bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review on: Smart Polymers used in Novel Ophthalmic Drug Delivery System
Authors: Tagalpallewar Amol , Chakankar Shivani , Patil Kalpesh , Baheti Akshay , Wani Manish , Polshettiwar Satish
Published: January 2022

Loss of sight or vision loss are utmost concerned worldwide health problems resulting in significant financial and public loss. Eyesight helps one to capture signals from the surrounding environment and depict clear visual images. Drug delivery to the eyes has been seen as a significant task for the reason that an eye has different defensive boundaries and drug clearance system resulting from an exceptional structural and functional nature of eyes. Formulation administered into the eye in the form of regular ophthalmic formulations leads to less absorption of drug. Therefore, approaches have been carried out to advance a novel, nontoxic and effective ophthalmic drug delivery system to control the difficulties occurring by the regular formulations. Latest innovation in pharmaceutical drug design has produced stimuli responsive in-situ gel system providing continuous release action and increased ocular drug bioavailability. They act by undergoing phase conversion from solution to gel owing to the variation in ocular temperature, ions and pH in the ocular environment. Stimuli transformed gel is formed in the region of cul de sac thus combating the limitations of regular ophthalmic formulations such as less retention time and fast nasolacrimal drainage within the eyes.
Cutaneous Manifestations of COVID-19
Authors: Dube Vartika , Singh Adarshlata , Dube Vineet
Published: January 2022

Although the pathogenesis of the newly discovered 2019 coronavirus disease is still unknown, it has several extrapulmonary manifestations, such as cutaneous lesions. Among those who took Covid, the American Academy of Dermatology reports that 22.2% of patients had morbilliform or pernio-like rashes; 17.8% had papulosquamous purpura; 16.8% had macular erythema, and 7.8% had retiform purpura. According to the available information, around 450 patients with (COVID-19) infectious disease have developed a variety of skin lesions. While it's understandable that dermatology consultations have been scarce during this pandemic and that the primary focus has been on systemic manifestations of covid, it's also far from surprising that cutaneous lesions have gone undiagnosed. The patient's ages ranged from 2 months to 75 years (The condition is most commonly encountered in elderly persons).

 Cutaneous symptoms are less common in India. According to reports compiled from various sources, skin lesions are more common in Albinos, Scandinavians, and Caucasians than in Indians, Mongolians, and Africans. On the other hand, skin lesions were more prevalent during India's second COVID-19 wave (most likely due to an increment in the number of people affected). Patients with a mild form of the disease were more likely to have pernio-like lesions, while critically ill patients only had retiform-purpura (those who required ventilator support and were on the verge of organ failure). Individuals with COVID-19 have been found to have urticarial rash, erythematous/morbilliform rash, papulovesicular exanthem, chilblain-like patterns, livedo reticularis, and purpuric-vasculitic patterns, among other dermatological issues. Chilblains and the Multisystem Inflammatory Syndrome (MIS) in children (2-15 years) are also skin manifestations of (COVID-19), which are more commonly seen in the UK and Western Europe. During the second wave, there were two cases of a multisystem inflammatory syndrome associated with chilblains in India.  Covid-19 cutaneous presentations occur in 0.2% to 19.4% of people, but the frequency and timing are difficult to pin down. There is also a variable degree of association between the severity of the illness and specific skin manifestations.
Morphological and Morphometrical Analysis of Dry Human Scaphoid Bone in South Indian Population and Its Clinical Implications
Authors: Maheswari K. Uma , Mohanraj Karthik Ganesh
Published: January 2022

Introduction: Scaphoid is the second largest among all the carpal bones, which is present on the radial side of the proximal row of carpal bones. Scaphoid Fractures are the most common of the carpal bone injuries. Scaphoid Fractures heal slowly due to thelimited blood circulation of the bone

Materials and Methods: The study was performed on 20 Scaphoid Bones,which were collected from the Department of Anatomy,Saveetha dental college. By using digital vernier callipers,morphological and morphometrical parameters (length and breadth)of scaphoid bones were measured,tabulated and statistically analysed.

Results: All the 20 scaphoids showed the presence of tubercle. Double foramina in the main dorsal sulcus were seen in 7 right and 6 left specimens. No significant differences were found in lengths and breadths of the bone.In the present study, at least one foramen is found in all the main dorsal sulcus and the number of specimens showing presence of double foramen in the main dorsal sulcus are 7 right and 6 left specimens.

