bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Acid/alkali All Covalent Organic Frameworks Battery
Authors: Xu Yunpeng , Cai Pingwei , Chen Kai , Chen Qingsong , Wen Zhenhai , Chen Long
Published: February 2023

Covalent organic frameworks (COFs), thanks to their adjustable porous structure and abundant build‐in functional motifs, have been recently regarded as promising electrode materials for a variety of batteries. There still remain grand opportunities to further utilizing their merits for developing advanced COFs‐based batteries. In this paper, we propose a hybrid acid/alkali all‐COFs battery by coupling pyrene‐4,5,9,10‐tetraone based COF cathode with anthraquinone based COF anode. In such a hybrid acid/alkali all‐COFs battery, the cathodic COF favorably works in acid with a relatively positive potential, while the anodic COF preferably runs in alkali with a relatively negative potential. It thus can deliver a decently high discharge capacity of 92.97 mAh g−1with a wide voltage window of 2.0 V, and exhibit high energy density of 74.2 Wh kg−1along with a considerable cyclic stability over 300 cycles. The development of the proof‐of‐concept all‐COFs battery may drive forward the improvement of newly cost‐effective and performance‐reliable energy storage devices.
Systematic Enzymatic Synthesis of dTDP‐Activated Sugar Nucleotides
Authors: Wei Fangyu , Yuan Rui , Wen Qin , Wen Liuqing
Published: February 2023

Deoxythymidine diphosphate (dTDP)‐activated sugar nucleotides are the most diverse sugar nucleotides in nature. They serve as the glycosylation donors of glycosyltransferases to produce various carbohydrate structures in living organisms. However, most of the dTDP‐sugars are difficult to obtain due to synthetic difficulties. The limited availability of dTDP‐sugars has hindered progress in investigating the biosynthesis of carbohydrates and exploring new glycosyltransferases in nature. In this study, based on the de novo and salvage biosynthetic pathways, a variety of dTDP‐activated sugar nucleotides were successfully prepared in high yields and on a large scale from readily available starting materials. The produced sugar nucleotides could provide effective tools for fundamental research in glycoscience.
Ferroptosis Detection: From Approaches to Applications
Authors: Zeng Fantian , Nijiati Sureya , Tang Longguang , Ye Jinmin , Zhou Zijian , Chen Xiaoyuan
Published: February 2023

Understanding the intricate molecular machinery that governs ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. Emerging approaches for the in situ detection of the major regulators and biological events across cellular, tissue, and in living subjects provide a multiscale perspective for studying ferroptosis. Furthermore, advanced applications that integrate ferroptosis detection and the latest technologies hold tremendous promise in ferroptosis research. In this review, we first briefly summarize the mechanisms and key regulators underlying ferroptosis. Ferroptosis detection approaches are then presented to delineate their design, mechanisms of action, and applications. Special interest is placed on advanced ferroptosis applications that integrate multifunctional platforms. Finally, we discuss the prospects and challenges of ferroptosis detection approaches and applications, with the aim of providing a roadmap for the theranostic development of a broad range of ferroptosis‐related diseases.
Anticooperative Supramolecular Oligomerization Mediated by V‐Shaped Monomer Design and Unconventional Hydrogen Bonds
Authors: Matarranz Beatriz , Díaz‐Cabrera Sandra , Ghosh Goutam , Carreira‐Barral Israel , Soberats Bartolome , García‐Valverde María , Quesada Roberto , Fernández Gustavo
Published: February 2023

After more than three decades of extensive investigations on supramolecular polymers, strategies for self‐limiting growth still remain challenging. Herein, we exploit a new V‐shaped monomer design to achieve anticooperatively formed oligomers with superior robustness and high luminescence. In toluene, the monomer‐oligomer equilibrium is shifted to the monomer side, enabling the elucidation of the molecular packing modes and the resulting (weak) anticooperativity. Steric effects associated with an antiparallel staircase organization of the dyes are proposed to outcompete aromatic and unconventional B−F⋅⋅⋅H−N/C interactions, restricting the growth at the stage of oligomers. In methylcyclohexane (MCH), the packing modes and the anticooperativity are preserved; however, pronounced solvophobic and chain‐enwrapping effects lead to thermally ultrastable oligomers. Our results shed light on understanding anticooperative effects and restricted growth in self‐assembly.
Enantioselective Synthesis of Bromodifluoromethyl‐containing Oxazolines by Concerted Lewis/Brønsted Base Catalysis with Chiral Bisphosphine Oxide
Authors: Hirokawa Ryo , Nakahara Yuki , Uchida Shotaro , Yamashita Kenji , Hamashima Yoshitaka
Published: February 2023

We describe regio‐ and enantioselective bromocyclization of difluoroalkenes catalyzed by chiral bisphosphine oxides. Owing to the simultaneous activation of both the brominating reagent and amide substrate, the desired cyclization reaction proceeds smoothly even at low temperature to provide bromodifluoromethyl‐containing oxazolines with a chiral quaternary center in a highly enantioselective fashion (up to 99% ee). This protocol features the use of commercially available brominating reagents and readily accessible chiral catalysts. The regioselectivity and enantioselectivity are influenced by the catalyst structure, the brominating reagent, and the reaction temperature. Under the optimal conditions, 5‐exo cyclization proceeds preferentially compared with 6‐endo cyclization, depending on the electronic properties of the alkene substrates. A gram‐scale synthesis of chiral oxazoline was achieved with as little as 1 mol % of the catalyst.
Cross‐replicating findings on unique motor impairments of children with ASD using confirmatory factor analysis and a novel SPARK study sample
Authors: Bhat Anjana , Tulsky David S. , Boulton Aaron J.
Published: February 2023

