bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Ong Sally S. , Peavey Jeremy J. , Hiatt Kevin D. , Whitlow Christopher T. , Sappington Rebecca M. , Thompson Atalie C. , Lockhart Samuel N. , Chen Haiying , Craft Suzanne , Rapp Stephen R. , Fitzpatrick Annette L. , Heckbert Susan R. , Luchsinger José A. , Klein Barbara E. K. , Meuer Stacy M , Cotch Mary Frances , Wong Tien Y. , Hughes Timothy M.
Published: October 2023

INTRODUCTION

Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment.

METHODS

Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi‐Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018).

RESULTS

After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (β = −0.0005, SE = 0.0024, p = 0.01) at Exam 6, while greater arteriolar FD at Exam 5 was associated with greater gray matter cortical volume (in mm3, β = 5458, SE = 20.17, p = 0.04) at Exam 6.

CONCLUSION

Greater arteriolar FD, reflecting greater complexity of the branching pattern of the retinal arteries, is associated with MRI biomarkers indicative of less neuroinflammation and neurodegeneration.
Use of a rat model to characterize 35 arterial pulse wave parameters in a comparative study of isoflurane and Zoletil/xylazine anesthesia and the effect ofAcanthopanax senticosusextract
Authors: Misak Anton , Grman Marian , Tomasova Lenka , Makara Ondrej , Rostakova Zuzana , Waczulikova Iveta , Ondrias Karol
Published: October 2023

Background

Information obtained from arterial pulse waveforms (APW) can be useful for characterizing the cardiovascular system. To achieve this, it is necessary to know the detailed characteristics of APWs in different states of an organism, which would allow APW parameters (APW‐Ps) to be assigned to particular (patho)physiological conditions. Therefore, our work aimed to characterize 35 APW‐Ps in rats under the influence of isoflurane (ISO) and Zoletil/xylazine (ZO/XY) anesthesia and to study the effect of root extract fromAcanthopanax senticosus(ASRE) in these anesthetic conditions.

Methods

The right jugular vein of anesthetized rats was cannulated for the administration of ASRE and the left carotid artery for the detection of APWs from which 35 APW‐Ps were evaluated.

Results

We obtained data on 35 APW‐Ps, which significantly depended on the anesthesia, and thus, they characterized the cardiovascular system under these two conditions. ASRE transiently modulated all 35 APW‐Ps, including a transient decrease in systolic and diastolic blood pressure (BP) and heart rate or increases in pulse BP, dP/dtmax, and systolic and diastolic areas. Whereas the transient effects of ASRE were similar, the extract had prolonged disturbing effects on the cardiovascular system in rats under ZO/XY but not under ISO anesthesia. This negative effect can result from the disturbance caused by ZO/XY anesthesia on the cardiovascular system.

Conclusions

We characterized 35 APW‐Ps of rats under ISO and ZO/XY anesthesia and found that ASRE contains compounds that can modulate the properties of the cardiovascular system, which significantly depended on the status of the cardiovascular system. This should be considered when using ASRE as a nutritional supplement by individuals with cardiovascular problems.
Epidemiology of sepsis in a Japanese administrative database
Authors: Imaeda Taro , Oami Takehiko , Takahashi Nozomi , Saito Daiki , Higashi Akiko , Nakada Taka‐aki
Published: October 2023

Sepsis is the leading cause of death worldwide. Considering regional variations in the characteristics of patients with sepsis, a better understanding of the epidemiology in Japan will lead to further development of strategies for the prevention and treatment of sepsis. To investigate the epidemiology of sepsis, we conducted a systematic literature review of PubMed between 2003 and January 2023. Among the 78 studies using a Japanese administrative database, we included 20 that defined patients with sepsis as those with an infection and organ dysfunction. The mortality rate in patients with sepsis has decreased since 2010, reaching 18% in 2017. However, the proportion of inpatients with sepsis is increasing. A study comparing short‐course (≤7 days) and long‐course (≥8 days) antibiotic administration showed lower 28‐day mortality in the short‐course group. Six studies on the treatment of patients with septic shock reported that low‐dose corticosteroids or polymyxin B hemoperfusion reduced mortality, whereas intravenous immunoglobulins had no such effect. Four studies investigating the effects of treatment in patients with sepsis‐associated disseminated intravascular coagulation demonstrated that antithrombin may reduce mortality, whereas recombinant human soluble thrombomodulin does not. A descriptive study of medical costs for patients with sepsis showed that the effective cost per survivor decreased over an 8‐year period from 2010 to 2017. Sepsis has a significant impact on public health, and is attracting attention as an ongoing issue. Further research to determine more appropriate prevention methods and treatment for sepsis should be a matter of priority.
Electrocatalytic Systems for NOx Valorization in Organonitrogen Synthesis
Authors: Liao Peisen , Kang Jiawei , Xiang Runan , Wang Shihan , Li Guangqin
Published: October 2023

