐dimensional model utilising the 52 principles provided by the OECD. It used a structural equation modelling in order to test the hypothesised associations between institutional pressures, CSP and competitive advantage to provide an institutional and contextualised perspectives from an emerging economy setting. The study found significant associations between the three types of institutional pressure with specific dimensions of CSP. The findings further revealed that specific CSP dimensions are diversely (positively and negatively) associated with competitive advantage. In line with the tenets of greenwashing, it highlighted the important role of institutional pressures from stakeholders (government, policy and customers) in implementing specific CSP. The findings inform managers, governments, foreign investors and other stakeholders in emerging economies about the influence of the institutional pressure in promoting the use of CSP and the effect of such practices on competitive advantage. From the context of an emerging economy, the study provides a unique empirical insight into the NIS perspective in promoting CSP and the subsequent impact on the strategic outcome, competitive advantage.
Modified one‐stage technique of laterally positioned flap with subepithelial connective tissue graft for the treatment of peri‐implant soft tissue dehiscence in the esthetic zone: A 5‐year follow‐up
Authors: de Almeida Juliano Milanezi , de Sá Daniela Pereira , Furquim Elisa Mara de Abreu , Matheus Henrique Rinaldi
Published: January 2023

Background

The state of art of tissue grafting allows significant improvements in the soft tissue phenotype. The importance of appropriate soft tissue phenotype around implants is supported by recent literature. The present case report aims to describe the application of a modified one‐stage technique of laterally positioned flap with subepithelial connective tissue graft (CTG) for the treatment of peri‐implant soft tissue dehiscence in the esthetic zone.

Methods and Results

A 38‐year‐old female presented 4 years following prosthetic restoration, with a localized soft tissue defect in height and thickness at the buccal aspect of the implant at #11, and the abutment exposed to the oral cavity. Incisions with internal and external bevels were performed in the medial and distal margins of the dehiscence, respectively, toward the alveolar mucosa. After intrasulcular incision, the area was de‐epithelialized and a split thickness flap from mesial #11 to distal #14 was elevated. A tunnel was prepared at #21. CTG was stabilized mesially, within the tunnel prepared, and distally, through simple interrupted sutures. Vertical compressive sutures were performed on the CTG. The flap was laterally positioned and secured by means of suspended sutures. Healing was uneventful, increased thickness and height of the peri‐implant mucosa were observed, with great esthetic outcome. The soft tissue margin was stable at the 5‐year follow‐up.

Conclusion

The technique described in this case report showed promising results for covering exposed implant abutment in the esthetic zone, as well as for modification of the soft tissue phenotype around dental implants.

Key points

Why is this case new information

A modified one‐stage technique that allows coverage of exposed metallic displays of titanium implants while modifying the soft tissue phenotype in the esthetic zone.

What are the keys to successful management of this case?

Meticulous incisions and internal and external bevels. Adequate elevation to allow repositioning without tension.

Adequate graft size that extends through all the recipient bed; and tension‐free suture.

What are the primary limitations to success in this case?

Presence of an implant installed in a non‐satisfactory three‐dimensional position.

And poor hygiene and plaque accumulation postoperatively.