A series of recent reports have shed light on the pervasive nature of motor impairments in children with ASD (Bhat, 2020, 2021, Bhat et al., 2022), underscoring the importance of providing ASD clinicians efficient and accurate tools for motor screening. The Developmental Coordination Disorder‐Questionnaire (DCD‐Q) is a widely used motor screening tool, yet scant evidence exists regarding its psychometric properties in children with ASD. In a recent Exploratory Factor Analysis (EFA) of the 15‐item DCD‐Q in a large sample of children with ASD (SPARK study), we found a 5‐factor latent structure that identified unique motor impairments in a large sample of children with ASD (Bhat et al., 2022). In the current study, we extend this work by cross‐replicating the EFA findings of unique ASD‐related motor issues using Confirmatory Factor Analysis (CFA) in a new, more recent wave of children with ASD from the SPARK study (N = 9721). The fits and interpretability of 11 hypothesis‐driven CFA models, including 8 correlated‐factors, 1 second‐order, and 2 bifactor models were compared. Our findings supported the previous 5‐factor model with 2 gross motor subdomains, 1 fine motor domain (similar to the original DCD‐Q) and 2 general coordination subdomains. This model demonstrated acceptable fit in the new sample as well as superior fit compared to several other parsimonious correlated‐factors models. However, the second‐order and bifactor models fit slightly better and supported the presence of a general motor skills factor, although 38% of the common variance in the DCD‐Q items remained attributable to the 5 subdomains. Using one of the bifactor models, measurement invariance was also supported for DCD‐Q across sex, race, and co‐occurring conditions of language disorder and intellectual disability. Only partial invariance was supported when testing DCD‐Q scores across different age groups. These findings reveal a more complex dimensional picture of the DCD‐Q in children with ASD. Results suggest that the DCD‐Q can be used in two ways, total scores adequately assess general motor skills for brief screening and subdomain scores offer unique information on the multidimensional motor problems of children with ASD. If subdomain data are of interest, our findings call into question the practice of relying on 3 original subscales of the DCD‐Q when screening for ASD‐related motor difficulties, whereas 4 out of 5 subscale scores may better highlight domain‐specific motor problems. Future studies should continue to further validate DCD‐Q's ability to screen for multidimensional motor problems.
Biological potential of polysaccharides extracted from Nostoc colonies for film production – Physical and biological properties
Authors: Jasińska Joanna Maria , Kamińska Iwona , Chmiel Maria J. , Jamróz Ewelina
Published: February 2023

Cyanobacteria of the Nostoc genus secrete a number of biologically active compounds, including polysaccharides, which may exhibit antioxidant, antimicrobial, anticancer, and anti‐inflammatory properties. The aim of the study was to investigate the biological properties of Nostoc polysaccharides (NPs) (antioxidative and antimicrobial) and the possibility of using NPs addition in the production of biofoils. Our results allow to indicate that NPs were compatible with the used biopolymer matrix (furcellaran and chitosan) and showed antioxidant properties. The tested polysaccharide extracts (0.14%) exhibited the ability to neutralize free radicals – 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) at a level of 4.46% and 10.14%, respectively. NP extracts demonstrated reducing properties of 15.35 and 30.07 mg Trolox equivalents (FRAP and CUPRAC methods, respectively) and 2.64 mg chlorogenic acid equivalents (tested with Folin's reagent). NP extracts showed: a growth‐stimulating effect (Escherichia coli, Staphylococcus aureus, and Saccharomyces cerevisiae), no effect (Penicillum sp.), or a slight inhibitory effect (Streptomyces sp.) on the tested microorganisms. The enrichment of the film with NPs influenced the physic‐chemical properties of the obtained biofoils. The addition of polysaccharides to furcellaran and chitosan films decreased their water solubility (by approximately 40% and 9%, respectively, compared to the control) and, at the same time increased, their water absorption.
Intelligent micro/nanorobots for improved tumor therapy
Authors: Sun Zhaoli , Hou Yanglong
Published: February 2023

A major bottleneck underlying nanomaterial‐based tumor therapy lies in complex biological environment and physiological barriers. Micro/nanorobots with the features of self‐propulsion and controllable navigation have gradually become a research hotspot in the tumor therapeutic community, exhibiting their advantages in efficient cargo loading, controllable cargo delivery, stimuli‐triggered cargo release, deeper tumor tissue penetration, and enhanced cargo accumulation in tumor tissue. In this review, the self‐propulsion and controllable navigation are introduced as two major properties of micro/nanorobots, in which micro/nanorobots are propelled by chemical reactions, physical fields, and biological systems and could be navigated by chemotaxis, remote magnetic guidance, and light. Then, the recent advances of micro/nanorobots for chemotherapy, immunotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, and multimodal tumor therapy would be discussed. Finally, the perspective and challenges are also mentioned. It is expected that this review gives an insight into intelligent micro/nanorobots for improved tumor therapy, aiming for more extensive and in‐depth investigations, and final applications in the clinic.
Gender and sex in eating disorders: A narrative review of the current state of knowledge, research gaps, and recommendations
Authors: Breton Édith , Juster Robert‐Paul , Booij Linda
Published: February 2023

Introduction

Eating disorders (EDs) have long been considered conditions exclusively affecting women, and studies in the ED field regularly exclude men. Research efforts are needed to better understand the role of gender and sex in EDs. This review describes the role of gender and sex in the development of EDs from a biopsychosocial perspective.