Inorganic nitrogen oxide (NOx) species, such as NO, NO2, NO3−, NO2− generated from the decomposition of organic matters, volcanic eruptions and lightning activated nitrogen, play important roles in the nitrogen cycle system and exploring the origin of life. Meanwhile, excessive emission of NOx gases and residues from industry and transportation causes troubling problems to the environment and human health. How to efficiently handle these wastes is a global problem. In response to the growing demand for sustainability, scientists are actively pursuing sustainable electrochemical technologies powered by renewable energy sources and efficient utilization of hydrogen energy to convert NOx species into high‐value organonitrogen chemicals. In this minireview, recent advances of electrocatalytic systems for NOx species valorization in organonitrogen synthesis are classified and described, such as amino acids, amide, urea, oximes, nitrile etc., that have been widely applied in medicine, life science and agriculture. Additionally, the current challenges including multiple side reactions and complicated paths, viable solutions along with future directions ahead in this field are also proposed. The coupling electrocatalytic systems provide a green mode for fixing nitrogen cycle bacteria and bring enlightenment to human sustainable development.
Lewis Acid Supported Nickel Nitrenoids
Authors: Juda Cristin E. , Casaday Claire E. , Clarke Ryan M. , Litak Nicholas P. , Campbell Brandon M. , Chang Tieyan , Zheng Shao‐Liang , Chen Yu‐Sheng , Betley Theodore A.
Published: October 2023

Metalation of the polynucleating ligand F,tbsLH6 (1,3,5‐C6H9(NC6H3−4‐F−2‐NSiMe2tBu)3) with two equivalents of Zn(N(SiMe3)2)2 affords the dinuclear product (F,tbsLH2)Zn2 (1), which can be further deprotonated to yield (F,tbsL)Zn2Li2(OEt2)4 (2). Transmetalation of 2 with NiCl2(py)2 yields the heterometallic, trinuclear cluster (F,tbsL)Zn2Ni(py) (3). Reduction of 3 with KC8 affords [KC222][(F,tbsL)Zn2Ni] (4) which features a monovalent Ni centre. Addition of 1‐adamantyl azide to 4 generates the bridging μ3‐nitrenoid adduct [K(THF)3][(F,tbsL)Zn2Ni(μ3‐NAd)] (5). EPR spectroscopy reveals that the anionic cluster possesses a doublet ground state (S =
). Cyclic voltammetry of 5 reveals two fully reversible redox events. The dianionic nitrenoid [K2(THF)9][(F,tbsL)Zn2Ni(μ3‐NAd)] (6) was isolated and characterized while the neutral redox isomer was observed to undergo both intra‐ and intermolecular H‐atom abstraction processes. Ni K‐edge XAS studies suggest a divalent oxidation state for the Ni centres in both the monoanionic and dianionic [Zn2Ni] nitrenoid complexes. However, DFT analysis suggests Ni‐borne oxidation for 5.
Titanium‐Based Superlattice with Fe(III)‐Regulable Bandgap and Performance for Optimal and Synergistic Sonodynamic–Chemotherapy Guided by Magnetic Resonance Imaging
Authors: Liu Yanjun , Qin Liying , Tan Guoying , Guo Yanan , Fan Yifan , Song Nan , Zhou Ping , Yan Chun‐Hua , Tang Yu
Published: October 2023

Superlattices have considerable potential as sonosensitizers for cancer therapy because of their flexible and tunable band gaps, although they have not yet been reported. In this study, a Ti‐based organic–inorganic superlattice with good electron–hole separation was synthesized, which consisted of orderly layered superlattices of 2,2′‐bipyridine‐5,5′‐dicarboxylic acid (BPDC) and Ti−O layers. In addition, the superlattice was coordinated with Fe(III) and encapsulated doxorubicin (DOX) to prepare Ti‐BPDC@Fe@DOX@PEG (TFDP) after biocompatibility modification. TFDP can realize the simultaneous generation of reactive oxygen species and release of DOX under ultrasound irradiation. Moreover, adjusting the Fe(III) content can effectively modulate the band gap of the superlattice and increase the efficiency of sonodynamic therapy (SDT). The mechanisms underlying this modulation were explored. TFDP with Fe(III) can also be used as a contrast agent for magnetic resonance imaging (MRI). Both in vitro and in vivo experiments demonstrated the ability of TFDP to precisely treat cancer using MRI‐guided SDT/chemotherapy. This study expands the applications of superlattices as sonosensitizers with flexible and tailored modifications and indicates that superlattices are promising for precise and customized treatments.
Lignin Upconversion by Functionalization and Network Formation
Authors: Chandna Sanjam , Olivares M. Carmen A. , Baranovskii Egor , Engelmann Gunnar , Böker Alexander , Tzschucke C. Christoph , Haag Rainer
Published: October 2023