Conclusion: This study showed that no significant morphological and morphometric differences were found between right and left sides. The data obtained in the present study will be helpful for the hand surgeons, radiologists and clinical anatomists for surgical reduction to follow up the reunion of fractured scaphoid bones.
Highly Anisotropic Organometal Halide Perovskite Nanowalls Grown by Glancing‐Angle Deposition
Authors: Castillo‐Seoane Javier , Contreras‐Bernal Lidia , Obrero‐Perez Jose Manuel , García‐Casas Xabier , Lorenzo‐Lázaro Francisco , Aparicio Francisco Javier , Lopez‐Santos Carmen , Rojas Teresa Cristina , Anta Juan Antonio , Borrás Ana , Barranco Ángel , Sanchez‐Valencia Juan Ramon
Published: January 2022

Polarizers are ubiquitous components in current optoelectronic devices as displays or photographic cameras. Yet, control over light polarization is an unsolved challenge, since the main drawback of the existing display technologies is the significant optical losses. In such a context, organometal halide perovskites (OMHP) can play a decisive role given their flexible synthesis with tunable optical properties such as bandgap and photoluminescence, and excellent light emission with a low non‐radiative recombination rate. Therefore, along with their outstanding electrical properties have elevated hybrid perovskites as the material of choice in photovoltaics and optoelectronics. Among the different OMHP nanostructures, nanowires and nanorods have lately arisen as key players in the control of light polarization for lighting or detector applications. Herein, the fabrication of highly aligned and anisotropic methylammonium lead iodide perovskite nanowalls by glancing‐angle deposition, which is compatible with most substrates, is presented. Their high alignment degree provides the samples with anisotropic optical properties such as light absorption and photoluminescence. Furthermore, their implementation in photovoltaic devices provides them with a polarization‐sensitive response. This facile vacuum‐based approach embodies a milestone in the development of last‐generation polarization‐sensitive perovskite‐based optoelectronic devices such as lighting appliances or self‐powered photodetectors.
Epitaxial Growth of Ultrathin Highly Crystalline Pt–Ni Nanostructure on a Metal Carbide Template for Efficient Oxygen Reduction Reaction
Authors: Ding Hui , Wang Peng , Su Caijie , Liu Hongfei , Tai Xiaolin , Zhang Nan , Lv Haifeng , Lin Yue , Chu Wangsheng , Wu Xiaojun , Wu Changzheng , Xie Yi
Published: January 2022

Structure engineering strategies such as core–shell and hollow nanostructures are effective pathways to improve the utilization of noble metals for catalysis. However, nowadays materials design based on these strategies still largely rely on precious metal templates. Herein, the epitaxial growth of highly crystalline Pt3Ni overlayer on earth‐abundant nickel carbide is reported, forming Ni3C@Pt3Ni core–shell nanoparticles with a well‐defined interface through a new lattice‐match‐directed synthetic strategy. Derived from such core–shell nanostructures, ultrathin highly crystalline Pt3Ni nanocages have an advantageous configuration of oxygen reduction reaction (ORR)‐favored facets and inherently high active surface area for the ORR, bringing high mass activity and specific activity as much as 4.71 A mgPt−1 and 5.14 mA cm−2, which are 26 and 20 times to that of commercial Pt/C, respectively. This novel epitaxial growth of platinum opens up new avenues to rationally design highly active and economical electrocatalysts.
How to Compute the Contact Angle inside an Opaque Capillary Tube: A Universal Equation
Authors: Zhao Kaiqi , Sun Lidong
Published: January 2022

Capillarity is a ubiquitous and important phenomenon in nature. The Jurin's law establishes a relationship between the contact angle and the liquid rising height inside a capillary tube and is widely employed to evaluate the wettability of transparent tubes since 1717. However, it fails once encounters the opaque counterparts because of the invisible rising height. Here, an idea that correlates the contact angle with an intrinsic property of a matter, i.e., the mass is proposed. A universal equation is thus established to compute the contact angle using the liquid mass inside the capillary tube. The equation is systematically verified against the height measurement method adopting a series of quartz capillary tubes, where a good agreement is attained. An in situ approach of high sensitivity is hence derived and demonstrated to evaluate the capillary tubes regardless of the wettability, transparency, or materials. A theoretical basis is provided to assess the surface wettability inside capillary tubes in a more general way and thus a new avenue is opened to investigate the heat and mass transfer under spatial limitation with well‐defined surfaces for portable devices, flexible electronics, etc.
Salivary alpha‐synuclein as a potential fluid biomarker in Parkinson’s disease: A systematic review and meta‐analysis
Authors: Kharel Sanjeev , Ojha Rajeev , Bist Anil , Joshi Surya Prakash , Rauniyar Robin , Yadav Jayant Kumar
Published: January 2022

Introduction

Lewy bodies are the pathological hallmarks of Parkinson's disease. There is a need for effective biomarker that is cost effective, less invasive, and easily reproducible with good sensitivity and specificity and can be used to diagnose the condition early and track its severity and progression. Alpha‐synuclein (α‐syn), an integral component of the Lewy body, is found in saliva and can be a potential answer to the above concerns.

Methods

PubMed, EMBASE, Google Scholar, and CNKI databases, along with additional sites, were searched from January 2010 to August 2021. Standard mean difference (Hedges' g) with 95% CI was used to show an association. Statistical analysis was done using STATA software version 16 (StataCorp).

Results

We found a significant reduction in the mean difference of total salivary α‐syn among PD patients compared to healthy controls. However, the mean difference of oligomeric α‐syn and oligo/total salivary α‐syn ratio was significantly increased among PD patients compared to healthy controls.