Methods

The primary hypothesis of this narrative review is that gender and sex interact to influence ED risk. The literature review was conducted using the PubMed database.

Results

This review first presents the general characteristics and prevalence of EDs according to gender and sex. Next, neurodevelopmental processes, neurobiology, gender roles, body image, and the minority stress model are addressed. Lastly, research perspectives to better include gender and sex in the field of EDs are discussed (e.g., representation of gender and sex diversities, development of appropriate assessment tools, and increasing awareness).

Conclusion

Although substantial knowledge gaps remain, there is a growing recognition of the importance of integrating gender and sex in ED research that holds promise for further development in the field.
Sustainable development‐oriented regulatory and competitive pressures to shift toward a circular economy: The role of environmental orientation and Industry 4.0 technologies
Authors: Al‐Swidi Abdullah Kaid , Hair Joseph F. , Al‐Hakimi Mohammed A.
Published: February 2023

Automakers' transition from a linear economy to a circular economy (CE) in response to sustainable development‐oriented regulatory and competitive pressures is a challenging process that requires innovative, practical technologies. However, Industry 4.0 (I4.0) technologies are an important part of the transition to CE for environmentally friendly companies. In this study, we examine whether regulatory pressure (RP) and competitive pressure (CP) toward sustainability motivate firms to implement I4.0 technologies for CE, along with the mediating effects of environmental orientation (EO). PLS‐SEM via SmartPLS software was used to analyze data from 230 managers in the automotive and auto component manufacturing industries in India. The findings of this study showed that RP and CP positively influence I4.0 adoption, which impacts CE capability. Furthermore, EO partially mediates the relationship between RP and CP with I4.0 technologies. As a practical implementation of this study, to transition to CE and contribute to sustainable development, managers need to deal effectively with RP and CP. Several implications for theory and practice are discussed at the end of the study.
Open strategy and dynamic capabilities: A framework for circular economy business models research
Authors: De Angelis Roberta , Morgan Robert , De Luca Luigi M.
Published: February 2023

The circular economy has attracted the interest of business leaders, policy makers and academics alike for its potential to contribute to a more resilient, prosperous and resource‐efficient economy. The transition towards a circular economy requires new business models that challenge the linear logic of value creation that is still endemic across most industries. In turn, the transition from linear to circular business models involves the rethinking of strategic decision‐making processes and the development of new organisational capabilities. This paper addresses these important strategic implications of the emergence and implementation of circular business models. Coupling business models with open strategy and dynamic capabilities, we develop a “three‐pronged” strategy framework that advances the emerging field of circular business model research. Our contribution is crystallised into a series of propositions and future research questions for scholars working at the intersection of the circular economy and the strategy literature.
Controlled Release of Doxorubicin from Magnetoliposomes Assisted by Low‐Frequency Magnetic Field
Authors: Maron Edyta , Krysinski Paweł , Chudy Michał
Published: February 2023

The article presents magnetoliposomes as potential carriers of doxorubicin. The magnetic properties of nanoparticles embedded in liposomes enable the targeting of drug‐loaded carriers to cancer cells and subsequent release of their payload using an external alternating magnetic field as a trigger. The cytotoxicity of empty and doxorubicin‐loaded magnetoliposomes in the absence and after exposure to magnetic field was evaluated in cancerous and normal breast cells. The characteristic shows the carrier with size distribution <130 nm, slightly negative zeta potential and polydispersity index <0.2. Doxorubicin was encapsulated in magnetoliposomes with an efficiency of 31 % and released in the presence of an alternating magnetic field at 50 %. Magnetoliposomes with drug provided high cytotoxic effect on tumor cells and low cytotoxic effect on normal cells. The research conducted in this article may indicate the potential application of the studied magnetoliposomes in release of drugs under the influence of magnetic field in cancer cells.
Clinical image report of a patient with cerebral schistosomiasis
Authors: Al‐Ameen Osamah , Faisal Mohanad , Yacout Khalid
Published: February 2023

Neuro‐schistosomiasis is one of the most severe manifestations of Schistosoma infection. We report an MRI image of a patient who presented with a headache and was found to have a space‐occupying lesion on an MRI of the brain that was suggestive of neuro‐schistosomiasis and was successfully treated without invasive testing.
A case of Eagle syndrome with a marked elongation of the styloid process; investigating its relation to ankylotic spondylitis
Authors: Angelou Dimitrios , Hope Nicholas , Canning John , Stewart Rosemary
Published: February 2023

Eagle syndrome is characterized by the presence of an abnormally elongated styloid process and has been related to different etiologies, including enthesitis, a known feature of spondyloarthropathies. We are describing a case of marked elongation of the styloid process in a patient with pre‐existing ankylosing spondylitis and associated enthesopathy.
Auricular mucormycosis complicated by parotid abscess and facial paralysis: A very rare case report
Authors: Hammemi Bouthaina , Achour Imen , Walha Omar , Yousfi Ghada , Mnejja Malek , Charfeddine Ilhem
Published: February 2023