Lignin, a complex and abundant biopolymer derived from plant cell walls, has emerged as a promising feedstock for sustainable material development. Due to the high abundance of phenylpropanoid units, aromatic rings, and hydroxyl groups, lignin is an ideal candidate for being explored in various material applications. Therefore, the demand on lignin valorization for development of value‐added products is significantly increasing. This mini‐review provides an overview of lignin upconversion, focusing on its functionalization through chemical and enzymatic routes, and its application in lignin‐based polymer resins, hydrogels, and nanomaterials. The functionalization of lignin molecules with various chemical groups offers tailored properties and increased compatibility with other materials, expanding its potential applications. Additionally, the formation of lignin‐based networks, either through cross‐linking or blending with polymers, generates novel materials with improved mechanical, thermal, and barrier properties. However, challenges remain in optimizing functionalization techniques, preserving the innate complexity of lignin, and achieving scalability for industrial implementation. As lignin‘s potential continues to be unlocked, it is poised to contribute significantly to the shift towards more eco‐friendly and resource‐efficient industries.
The astrophysical parameters of Majaess‐95 and Majaess‐225
Authors: Tadross A. L.
Published: October 2023

Most astrophysical parameters of the two stellar clusters Majaess 95 and Majaess 225 have been investigated here for the first time using the third data release of the Gaia space mission (Gaia‐DR3). The membership probabilities of stars were assigned using the pyUPMASK algorithm. The parallaxes offset has been corrected using the zero‐point correction code of Lindegren et al. (Lindegren et al. 2021, A&A, 649, A4). Using the clusters' members with membership probabilities >0.50, we calculated the distance to the clusters of 3311 and 3020 (±130) pc, respectively, which agree with the results from our isochrone fitting on the color‐magnitude diagram. The ages are found to be 282 (±20) and 12.6 (±2) Ma. Also, the reddening, heliocentric distances, luminosity function, mass function, and total mass were estimated. On studying the dynamic state (relaxation time), we found that Majaess‐95 is a relaxed cluster, while Majaess‐225 is not relaxed yet.
Cathode Atomic Structures and Their Electrolyte Interfaces in Lithium‐sulfur Batteries
Authors: Duivenvoorden Tanika , Sanderson Stephen , Searles Debra J.
Published: October 2023

Lithium‐sulfur batteries (LSBs) are a promising alternative to conventional battery technologies due to their high theoretical energy density. However, the insulating nature of sulfur and the polysulfide shuttle effect present practical challenges to achieving this. This study employs molecular dynamics simulations with a ReaxFF reactive force field to investigate the structure of LSB cathode‐electrolyte interfaces, with cathode materials made from different sized graphene flakes and elemental sulfur (S8). Smaller graphene flakes were seen to bond more with the sulfur, while structures with larger graphene flakes featured fewer C−S bonds and more long‐chain sulfur species. Observing the interface between the cathode and an organic electrolyte revealed that cathode structures with larger graphene flakes could orientate to shield the long‐chain sulfur and lithium polysulfide species from interacting with and dissolving into the electrolyte. Additional simulations were performed to investigate cathode materials with regions of crystalline α‐S8. However, it was found that the ReaxFF force field used for LSB systems cannot effectively model crystalline sulfur under constant pressure conditions. Further development of reactive force fields for simulation of graphene flake and sulfur electrodes in the presence of electrolyte are therefore required to explore the full range of likely structures using these methods.
Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects
Authors: Li Liling , Chen Dan , Lin Xuexin , Luo Jia , Tan Jingqian , Li Peng
Published: October 2023

Sensorineural hearing loss (SNHL) is a common otologic condition caused by damage to hair cells and spiral ganglion neurons that affects transmission pathways. Most of these cells cannot be regenerated, and there has been no breakthrough in regeneration techniques for inner ear cells. SNHL has a high incidence rate and can cause a variety of clinical symptoms, greatly impacting people's daily lives. With limited clinical treatments, the search for critical targets is urgent. Studies have shown that inflammation is prevalent in the pathogenesis of SNHL and plays a significant role in it. Inflammation is a normal body defense response, and a systemic anti‐inflammatory approach is undesirable. It is crucial for us to identify potential targets of inflammation in SNHL and take measures specifically targeting those targets with minimal systemic impact. This paper firstly describes the role of inflammation in various types of SNHL and then provides an overview of the interactions between inflammation and cochlear immunity, cochlear microcirculation, vascular spasm, and glutamate metabolism and finally comprehensively examines the feasibility of targets in these interactions. This paper is expected to facilitate the development of targeted anti‐inflammation for SNHL and provide strategies and approaches for treating clinical SNHL.
Molecular Insights into the Macrophage Immunomodulatory Effects of Scrophulariae Radix Polysaccharides
Authors: Zhao Ming , Zheng Sichun , Wang Mengyu , Wu Jiahui , Ma Xiaodan , Xu Wei
Published: October 2023

Scrophulariae Radix (SR) has been widely used in Chinese herbal compound prescriptions, health care products and functional foods. The present study aimed to investigate the immunomodulatory activity of polysaccharides from SR (SRPs) in macrophages and explore the potential mechanisms. The results showed that four SRPs fractions (SRPs40, SRPs60, SRPs80 and SRPs100) had similar absorption peaks and monosaccharide compositions, but the intensities of absorption peaks and monosaccharide contents were distinguished. All SRPs fractions significantly enhanced the pinocytic activity, promoted the production of NO and TNF‐α, increased the mRNA expressions of inflammatory factors (IL‐1β, IL‐6, TNF‐α and PTGS2) and TLR2, and elevated the phosphorylation levels of p38, ERK, JNK, p65 and IκB. Moreover, the production of NO and TNF‐α stimulated by SRPs was dramatically suppressed by anti‐TLR2 antibody. These results indicated that SRPs activated macrophages through MAPK and NF‐κB signaling pathways via recognition of TLR2.
Dioxygen Activation and Reduction by a Soluble Iron Phthalocyanine
Authors: Iwanov Christian , Hopp Moritz Philipp , Lorenz Domenik , Ballmann Joachim , Enders Markus
Published: October 2023