Conclusion

Our systematic review and meta‐analysis found that salivary α‐syn parameters (total, oligomeric, oligo/total) can be considered a simple, easy‐to‐use, cost‐effective, and reliable diagnostic biomarker for PD and its progression.
Linear relationships for modeling CO2 absorption in aqueous alkanolamine solutions in a thermodynamically consistent way
Authors: Yuan Xiaoshuai , Ng Chin Feng , Nikolic Heather , Liu Kunlei
Published: January 2022

A thermodynamically consistent model for the carbon dioxide (CO2) absorption in aqueous alkanolamine system is of great importance in the research and development of a CO2 capture process. To facilitate the development of thermodynamic models, linear Gibbs free energy, enthalpy, and heat capacity relationships using well‐known amines as reference are used to correlate the standard reference state properties of ionic species with those of molecular species in the electrolyte system, which has been approved to provide a reliable and consistent way to estimate required parameters when there is minimal or no appropriate experimental data available. The proposed relationships have been applied to the development of an electrolyte nonrandom two liquid (NRTL) activity coefficient model for CO2 absorption in aqueous 1‐amino‐2‐propanol (A2P) solution, as an example to demonstration the methodology. With limited vapor–liquid equilibrium data and other thermodynamic properties, the parameters in the electrolyte NRTL model are identified with good accuracy.
A Novel Self‐Updating Design Method for Complex 3D Structures Using Combined Convolutional Neuron and Deep Convolutional Generative Adversarial Networks
Authors: Gu Zewen , Hou Xiaonan , Saafi Mohamed , Ye Jianqiao
Published: January 2022

Mechanical design is one of the essential disciplines in engineering applications, while inspirations of design ideas highly depend on the ability and prior knowledge of engineers or designers. With the rapid development of machine learning (ML) techniques, artificial intelligence (AI)‐based design methods are promising tools for the design of advanced engineering systems. So far, there have been some studies of 2D patterns and structural designs based on ML techniques. However, a particular challenge remains in allowing complex 3D mechanical designs using ML techniques. Herein, a novel and experience‐free method to equip ML models with 3D design capabilities by combining a convolutional neuron network (CNN) with a deep convolutional generative adversarial network (DCGAN) is developed. The model directly receives 2D image‐based training data that define the complex 3D structures of a specific machine part. After the training process, an infinite number of new 3D designs can be generated by the proposed model, with their geometric and mechanical properties being accurately predicted at the same time. Moreover, the generated new designs can be fed back to expand the original input datasets for further ML model training and updating.
Stable heterocyclic stannylene: The metal, ligand‐centered reactivity, and effective catalytic hydroboration of aldehydes
Authors: Arsenyeva Kseniya V. , Klimashevskaya Anastasiya V. , Pashanova Kira I. , Trofimova Olesya Yu. , Chegerev Maxim G. , Starikova Alyona A. , Cherkasov Anton V. , Fukin Georgy K. , Yakushev Ilya A. , Piskunov Alexandr V.
Published: January 2022

A stable O,N‐heterocyclic stannylene 1 bearing novel tetradentate 2,4‐di‐tert‐butyl‐6‐((2‐(1‐((pyridin‐2‐ylmethyl)imino)ethyl)phenyl)amino)phenolate ligand (RAPH2) was synthesized and characterized. Complex 1 is monomeric in crystal and solution due to two additional intramolecular N → Sn donor–acceptor interactions. The diverse reactivity of compound 1 towards various iron carbonyl compounds was studied. Oxidative addition of [Fe2(μ‐S2)(CO)6]2 to the tin center of 1 resulted in a new six‐coordinate Sn(IV) compound 2 containing two Sn–S bonds. The reaction of 1 with Fe2(CO)9 led to the formation of a stable tin(II) adduct 3 – RAPSn‐Fe(CO)4. The interaction between 1 and [(η5‐C5H5)Fe(CO)2]2 resulted in a transformation of the ligand skeleton. During this reaction, the tin center is oxidized to the tetravalent state, and the donor ═N–CH2–Py group is converted into an anionic one with the loss of the methylene hydrogen atom. The molecular structures of all obtained compounds were determined by single‐crystal X‐ray diffraction. The novel stannylene 1 demonstrates striking activity in benzaldehydes' hydroboration reactions down to 0.02 mole percent of the catalyst loading under mild conditions.
Highly efficient photocatalytic organic dyes degradation based on 1D magnetic Bi2Fe4O9/C@AgBr composite
Authors: Ma Mingliang , Chen Yan , Liu Yanyan , Jiang Jiabin , Jiao Zhengguo , Ma Yong
Published: January 2022

