bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage
Authors: Sandy Jessica L. , Perez Darazel , Goh Shuxiang , Forsey Jonathan , Rajagopalan Sulekha , Trivedi Amit , Munns Craig F.
Published: October 2022

Bruck syndrome is a rare collagen disorder with autosomal recessive inheritance caused by pathogenic variants in either FKBP10 or PLOD2 genes. It is characterized by bone fragility and fractures similar in severity and variability to osteogenesis‐imperfecta as well as congenital joint contractures. This article describes an infant with a homozygous (partial) gene deletion of PLOD2 that includes the start codon and would be expected to lead to nonfunctional protein product. The infant had a severe phenotype of Bruck syndrome and is the only reported case of Bruck syndrome with congenital cardiac disease (triscuspid valve dysplasia with severe regurgitation, mitral valve prolapses with moderate regurgitation, and pulmonary hypertension) and pulmonary hemorrhage. We hypothesize that the additional feature of congenital cardiac disease in this case was due to the underlying defect in type I collagen, and that the pulmonary hemorrhage was multifactorial, with underlying vessel fragility, rib fractures, and high pulmonary pressures likely to be major contributing factors. Management was largely supportive with the use of bisphosphonates to assist in pain management. Care was complicated by comorbid cardiopulmonary compromise, limited evidence‐base guiding care, and difficulties in discussing end‐of‐life care.
One‐Shot Synthesis of B/N‐Doped Calix[4]arene Exhibiting Narrowband Multiple Resonance Fluorescence
Authors: Fan Tianjiao , Zhang Yuewei , Wang Lu , Wang Qian , Yin Chen , Du Mingxu , Jia Xiaoqin , Li Guomeng , Duan Lian
Published: October 2022

A novel macrocycle of B/N‐doped calix[4]arene (C‐BN) was synthesized by a one‐shot double boronation. Owing to the structural tension and electron‐donating properties of the nitrogen atoms in the macrocycle, reaction selectively proceeds between the adjacent benzene rings outside the macrocycle. C‐BN shows a highly centrosymmetric structure with two multiple resonance (MR) fragments bridged by tertiary amine groups at the 1,3 positions of the benzene ring. Benefiting from the large intermolecular distance (>4.6 Å) between adjacent MR‐emitting cores, C‐BN also exhibits excellent narrowband emitting features against aggregation‐induced quenching and spectrum broadening. Optimized organic light‐emitting diode devices based on C‐BN exhibit high maximum external quantum efficiencies of 24.7–26.6 % and small full width at half maximums of 25–28 nm over a wide doping range of 1–12 wt %.
Low‐temperature performance optimization of LiFePO4‐based batteries
Authors: Ma Chunxiang , Wang Xiaoning , Song Yijun , Hu Haoyu , Li Wei , Qiu Zhijian , Cui Yongpeng , Xing Wei
Published: October 2022

LiFePO4 is one of the most widely used cathode materials for lithium‐ion batteries, and the low‐temperature performance of LiFePO4‐based batteries has been widely studied in recent years. Herein, a 3.5 Ah pouch‐type full battery was assembled using LiFePO4 as the cathode and artificial graphite as the anode. For the LiFePO4‐based cathode, carbon‐coated aluminum foil was selected as the current collector, and a 0D–1D–2D multi‐scale conductive network was introduced into the electrode. Notably, both the carbon‐coated current collector and novel conductive network could significantly reduce the internal resistance of the LiFePO4‐based battery, thus improving its electrochemical dynamics and low‐temperature performance. This paper provides a theoretical basis for the development of low‐temperature LiFePO4‐based batteries.
Edible hydrogel from gelatin and alginate as functional low‐calorie noodle
Authors: Wang Lini , Zhang Hui Jie , Wang Xinyi , Zhao Wenying , Yan Weihua , Zhang Fangjian , Li Yanjun , You Xiangyu
Published: October 2022

There is an urgent need to develop edible hydrogels that can be served as a main dish with low‐calorie content and high satiety value, yet are easy to digest. However, the development of such hydrogels remains challenging. In this study, low‐calorie edible hydrogels were prepared from gelatin and sodium alginate (gel/SA hydrogels) through a facile acid soaking‐drying method. These gel/SA hydrogels exhibited excellent mechanical properties with texture characteristics similar to that of Liangpi. The sensitivity of gelatin and acidified sodium alginate to pH resulted in a high swelling ratio of the hydrogels, contributing to weight retention in a simulated stomach environment and rapid degradation in a simulated intestinal environment. These properties indicate that these gel/SA hydrogels have a good prospect of being used as low‐calorie food with high satiety value and are easy to digest. Konjac glucomannan can also be incorporated into the gel/SA hydrogels to further improve their biological functionality.
Organics‐MXene Composites as Electrode Materials for Energy Storage
Authors: Tang Mi , Sun Hao , Su Lun , Gao Yijun , Chen Fu , Wang Zhengbang , Wang Chengliang
Published: October 2022

Two‐dimensional (2D) transition metal carbides and/or nitrides (MXene) have emerged as a family of multifunctional materials due to the high electrical conductivity, good stability, abundant and tunable surface functional groups, showing competitive applications in energy storage and conversion. The surface functional groups and their Zeta negative potential properties facilitate the assembly of positively charged organic compounds between the MXene nanosheets to form a stable hybrid, which endow the MXene‐based composite materials better electrochemical performance compared to the individual component. As such, this review exclusively highlights the development of organics/MXene‐based composites and summarizes the various strategies for assembling or fabricating organics/MXene‐based hybrid composites. Applications of these organics/MXene‐based electrode materials in supercapacitors and batteries are also discussed in brief along with analysis of their excellent electrochemical performances and the charge storage mechanisms. Finally, some remaining challenging issues and future opportunities of organics/MXene composites as electrode materials for the high‐power and low‐cost rechargeable batteries or supercapacitors are also discussed.
Enhancing long‐term storage and stability of engineered living materials through desiccant storage and trehalose treatment
Authors: Brooks Sierra M. , Reed Kevin B. , Yuan Shuo‐Fu , Altin‐Yavuzarslan Gokce , Shafranek Ryan , Nelson Alshakim , Alper Hal S.
Published: October 2022

Engineered living materials (ELMs) have broad applications for enabling on‐demand bioproduction of compounds ranging from small molecules to large proteins. However, most formulations and reports lack the capacity for storage beyond a few months. In this study, we develop an optimized procedure to maximize stress resilience of yeast‐laden ELMs through the use of desiccant storage and 10% trehalose incubation before lyophilization. This approach led to over 1‐year room temperature storage stability across a range of strain genotypes. In particular, we highlight the superiority of exogenously added trehalose over endogenous, engineered production in yielding robust preservation resilience that is independent of cell state. This simple, effective protocol enables sufficient accumulation of intracellular trehalose over a short period of contact time across a range of strain backgrounds without requiring the overexpression of a trehalose importer. A variety of microscopic analysis including µ‐CT and confocal microscopy indicate that cells form spherical colonies within F127‐BUM ELMs that have variable viability upon storage. The robustness of the overall procedure developed here highlights the potential for widespread deployment to enable on‐demand, cold‐chain independent bioproduction.
Multi‐level natural capital implementation within planetary boundaries
Authors: Small Angela Naomi , Paavola Jouni , Owen Alice
Published: October 2022

In this conceptual paper, we examine current theories of natural capital approach implementation and identify areas where further research is needed to help humanity live within planetary boundaries. Natural capital and ecosystem service approaches offer an advanced understanding of Earth's life‐support systems and their interaction with human well‐being at multiple scales, particularly organizations. The insights they offer are present in conservation and accounting literature but are not yet reflected in corporate environmental sustainability literature, a gap this paper seeks to bridge. Without considering scale, it is difficult to understand how micro (individual) and meso (organizational or national) actions contribute to global goals (planetary boundaries). We suggest a multi‐level natural capital implementation framework for corporate environmental sustainability and explain how it can advance natural capital implementation by including scoping and monitoring phases and increasing awareness of natural resource dependencies and how it advances multi‐level environmental management theory.
Tumor immune microenvironment in therapy‐naive esophageal adenocarcinoma could predict the nodal status
Authors: Kotsafti Andromachi , Fassan Matteo , Cavallin Francesco , Angerilli Valentina , Saadeh Luca , Cagol Matteo , Alfieri Rita , Pilati Pierluigi , Castoro Carlo , Castagliuolo Ignazio , Scarpa Melania , Scarpa Marco
Published: October 2022

Background

Currently, preoperative staging of esophageal adenocarcinoma (EAC) has modest reliability and accuracy for pT and pN stages prediction, which heavily affects overall survival. The interplay among immune checkpoints, oncogenes, and intratumoral and peritumoral immune infiltrating cells could be used to predict loco‐regional metastatic disease in early EAC.

Methods

We prospectively evaluated immune markers expression and oncogenes status as well as intratumoral and peritumoral immune infiltrating cells populations in esophageal mucosa samples obtained from neoadjuvant therapy‐naïve patients who had esophagectomy for EAC.

Results

Vascular invasion and high infiltration of lamina propria mononuclear cells resulted associated with nodal metastasis. Low infiltration of activated CD8+CD28+ T cells was observed in both intratumoral and peritumoral mucosa of patients with nodal metastasis. Low levels of CD69, MYD88, and TLR4 transcripts were detected in the intratumoral specimen of patients with lymph node involvement. Receiver operating characteristic curve analysis showed good accuracy for detecting nodal metastasis for all the markers tested. Significant lower infiltration of CD8 T cells and M1 macrophages and a lower expression of CD8A, CD8B, and TBX21 were found also in Esophageal Adenocarcinoma TCGA panCancer Atlas in the normal tissue of patients with nodal metastasis.