Iron ions in a square‐planar coordination can bind molecules at the vacant axial positions and are able to transform them in stoichiometric and catalytic reactions. Nature takes advantage of these properties by incorporating iron into porphyrin systems, which play a key role not only in the binding and transport of oxygen, but also in catalytic oxidation and reduction reactions involving cytochrome P450. Although these systems have been studied extensively, there are still unresolved questions regarding the interplay between the iron ions and the surrounding ligands. Phthalocyanines (Pc) create a similar environment for metal atoms and FePc is known for a long time. However, without axial ligands FePc aggregates leading to solids of low solubility. In this work we used a known six‐coordinate iron phthalocyanine derivative with bulky substituents and removed the stabilizing axial ligands. The resulting paramagnetic, four‐coordinate compound does not aggregate and dissolves well so that NMR spectroscopy can be employed for studying the molecular structure and the reactivity. Solvent molecules bind weakly to the iron centers and oxygen is reduced in the presence of H‐atom donors. The stoichiometric and catalytic reactivity with oxygen was studied in more detail.
Trajectories of health‐related quality of life and symptom burden in patients with advanced cancer towards the end of life: Longitudinal results from the eQuiPe study
Authors: Versluis Moyke A. J. , Raijmakers Natasja J. H. , Baars Arnold , van den Beuken‐van Everdingen Marieke H. J. , de Graeff Alexander , Hendriks Mathijs P. , de Jong Wouter K. , Kloover Jeroen S. , Kuip Evelien J. M. , Mandigers Caroline M. P. W. , Sommeijer Dirkje W. , van der Linden Yvette M. , van de Poll‐Franse Lonneke V.
Published: October 2023

Background

Support for health‐related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking.

Aim

To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care–related factors, cancer‐specific treatment, and comorbidity.

Methods

A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life‐C30 and reported continuity of care. Multivariable mixed‐effects analysis was used to assess the association between HRQOL and health care–related factors.

Results

A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (β –16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (β –7.5) and a better reported continuity of care (β 0.7) were both significantly associated with the trajectory of HRQOL.

Conclusion

Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL.
Single‐Molecule Localization Microscopy Using Time‐Lapse Imaging of Single‐Antibody Labeling
Authors: Perera Thilini , Gunasekara Hirushi , Hu Ying S.
Published: October 2023

In single‐molecule localization microscopy (SMLM), immunofluorescence (IF) staining affects the quality of the reconstructed superresolution images. However, optimizing IF staining remains challenging because IF staining is a one‐step, irreversible process. Sample labeling through reversible binding presents an alternative strategy, but such techniques require significant technological advancements to enhance the dissociation of labels without sacrificing their binding specificity. In this article, we introduce time‐lapse imaging of single‐antibody labeling. Our versatile technique utilizes commercially available dye‐conjugated antibodies. The method controls the antibody concentrations to capture single‐antibody labeling of subcellular targets, thereby achieving SMLM through the labeling process. We further demonstrate dual‐color single‐antibody labeling to enhance the sample labeling density. The new approach allows the evaluation of antibody binding at the single‐antibody level and within the cellular environment. This comprehensive guide offers step‐by‐step instructions for time‐lapse imaging of single‐antibody labeling experiments and enables the application of the single‐antibody labeling technique to a wide range of targets. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Sample preparation for single‐antibody labeling

Basic Protocol 2: Data acquisition for single‐molecule localization microscopy

Alternate Protocol: Dual‐color single‐antibody labeling using OptoSplit II equation

Basic Protocol 3: Image analysis
Exploring the Genomic Landscape: An In‐depth ChIP‐seq Analysis Protocol for Uncovering Protein‐DNA Interactions
Authors: Zeng Liping , Zhang Bailong
Published: October 2023

Chromatin immunoprecipitation followed by sequencing (ChIP‐seq) is a widely employed technique for investigating protein‐DNA interactions. However, the absence of a standardized and clear workflow necessitates researchers to independently assemble methodologies from diverse resources. This lack of uniformity hampers reproducibility and makes version control a complex endeavor, thereby limiting the accessibility of ChIP‐seq analyses to individuals with extensive training in bioinformatics. In light of these challenges, we have developed an executable protocol that addresses these limitations. Our protocol encompasses all aspects of ChIP‐seq analysis, ranging from quality control of raw reads to peak calling and downstream functional analyses. We have implemented two distinct approaches for peak calling, providing researchers with flexibility to choose the most suitable method for their specific experimental needs. This protocol will contribute to the scientific community by providing a standardized and clear resource that will enhance the reproducibility and accessibility of ChIP‐seq analyses. © 2023 Wiley Periodicals LLC.