Wastewater treatment has become a research hot issue in recent decade. Organic dyes as one of the main pollutants can change the water behavior. To deracinate the organic pollutants from wastewater, there are numerous methods have been taken into consideration. Photocatalysis is the promising strategy for the dye degradation with low cost, high efficiency, and environmental friendliness. Hence, a novel one‐dimensional (1D) magnetic Bi2Fe4O9/C@AgBr composite photocatalyst was prepared employing electrospinning, calcination, and deposition–precipitation methods. The morphology and composition of photocatalyst were characterized, as well as the photocatalytic activities of degrading methylene blue (MB) under visible light were investigated. And the results exhibited that the efficiency of Bi2Fe4O9/C@AgBr under visible light for 60 min is 97.4%. After three cycles, the degradation efficiency of MB could still reach 88.0%. Moreover, radical quenching experiment implicated superoxide radical anions as the primary active species responsible for photodegradation of MB. This work provides a new insight into the design of effective photocatalysts for practical application.
Novel flexible piezoelectric‐conductive Janus nanofibers integrated membrane with enhanced pressure sensing performance
Authors: Hu Kongsen , Feng Jiyuan , Lv Nan , Jiang Wenbo , Lyu Zhiwei , Hai Qing
Published: January 2022

Exploitation of soft piezoelectric sensing materials is fundamental to the research of energy‐harvesting devices and wearable electronics. However, a big challenge of piezoelectric materials application in micro‐scale sensing systems is to address the restrictions of electrode compatibility, miniaturization, multistep assembly, and high cost. Here, we propose a simple strategy to develop the coinstantaneous construction of piezoelectric materials and nanoresistance networks by fabricating electrospun piezoelectric‐conductive (polyacrylonitrile)//(polyaniline/polyvinyl pyrrolidone) (denoted [PAN]//[PANI/PVP]) Janus nanofibers (NFs). This peculiar Janus structure can collect and output voltage by conductive paths based on the Wheatstone bridge principle. Moreover, owing to the nanoscale asymmetric geometry for efficient polarization and induced charges collection, the Janus NFs show superior piezoelectric properties. As a result, flexible (PAN)//(PANI/PVP) Janus nanofibers integrated membrane (JNFIM) dispensing with two flat electrodes can directly output a high voltage of 2 V under a tiny force of 1 N. Furthermore, the JNFIM enables to detect pressures with extra‐high linear sensitivity (1.88 V N−1) and low detection limit (0.1 N). Thus, our work provides a simple route for the development of nanoscale, low‐cost, and high‐sensitivity integrated materials for pressure sensing, revealing promising applications in miniature robotics and wearable devices.
Marine mammal sensory systems: Special issue overview
Authors: Reidenberg Joy S. , Hanke Frederike D.
Published: January 2022

Marine mammals are a unique group of organisms that are secondarily adapted to the aquatic environment. Their specific lifestyle requires numerous adaptations of anatomy and physiology in general, and sensory physiology in particular. During the course of evolution, marine mammal senses changed to fit with the specific requirements of underwater sensing, while at the same time retaining aerial sensing to various degrees. In this special issue, state of the art science in the field of marine mammal sensory research is reported for representatives of all marine mammal groups, unfortunately with the exclusion of the polar bear. The articles focus on somatosensation of the glabrous skin of cetaceans and mechanoreception, including haptics, hydrodynamics, and acoustics, to chemoreception. Articles even deal with electroreception, highlighting that the bottlenose dolphin can perceive weak electric stimuli, and vision, indicating that harbor seals are able to derive temporal information from an optical stimulus. Altogether this special issue illustrates the diversity of research in the field regarding sensory systems, species, or experimental approaches. The strength of this special issue lies in the combination of carefully conducted anatomical studies paired with observations and behavioral studies attempting to relate “form” and “function” as well as in the many impulses and future avenues mentioned by numerous contributions.
Brain Structural Changes During Juvenile Fibromyalgia: Relationships With Pain, Fatigue, and Functional Disability
Authors: Suñol Maria , Payne Michael F. , Tong Han , Maloney Thomas C. , Ting Tracy V. , Kashikar‐Zuck Susmita , Coghill Robert C. , López‐Solà Marina
Published: January 2022

Objective

Juvenile fibromyalgia (FM) is a prevalent chronic pain condition affecting children and adolescents worldwide during a critical period of brain development. To date, no published studies have addressed the pathophysiology of juvenile FM. This study was undertaken to characterize gray matter volume (GMV) alterations in juvenile FM patients for the first time, and to investigate their functional and clinical relevance.

Methods

Thirty‐four female adolescents with juvenile FM and 38 healthy adolescents underwent a structural magnetic resonance imaging examination and completed questionnaires assessing core juvenile FM symptoms. Using voxel‐based morphometry, we assessed between‐group GMV differences and associations between GMV and functional disability, fatigue, and pain interference in juvenile FM. We also studied whether validated brain patterns predicting pain, cognitive control, or negative emotion were amplified/attenuated in juvenile FM patients and whether structural alterations reported in adult FM were replicated in adolescents with juvenile FM.

Results

Compared to controls, juvenile FM patients showed GMV reductions in the anterior midcingulate cortex (aMCC) region (family‐wise error corrected P [PFWE‐corr] = 0.04; estimated with threshold‐free cluster enhancement [TFCE]; n = 72) associated with pain. Within the juvenile FM group, patients reporting higher functional disability had larger GMV in inferior frontal regions (PFWE‐corr = 0.006; TFCE estimated; n = 34) linked to affective, self‐referential, and language‐related processes. Last, GMV reductions in juvenile FM showed partial overlap with findings in adult FM, specifically for the anterior/posterior cingulate cortices (P = 0.02 and P = 0.03, respectively; n = 72).