Mucormycosis is a serious and relatively rare invasive fungal infection. The rhino‐orbito‐cerebral localization is the most frequent. Other localizations have been reported including: cutaneous, pulmonary, disseminated, gastrointestinal, and miscellaneous. Mucormycosis of external ear with facial palsy is extremely rare and only few cases have been reported in the literature. We describe a case of mucormycosis of the external and middle in a 44‐years‐old diabetic patient which had a very aggressive form of necrotic infection of the ear auricle complicated by parotid abscess, facial, and vagal nerve paralysis. Auricular mucormycosis was suspected and the diagnosis was established after biopsy and histological examination. The patient was treated immediately with intravenous amphotericin B followed by extensive surgical debridement of the necrotic lesions. The patient responded well to the treatment despite the persistence of facial palsy.
Acute ethmoiditis complicated by intraorbital abscess, orbital cellulitis, and cerebral empyema in a 14‐year‐old girl
Authors: Colombe Moise Mbaluku , Nabuloho Erick Heri , Opondjo Fernand Manga , Bianga Viviane Feza , Rodrigue Fikiri Bavurhe , Isonga Stéphanie Sifa , Shemahamba Peniel Kundo , Birindwa Archippe Muhandule
Published: February 2023

We report the case of a 14‐year‐old girl with pain and protrusion of the left eye and treated with diclofenac. Clinical and paraclinical examinations revealed a cerebral empyema and a left retro‐orbital abscess complicating an acute ethmoiditis. Parenteral antibiotic remains essential in the management of acute ethmoiditis to prevent complications.
Hepatic portal venous gas in the case of superior mesenteric artery thrombosis in a young adult‐case report
Authors: Dhakal Prakash , Sharma Suraj , Sharma Abhishek , Pandey Shailendra , Aryal Sajiva , Bhandari Seema
Published: February 2023

Hepatic portal venous gas is diagnosed via computed tomography due to unusual imaging features. HPVG when linked with pneumatosis intestinalis has a high mortality rate and required urgent intervention. We present a case of a 26‐year‐old young adult with superior mesenteric artery thrombosis who presented with severe abdominal pain. On imaging, HPVG and pneumatosis intestinalis were seen owing to the urgent intervention of the patient. The reliable interpretation of the imaging findings along with quick intervention led to a favorable outcome in our case. Herein, we present a thorough review of the imaging findings of HPVG to make a reliable diagnosis when presented with such a case.
Spontaneous idiopathic spinal subdural hemorrhage in a 16‐year‐old boy: A rare case in pediatrics and review of literature
Authors: Ahrari Iman , Jamali Mohamad , Mohammadi Somayeh , Ghavipisheh Mahsa , Eghbal Keyvan , Saffarian Arash , Rahmanian Abdolkarim , Ghahramani Soulmaz , Taheri Reza
Published: February 2023

Idiopathic spinal subdural hematoma (SSDH) is a rare phenomenon. Here, we present a 16‐year‐old‐boy who presented with acute sudden onset weakness and brown squared syndrome; the cervical MRI findings showed acute subdural hematoma from C2 to C6. Emergent surgical intervention was performed, and significant improvement was seen in follow‐ups.
Erdheim‐Chester disease: A multisystem disease case illustration with rare manifestations and treatment challenges
Authors: Jridi Maysam , Ben Achour Tayssir , Naceur Ines , Smiti Monia , Ben Ghorbel Imed , Lamloum Mounir , Said Fatma , Houman Mohamed Habib
Published: February 2023

Erdheim‐Chester disease is a rare multisystemic disease. A 50‐year‐old woman, presented with a recurrent pain and swelling of the left knee. Bone scintigraphy showed increased tracer uptake of peripheral skeleton. The computed tomography showed tissular infiltration in the retroperitoneum, around the vessels. Immunohistochemistry showed CD68 (+) and CD1a (−).
Hematuria during the right heart catheterization procedure: Renal perforation as a very rare complication
Authors: Jenab Yaser , Tofighi Saeed , Navid Hossein , Riazi Homan , Samimi Sahar
Published: February 2023

The occurrence of hematuria during a right heart catheterization can be a sign of renal perforation, a rare but life‐threatening complication that could be developed due to the misdirection of wire into the abdominopelvic venous plexus. We showed this complication could be managed with venoplasty of the common iliac vein.
Benocyclidine (BTCP) as Non‐labelled Reporter Ligand for MS Binding Assays for the PCP Ion Channel Binding Site of the Desensitized Torpedo Nicotinic Acetylcholine Receptor (nAChR)
Authors: Währa Mark , Allmendinger Lars , Höfner Georg , Wanner Klaus T.
Published: February 2023