Conclusions

Our data suggest that immune surveillance failure is the main driver of nodal metastasis onset. Moreover, nodal metastasis containment also involves the immune microenvironment of the peritumoral healthy tissue.
Bone construction surgery: A case report using recombinant human platelet‐derived growth factor‐BB
Authors: Mandelaris George A. , DeGroot Bradley
Published: October 2022

Background

The position and condition of bone largely sets the stage for functional and esthetic implant success. In bone construction surgery, creating a sustainable functional matrix is complex, but necessary, to enable long‐term mechanotransduction and maintenance of soft tissue support.

Methods

A patient with a severe peri‐implantitis ridge defect in the anterior maxilla underwent bone construction surgery simultaneous with implant removal using a composite bone graft (mineralized freeze dried bone allograft + xenograft) enhanced with recombinant human platelet‐derived growth factor (rhPDGF‐BB). Space maintenance for bone construct immobility and unimpeded wound healing was ensured via a nonresorbable titanium reinforced polytetrafluoroethylene membrane and an absorbable porcine collagen membrane.

Results

Primary closure was maintained throughout the 6 month healing process at which time implant diagnostics commenced for prosthetically directed implant placement using dynamic navigation and involving soft tissue augmentation. Uncovery was performed 3 months thereafter leading to provisionalization and prosthetic phase completion.

Conclusion

This case report highlights a severe maxillary anterior ridge defect secondary to advanced peri‐implantitis in a systemically healthy Caucasian male patient. The surgical outcome success, both clinically and radiographically, underscores the complexities of complete regional anatomy rehabilitation after suffering catastrophic and debilitating bone loss from inflammatory peri‐implantitis. Further, it demonstrates the importance of incorporating optimized angiogenetic therapeutics to help establish a vascularized functional bone matrix for implant success.
The treatment of multiple gingival recession defects with connective tissue grafting and enamel matrix derivative in a private practice setting: Two case reports
Authors: Scheyer E. Todd , Gomes Patricia , Rossi Andrew
Published: October 2022

Background

Dentofacial esthetics has become a mainstay treatment in periodontics. For a periodontal private practice to succeed in a referral‐based environment, predictability and stability in treatment results are crucial. The scientific literature provides a guide to successfully treating multiple recession defects with non‐carious cervical lesions and lingual recession. These case reports show how the use of biologic mediators, proper case selection, and proper surgical technique may provide a better treatment outcome for our patients.

Methods

Two patients with multiple gingival recession defects were treated with autogenous tissue grafting in conjunction with the application of enamel matrix derivative (EMD) to attempt root coverage. Based on the Cairo classification, the recession defects were classified as type I in the maxillary buccal and lingual recession in the mandibular anterior. There were areas of no attached gingiva, loss of enamel, and the presence of non‐carious cervical lesions.

Results

At 3‐month post‐treatment in case #1 and 6‐month post‐treatment in case #2, satisfactory esthetic results for the patients and clinician were achieved. These short‐term follow‐ups were favorable for root coverage and soft tissue healing, especially at the 1‐week visit. There was noticeably less edema and erythema. Additionally, dental hypersensitivity was no longer reported for both patients.

Conclusion

By using biologic mediators, such as an EMD combined with connective tissue grafting, both multiple recession defects with non‐carious cervical lesions, and lingual recession cases, can be treated successfully in a private practice setting. Using an EMD provides no additional risks to patients, may result in faster healing, and would afford stability of long‐term success by influencing true periodontal regeneration.
Catalytic Profile Reactor for Multimodal Operando Measurements during Periodic Operation
Authors: Espinoza Diego , Wollak Birte , Sheppard Thomas L. , Dippel Ann‐Christin , Sturm Marina , Gutowski Olof , Schmidt Michael , Korup Oliver , Horn Raimund
Published: October 2022

Multimodal operando measurement concepts aim to provide structure‐activity relations of heterogeneously catalyzed reactions during operation. While the utilization of multiple characterization and spatiotemporally‐resolved techniques provides complementary information at relevant time and length scales, different reactor operation modes allow to track catalyst dynamics. However, combining these measurement concepts require complex experimental setups with high demands from a strongly interdisciplinary field of reaction engineering, physics and chemistry. In this study, a fully automated and integrated catalytic profile reactor setup is introduced which is capable of measuring spatiotemporally‐resolved species concentration, temperature and catalyst structure information under periodic reaction conditions. The oxidative dehydrogenation of C2H6 to C2H4 over MoO3/γ‐Al2O3 was used as a test system. Using the periodic profile approach, the catalytic system was investigated through activity measurements resolved in time and space combined with reactor simulations and operando high‐energy X‐ray diffraction. The presented catalytic profile reactor setup is a versatile technology, aiming to promote combined and detailed analysis of local catalyst activity and structure, for improved reproducibility and quality of operando measurements.
Effects of Adding Different Proportions of H2 to the Simulated Hydrogen‐Rich Blast Furnace
Authors: Fan Xiangyu , Li Chao , Wang Mingdeng , Liu Yang , Feng Yifei , Liu Yang , Zhong Xiangyun , Xu Guozhong , Zhang Yaru , Zheng Yajie , Bai Bin , Bai Jinfeng
Published: October 2022