Conclusion

Pain‐related aMCC reductions may be a structural hallmark of juvenile FM, whereas alterations in regions involved in emotional, self‐referential, and language‐related processes may predict disease impact on patients’ well‐being. The partial overlap between juvenile and adult FM findings strengthens the importance of early symptom identification and intervention to prevent the transition to adult forms of the disease.
Understanding and Performance of the Zinc Anode Cycling in Aqueous Zinc‐Ion Batteries and a Roadmap for the Future
Authors: Shang Yuan , Kundu Dipan
Published: January 2022

By virtue of environmental benignity, inherent safety, and affordable cost of raw materials, aqueous zinc‐ion batteries (AZIBs) have witnessed tremendous upheaval in research interest and are considered to have enormous potential for stationary and renewable storage applications. Yet, the high activity of Zn in aqueous electrolytes triggers metal corrosion and hydrogen evolution, which, together with dendrite formation on zinc surface during its electrodeposition, leads to poor Coulombic efficiency and rapid short‐circuit failure during cycling. Therefore, to divulge a critical and in‐depth understanding of these underlying issues, (electro)chemical behavior of the Zn metal in aqueous electrolytes and corresponding theories are first discussed in this review. This is followed by a thorough discussion of various strategies, categorized based on the intrinsic mechanism, for the suppression of dendrite and parasitic side reactions that are ultimately intertwined. Finally, strategic recommendations are provided as a roadmap to coordinate research and development efforts, and the energy density analyses of a representative AZIB cell is presented to highlight technical and functional needs for the practical development of the technology. This review is expected to provide a comprehensive understanding of the Zn metal anode development for AZIBs and draw attention to pertinent criteria for performance assessment.
Dynamics of a DNA minicircle: Poloidal rotation and in‐plane circular vibration
Authors: Kim Minjung , Hong Chi Cheng , Lee Saeyeon , Kim Jun Soo
Published: January 2022

We investigated the dynamics of a 90‐base pair‐long DNA minicircle with the sequence of (AT)45/(AT)45 using the all‐atom molecular dynamics (MD) simulation. The simulation was run for a duration of 5 μs and the internal dynamics was analyzed in terms of the poloidal rotation and the in‐plane circular vibration. The poloidal rotation was defined by the directional variation of each base pair relative to the plane of the DNA minicircle, and its correlation time was estimated to be 61 ns. The in‐plane circular vibration was measured as the radial distance variation of each base pair from the center‐of‐mass of the DNA, and the correlation time was 6.3 ns. The characteristic time scales determined for the poloidal rotation and the radial fluctuation suggest that the internal motion of a small DNA minicircle is highly dynamic. This work provides a new set of dynamic information for small DNA minicircles, available for future applications.
Being good at being good—The mediating role of an environmental management system in value‐creating green supply chain management practices
Authors: Jell‐Ojobor Maria , Raha Aveed
Published: January 2022

This study adopts a resource‐based view to explain the complementary role of the corporate structure in the value creation of green supply chain management (GSCM) practices. Using 8‐year panel data collected from 317 US international manufacturers, we analyze the influence of GSCM practices on corporate financial performance (CFP) and the mediating role of a certified environmental management system (EMS) in this relationship. We show that GSCM practices have a positive impact on accounting‐based financial performance, meaning, return on assets (ROA) and return on equity (ROE). In contrast, firms that implement GSCM practices and a certified EMS simultaneously achieve a higher market valuation in terms of Tobin's Q in addition to a higher ROA and ROE in the following year. Our study demonstrates that, through their synergistic combination with a firm's complementary EMS, utilizing GSCM practices can result in intangible assets as sources of long‐term financial benefits. Our results have several theoretical and managerial implications. They also address the limitations of the prior use of varying survey‐based items for internal and external GSCM practices and add nuance to the existing GSCM practices in the literature.
Paraganglioma masquerading as a primary liver lesion: A rare entity discovered during surgery
Authors: Miller Michelle E. , Vietor Nicole O. , Park Edward J. , Sweeney Shane P. , Katz Matthew , Vietor Robert C.
Published: January 2022

A 54‐year‐old woman with controlled hypertension presented with abdominal pain and weight loss. Imaging revealed a 6.6 cm liver lesion. During resection, she became severely hypertensive and diagnosis was paraganglioma. Hepatic paragangliomas are exceedingly rare but must be considered in the differential of abdominal mass even without typical clinical symptoms.
Interaction of a Jaundice Marker Molecule with a Redox‐Modulatory Nano‐Hybrid: A Combined Electrochemical and Spectroscopic Study toward the Development of a Theranostic Tool
Authors: Mondal Susmita , Pan Nivedita , Ghosh Ria , Bera Arpan , Mukherjee Dipanjan , Maji Tuhin Kumar , Adhikari Anirudddha , Ghosh Sangeeta , Bhattacharya Chinmoy , Pal Samir Kumar
Published: January 2022