In this study we present MS Binding Assays for the PCP ion channel binding site of Torpedo californica nicotinic acetylcholine receptor (nAChR) as an alternative to radioligand binding assays. As MS Marker Benocyclidine (BTCP) was employed, found to be more affine (Kdof 84.2 nM) than the radioligands, e. g. [3H]PCP, used so far in respective binding assays. Based on a highly sensitive and fast LC‐ESI‐MS/MS method for quantification of BTCP samples, BTCP MS Binding Assays for the PCP ion channel binding site of Torpedo nAChR could be established comprising saturation, kinetic and competition experiments. The affinities obtained in competitive BTCP MS Binding Assays for ligands addressing the PCP ion channel binding site of Torpedo nAChR were in excellent accord with those reported from radioligand experiments. Thus, the new BTCP MS Binding Assays represent a potent and reliable alternative to radioligand binding assays used so far for the characterization of ligand binding to the PCP ion channel binding site of the nAChR.
Applying a risk prediction model for bloodstream infection in a febrile, nonseverely neutropenic cohort of pediatric stem cell transplant patients
Authors: Jackson Kasey , Anderson Victoria , Zhao Zhiguo , Kitko Carrie L. , Connelly James A. , Ho Richard H. , Banerjee Ritu , Dulek Daniel E. , Friedman Debra L. , Esbenshade Adam J.
Published: February 2023

Background

The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC] ≥ 500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT‐specific data are limited.

Methods

All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c‐statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model (EsVanAlloSCT), was developed and internally validated.

Results

For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p < .01). All versions of the EsVan model performed well for the overall SCT cohort (c‐statistics, 0.759–0.795). The EsVan models performed better for the autologous episodes (c‐statistics, 0.869–0.881) than the allogeneic SCT episodes (c‐statistics, 0.678–0.717). The new allogeneic transplant–specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c‐statistic of 0.792 (bootstrap‐corrected, 0.750).

Conclusions

The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.
Direct Conversion of CO2 in Lime Kiln Waste Gas Catalyzed by a Copper‐Based N‐heterocyclic Carbene Porous Polymer
Authors: Rao Zhi‐Xiu , Chen Pei‐Bo , Xu Jin , Wang Qing , Tang Hai‐Tao , Liang Ying , Pan Ying‐Ming
Published: February 2023

Industrial waste gas is one of the major sources of atmospheric CO2, yet the direct conversion of the low concentrations of CO2 in waste gases into high value‐added chemicals have been a great challenge. Herein, a copper‐based N‐heterocyclic carbene porous polymer catalyst (Cu@NHC‐1) for the direct conversion of low concentration CO2 into oxazolidinones was successfully fabricated via a facile copolymerization process followed by the complexation with Cu(OAc)2. A continuous flow device was designed to deliver a continuous and stable carbon source for the reaction. Due to the triple synergistic effect of its porous structure, nitrogen activation sites and catalytic Cu center, Cu@NHC‐1 shows highly efficient and selective adsorption, activation, and conversion of the low concentration CO2 (30 vol%). Its practical application potential is demonstrated by the ability to successfully convert the CO2 in lime kiln waste gas into oxazolidinones in satisfactory yields under mild conditions.
Do dried blood spots have the potential to support result management processes in routine sports drug testing?—Part 3: LC–MS/MS‐based peptide analysis for dried blood spot sampling time point estimation
Authors: Brockbals Lana , Thomas Andreas , Schneider Tom D. , Kraemer Thomas , Steuer Andrea E. , Thevis Mario
Published: February 2023

Along with the recent acknowledgement of the World Anti‐Doping Agency to use dried blood spot (DBS) samples for routine doping control purposes, there have been propositions to use DBS as a matrix that allows regular proactive remotely supervised self‐sampling, providing potential longitudinal monitoring of an athlete's exposure to doping agents. However, several organizational aspects have to be considered before implementation, such as the verification of the sample collections time point. Based on a previous untargeted proteomics workflow utilizing liquid chromatography–high‐resolution mass spectrometry (LC–HRMS) to identify protein/peptide markers to define the time since deposition of a bloodstain, the aim of the current study was to develop a targeted LC–HRMS/MS analytical method for promising peptidic target analytes. A long‐term DBS storage experiment was carried out over a 3‐month period (sample collection time points: 0, 2, 4, 7, 14, 21, 28, 42, 56, 70, 84 and 91 days) with DBS samples of 10 volunteers for longitudinal investigation of signal abundance changes of targeted peptide sequences at different storage temperatures (room temperature [RT], 4°C and −20°C). Prior to experimental analysis, LC–HRMS/MS method characteristics were successfully assessed, including intraday precision, carryover and sample extract stability. For estimation of DBS sample collection time points, ratios of two peptides that originate from the same protein prior to tryptic digestion were created. Two targeted peptide area ratios were found to significantly increase after being stored at RT for 28 days, representing potential markers for future use in routine doping controls that contribute to advancing complementary avenues in anti‐doping.
Cell‐type profiling of the sympathetic nervous system using spatial transcriptomics and spatial mapping of mRNA
Authors: Kasemeier‐Kulesa Jennifer C. , Morrison Jason A. , McKinney Sean , Li Hua , Gogol Madelaine , Hall Kate , Chen Shiyuan , Wang Yongfu , Perera Anoja , McLennan Rebecca , Kulesa Paul M.
Published: February 2023

Background

The molecular identification of neural progenitor cell populations that connect to establish the sympathetic nervous system (SNS) remains unclear. This is due to technical limitations in the acquisition and spatial mapping of molecular information to tissue architecture.