The volume‐fraction changes of CO2 and H2O after adding different proportions of H2 to the hydrogen‐rich blast furnace were simulated by thermodynamic calculations to evaluate the effects of H2 on coke gasification in a blast furnace. Thermodynamic calculations indicated that the H2O content in the mixed gas gradually increased with higher H2 content. The coke gasification kinetics effective diffusion coefficient De and interfacial reaction rate constant k+ of the coke gasification reaction improved with higher H2 content. In addition, the reactivity of cokes enhanced and the coke strength after reaction decreased with higher H2 content. Mercury porosimeter experiments demonstrated that the coke gasification reaction mainly occurred on the surface.
In operando‐formed interface between silver and perovskite oxide for efficient electroreduction of carbon dioxide to carbon monoxide
Authors: Wu Xinhao , Guo Yanan , Gu Yuxing , Xie Fenghua , Li Mengran , Hu Zhiwei , Lin Hong‐Ji , Pao Chih‐Wen , Huang Yu‐Cheng , Dong Chung‐Li , Peterson Vanessa K. , Ran Ran , Zhou Wei , Shao Zongping
Published: October 2022

Electrochemical carbon dioxide (CO2) reduction (ECR) is a promising technology to produce valuable fuels and feedstocks from CO2. Despite large efforts to develop ECR catalysts, the investigation of the catalytic performance and electrochemical behavior of complex metal oxides, especially perovskite oxides, is rarely reported. Here, the inorganic perovskite oxide Ag‐doped (La0.8Sr0.2)0.95Ag0.05MnO3–δ (LSA0.05M) is reported as an efficient electrocatalyst for ECR to CO for the first time, which exhibits a Faradaic efficiency (FE) of 84.3%, a remarkable mass activity of 75 A g−1 (normalized to the mass of Ag), and stability of 130 h at a moderate overpotential of 0.79 V. The LSA0.05M catalyst experiences structure reconstruction during ECR, creating the in operando‐formed interface between the perovskite and the evolved Ag phase. The evolved Ag is uniformly distributed with a small particle size on the perovskite surface. Theoretical calculations indicate the reconstruction of LSA0.05M during ECR and reveal that the perovskite–Ag interface provides adsorption sites for CO2 and accelerates the desorption of the *CO intermediate to enhance ECR. This study presents a novel high‐performance perovskite catalyst for ECR and may inspire the future design of electrocatalysts via the in operando formation of metal–metal oxide interfaces.
Hydrogen Bonded Foldamers with Axial Chirality: Chiroptical Properties and Applications
Authors: Liu Bingyu , Xing Pengyao
Published: October 2022

Folding phenomenon refers to the formation of a specific conformation widely featured by the intramolecular interactions, which broadly exist in biomacromolecules, and are closely related to their structures and functions. A variety of oligomeric folded molecules have been designed and synthesized, namely “foldamer”, exhibiting potentials in pharmaceutical and catalysis. Molecular folding is a promising strategy to transfer chirality from substituents to the whole skeleton, when chirality transfer, amplification, evolution, and other behaviors could be achieved. Investigating chirality using foldamer model deepens the understanding of the structure‐function correlation in biomacromolecules and expands the molecular toolbox towards chiroptical and asymmetrical chemistry. Substitutes with abundant hydrogen bonding sites conjugated to a rotatable aryl group afford a parallel β‐sheet‐like conformation, which enables the emergence and manipulation of axial chirality. This concept aims to give a brief introduction and summary of the hydrogen bonded foldamers with anchored axial chirality, by taking some recent cases as examples. Design principles, control over axial chirality and applications are also reviewed.
Experimentally Calibrated Computational Prediction Enables Accurate Fine‐Tuning of Near‐Infrared Rhodamines for Multiplexing
Authors: DiMeglio David , Zhou Xinqi , Wirth Tatiana , Brøndsted Frederik , Lesiak Lauren , Fang Yuan , Shadmehr Mehrdad , Stains Cliff I.
Published: October 2022

A significant barrier inhibiting multiplexed imaging in the near‐infrared (NIR) is the extensive trial and error associated with fine‐tuning NIR dyes. In particular, the need to synthesize and experimentally evaluate dye derivatives in order to empirically identify those that can be used in multiplexing applications, requires a large investment of time. While coarse‐tuning efforts benefit from computational prediction that can be used to identify target dye structures for synthetic campaigns, errors in computational prediction remain too large to accurately parse modifications aimed at fine‐tuning changes in dye absorbance and emission. To address this issue, we screened different levels of theory and identified a time‐dependent density functional theory (TD‐DFT) approach that can rapidly, as opposed to synthesis and experimental evaluation, estimate absorbance and emission. By calibrating these computational estimations of absorbance and emission to experimentally determined parameters for a panel of existing NIR dyes, we obtain calibration curves that can be used to accurately predict the effect of fine‐tuning modifications in new dyes. We demonstrate the predictive power of this calibrated dataset using seven previously unreported dyes, obtaining mean percent errors in absorbance and emission of 2.2 and 2.8 %, respectively. This approach provides a significant timesavings, relative to synthesis and evaluation of dye derivatives, and can be used to focus synthetic campaigns on the most promising dye structures. The new dyes described herein can be utilized for multiplexed imaging, and the experimentally calibrated dataset will provide the dye chemistry community with a means to rapidly identify fine‐tuned NIR dyes in silico to guide subsequent synthetic campaigns.
Finding a Deep‐UV Borate BaZnB4O8 with Edge‐sharing [BO4] Tetrahedra and Strong Optical Anisotropy
Authors: Han Jian , Liu Kaitong , Chen Long , Li Fuming , Yang Zhihua , Zhang Fangfang , Pan Shilie , Mutailipu Miriding
Published: October 2022

The polarization modulation of deep‐UV light is an important process that incorporates functionality to selectively respond to light‐mater interaction. Typically, optical anisotropy is foremost to the use efficiency of deep‐UV birefringent crystals. Herein, a new congruently melting polyborate with extremely large birefringence (Δn(001)=0.14@589.3 nm) and band gap (6.89 eV) is discovered as a high performance birefringent crystal, which breaks the current deadlock of deep‐UV polyborates that usually show small birefringence. The rigid tetrahedra, including [ZnO4] and edge‐sharing [BO4] tetrahedra, make all the planar [BO3] triangles in the lattice adopt preferential arrangement and thereby lead to an extraordinary large birefringence that is larger than all the deep‐UV borates with experimentally measured values. Structural analyses with the additional theoretical calculations were used to study the origin of strong optical anisotropy in BaZnB4O8.
An overview of mono‐ethylene glycol synthesis via CO coupling reaction: Catalysts, kinetics, and reaction pathways
Authors: Gor Nikhil K. , Chinthala Praveen Kumar , Das Asit , Vaidya Prakash D.
Published: October 2022

Monoethylene glycol (MEG) is a promising chemical and a useful feedstock for the synthesis of several industrial products. The current commercial process of MEG production utilizes petroleum feedstock (ethylene) and an expensive catalyst, and the yield is low. Syngas is an attractive alternate feedstock for MEG. Syngas to MEG proceeds in two steps: the self‐closing, green step of carbonylation of alkyl nitrile to produce dialkyl oxalate, and further hydrogenation of oxalate to MEG. Many reviews which focused on catalyst development, reaction mechanisms, and process variables were published earlier. The present work covers the developments in the syngas‐to‐MEG synthesis process after 2014. It overviews the performance of novel catalyst systems reported in literature. A discussion on reaction pathways and kinetic models is also presented. This work will provide useful insight into syngas‐to‐MEG conversion.
Comparison of Treatment Efficiency and Energy Consumption of Batch and Continuous Electrocoagulation in Urban Wastewater
Authors: Yılmaz Alper Erdem , Sağsöz Yeşim Dede , Fil Baybars Ali , Yılmaz Murat Tolga
Published: October 2022

In this study, domestic wastewater was used as the electrolyte. The work was carried out with an up‐flow tubular reactor, made of stainless steel that was used as cathode, while the anode electrode material was aluminum and varying values of flow regime (25, 50, 75 and 100 mL/s for continuous system), initial pH value (5, 6, 7 and 7.8) and current intensity (10, 15 and 20 A) were applied. For domestic wastewater with natural pH, the effluent pH was >9 in the batch system, while in the continuous system the pH was 8–8.5. Likewise, while the effluent temperature was up to 60°C in the batch system, it was at most 35°C in the continuous system. However, the energy consumption values in the continuous system were considerably lower compared with the batch system. At a current intensity of 10 A, 80 kWh of energy per unit volume was consumed in the batch system, while it was 50 kWh for the continuous system. The present results show that the batch system can be used for small wastewater streams whereas the continuous system can be used for large wastewater streams for domestic wastewater treatment.
Effect of particularisation size on the accuracy and efficiency of a multiscale tumours' growth model
Authors: Varella Vinicius , Quintela Barbara de M. , Kasztelnik Marek , Viceconti Marco
Published: October 2022

In silico, medicine models are frequently used to represent a phenomenon across multiples space–time scales. Most of these multiscale models require impracticable execution times to be solved, even using high performance computing systems, because typically each representative volume element in the upper scale model is coupled to an instance of the lower scale model; this causes a combinatory explosion of the computational cost, which increases exponentially as the number of scales to be modelled increases. To attenuate this problem, it is a common practice to interpose between the two models a particularisation operator, which maps the upper‐scale model results into a smaller number of lower‐scale models, and an operator, which maps the fewer results of the lower‐scale models on the whole space–time homogenisation domain of upper‐scale model. The aim of this study is to explore what is the simplest particularisation / homogenisation scheme that can couple a model aimed to predict the growth of a whole solid tumour (neuroblastoma) to a tissue‐scale model of the cell‐tissue biology with an acceptable approximation error and a viable computational cost. Using an idealised initial dataset with spatial gradients representative of those of real neuroblastomas, but small enough to be solved without any particularisation, we determined the approximation error and the computational cost of a very simple particularisation strategy based on binning. We found that even such simple algorithm can significantly reduce the computational cost with negligible approximation errors.
Cation Engineering by Three‐Dimensional Organic Spacer Cations for Effective Defect Passivation in Perovskite Solar Cells
Authors: Shang Xueni , Zhang Boxue , Gao Deyu , Li Mengjia , Wang Chenglin , Meng Fanbin , Chen Cong
Published: October 2022

Low‐dimensional additive engineering could effectively reduce the high‐density trap defect density and improve the stability of perovskite solar cells (PSCs). To avoid the limiting effect of charge carrier transfer by incorporating the large‐size long alkyl chain organic cations, we developed a new three‐dimensional organic spacer cation, 1,4‐diazabicyclo [2,2,2] octane‐1,4‐diium (DABCO2+), to passivate the defects and enhance the device stability. DABCO2+ with fine crystal structure and thermal stability could result in substantially fewer structural defects, enhance carrier lifetime, and inhibit nonradiative recombination loss. Structural analysis of CsFAPbI3 perovskite doped with different concentrations of the three‐dimensional organic spacer cations shows a clear correlation between the structure and the resultant perovskite films. Consequently, DABCO2+ modified CsFAPbI3‐based PSCs could achieve an optimized PCE of 23.02% with high stability exceeding 1500 h. This work opens a new approach to fabricating PSCs with enhanced stability for future commercial applications.
Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development – (I) A Randomized Trial with PCSK9 Inhibitors
Authors: Sheikhy Morasa , Schrieber Sarah J. , Sun Qin , Gershuny Victoria , Matta Murali K. , Bai Jane P.F. , Du Xiulian , Vegesna Giri , Shah Aanchal , Prentice Kristin , Nalepinski Colleen , Zineh Issam , Wang Yow‐Ming , Strauss David G. , Florian Jeffry
Published: October 2022

US Food and Drug Administration (FDA) guidance outlines how biosimilars can be developed based on pharmacokinetic (PK) and pharmacodynamic (PD) similarity study data in lieu of a comparative clinical efficacy study. There is a paucity of PD comparability studies in biosimilar development, leaving open questions about how best to plan these studies. To that end, we conducted a randomized, double‐blinded, placebo‐controlled, single‐dose, parallel‐arm clinical study in healthy participants to evaluate approaches to address information gaps, inform analysis best practices, and apply emerging technologies in biomarker characterization. Seventy‐two healthy participants (n = 8 per arm) received either placebo or one of four doses of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab (15–100 mg) or evolocumab (21–140 mg) to evaluate the maximum change from baseline (ΔPDmax) and the baseline‐adjusted area under the effect curve (AUEC) for the biomarkers low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) in serum. We investigated approaches to minimize variability in PD measures. Coefficient of variation was lower for LDL‐C than apoB at therapeutic doses. Modeling and simulation were used to establish the dose–response relationship and provided support that therapeutic doses for these products are adequately sensitive and are on the steep part of the dose–response curves. Similar dose–response relationships were observed for both biomarkers. ΔPDmax plateaued at lower doses than AUEC. In summary, this study illustrates how pilot study data can be leveraged to inform appropriate dosing and data analyses for a PK and PD similarity study.
From Cold to Hot: Changing Perceptions and Future Opportunities for Quantitative Systems Pharmacology Modeling in Cancer Immunotherapy
Authors: Lemaire Vincent , Bassen David , Reed Mike , Song Roy , Khalili Samira , Lien Yi Ting (Kayla) , Huang Lu , Singh Aman P. , Stamatelos Spyros , Bottino Dean , Hua Fei
Published: October 2022

Immuno‐oncology (IO) is a fast‐expanding field due to recent success using IO therapies in treating cancer. As IO therapies do not directly kill tumor cells but rather act upon the patients’ own immune cells either systemically or in the tumor microenvironment, new and innovative approaches are required to inform IO therapy research and development. Quantitative systems pharmacology (QSP) modeling describes the biological mechanisms of disease and the mode of action of drugs with mathematical equations, which has significant potential to address the big challenges in the IO field, from identifying patient populations that respond to different therapies to guiding the selection, dosing, and scheduling of combination therapy. To assess the perspectives of the community on the impact of QSP modeling in IO drug development and to understand current applications and challenges, the IO QSP working group—under the QSP Special Interest Group (SIG) of the International Society of Pharmacometrics (ISoP)—conducted a survey among QSP modelers, non‐QSP modelers, and non‐modeling IO program stakeholders. The survey results are presented here with discussions on how to address some of the findings. One of the findings is the differences in perception among these groups. To help bridge this perception gap, we present several case studies demonstrating the impact of QSP modeling in IO and suggest actions that can be taken in the future to increase the real and perceived impact of QSP modeling in IO drug research and development.
Antibacterial effects of natural compounds on biofilm formation of Streptococcus mutans
Authors: Kamarehei Farideh , Mehdiabadi Mohsen , Naderi Fariba
Published: October 2022

Streptococcus mutans is the main cariogenic pathogen in the oral cavity, considered to contribute toward oral diseases. S. mutans is predominantly entrapped in plaque biofilms.

Objectives

In this study, we surveyed the antibacterial activity of natural compounds in terms of the biofilm production of S. mutans.

Material and Methods

We extracted the studies related to natural compounds affected on S. mutans biofilm from different databases.

Results

Disruption of S. mutans viability in biofilms by a potent new pharmacological factor could inhibit and remove cavities. Various antibacterial agents are needed to destroy biofilms that remove both pathogens and commensal bacteria, and also exert inhibitory effects on many bacterial species.

Conclusions

An effective therapeutic agent for dental caries has to be capable of removing pathogens and their biofilms. Specific virulence attributes of S. mutans exist; hence, natural compounds that have excellent properties to combat such pathogens need to be selected.
1‐Sulfonylated 1,2,3,4‐tetrahydroquinoline‐6‐carboxylic acids as simple, readily‐accessible MCL‐1 inhibitors
Authors: Chen Lijia , Chan Alexandria M. , Wilder Paul T. , Fletcher Steven
Published: October 2022

MCL‐1 is a member of the BCL‐2 family of proteins that regulates the mitochondrial pathway of apoptosis. Overexpression of MCL‐1 is associated with the development and progression of a range of human cancers, and is also responsible for the onset of resistance to conventional chemotherapies. Although several MCL‐1 inhibitors have now advanced to clinical trials, recent suspensions and terminations reveal the urgency with which new inhibitor chemotypes must be discovered. Building on our previous studies of a chiral, isomeric lead, we report the discovery of a new chemotype to inhibit MCL‐1: 1‐sulfonylated 1,2,3,4‐tetrahydroquinoline‐6‐carboxylic acid. The nature of the sulfonyl moiety contributed significantly to the resulting inhibitory ability. For example, transforming a phenylsulfonyl group into a 4‐chloro‐3,5‐dimethylphenoxy)phenyl)sulfonyl moiety elicited more than a 73‐fold enhancement in inhibiton of MCL‐1, possibly through targeting the p2 pocket in the BH3‐binding groove, and so it is anticipated that further structure‐activity studies here will lead to continued improvements in binding. It should be underscored that this class of MCL‐1 inhibitors is readily accessible in four simple steps, is achiral and offers many avenues for optimization, all factors that are welcomed in the search for safe and effective inhibitors of this driver of cancer cell survival.
Quantitative biogeography: Decreasing and more variable dynamics of critical species in an iconic meta‐ecosystem
Authors: Menge Bruce A. , Robinson Jonathan W. , Poirson Brittany N. , Gravem Sarah A.
Published: October 2022

Ecosystem stability has intrigued ecologists for decades, and the realization that the global climate was changing has sharpened and focused this interest. One possible early warning signal of decreasing stability is increasing variability in ecosystems over time with increasing climate variability. Determining climate change effects on community stability, however, requires long‐term studies of structure and underlying dynamics, including bottom‐up and top‐down effects in natural ecosystems. Although relevant datasets were rare in the early years of community ecology, such information has increased in recent decades. We investigated spatiotemporal changes in mean and variability of ecological subsidies (nutrients, phytoplankton, prey colonization), performance metrics of a dominant space occupier (mussels) and its primary predator (sea stars), and sea star predation rates on mussels in relation to climatic oscillations, temperature, and disease on rocky shores. The research involved annually repeated multiyear (~1999–2018), multisite (13 sites nested within five regions along ~260 km of the Oregon coast) observations, measurements, and experiments. We analyzed associations between environmental variables and ecological performance of key elements of the sea star‐mussel‐dominated mid intertidal system. We found that upwelling declined in some regions, but became more variable across all study regions. Air and water temperatures oscillated, but their mean and variation increased through time, with peak values coinciding with the 2014–2016 combined El Niño and Marine Heat Wave. Ecological subsidies generally declined during the study period but increased in variability. Excepting growth rate, mussel (Mytilus californianus) performance (condition index, reproductive output) generally decreased and became more variable. Primarily due to a sea star wasting epidemic, reproductive output of the top predator Pisaster ochraceus decreased and became more variable, and predation rate on mussels decreased. Analyses indicated that the primary drivers of these changes were temperature‐related environmental factors. As declining means and increasing variability of ecological performances can typify destabilizing ecosystems, and environmental trends are toward ever more stressful conditions, the outlook for this iconic ecosystem is discouraging. Immediate and rapid action to mitigate and ultimately reverse climate change likely is the only option available to prevent an irreversible shift in the future of this, and most other ecosystems.
Effects of Dietary Copper and Escherichia coli Challenge on the Immune Response and Gill Oxidative Balance in the Freshwater Mussel Diplodon chilensis
Authors: Castro Juan M. , Bianchi Virginia A. , Felici Emiliano , De Anna Julieta S. , Venturino Andrés , Luquet Carlos M.
Published: October 2022

Copper is a water and sediment pollutant that can be biomagnified by phytoplankton, and it often co-occurs with fecal bacteria. We addressed the combined effects of copper and Escherichia coli on the immune response and gill oxidative balance of the freshwater mussel Diplodon chilensis. Bivalves were sorted into four groups fed with 1) control algae, 2) bacteria (E. coli), 3) copper-enriched algae (Cu2+) algae, and 4) copper-enriched algae followed by bacteria (Cu2+ + E. coli). Cellular and humoral immune and cytotoxic variables were analyzed in hemolymph, and detoxifying/antioxidant enzyme activities (glutathione S-transferase [GST] and catalase [CAT]) and lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) were studied in gill tissue. The total hemocyte number increased after Cu2+ exposure, independently of the E. coli challenge. The proportion of hyalinocytes significantly diminished in the E. coli and Cu2+ groups but not in Cu2+ + E. coli groups; granulocytes significantly increased with E. coli but not with Cu2+ + E. coli treatments. Phagocytic activity was higher in all treatments than in control mussels. Acid phosphatase activity was increased by E. coli and inhibited by Cu2+ and Cu2+ + E. coli. Both E. coli and Cu2+ but not Cu2+ + E. coli augmented alkaline phosphatase activity. The Cu2+ and Cu2+ + E. coli treatments reduced the lysosomal membrane stability and cell viability. Humoral bacteriolytic and phenol oxidase activities were not affected by any treatment. The Cu2+ treatment induced gill CAT and GST activities and increased TBARS levels. The Cu2+ + E. coli treatment reversed this CAT and GST stimulation and increased the Cu2+ effect on TBARS. Dietary Cu2+ affects bivalves' immunological and oxidative status and impairs defensive responses against bacteria. In turn, E. coli potentiates the gill oxidative effects of Cu2+. Environ Toxicol Chem 2023;42:154–165. © 2022 SETAC
The impact of the first UK COVID‐19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London
Authors: Simkin Lauren , Yung Paul , Greig Flora , Perera Gayan , Tsamakis Konstantinos , Rizos Emmanouil , Stewart Robert , Velayudhan Latha , Mueller Christoph
Published: October 2022

Objectives

Social distancing restrictions in the COVID‐19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well‐described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre‐pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16‐week period of the UK lockdown starting in March 2020, and in the comparable pre‐pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre‐pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non‐White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13–2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91–4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre‐COVID period (adjusted OR: 1.55; 95% CI: 1.19–2.03), interaction terms indicated higher odds of patients of non‐White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non‐White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID‐19 pandemic.
Risk factors for cardiovascular disease among individuals with hepatic steatosis
Authors: Karády Julia , Ferencik Maros , Mayrhofer Thomas , Meyersohn Nandini M. , Bittner Daniel O. , Staziaki Pedro V. , Szilveszter Balint , Hallett Travis R. , Lu Michael T. , Puchner Stefan B. , Simon Tracey G. , Foldyna Borek , Ginsburg Geoffrey S. , McGarrah Robert W. , Voora Deepak , Shah Svati H. , Douglas Pamela S. , Hoffmann Udo , Corey Kathleen E.
Published: October 2022

Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all‐cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18–1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03–1.07; p < 0.001), and n‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP; aOR = 1.90, 95% CI 1.38–2.62; p < 0.001) were independently associated with obstructive CAD. In the 25‐months median follow‐up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27–5.03; p = 0.008) and NT‐proBNP (aOR = 1.50, 95% CI 1.01–2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01–1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT‐pro‐BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT‐proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk‐stratify adults with HS for incident CAD and MACE.
Influence of COVID‐19 pandemic on research and fieldwork: Perspectives from Ghana
Authors: Fordjour Fatima Amponsah
Published: October 2022

The insurgence of COVID‐19 has received all attention at the detriment of research on most diseases. Procedures and protocols devised to curb the pandemic continues to affect lives and work. As most countries prepare to tune back to normalcy, working conditions undoubtedly will not be the same as the World Health Organization still urges nations to scale up procedures and strategies against the pandemic. As research groups and projects across the globe and especially in Ghana begins work, these protocols must be fashioned into their study protocol before approval will be granted by ethical institutions. This has led to increase in research cost, with additional responsibilities aside their normal research activities. This perspective clearly points out the impact of the pandemic on research, especially fieldwork.