This study explores a combined electrochemical and spectroscopic approach to investigate the degradation of bilirubin, a molecular marker of jaundice in humans using a biocompatible nanohybrid (citrate‐functionalized Mn3O4 nanohybrid; C−Mn3O4 NH). The approach is aimed at the development of a facile theranostic tool for treatment, detection, and prognosis of jaundice. Linear sweep voltammetry (LSV) studies on bilirubin, C−Mn3O4 NH, a model carrier protein, and its complex with bilirubin reveal the efficacy of the nanohybrid for both degradation and detection of bilirubin. Furthermore, spectroscopic studies depict that distal electron transfer to be the probable mechanism behind the observed bilirubin degradation in physiological milieu.
Synthesis of Aminoethyl‐Substituted Piperidine Derivatives as σ1 Receptor Ligands with Antiproliferative Properties
Authors: Holtschulte Catharina , Börgel Frederik , Westphälinger Stefanie , Schepmann Dirk , Civenni Gianluca , Laurini Erik , Marson Domenico , Catapano Carlo V. , Pricl Sabrina , Wünsch Bernhard
Published: January 2022

A series of novel σ1 receptor ligands with a 4‐(2‐aminoethyl)piperidine scaffold was prepared and biologically evaluated. The underlying concept of our project was the improvement of the lipophilic ligand efficiency of previously synthesized potent σ1 ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin‐4(1H)‐ones 7, homologation of the ketones 8 and introduction of diverse amino moieties and piperidine N‐substituents. 1‐Methylpiperidines showed particular high σ1 receptor affinity and selectivity over the σ2 subtype, whilst piperidines with a proton, a tosyl moiety or an ethyl moiety exhibited considerably lower σ1 affinity. Molecular dynamics simulations with per‐residue binding free energy deconvolution demonstrated that different interactions of the basic piperidine‐N‐atom and its substituents (or the cyclohexane ring) with the lipophilic binding pocket consisting of Leu105, Thr181, Leu182, Ala185, Leu186, Thr202 and Tyr206 are responsible for the different σ1 receptor affinities. Recorded logD7.4 and calculated clogP values of 4a and 18a indicate low lipophilicity and thus high lipophilic ligand efficiency. Piperidine 4a inhibited the growth of human non‐small cell lung cancer cells A427 to a similar extent as the σ1 antagonist haloperidol. 1‐Methylpiperidines 20a, 21a and 22a showed stronger antiproliferative effects on androgen negative human prostate cancer cells DU145 than the σ1 ligands NE100 and S1RA.
Patient‐derived organoids for personalized gallbladder cancer modelling and drug screening
Authors: Yuan Bo , Zhao Xiaofang , Wang Xiang , Liu Erdong , Liu Chunliang , Zong Yali , Jiang Youhai , Hou Minghui , Chen Yao , Chen Lei , Zhang Yongjie , Wang Hongyang , Fu Jing
Published: January 2022

Background

Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies.

Methods

We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole‐exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC‐101 and CUDC‐907, were evaluated in vitro and in vivo.

Results

The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single‐cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC‐907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids.

Conclusions

Patient‐derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.
The soil microbiome increases plant survival and modifies interactions with root endosymbionts in the field
Authors: Markalanda Shaniya H. , McFadden Connor J. , Cassidy Steven T. , Wood Corlett W.
Published: January 2022

Evidence is accumulating that the soil microbiome—the community of microorganisms living in soils—has a major effect on plant traits and fitness. However, most work to date has taken place under controlled laboratory conditions and has not experimentally disentangled the effect of the soil microbiome on plant performance from the effects of key endosymbiotic constituents. As a result, it is difficult to extrapolate from existing data to understand the role of the soil microbiome in natural plant populations. To address this gap, we performed a field experiment using the black medick Medicago lupulina to test how the soil microbiome influences plant performance and colonization by two root endosymbionts (the mutualistic nitrogen‐fixing bacteria Ensifer spp. and the parasitic root‐knot nematode Meloidogyne hapla) under natural conditions. We inoculated all plants with nitrogen‐fixing bacteria and factorially manipulated the soil microbiome and nematode infection. We found that plants grown in microbe‐depleted soil exhibit greater mortality, but that among the survivors, there was no effect of the soil microbiome on plant performance (shoot biomass, root biomass, or shoot‐to‐root ratio). The soil microbiome also impacted parasitic nematode infection and affected colonization by mutualistic nitrogen‐fixing bacteria in a plant genotype‐dependent manner, increasing colonization in some plant genotypes and decreasing it in others. Our results demonstrate the soil microbiome has complex effects on plant–endosymbiont interactions and may be critical for survival under natural conditions.
A meta‐analysis of the effects of climate change on the mutualism between plants and arbuscular mycorrhizal fungi
Authors: Duarte André G. , Maherali Hafiz
Published: January 2022