Results

To address this, we applied Slide‐seq spatial transcriptomics to intact fresh frozen chick trunk tissue transversely cryo‐sectioned at the developmental stage prior to SNS formation. In parallel, we performed age‐ and location‐matched single cell (sc) RNA‐seq and 10× Genomics Visium to inform our analysis. Downstream bioinformatic analyses led to the unique molecular identification of neural progenitor cells within the peripheral sympathetic ganglia (SG) and spinal cord preganglionic neurons (PGNs). We then successfully applied the HiPlex RNAscope fluorescence in situ hybridization and multispectral confocal microscopy to visualize 12 gene targets in stage‐, age‐ and location‐matched chick trunk tissue sections.

Conclusions

Together, these data demonstrate a robust strategy to acquire and integrate single cell and spatial transcriptomic information, resulting in improved resolution of molecular heterogeneities in complex neural tissue architectures. Successful application of this strategy to the developing SNS provides a roadmap for functional studies of neural connectivity and platform to address complex questions in neural development and regeneration.
Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF‐3845: A regional analysis of the contribution of endocannabinoid signaling machinery
Authors: de Ceglia Marialuisa , Micioni Di Bonaventura Maria Vittoria , Romano Adele , Friuli Marzia , Micioni Di Bonaventura Emanuela , Gavito Ana L. , Botticelli Luca , Gaetani Silvana , de Fonseca Fernando Rodríguez , Cifani Carlo
Published: February 2023

Objective

Consumption of energy‐dense palatable “comfort” food can alleviate stress and negative emotions, while abrupt withdrawal from a palatable diet can worsen these symptoms, causing difficulties with adherence to weight‐loss diets. Currently, no pharmacological treatment is effective for obesity‐related anxiety, so we investigated the endocannabinoid system (ECS), and specifically the fatty acid amide hydrolase (FAAH), as an interesting emerging target in this context because of its key role in the regulation of both energy homeostasis and emotional behavior.

Methods

Rats were subjected to exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence period, rats were treated with the selective FAAH inhibitor PF‐3845 (10 mg/kg; intraperitoneal administration every other day).

Results

Abstinent rats displayed an anxiogenic‐like behavior and changes in the proteins of ECS signaling machinery in brain areas involved both in anxiety and food intake regulation. In particular, withdrawal caused a reduction of the expression of cannabinoid receptors in the nucleus accumbens and of enzymes diacylglycerol lipase alpha and monoacylglycerol lipase (MAGL) in the amygdala. Pharmacological inhibition of FAAH exerted an anxiolytic‐like effect in abstinent animals and increased both MAGL expression in amygdala and CB2 expression in prefrontal cortex.

Discussion

Overall, our results suggest that emotional disturbances associated with dieting are coupled with region‐specific alterations in the cerebral expression of the ECS and that the enhancement of the endocannabinoid signaling by FAAH inhibition might represent a novel pharmacological strategy for the treatment of anxiety related to abstinence from palatable food.

Public Significance

The present study focused on evaluating the role of the endocannabinoid system in modulating withdrawal from naturally rewarding activities that have an impact on mood, such as feeding. The variations observed in the emotional behavior of abstinent rats was linked to neuroadaptations of the ECS in specific brain areas.
The role of readiness and confidence to change in the treatment of atypical anorexia nervosa and bulimia nervosa
Authors: Keegan Ella , Wade Tracey D.
Published: February 2023

Objective

Atypical anorexia nervosa (AN) is a serious eating disorder that is more common in the population than AN. Despite this, people with atypical AN are less likely to be referred or admitted for eating disorder treatment and there is evidence that they are less likely to complete or benefit from existing interventions. This study examined whether baseline readiness and/or confidence moderated outcomes from 10‐session cognitive behavioral therapy among people with atypical AN and bulimia nervosa (BN), and whether the impact of these variables differed between diagnoses.

Methods

Participants (n = 67; 33 with atypical AN) were a subset from an outpatient treatment study. Linear mixed model analyses were conducted to examine whether baseline readiness and/or confidence moderated outcomes.

Results

People with BN who had higher levels of readiness or confidence at baseline had steeper decreases in eating disorder psychopathology over time. There was no evidence that readiness or confidence moderated outcomes for people with atypical AN.

Discussion

This study suggests that the moderators that have been identified for other eating disorders may not apply for people with atypical AN and highlights a need for future work to routinely investigate whether theoretically or empirically driven variables moderate outcomes in this little‐understood population.

Public Significance Statement

People with bulimia nervosa with higher readiness and confidence experienced greater decreases in eating disorder symptoms than people with lower readiness and confidence when treated with cognitive behavioral therapy. These findings did not apply to people with atypical anorexia nervosa. Results demonstrate that future work is urgently required to identify helpful treatments for people with atypical anorexia nervosa as well as the variables that have a positive impact on outcomes in treatment for these individuals.
Long‐term risk stratification for hospitalized patients with acute heart failure at a single rural cardiovascular centre
Authors: Satogami Keisuke , Katayama Yosuke , Ozaki Yuichi , Taruya Akira , Taniguchi Motoki , Ota Shingo , Kuroi Akio , Shiono Yasutsugu , Tanimoto Takashi , Yamano Takashi , Kitabata Hironori , Ino Yasushi , Tanaka Atsushi
Published: February 2023

Aims

Early risk stratification of patients with acute heart failure (AHF) is critical for appropriate triage and outcome improvement. The serum sodium, blood urea nitrogen, age, serum albumin, systolic blood pressure, and natriuretic peptide level (SOB‐ASAP) score can predict in‐hospital mortality of AHF. However, the relationship between the SOB‐ASAP score and long‐term prognosis is unknown. This study investigated the determinants of the long‐term prognosis of AHF by evaluating the SOB‐ASAP score.

Methods

This retrospective cohort study included all patients with acute decompensated heart failure who were admitted to our hospital between April 2017 and March 2018. And those who discharged were analysed retrospectively. The follow‐up period was 3 years. Primary end point was all‐cause death.

Results

Total of 140 patients were analysed. The median SOB‐ASAP score of entire cohort on admission was 3 points (interquartile range; 1–5). The Kaplan–Meier curve demonstrated that patients in the higher SOB‐ASAP group (score ≥3) had a higher incidence of all‐cause death (log‐rank test; P < 0.001) than those in the lower SOB‐ASAP (group score <3).

Conclusions

At admission, the SOB‐ASAP score may be useful for predicting the long‐term prognosis of hospitalized patients with AHF.
Fibrosis‐4 index identifies worsening renal function associated with adverse outcomes in acute heart failure
Authors: Tsuda Kosuke , Maeda Daichi , Kanzaki Yumiko , Sakane Kazushi , Okuno Takahiro , Nakayama Sayuri , Tokura Daisuke , Hasegawa Hitomi , Hoshiga Masaaki
Published: February 2023

Aims

Worsening renal function (WRF) often develops during heart failure (HF) treatment. However, prognostic implications of WRF in acute HF remain controversial, and risk stratification of WRF is challenging. Although the fibrosis‐4 index (FIB‐4) was initially established as a liver fibrosis marker, recent studies show that high FIB‐4 is associated with venous congestion and poor prognosis in acute HF. This study aimed to evaluate whether FIB‐4 could identify prognostically relevant and non‐relevant WRF in patients with acute HF.

Methods and results

We retrospectively analysed data from a single‐centre registry on acute HF at our university hospital between January 2015 and June 2021. This study included patients with acute HF aged ≥20 years who were immediately hospitalized and had brain natriuretic peptide levels ≥100 pg/mL at admission. WRF was defined as increases of ≥0.3 mg/dL and >25% in serum creatinine level from admission to discharge. FIB‐4 scores were calculated before discharge. The primary endpoint was all‐cause mortality within 1 year of discharge. Based on the presence of WRF and whether FIB‐4 scores were above the median, patients were stratified into four groups: no WRF and lower FIB‐4 scores, no WRF and higher FIB‐4 scores, WRF and lower FIB‐4 scores, and WRF and higher FIB‐4 scores. The patients were followed up via clinical visits or telephone interviews. Clinical outcomes were collected from the electronic medical records.

Results

Of the 969 patients hospitalized for acute HF (76 ± 11 years, 59% men), 118 patients (12%) had WRF at discharge. The median (interquartile range) FIB‐4 score at discharge was 2.36 (1.55–3.25). The primary endpoint occurred in 136 patients (14.0%). The 1 year mortality rates were 10.5% in the no WRF and lower FIB‐4 scores (≤2.36) group (n = 428), 16.1% in the no WRF and higher FIB‐4 scores (>2.36) group (n = 423), 12.5% in the WRF and lower FIB‐4 scores group (n = 56), and 25.8% in the WRF and higher FIB‐4 scores group (n = 62) (P = 0.005). Kaplan–Meier analysis demonstrated higher all‐cause mortality in the WRF and higher FIB‐4 group (log‐rank P = 0.003). In the Cox regression analysis, only the WRF and higher FIB‐4 scores group was associated with an increased risk of mortality compared with the no WRF and lower FIB‐4 scores group (hazard ratio = 2.11, 95% confidence interval: 1.07–4.18, P = 0.032), despite adjusting for other confounding factors.

Conclusions

FIB‐4 is a valuable risk stratification marker for WRF in patients with acute HF. The underlying mechanism and potential clinical importance of these observations require further investigation.
The effects of alginate lyase treatment on structural characteristics and anti‐photoaging activity of alginate from Sargassum fusiforme
Authors: Chang Shiyuan , Hu Jinhong , Zhu Biyang , You Lijun , Pedisić Sandra , Hileuskaya Kseniya
Published: February 2023

An alginate (named P1) prepared from Sargassum fusiforme has been proven to have significant anti‐photoaging activity in our previous study. In this study, alginate lyase was used to obtain P1 hydrolysates with different molecular weights, and their structural characteristics and anti‐photoaging activity were compared. Results showed that alginate lyases could rapidly degrade the molecular weight of P1 and slightly changed its chemical composition. Fourier transform infrared spectra indicated that alginate lyase treatment did not change the main functional groups of P1. Moreover, the inhibitory effects of P1 on MMPs (MMP‐1, MMP‐3 and MMP‐9) and reactive oxygen species were also improved after hydrolyzed with alginate lyase, especially sample A‐30 (hydrolysis for 30 min). Methylation and nuclear magnetic resonance results indicated that the main chain of A‐30 was →4)‐β‐ManA‐(1→4)‐α‐GulA‐(1→4)‐β‐ManA‐(1→4)‐β‐ManA‐(1→4)‐α‐GulA‐(1→4)‐β‐ManA‐(1→3, 4)‐β‐ManA‐(1→, with the end group of α‐Fucp‐(1→ attached to the O‐3 position of →3, 4)‐β‐ManA‐(1→ on the side chain. It indicated that alginate lyase did not change the backbone of P1 but decreased the molecular or degree of polymerization at 30 min of hydrolysis. This is the first report on the anti‐photoaging activity of alginate hydrolysates. The results will provide effective theoretical support for improving the utilization and promoting the application of S. fusiforme.
Assessing components of uncertainty in demographic forecasts with an application to fiscal sustainability
Authors: Alho Juha , Lassila Jukka
Published: February 2023

When the future evolution of demographic processes is described in a stochastic setting, the challenge is to communicate the meaning of forecast uncertainty in an understandable way, to decision makers and public at large. For the purpose of risk communication, a formal setting is developed in which the roles of the demographic processes on point forecasts, and more generally, on predictive distributions, can be elucidated. The communication problem becomes central in fiscal decision making, when eventual forecast errors have differential implications on the value of the policy options being considered. Tax rate that is required to maintain financial sustainability, until a given target year, is used for illustration.
Immediate effects of individualized music listening on behavioral and psychological symptoms of dementia: A randomized controlled trial
Authors: Hillebrand Mareike C. , Weise Lisette , Wilz Gabriele
Published: February 2023

Objectives

Evidence suggests that individualized music listening (IML) can effectively reduce the behavioral and psychological symptoms of dementia (BPSD). So far, however, studies have been primarily based on questionnaire measures of BPSD completed by proxy. We therefore investigate effects of IML on BPSD based on systematic observation. We address the methodological limitations of previous observational studies by using a validated instrument, time‐based sampling, and longitudinal analytical methods.

Methods

We compared BPSD of nursing home residents with dementia in an IML intervention group (IG; n = 44) and a control group (CG; n = 46) in a randomized controlled trial (DRKS00013793; ISRCTN59052178). Trained raters observed 18 BPSD in 15 four‐minute intervals before, during and after an IML session. We used t‐tests to compare BPSD in the IG and CG before, during and after the session and piecewise latent curve modelling to compare BPSD trajectories across 1 hour.

Results

BPSD were observed less frequently in the IG than in the CG during, but not before or after the session. Likewise, whereas the CG experienced a stable trajectory of BPSD, the IG experienced a u‐shaped trajectory characterized by stability before the session, a decrease during the session, and increase after the session. There was significant interindividual variability in baseline BPSD and in the pre‐ and post‐session slopes.

Discussion

Our results provide additional evidence that IML effectively reduces BPSD, although the effect is short‐lived. As IML rarely has negative side effects, is highly accepted and easily implemented, IML should be integrated into the everyday care routines for people with dementia.

Clinical Trial Registration

German Clinical Trials Register DRKS00013793; ISRCTN registry, ISRCTN59052178.
Alcohol consumption from midlife and risk of disabling dementia in a large population‐based cohort study in Japan
Authors: Shimizu Yoko , Sawada Norie , Ihira Hikaru , Abe Sarah Krull , Inoue Manami , Yasuda Nobufumi , Yamagishi Kazumasa , Iwasaki Motoki , Tsugane Shoichiro
Published: February 2023

Objectives

The association between alcohol consumption and dementia in Japanese is poorly understood, and use of single‐point alcohol assessment may cause measurement error. We explored this association in Japanese using repeated alcohol assessments.

Methods

Participants in the Japan Public Health Center‐based Prospective Study (JPHC Study) since 1990 and who were alive in 2006 were followed from 2006 until 2016 for dementia ascertainment. Disabling dementia was identified through long‐term care insurance records. Alcohol consumption was assessed at the 5‐year questionnaire survey (1995–1999) and drinking patterns were assessed on repeated follow‐up (2000–2003). We performed Cox proportional hazards models with age as the time‐scale with adjustment for various lifestyle factors and medical history using light consumption (<75 g ethanol/week, hereinafter “g”) as reference. Analysis considering death as a competing risk was also conducted.

Results

Among 42,870 participants aged 54–84 years, 4802 cases of disabling dementia were newly diagnosed. Average years from alcohol assessment until dementia incidence was 14.9 years. Non‐drinkers and regular drinkers with ≥450 g at 5 years had adjusted HRs (95% CI) of 1.29 (1.12–1.47) and 1.34 (1.12–1.60). Patterns of long‐term abstinence, former drinking, and regular heavy weekly consumption of ≥450 g showed increased adjusted HRs of 1.61 (1.28–2.03), 2.54 (1.93–3.35), and 1.96 (1.49–2.59), respectively. Competing risk analysis yielded similar results.

Conclusions

In Japanese, non‐drinking and regular weekly consumption of ≥450 g from midlife were associated with high risk of disabling dementia compared with light drinking.
The Obligation of Engagement
Authors: Chambers Tod
Published: February 2023

As many in the United States feel a need to take a side in the ongoing culture wars, the people who make up the field of bioethics have an obligation to directly engage with those who hold different political views. If bioethics is an academic field, it must also affirm the overall values of the academy to continually challenge central assumptions. If the field wishes to be a part of the development of public policy, it must be able to construct such policies that in some fundamental manner honor the values of the opposition.