Basic Protocol: ChIP‐seq analysis workflow

Alternative Protocol: Call differentially enriched peaks by using MACS3
Lp(a) and inflammation: a new insight into atherosclerosis
Authors: Pan Hangyu , Hu Kexin , Wu Qiao , Tu Yan , Guo Zhigang
Published: October 2023

Background

Lipid‐lowering therapy is of utmost importance in both primary and secondary prevention of atherosclerotic cardio vascular disease (ASCVD). However, the presence of residual risk allows cardiovascular events to occur even when low‐density lipoprotein cholesterol (LDL‐C) levels are very low. A large number of clinical studies have provided evidence confirming the association between elevated plasma Lp(a) and the development of ASCVD. Clinical studies have also suggested that reducing Lp(a) may help decrease the occurrence of cardiovascular events.

Main

Lp(a) consists of LDL‐like particles, apo(a) and OxPL. The level of Lp(a) in thehuman body is predominantly determined by genetics, with external factorshaving minimal impact. Additionally, Lp(a) levels have been found to vary among different ethnicities. There is a notable correlation between elevated levels of Lp(a) and coronary artery disease (CAD), which is independent of other lipoproteins. Furthermore, there exists a linear relationship between Lp(a) levels and the risk of developing ASCVD. It is now wildly believed that Lp(a) primarily contributes to the development of cardiovascular events through pro‐inflammation, pro‐thrombosis and pro‐atherosclerosis. From the perspective of Lp(a) influencing inflammation, it primarily promotes the release of inflammatoryfactors. This, in turn, increases levels of vascular inflammation and facilitates the recruitment of monocytes‐macrophages. Moreover, it also affects the function of endothelial cells during the development process of atherosclerosis. All these aspects complement each other and contribute to the progression of at herosclerosis. Currently, the lipid‐lowering treatment used inclinical practice can partially reduce the levels of Lp(a), but its impact on inflammation is not significant.

Conclusion

Lp(a) is an independent risk factor for CAD, as it promotes inflammation in the body and accelerates theprogression of atherosclerosis. Further research on effective methods to reduce Lp(a) levels can provide new insights for the treatment of atherosclerosis.
Haematopoietic cell‐derived exosomes in cancer development and therapeutics: From basic science to clinical practice
Authors: Lin Wen‐Chun , Lin You‐Tong , Chao Hui‐Ching , Lin Yen‐Yu , Hwang Wei‐Lun
Published: October 2023

Background

The tumour microenvironment (TME) is a specialised niche involving intercellular communication among cancer cells and various host cells. Among the host cells, the quantity and quality of immune cells within the TME play essential roles in cancer development and management. The immunologically suppressive, so‐called ‘cold’ TME established by a series of tumour–host interactions, including generating immunosuppressive cytokines and recruiting regulatory host immune cells, is associated with resistance to therapies and worse clinical outcomes.

Main body

Various therapeutic approaches have been used to target the cold TME, including immune checkpoint blockade therapy and adoptive T‐cell transfer. A promising, less explored therapeutic strategy involves targeting TME‐associated exosomes. Exosomes are nanometer‐sized, extracellular vesicles that transfer material from donor to recipient cells. These particles can reprogram the recipient cells and modulate the TME. In particular, exosomes from haematopoietic cells are known to promote or suppress cancer progression under specific conditions. Understanding the effects of haematopoietic cell‐secreted exosomes may foster the development of therapeutic exosomes (tExos) for personalised cancer treatment. However, the development of exosome‐based therapies has unique challenges, including scalable production, purification, storage and delivery of exosomes and controlling batch variations. Clinical trials are being conducted to verify the safety, feasibility, availability and efficacy of tExos.

Conclusion

This review summarises our understanding of how haematopoietic cell‐secreted exosomes regulate the TME and antitumour immunity and highlights present challenges and solutions for haematopoietic cell‐derived exosome‐based therapies.
Granulomatous mastitis: A diagnostic challenge—3 year single institutional experience
Authors: Khan Adil Aziz , Ahuja Sana , Zaheer Sufian , Ahluwalia Charanjeet , Singh Mukul , Kolte Sachin , Ranga Sunil
Published: October 2023

Background

Granulomatous mastitis (GM) is often clinico‐radiologically misdiagnosed as breast malignancy. Tuberculosis, foreign body reactions, fungal and parastic infections, and autoimmune diseases can cause GM. The present study aimed to assess the spectrum of GM on fine‐needle aspiration biopsy (FNAB) smears along with its histopathological and clinico‐radiological findings.

Materials and Methods

It was a retrospective study which included all cases of GM diagnosed on FNAB over a period of 3 years. The histopathological diagnosis was retrieved, wherever possible. All the FNA smears and histopathological sections were reviewed for the presence of epithelioid granulomas, necrosis, epithelioid histiocytes, inflammatory cells including plasma cells, neutrophils, eosinophils, multinucleated giant cells, and epithelial component and associated atypia, if any. The inflammatory cells and multinucleated giant cells were graded on a scale of 0 to 3+ in every case.

Results

Among the 22 cases evaluated, the most common inflammatory infiltrate was lymphocyte followed by neutrophils and eosinophils. Caseous necrosis was appreciated in 7 (31.8%) cases, out of which 5 (22.7%) were diagnosed as tubercular mastitis on FNA smears. Ziehl Neelson stain was done in all FNAB smears and AFB was positive in 7 (31.8%) cases.

Histopathological correlation was available for 14 cases (63.6%). The most common diagnosis on histopathology was idiopathic GM having lobulo‐centric granulomatous inflammation, epithelioid histiocytes, neutrophils, and lymphocytes.

Conclusion

FNAB is a reliable and minimally invasive tool to diagnose tubercular mastitis, idiopathic GM and also ruling out clinicoradiological suspicion of malignancy. Careful examination of cytological smears can prevent an unnecessary biopsy in granulomatous lesions of breast.
Evaluating new cosmeceuticals
Authors: Draelos Zoe D.
Published: October 2023

Evaluating cosmeceuticals can be challenging, as this category of functional cosmetics is rapidly changing and complex. The following nine steps can be followed to logically evaluate a new cosmeceutical and determine its value for a given patient: (1) Examine the packaging. (2) Note what claims are being made. (3) Read the ingredient disclosure to obtain a basic understanding of what skin benefit the product delivers. (4) Identify those active ingredients designed to improve skin appearance. These ingredients should provide longer‐lasting cumulative improvement with continued use. (5) Identify those inactive ingredients that are part of the vehicle providing improvement in skin texture and feel. These are more temporary in nature. (6) Perform an Internet search on those ingredients with which you are unfamiliar. (7) Evaluate the research supporting the product benefits to include white papers or published papers. (8) Determine the mechanisms of action for the ingredients and what the product actually accomplishes on the skin surface. (9) Put some product on the back of your hand and assess dry‐down characteristics, smell, viscosity, and so forth.
Chrononutrition in the context of Ramadan: Potential implications
Authors: Ali Tomader , Lessan Nader
Published: October 2023

Every year, healthy adult Muslims practice dawn to sunset fasting for a whole lunar month. No food or fluid is allowed for the fasting time window. After sunset, eating is allowed. The dramatic change in the timing of meals is accompanied by changes in sleeping hours and thus alterations in circadian rhythms. Hormonal mechanisms mainly determined by the latter also change. These include shifts in cortisol and melatonin. Food‐dependent hormones such as Ghrelin and leptin also show changes. A well‐established principle of chrononutrition is that the timing of eating may be as or more important than the content of food. Ramadan fasting (RF) is distinct from other forms of intermittent fasting, although there are also some similarities with time restricted eating (TRE). Both have been shown to have health benefits. Here, we examine existing literature to understand and learn from this very commonly practiced form of fasting and its relationships to circadian rhythms and homoeostatic mechanisms.
Engrailed: Pathological and physiological effects of a multifunctional developmental gene
Authors: Ma Xiang , Zhao Liang‐Liang , Yu Yi‐Chun , Cheng Yan
Published: October 2023

Engrailed‐1 (EN1) is a developmental gene that encodes En1, a highly conserved transcription factor involved in regionalization during early embryogenesis and in the later maintenance of normal neurons. After birth, EN1 still plays a role in the development and physiology of the body; for example, it exerts a protective effect on midbrain dopaminergic (mDA) neurons, and loss of EN1 causes mDA neurons in the ventral midbrain to gradually die approximately 6 weeks after birth, resulting in motor and nonmotor symptoms similar to those observed in Parkinson's disease. Notably, EN1 has been identified as a possible susceptibility gene for idiopathic Parkinson's disease in humans. EN1 is involved in the processes of wound‐healing scar production and tissue and organ fibrosis. Additionally, EN1 can lead to tumorigenesis and thus provides a target for the treatment of some tumors. In this review, we summarize the effects of EN1 on embryonic organ development, describe the consequences of the deletion or overexpression of the EN1 gene, and discuss the pathways in which EN1 is involved. We hope to clarify the role of EN1 as a developmental gene and present potential therapeutic targets for diseases involving the EN1 gene.
Geophysics reveals forest vulnerability to drought
Authors: McGrath Gavan S. , Fontaine Joe B. , Van Dongen Ricky , Hyde Josephine , Leopold Matthias , Matusick George , Ruthrof Katinka X.
Published: October 2023

Drought and heat‐induced forest die‐off are being increasingly reported across the planet. As vulnerable areas tend to have thin soils and poor water holding capacities, quantification of soil depth thresholds, relative to drought intensity, has global implications for identifying forest areas at risk. Measuring soil depth at forest stand or regional scales is, however, difficult. Our aim was to quantify soil thickness across drought impacted forest stands using geophysics. We asked whether impacted sites had shallow soils and whether soil thickness was associated with drought effects and forest structure. Electrical resistivity measurements were conducted at three sites in the Northern Jarrah Forest, Western Australia, which experienced die‐off during a 2010 drought and subsequent 2011 heatwave. Multispectral imaging quantified stand structure and vegetation cover. Geophysics identified shallow bedrock in the centre of all drought sites. Soil thicknesses correlated well with stand structure and cover, consistent with increasing water limitation in thinner soils. Smaller cover by trees and shrubs, more ground cover and shorter canopies were observed in soils <20 m thick and were more likely in soils <12 m thick, while treeless areas had thin soils, <2 m thick. The apparent resilience of this forest to long‐term drying looks to be due to the region's deep soils. With predicted future drying it is expected die‐off patches will expand outwards and new die‐off patches will emerge over thin soils. Geophysics can identify areas of forest vulnerable to future drought events, suggesting the potential for landscape‐scale mapping of drought vulnerability via airborne methods.
Accounting for heterogeneous density and detectability in spatially explicit capture–recapture studies of carnivores
Authors: McLellan Brynn A. , Howe Eric , Marrotte Robby R. , Northrup Joseph M.
Published: October 2023

Reliable estimates of population density are fundamental for managing and conserving wildlife. Spatially explicit capture–recapture (SECR) models in combination with information‐theoretic model selection criteria are frequently used to estimate population density. Variation in density and detectability is inevitable and, when unmodeled, can lead to erroneous estimates. Despite this knowledge, the performance of SECR models and information‐theoretic criteria remain relatively untested for populations with realistic levels of variation in density and detectability. We addressed this issue using simulations of American black bear (Ursus americanus) populations with variable density and detectability between sexes and across study areas. We first assessed the reliability of Akaike information criterion adjusted for small sample sizes (AICc) to correctly identify the true data generating model or a good approximating model. We then assessed the bias, accuracy, and precision of density estimates when such a model was selected or not. We demonstrated that unmodeled heterogeneity in detection and, more importantly, density can lead to pronounced bias. However, when a good approximating model is included in the candidate set, models with lower AICcincluded important forms of variation and yielded accurate estimates. We encourage researchers and practitioners to consider the impact of unmodeled variation in SECR models when making inferences and to strive to include covariates likely to be the most influential based on the species biology and ecology in candidate model sets. Doing so can improve the robustness of wildlife density estimation methods that can be leveraged to make more sound conservation and management decisions.
No impact of habitat fragmentation on condition and dispersal ability in the highly mobile butterfly Pieris rapae
Authors: Deppe Franziska , Achterberg Christoph , Dittmar Johanna‐Marie , Kunz Steffen , Näckel Lara , Wittkamp Luisa , Fischer Klaus
Published: October 2023

The loss and fragmentation of natural habitats due to agricultural intensification have a strong negative impact on farmland biodiversity. The concomitant isolation of essential resources may exert selection pressures toward increased dispersal performance in flying insects, possibly resulting in differences in flight morphology and dispersal propensity across landscapes. Here, we compared condition, flight morphology, dispersal capacity, and propensity of the common butterfly Pieris rapae among four pairs of highly fragmented “modern” and less fragmented “traditional” agricultural landscapes. We did not find differences between landscape types, but between locations and sexes. These results are not entirely unexpected, as P. rapae is a highly mobile generalist species, able to exploit temporarily available resources such as rapeseed in modern agricultural landscapes. In addition, our negative results may suggest a lack of time for evolutionary change such that differences may appear in the future. However, more specialized species with low dispersal ability may show clearer patterns and may well suffer from habitat fragmentation, and investigating such interrelation is an important task for future research.
The influence of advanced age on long‐term postsurgical analgesic use in patients receiving neuraxial anaesthesia for elective surgery
Authors: Sun Mingyang , Chen Wan‐Ming , Wu Szu‐Yuan , Zhang Jiaqiang
Published: October 2023

Objective

To determine the relationship between age and long‐term postsurgical analgesic use in patients who underwent elective surgery with neuraxial anaesthesia.

Design

Retrospective observational study using data from the National Health Insurance Research Database of Taiwan from 2015 to 2019.

Setting

National Health Insurance Research Database of Taiwan.

Patients

A total of 12,810 patients (6405 younger and 6405 older) matched using propensity score matching.

Interventions

Older (≥65 years).

Measurements

The use of long‐term (3 or 6 months) postoperative analgesics, including opioids, as a surrogate marker of chronic postsurgical pain (CPSP) was analysed using logistic regression.

Main Results

After 3 months of surgery, older adults had higher use of all analgesics (odds ratio [OR] = 1.15; 95% CI = 1.03–1.28) and opioids (OR = 1.18; 95% CI = 1.09–1.28) compared to younger patients. Similar results were observed after 6 months of surgery (all analgesic use: OR = 1.11; 95% CI = 1.03–1.20; opioid use: OR = 1.33; 95% CI = 1.07–1.81).

Conclusion

The findings from this study suggest that older adults are more likely to experience CPSP and have increased use of long‐term analgesics, including opioids, after undergoing elective surgery with neuraxial anaesthesia. The study highlights the need for improved pain management strategies for older adults after surgery.

Significance

Older age is an independent risk factor for long‐term analgesic use after surgery under neuraxial anaesthesiaanesthesia, indicating an increased risk for chronic postsurgical pain.
Haplotype reconstruction for genetically complex regions with ambiguous genotype calls: Illustration by the KIR gene region
Authors: van der Burg Lars L. J. , de Wreede Liesbeth C. , Baldauf Henning , Sauter Jürgen , Schetelig Johannes , Putter Hein , Böhringer Stefan
Published: October 2023

Advances in DNA sequencing technologies have enabled genotyping of complex genetic regions exhibiting copy number variation and high allelic diversity, yet it is impossible to derive exact genotypes in all cases, often resulting in ambiguous genotype calls, that is, partially missing data. An example of such a gene region is the killer‐cell immunoglobulin‐like receptor (KIR) genes. These genes are of special interest in the context of allogeneic hematopoietic stem cell transplantation. For such complex gene regions, current haplotype reconstruction methods are not feasible as they cannot cope with the complexity of the data. We present an expectation–maximization (EM)‐algorithm to estimate haplotype frequencies (HTFs) which deals with the missing data components, and takes into account linkage disequilibrium (LD) between genes. To cope with the exponential increase in the number of haplotypes as genes are added, we add three components to a standard EM‐algorithm implementation. First, reconstruction is performed iteratively, adding one gene at a time. Second, after each step, haplotypes with frequencies below a threshold are collapsed in a rare haplotype group. Third, the HTF of the rare haplotype group is profiled in subsequent iterations to improve estimates. A simulation study evaluates the effect of combining information of multiple genes on the estimates of these frequencies. We show that estimated HTFs are approximately unbiased. Our simulation study shows that the EM‐algorithm is able to combine information from multiple genes when LD is high, whereas increased ambiguity levels increase bias. Linear regression models based on this EM, show that a large number of haplotypes can be problematic for unbiased effect size estimation and that models need to be sparse. In a real data analysis of KIR genotypes, we compare HTFs to those obtained in an independent study. Our new EM‐algorithm‐based method is the first to account for the full genetic architecture of complex gene regions, such as the KIR gene region. This algorithm can handle the numerous observed ambiguities, and allows for the collapsing of haplotypes to perform implicit dimension reduction. Combining information from multiple genes improves haplotype reconstruction.
Potential biomarker for diagnosis and therapy of sepsis: Lactylation
Authors: Sun ZeXian , Song Yu , Li Jie , Li Yize , Yu YongHao , Wang Xin
Published: October 2023

Introduction

As a disease that has plagued human health for decades, sepsis has so far had no specific diagnostic or therapeutic indicators. The discovery of lactylation modifications not only uncovered the deep‐rooted causes of changing between lactate level and pathophysiology and immunology of sepsis, but also reaffirmed the inevitable link between metabolic reprogramming and epigenetic reprogramming in sepsis. Lactylation modification became a potential marker for diagnosis and guiding the treatment of sepsis.

Aim

In this paper, we will summarize the discovery and regulation of lactylation modifications, discuss the study of lactylation modifications in sepsis, and evaluate their possibility and potential as diagnostic and therapeutic indicators of sepsis.

Conclusion

Lactylation modification is directly regulated by glycolysis and lactate, and inhibition of glycolytic pathway‐related enzymes can regulate the level of lactylation modification, and more importantly, lactylation modification can act on these enzymes to regulate their functions and feedback regulate the level of glycolysis, this finding provides more ideas for clinical treatment of sepsis. We use “epigenetic modification”, “glycolysis”, “lactate”, “lactylaiton” and “sepsis” as keywords and search the relevant literature through Pubmed and Web of science up to 2023.
Mechanistic insights into the role of probiotics in modulating immune cells in ulcerative colitis
Authors: Guo Ni , Lv Lu‐lu
Published: October 2023

Background

Ulcerative colitis (UC) is a persistent inflammatory disorder that affects the gastrointestinal tract, mainly the colon, which is defined by inflammatory responses and the formation of ulcers. Probiotics have been shown to directly impact various immune cells, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and T and B cells. By interacting with cell surface receptors, they regulate immune cell activity, produce metabolites that influence immune responses, and control the release of cytokines and chemokines.

Methods

This article is a comprehensive review wherein we conducted an exhaustive search across published literature, utilizing reputable databases like PubMed and Web of Science. Our focus centered on pertinent keywords, such as “UC,” ‘DSS,” “TNBS,” “immune cells,” and “inflammatory cytokines,” to compile the most current insights regarding the therapeutic potential of probiotics in managing UC.

Results

This overview aims to provide readers with a comprehensive understanding of the effects of probiotics on immune cells in relation to UC. Probiotics have a crucial role in promoting the proliferation of regulatory T cells (Tregs), which are necessary for preserving immunological homeostasis and regulating inflammatory responses. They also decrease the activation of pro‐inflammatory cells like T helper 1 (Th1) and Th17 cells, contributing to UC development. Thus, probiotics significantly impact both direct and indirect pathways of immune cell regulation in UC, promoting Treg differentiation, inhibiting pro‐inflammatory cell activation, and regulating cytokine and chemokine release.

Conclusion

Probiotics demonstrate significant potential in modulating the immune reactions in UC. Their capacity to modulate different immune cells and inflammation‐related processes makes them a promising therapeutic approach for managing UC. However, further studies are warranted to optimize their use and fully elucidate the molecular mechanisms underlying their beneficial effects in UC treatment.