Climate change and other anthropogenic activities have the potential to alter the dynamics of resource exchange in the mutualistic symbiosis between plants and mycorrhizal fungi, potentially altering its stability. Arbuscular mycorrhizal (AM) fungi, which interact with most plant species, are less cold‐tolerant than other groups of fungi; warming might therefore lead to increased fungal‐mediated nutrient transfers to plants, which could strengthen the mutualism. By stimulating photosynthesis, rising CO2 could reduce the carbon cost of supporting AM fungi, which may also strengthen the mutualism. Furthermore, rising temperature and CO2 could have stronger effects on the mutualism in wild plants than in domesticated plants because the process of domestication can reduce the dependence of plants on mycorrhizal fungi. We conducted a multi‐level random effects meta‐analysis of experiments that quantified the strength of the mutualism as plant growth response to AM fungal inoculation (i.e., mycorrhizal growth response) under contrasting temperature and CO2 treatments that spanned the Last Glacial Maximum (LGM) to those expected with future climate change. We tested predictions using a three‐level mixed effects meta‐regression model with temperature or CO2, domestication status and their interaction as moderators. Increases from subambient to ambient temperature stimulated mycorrhizal growth response only for wild, but not for domesticated plant species. An increase from ambient to superambient temperature stimulated mycorrhizal growth response in both wild and domesticated plants, but the overall temperature effect was not statistically significant. By contrast, increased CO2 concentration, either from subambient to ambient or ambient to super ambient levels, did not affect mycorrhizal growth response in wild or domesticated plants. These results suggest the mutualism between wild plants and AM fungi was likely strengthened as temperature rose from the past to the present and that forecasted warming due to climate change may have modest positive effects on the mutualistic responses of plants to AM fungi. Mutualistic benefits obtained by plants from AM fungi may not have been altered by atmospheric CO2 increases from the past to the present, nor are they likely to be affected by a forecasted CO2 increase. This meta‐analysis also identified gaps in the literature. In particular, (i) a large majority of studies that examined temperature effects on the mutualism focus on domesticated species (>80% of all trials) and (ii) very few studies examine how rising temperature and CO2, or other anthropogenic effects, interact to influence the mutualism. Therefore, to predict the stability of the mycorrhizal mutualism in the Anthropocene, future work should prioritize wild plant species as study subjects and focus on identifying how climate change factors and other human activities interact to affect plant responses to AM fungi.
Does ant–plant mutualism have spillover effects on the non‐partner ant community?
Authors: Donald Marion L. , Miller Tom E. X.
Published: January 2022

Mutualism benefits partner species, and theory predicts these partnerships can affect the abundance, diversity, and composition of partner and non‐partner species. We used 16 years of monitoring data to determine the ant partner species of tree cholla cacti (Cylindropuntia imbricata), which reward ants with extrafloral nectar in exchange for anti‐herbivore defense. These long‐term data revealed one dominant ant partner (Liometopum apiculatum) and two less common partners (Crematogaster opuntiae and Forelius pruinosus). We then used short‐term characterization of the terrestrial ant community by pitfall trapping to sample partner and non‐partner ant species across ten plots of varying cactus density. We found that the dominant ant partner tended a higher proportion cacti in plots of higher cactus density, and was also found at higher occurrence within the pitfall traps in higher density plots, suggesting a strong positive feedback that promotes ant partner occurrence where plant partners are available. Despite the strong association and increased partner occurrence, ant community‐wide effects from this mutualism appear limited. Of the common ant species, the occurrence of a single non‐partner ant species was negatively associated with cactus density and with the increased presence of L. apiculatum. Additionally, the composition and diversity of the ant community in our plots were insensitive to cactus density variation, indicating that positive effects of the mutualism on the dominant ant partner did not have cascading impacts on the ant community. This study provides novel evidence that exclusive mutualisms, even those with a strong positive feedback, may be limited in the scope of their community‐level effects.
Border Collie optimization algorithm‐based node clustering technique in vehicular ad hoc networks
Authors: Godi Rakesh Kumar , Janakiraman Sengathir
Published: January 2022

In vehicular ad hoc networks (VANETs), the nodes are vehicles and these vehicles communicate with one another on the road. The vehicular nodes on the road move continuously and it introduces dynamic changes in the topology of the network. When the node density in the vehicular network is high, then it is still more challenging as these situations introduce different challenges for network scalability and hurdles the process of determining an optimal route in the vehicular network. At this juncture, clustering protocols are often utilized for resolving the issue of network scalability and the factors that hinders process of identifying optimal routes in vehicular network. In this article, Border Collie optimization algorithm‐based node clustering technique (BCOA‐NCT) is proposed for achieving optimal cluster head selection that minimizes network overhead in uncertain node density situations. This BCOA‐NCT is proposed for facilitating equal concentration on both exploitation and exploration during the process of clustering. It utilized the strategy of eyeing for preventing the algorithm from being stuck into local optima during the cluster head selection process. The simulation experiments of the proposed BCOA‐NCT and the benchmarked schemes confirmed better throughput of 6.19%, minimized end‐to‐end delay of 7.24%, reduced mean energy consumptions of 6.89%, and reduction in the number of beacon messages utilized by 8.26% under the impact of different density of vehicular node. The outcome of the results indicated that the proposed BCOA‐NCT on par with the baseline approaches is capable enough in handling the issue of scalability and better estimation of optimal routes under the increase of node density in the vehicular network.
Shared genetic influences on resting‐state functional networks of the brain
Authors: P.O.F.T. Guimarães João , Sprooten E. , Beckmann C. F. , Franke B. , Bralten J.
Published: January 2022

The amplitude of activation in brain resting state networks (RSNs), measured with resting‐state functional magnetic resonance imaging, is heritable and genetically correlated across RSNs, indicating pleiotropy. Recent univariate genome‐wide association studies (GWASs) explored the genetic underpinnings of individual variation in RSN activity. Yet univariate genomic analyses do not describe the pleiotropic nature of RSNs. In this study, we used a novel multivariate method called genomic structural equation modeling to model latent factors that capture the shared genomic influence on RSNs and to identify single nucleotide polymorphisms (SNPs) and genes driving this pleiotropy. Using summary statistics from GWAS of 21 RSNs reported in UK Biobank (N = 31,688), the genomic latent factor analysis was first conducted in a discovery sample (N = 21,081), and then tested in an independent sample from the same cohort (N = 10,607). In the discovery sample, we show that the genetic organization of RSNs can be best explained by two distinct but correlated genetic factors that divide multimodal association networks and sensory networks. Eleven of the 17 factor loadings were replicated in the independent sample. With the multivariate GWAS, we found and replicated nine independent SNPs associated with the joint architecture of RSNs. Further, by combining the discovery and replication samples, we discovered additional SNP and gene associations with the two factors of RSN amplitude. We conclude that modeling the genetic effects on brain function in a multivariate way is a powerful approach to learn more about the biological mechanisms involved in brain function.
Hidden in plain sight: Considerations for an ulcer of the scalp
Authors: Young Jade N. , Elgash May , Ortega‐Loayza Alex G.
Published: January 2022

Background

Pyoderma gangrenosum (PG) is a rare inflammatory skin condition characterized by painful, irregularly shaped skin ulcers mainly affecting the lower extremities. PG rarely affects the head and neck, making the diagnosis of this condition even more challenging. A high index of suspicion is paramount in the diagnosis of PG, especially after surgical procedures.

Methods

We describe a clinical case of a patient with initially undiagnosed PG of the scalp who underwent surgical excision and full thickness skin graft with subsequent graft necrosis as initial clue for the diagnosis.

Results

Twenty months after initial presentation, this patient healed with a multimodal medical approach of immunosuppressive therapy and wound care.

Conclusion

Prompt recognition of PG by physicians assessing any surgical wounds is vital in reducing misdiagnosis and improving patient outcomes.
Subcutaneous immunoglobulins in chronic lymphocytic leukemia with secondary antibody deficiency. A monocentric experience during Covid‐19 pandemics
Authors: Innocenti Idanna , Tomasso Annamaria , Benintende Giulia , Autore Francesco , Fresa Alberto , Vuono Florenzia , Stirparo Luca , Galli Eugenio , D’Arena Giovanni , Sorà Federica , Efremov Dimitar , Laurenti Luca
Published: January 2022

Secondary antibody deficiency (SAD) is a frequent manifestation of chronic lymphocytic leukemia (CLL) that increases the risk of infections. However, no formal guideline are available regarding the eligibility for prophylaxis or the delivery method, dosage, frequency of administration and duration of immunoglobulin replacement therapy (IgRT). The aim of this study was to assess the efficacy and safety of subcutaneous IgRT (SCIg) and its impact on quality of life (QoL) of CLL pts in the Covid‐19 era. Ten CLL pts with SAD were treated with subcutaneous IgRT (SCIg) at our institution between October 2019 and December 2020. Median age was 66 years and five patients had comorbidities. Seven patients were receiving therapy for CLL when treatment with SCIg was initiated. All pts received 10 g total dose hyaluronidase‐free SCIg independently from body weight. The IgG level and CD4/CD8, CD19 and CD16/56 lymphocytes subset were recorded at baseline and every 3 months. No patient experienced infectious events nor Covid‐19 mediated interstitial pneumonia while on SCIg therapy. All patients tolerated well the therapy and experienced an increase of IgG levels, which was then stable in time. We conclude that SCIg administration in CLL pts with SAD is efficacious and safe as infectious prophylaxis. This route of administration appears particularly advantageous in the Covid‐19 era, because of the self‐administration at home which results in improvement in the QoL and reduced treatment expenditures.
The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies
Authors: Ahmadi Alireza , Fallah Vastani Zahra , Abounoori Mahdi , Azizi Mahdieh , Labani‐Motlagh Alireza , Mami Sajad , Mami Sanaz
Published: January 2022

Background

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56bright NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56dim NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway.

Aim

We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes.

Materials and Methods

The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease‐modifying therapies on the number of NK and NKT subtypes.

Results

Expansion of CD56bright NK cells, reduction in the CD56dim cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease‐modifying therapies.

Conclusion

Expansion of CD56bright NK cells or reduction in the CD56dim cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow.