bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed‐Valence BN‐Doped Corannulene Trimer Radical Cations
Authors: Gao Yapei , Liu Zheming , Li Tao , Zhao Wanxiang
Published: October 2023

Mixed‐valence (MV) dimers have been extensively investigated, however, the structure and properties of purely organic MV trimers based on open‐shell polycyclic aromatic hydrocarbons remain elusive. Herein, unprecedented MV BN‐doped corannulene radical cations [BN‐Cor1]3⋅⋅2+ ⋅ 2[BArylF4]− and [BN‐Cor2]3⋅⋅2+ ⋅ 2[BArylF4]− were synthesized via chemical oxidation, and their structures were unambiguously confirmed by single‐crystal X‐ray diffraction. These uncommon radical cations consist of three corannulene cores and two [BArylF4]− anions, and three corannulene motifs [BN‐Cor1]3⋅⋅2+ and [BN‐Cor2]3⋅⋅2+ in the unit cell exhibit a trimer structure with a slipped π‐stacking configuration. Detailed structural analyses further revealed that the corannulene cores exhibit an infinite layered self‐assembly configuration, allowing their potential applications as building blocks for molecular conductors. The detection of a forbidden transition (Δms=±2) by electron paramagnetic resonance (EPR) spectroscopy further confirmed the existence of two unpaired electrons in the π‐trimers and the MV characteristic of these two species. Variable‐temperature EPR and conductivity measurements suggested that the BN‐doped π‐trimers exhibited antiferromagnetic coupling and conductivity properties.
Tetrahedraphene: A Csp3‐centered 3D Molecular Nanographene Showing Aggregation‐Induced Emission
Authors: Oró Arturo , Romeo‐Gella Fernando , Perles Josefina , Fernández‐García Jesús M. , Corral Inés , Martín Nazario
Published: October 2023

The bottom‐up synthesis of 3D tetrakis(hexa‐peri‐hexabenzocoronenyl)methane, “tetrahedraphene”, is reported. This molecular nanographene constituted by four hexa‐peri‐hexabenzocoronene (HBC) units attached to a central sp3 carbon atom, shows a highly symmetric arrangement of the HBC units disposed in the apex of a tetrahedron. The X‐ray crystal structure reveals a tetrahedral symmetry of the molecule and the packing in the crystal is achieved mostly by CH⋅⋅⋅π interactions since the interstitial solvent molecules prevent the π⋅⋅⋅π interactions. In solution, tetrahedraphene shows the same electrochemical and photophysical properties as the hexa‐tBu‐substituted HBC (tBu‐HBC) molecule. However, upon water addition, it undergoes a fluorescence change in solution and in the precipitated solid, showing an aggregation induced emission (AIE) process, probably derived from the restriction in the rotation and/or vibration of the HBCs. Time‐Dependent Density Functional Theory (TDDFT) calculations reveal that upon aggregation, the high energy region of the emission band decreases in intensity, whereas the intensity of the red edge emission signal increases and presents a smoother decay, compared to the non‐aggregated molecule. All in all, the excellent correlation between our simulations and the experimental findings allows explaining the colour change observed in the different solutions upon increasing the water fraction.
Stereospecific Aminative Cyclizations Triggered by Intermolecular Aza‐Prilezhaev Alkene Aziridination
Authors: Smith Matthew J. S. , Tu Wenbin , Robertson Craig M. , Bower John F.
Published: October 2023

Under acidic reaction conditions (TFA), deprotection of BocNR(OSO2R) reagents triggers intermolecular aminative cyclizations of alkenes equipped with pendant nucleophiles. The processes are predicated on a sequence of stereospecific intermolecular aza‐Prilezhaev aziridination followed by stereospecific SN2‐like opening by the pendant nucleophile. The method offers broad scope with respect to the nucleophile (N‐, O‐ or C‐based), alkene and cyclization mode, allowing the installation of two contiguous stereocenters under operationally simple conditions.
Metal‐free sp2‐C7−H Borylation of Tryptophan Containing Peptides and Late‐stage Modification
Authors: Meena Rachana , Shekhar Shashank , Ansari Shabina B. , Tiwari Ashwani , Lal Jhajan , Reddy Damodara N.
Published: October 2023

The discovery of milder and robust strategies to enable the introduction of organoboronates in peptides remains conspicuously underdeveloped. Herein, we demonstrate an efficient method for the site‐selective sp2‐C7−H borylation of tryptophan under metal‐free condition using BBr3 directed by pivaloyl group. The versatility of this approach is that gram scale synthesis and C7‐borylated N‐Phth‐Trp(N‐Piv)(C7‐BPin)‐OMe was modified into various C7‐substituted derivatives. Moreover, the strategy enables for the peptide elongation and late‐stage borylation of peptides, natural product Brevianamide F and drug Oglufanide.
Effect of Host Cholesterol on the Membrane Dynamics of Outer Membrane Lipids of Mycobacteria
Authors: Adhyapak Pranav , Liang Kuan , Duan Mojie , Kapoor Shobhna
Published: October 2023

The ability of Mycobacterium tuberculosis to remain dormant after primary infection represents the prime cause of new TB cases throughout the world. Hence, diagnosis and treatment of individuals hosting dormant mycobacterium is one of the crucial strategies to be adopted for the prevention of Tuberculosis. Among many strategies unleashed by the latent bacterium, one of them is scavenging host cholesterol for carbon source. Cholesterol modifies lipid membranes over many scales and here, its effect on mycobacterial membrane biophysics and the subsequent effect on partitioning of antibiotics into cholesterol‐ enriched mycobacterial membranes was investigated. Our research showed that cholesterol alters the phase state behavior of mycobacterial outer membrane lipids by enhancing the overall membrane order at the headgroup and acyl chain region and is integrated into both ordered and disordered domains/phases, with a preference for the latter. Exogenous cholesterol further alters the drug partitioning behavior of structurally different drugs, pointing to a larger clinical potential of using more hydrophobic medications to target dormant bacteria.
Branched poly‐l‐lysine for cartilage penetrating carriers
Authors: Gonzales Gavin , Hoque Jiaul , Gilpin Anna , Maity Biswanath , Zauscher Stefan , Varghese Shyni
Published: October 2023

Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra‐articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem is further exacerbated by the dense and negatively charged cartilage extracellular matrix (ECM). Cationic nanocarriers that form reversible electrostatic interactions with the anionic ECM can be an effective approach to overcome the electrostatic barrier presented by cartilage tissue. For an effective therapeutic outcome, the nanocarriers need to penetrate, accumulate, and be retained within the cartilage tissue. Nanocarriers that adhere quickly to cartilage tissue after intra‐articular administration, transport through cartilage, and remain within its full thickness are crucial to the therapeutic outcome. To this end, we used ring‐opening polymerization to synthesize branched poly(l‐lysine) (BPL) cationic nanocarriers with varying numbers of poly(lysine) branches, surface charge, and functional groups, while maintaining similar hydrodynamic diameters. Our results show that the multivalent BPL molecules, including those that are highly branched (i.e., generation two), can readily adhere and transport through the full thickness of cartilage, healthy and degenerated, with prolonged intra‐cartilage retention. Intra‐articular injection of the BPL molecules in mouse knee joint explants and rat knee joints showed their localization and retention. In summary, this study describes an approach to design nanocarriers with varying charge and abundant functional groups while maintaining similar hydrodynamic diameters to aid the delivery of macromolecules to negatively charged tissues.
Pott's puffy tumor: A case report
Authors: Vadiee Gholamreza , Beshali Mohamad , Jahangiri Soodeh , Eghlidos Zahra , Rahimian Zahra , Mirzaei Farhad
Published: October 2023

Key Clinical Message

Pott's puffy tumor is a rare condition primarily occurring in the younger population. This report highlights the clinical suspicion and diagnosis of Pott's puffy tumor in those presenting with favorable presentations, especially adolescents.

Pott's puffy tumor (PPT) is characterized as frontal bone subperiosteal abscess and osteomyelitis, a rare condition primarily occurring in adolescents following frontal sinusitis or head trauma. We present a case of atypical PPT in a 12‐year‐girl following an insect bite. The patient presented with painful forehead swelling for 4 weeks without any history of head trauma or signs of sinusitis. She had a history of a purulent pimple 2 months before presentation, following an insect bite. The primary diagnosis of PPT was made based on clinical and imaging findings. The patient was treated surgically and medically with intravenous antibiotics and had a satisfactory recovery upon the 6‐month follow‐up visit. This case highlights the differential diagnosis and thorough evaluation for PPT in a child with acute headache and forehead swelling, even without sinusitis symptoms.
A challenging diagnosis of idiopathic multicentric Castleman disease with complex systemic presentation: A case report
Authors: Strach Magdalena , Kuszmiersz Piotr , Chmura Łukasz , Korkosz Mariusz
Published: October 2023

Key Clinical Message

Idiopathic multicentric Castleman disease (iMCD) is challenging to diagnose due to clinical similarities with other conditions, such as Still's disease. Once diagnosed, iMCD may be effectively managed with the anti‐interleukin‐6 antibody siltuximab.

Here, we present the case of a 19‐year‐old Polish woman with persistent fever and enlarged lymph nodes and whose diagnosis remained inconclusive following initial clinical assessments and extensive laboratory analyses. The patient had subsequent complaints of joint pain and erythema which were suspicious of Still's disease and resolved with treatment with tocilizumab. Later, the progression of symptoms, such as lymphadenopathy, and elevated interleukin‐6 levels were consistent with Castleman disease, leading to the diagnosis of idiopathic multicentric Castleman disease seven years after the patient first reported symptoms. Treatment with the anti‐interleukin‐6 antibody siltuximab resulted in complete symptom resolution and normalization of inflammatory parameters. No adverse events were reported due to treatment with siltuximab.
Metastatic signet‐ring cell carcinoma of the testis: An unusual case report in Syria
Authors: Alsayed‐Ahmad Zein A. , Mayo Mohammed , Alshaker Hassan , Jarjanazi Leen , Zakkour Zeina , Sanaa Rima , Bilal Yara , Chammout Anwar
Published: October 2023

Key Clinical Message

The case of a 44‐year‐old male with signet‐ring cell adenocarcinoma metastasis in the testis emphasizes the significance of immunohistochemistry in identifying the primary site of metastatic tumors. Further research is needed to establish effective treatment strategies for rare malignancies like small intestine signet‐ring cell carcinoma. Early diagnosis and appropriate treatment are crucial for improved patient outcomes.

Metastasis to the testes is a rare occurrence, and identifying the primary site of origin can pose a significant challenge. Signet‐ring cell carcinoma (SRCC) is an uncommon subtype of adenocarcinoma typically found in the stomach but can also occur in other organs. This case report presents a 44‐year‐old male with signet‐ring cell adenocarcinoma metastasis in the right testis. The patient's initial clinical manifestation was testicular painful swelling, and subsequent immunohistochemical analysis using CK7, CK20, and CDX2 markers suggested a gastrointestinal origin. Normal upper and lower endoscopies rise suspicion of a small intestinal origin. The rarity of SRCC of the small intestine and the lack of clinical trials make treatment decisions difficult. This case highlights the importance of immunohistochemistry in determining the primary site of metastatic tumors and underscores the need for further research to establish optimal treatment strategies for rare malignancies like SRCC of the small intestine. As early diagnosis and appropriate treatment are critical for better patient outcomes.
Unobstructed infracardiac total anomalous pulmonary venous connection in a 7‐month‐old infant: A rare case report
Authors: Shhada Eman , Nahle Ali Alakbar , Hamdar Hussein , Jawad Ali , Hasan Hasan , Hamra Mohammad Shadi , Saleh Mohannad , Al‐dairy Alwaleed , Daood Huda
Published: October 2023

Key Clinical Message

This case underscores the importance of early detection and treatment for total anomalous pulmonary venous connection, a rare congenital heart condition, through comprehensive newborn physical exams and prompt specialist referrals.

Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease that is typically diagnosed in neonates. TAPVC has four subtypes, with the infracardiac type at risk of obstruction. TAPVC is usually diagnosed in newborns but can occur in other age groups. In this case, a 7‐month‐old male with recurrent cyanotic episodes was diagnosed with TAPVC of the infracardiac type using computed tomography angiography. The patient underwent successful surgical repair with a favorable postoperative course and was discharged in stable condition, and further follow‐up was not possible beyond 2 months. This case emphasizes the importance of early recognition and management of this condition to prevent the progression of subsequent complications.
Development of a Reference Process Model for the Modularization of Production‐Related Logistics in the Chemical Industry
Authors: Gryczycha Kai , Pannok Maik , Lier Stefan
Published: October 2023

Trends towards product differentiation, fast changing market conditions, and shorter product lifecycles demand flexible production solutions for the chemical industry. Modular production systems promise to provide the required capacities as needed in a short period of time. However, the potential of modular production systems can only be fully utilized if they are embedded in modular and thus flexible logistics processes. For this reason, standardized logistic modules need to be defined. Process standardization is the starting point for reducing the number of variants and minimizing the number modules. Thus, in this paper a reference process model is developed. The standardized processes defined in this model are then used to form modules by applying a method from cluster analysis.
Reaction‐Based Electrochemiluminescent Chemodosimeters for Reactive Species Detection in Biomedical Applications
Authors: Cheekatla Subba Rao , Yoon Hey Young , Choi Sang‐Hyun , Lee Jun‐Seok
Published: October 2023

Electrochemiluminescence (ECL) probes are powerful molecular sensors that surpass the capabilities of conventional fluorescence or absorbance techniques. ECL offers distinct advantages, including exceptional photophysical properties, cost‐effectiveness, rapid response in sample analysis, high selectivity and sensitivity, ease of operation, portability, and high quantum yields. These advantages make ECL an ideal modality for quantifying biologically relevant species without disrupting regular cellular processes. The development of highly sensitive strategies for disease targets is of paramount importance in the fields of biological science and medicine. Furthermore, the increasing concerns surrounding the environment and health have resulted in the urgent need of discovering new sensors and biomarker detection approaches that are economically viable. Significant research has been conducted on chemosensors, called chemodosimeters, which utilize selective reaction‐based turn‐on phenomena. This review presents the research achievements in the design protocols, mechanisms, and recognition applications of various types of the reaction‐based ECL chemodosimeter. It specifically covers applications in the quantification of thiols, reactive oxygen‐nitrogen species (ROS/RNS), and gaseous signalling molecules. By shedding light on the ECL potential, we aim to inspire chemists and chemical biologists to explore novel strategies. These advancements will lead to the improved detection and visualization of biomedical targets.
An effective autism spectrum disorder screening method using machine learning classification techniques
Authors: Balasubramanian Jaishankar , Gururaj Bharathi , Gayatri Nandam
Published: October 2023

Nowadays, autism spectrum disorder (ASD) is one of the fastest‐growing developmental disorders globally. Screening test consumes more time and expensive to detect the autism signs. Due to advances in artificial intelligence and machine learning (ML), Autism can be predicted at the initial stage. Numerous researches have been conducted using different methods, but none of these researches presented any anticipated results about the capability to predict autism traits under different age groups. Therefore, this paper proposes an effectual prediction method based upon ML strategy to develop a mobile application for predicting ASD of any age people. The autism prediction model is developed by five ML classifiers, such as Gaussian Naive Bayes, Decision Tree Classifier, K‐Nearest Neighbors (KNN), Multinomial Logistic Regression (MLR), Support Vector Machine (SVM) and also a mobile application is developed using proposed prediction method. The proposed method is analyzed with IAPQ records gathered from certain areas in Erode district, Tamil Nadu, India. From the analysis, the SVM classifier achieves maximum sensitivity of 23.14%, 6.04%, 5.89%, 11.03% than other classifiers, like Gaussian Naive Bayes, Decision Tree Classifier, KNN, and MLR.
Federated malware detection based on many‐objective optimization in cross‐architectural IoT
Authors: Zhang Zhigang , Zhang Zhixia , Cui Zhihua
Published: October 2023

With the rising adoption of the Internet of Things (IoT) across a variety of industries, malware is increasingly targeting the large number of IoT devices that lack adequate protection. Malware hunting is challenging in the IoT due to the variety of instruction set architectures of devices, as shown by the differences in the relevant characteristics of malware on different platforms. There are also serious concerns about resource utilization and privacy leaks in the development of conventional detection models. This study suggests a novel federated malware detection framework based on many‐objective optimization (FMDMO) for the IoT to overcome the problems. First, the framework provides a cross‐platform compatible basis with the federated mechanism as the backbone, while avoiding raw data sharing to improve privacy protection. Second, an intelligent optimization‐based client selection method is designed for four objectives: learning performance, architectural selection deviation, time consumption, and training stability, which leads malware detection to retain a high degree of cross‐architectural generalization while enhancing training efficiency. Based on a large IoT malware dataset we constructed, containing 62,515 malware samples across seven typical architectures, the FMDMO is evaluated comprehensively in three scenarios. The experimental results demonstrate the FMDMO substantially enhances the model's cross‐platform detection performance while preserving effective training and flexibility.
Special issue on High‐Performance Computing Conference (BASARIM 2022)
Authors: Kaya Kamer , Şener Cevat , Yenigün Hüsnü
Published: October 2023

This is an editorial for the Special Issue on the 7th High‐Performance Computing Conference (BAŞARIM 2022) organized on May 11–13, 2022, at Sabanci University Altunizade Digital Campus, İstanbul.
Prebiotic Vitamin B3 Synthesis in Carbonaceous Planetesimals
Authors: Paschek Klaus , Lee Mijin , Semenov Dmitry A. , Henning Thomas K.
Published: October 2023

Aqueous chemistry within carbonaceous planetesimals is promising for synthesizing prebiotic organic matter essential to all life. Meteorites derived from these planetesimals delivered these life building blocks to the early Earth, potentially facilitating the origins of life. Here, we studied the formation of vitamin B3 as it is an important precursor of the coenzyme NAD(P)(H), which is essential for the metabolism of all life as we know it. We propose a new reaction mechanism based on known experiments in the literature that explains the synthesis of vitamin B3. It combines the sugar precursors glyceraldehyde or dihydroxyacetone with the amino acids aspartic acid or asparagine in aqueous solution without oxygen or other oxidizing agents. We performed thermochemical equilibrium calculations to test the thermodynamic favorability. The predicted vitamin B3 abundances resulting from this new pathway were compared with measured values in asteroids and meteorites. We conclude that competition for reactants and decomposition by hydrolysis are necessary to explain the prebiotic content of meteorites. In sum, our model fits well into the complex network of chemical pathways active in this environment.
Solid‐State Electrolytes and Electrode/Electrolyte Interfaces in Rechargeable Batteries
Authors: Chai Simin , He Qiong , Zhou Ji , Chang Zhi , Pan Anqiang , Zhou Haoshen
Published: October 2023

Solid‐state batteries (SSBs) are considered to be one of the most promising candidates for next‐generation energy storage systems due to the high safety, high energy density and wide operating temperature range of solid‐state electrolytes (SSEs) they use. Unfortunately, the practical application of SSEs has rarely been successful, which is largely attributed to the low chemical stability and ionic conductivity, ineluctable solid‐solid interface issues including limited ion transport channels, high energy barriers, and poor interface contact. A comprehensive understanding of ion transport mechanisms of various SSEs, interactions between fillers and polymer matrixes and the role of the interface in SSBs are indispensable for rational design and performance optimization of novel electrolytes. The categories, research advances and ion transport mechanism of inorganic glass/ceramic electrolytes, polymer‐based electrolytes and corresponding composite electrolytes are detailly summarized and discussed. Moreover, interface contact and compatibility between electrolyte and cathode/anode are also briefly discussed. Furthermore, the electrochemical characterization methods of SSEs used in different types of SSBs are also introduced. On this basis, the principles and prospects of novel SSEs and interface design are curtly proposed according to the development requirements of SSBs. Moreover, the advanced characterizations for real‐time monitoring of interface changes are also brought forward to promote the development of SSBs.
Adaptive droop control strategy of parallel LLC converters
Authors: Tang Yu , Xu Hucheng , Pei Yushuo , Yao Fang , Ge Leijiao
Published: October 2023

When the resonant converters are connected in parallel, the output current is unbalanced without additional current‐sharing measures due to differences in resonant component. In the input‐parallel output‐parallel resonant converter system, the output voltage accuracy of the converter under the traditional droop control is analyzed when the load changes. In this paper, an adaptive droop control is proposed, in which the droop coefficient is adaptively adjusted as the load changes. The control method proposed in this paper realizes the current sharing between the converters and solves the shortcomings of the output voltage changing under different loads in the conventional droop control. Taking two parallel LLC converters as an example, the control block diagram of the parallel control method for adaptive adjustment of the droop coefficient proposed in this paper is given, and the stability of the control loop is analyzed. Finally, two parallel prototypes of LLC converters with input 200 V/output 24 V input are built by digital control, and the experiment shows that the proposed control method improves the shortcomings of excessive output voltage droop caused by traditional droop control during dynamic load switching, which verifies the effectiveness of the method.
Gut microbiota–bile acid‐vitamin D axis plays an important role in determining oocyte quality and embryonic development
Authors: Li Ang , Li Fei , Song Wei , Lei Zi‐Li , Sha Qian‐Qian , Liu Shao‐Yuan , Zhou Chang‐Yin , Zhang Xue , Li Xiao‐Zhen , Schatten Heide , Zhang Teng , Sun Qing‐Yuan , Ou Xiang‐Hong
Published: October 2023

Objective

To reveal whether gut microbiota and their metabolites are correlated with oocyte quality decline caused by circadian rhythm disruption, and to search possible approaches for improving oocyte quality.

Design

A mouse model exposed to continuous light was established. The oocyte quality, embryonic development, microbial metabolites and gut microbiota were analyzed. Intragastric administration of microbial metabolites was conducted to confirm the relationship between gut microbiota and oocyte quality and embryonic development.

Results

Firstly, we found that oocyte quality and embryonic development decreased in mice exposed to continuous light. Through metabolomics profiling and 16S rDNA‐seq, we found that the intestinal absorption capacity of vitamin D was decreased due to significant decrease of bile acids such as lithocholic acid (LCA), which was significantly associated with increased abundance of Turicibacter. Subsequently, the concentrations of anti‐Mullerian hormone (AMH) hormone in blood and melatonin in follicular fluid were reduced, which is the main reason for the decline of oocyte quality and early embryonic development, and this was rescued by injection of vitamin D3 (VD3). Secondly, melatonin rescued oocyte quality and embryonic development by increasing the concentration of lithocholic acid and reducing the concentration of oxidative stress metabolites in the intestine. Thirdly, we found six metabolites that could rescue oocyte quality and early embryonic development, among which LCA of 30 mg/kg and NorDCA of 15 mg/kg had the best rescue effect.

Conclusion

These findings confirm the link between ovarian function and gut microbiota regulation by microbial metabolites and have potential value for improving ovary function.
Enabling successful science‐policy knowledge exchange between marine biodiversity research and management: An Australian case study
Authors: Karcher Denis B. , Cvitanovic Christopher , Colvin Rebecca , van Putten Ingrid
Published: October 2023

Knowledge exchange (KE) between research and decision‐making is increasingly demanded for tackling environmental challenges, yet there is still much to learn about how to enable that effectively. Here, we analyze a distributor of research funding (i.e., the Australian National Environmental Science Program Marine Biodiversity Hub (‘the hub’)) which actively coordinated KE between researchers and state‐ and Commonwealth Government end‐users. Through 30 in‐depth qualitative interviews with researchers, hub executives and end‐users we identify enablers of KE engagement, compare what researchers and decision‐makers found most important, and highlight what research programs and funding organizations can learn from this case study. Through an evolution of programs, the hub had a strong governance structure, co‐identified priority setting, and funding for emerging priorities. Additional enablers were a legacy of longstanding interpersonal working relationships, regular engagement, knowledge brokering roles, and the nationally trusted role of the hub. Researchers more so than end‐users found trust, the focus on clear end‐user needs as well as the hub's governance and progress‐monitoring key to success. End‐users more often indicated the early engagement, collaborative nature, and flexibility to adjust as important assets to effective interaction. Visions for future KE included better engagement of Traditional Owners, streamlining direct access to expertise, more accessible outputs, and earlier involvement of researchers in policy development. In sum, we find that time (e.g., pre‐story, early engagement) and boundary roles (e.g., knowledge brokering individuals, engaged research funders or coordinators) are key to success underlining that there are substantial components to KE success that can be nurtured and planned for.
Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP‐HF registry
Authors: Pagnesi Matteo , Lombardi Carlo Mario , Tedino Chiara , Chiarito Mauro , Stolfo Davide , Baldetti Luca , Adamo Marianna , Calì Filippo , Inciardi Riccardo Maria , Tomasoni Daniela , Loiacono Ferdinando , Maccallini Marta , Villaschi Alessandro , Gasparini Gaia , Montella Marco , Contessi Stefano , Cocianni Daniele , Perotto Maria , Barone Giuseppe , Merlo Marco , Cappelletti Alberto Maria , Sinagra Gianfranco , Pini Daniela , Metra Marco
Published: October 2023

Aims

Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one ‘I NEED HELP’ marker for advanced HF.

Methods and results

Patients with HF and at least one high‐risk ‘I NEED HELP’ criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41–49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF < 50% and EF > 50% was also evaluated. All‐cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow‐up 260 days (inter‐quartile range 105–390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log‐rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all‐cause death [adjusted hazard ratio (HRadj) 0.67, 95% confidence interval (CI) 0.48–0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all‐cause death (HRadj for 5% increase 0.94, 95% CI 0.89–0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88–1.00, P = 0.049) was observed at higher EF values. Beta‐blockers and renin–angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF < 50% and EF ≥ 50% groups.

Conclusions

Among patients with HF and at least one ‘I NEED HELP’ marker for advanced HF, left ventricular EF is still of prognostic value.
Caspian Tern Management to Increase Survival of Juvenile Salmonids in the Columbia River Basin: Progress and Adaptive Management Considerations
Authors: Collis Ken , Roby Daniel D , Evans Allen F , Lawes Timothy J , Lyons Donald E
Published: October 2023

Predation by Caspian terns Hydroprogne caspia is a factor limiting the recovery of some Endangered Species Act-listed populations of salmonids from the Columbia River basin, especially steelhead Oncorhynchus mykiss. This prompted the development and implementation of two separate management plans, one in the Columbia River estuary and the other in the Columbia Plateau region, to reduce the impact of Caspian tern predation on smolt survival. Caspian terns nesting at managed breeding colonies within the basin were relocated to alternative nesting islands created for terns outside the basin. Both plans were successful in significantly reducing smolt losses to Caspian terns nesting at managed sites; however, new developments have led to regression in smolt survival gains associated with tern management. Adaptive management to prevent terns at managed colonies from relocating to nest elsewhere in the basin and to improve nesting opportunities for Caspian terns outside the basin are needed to maximize the survival benefits to Endangered Species Act-listed salmonids from management. Adaptive management is also necessary to ensure the long-term viability of the Pacific Flyway population of Caspian terns, whose breeding population has declined by more than 50% since the two management plans were implemented.
Comorbid cerebral amyloid angiopathy in dementia and prodromal stages—Prevalence and effects on cognition
Authors: Haussmann Robert , Homeyer Patricia , Sauer Cathrin , Grey Arne , Krukowski Pawel , Brandt Moritz D. , Donix Markus , Linn Jennifer
Published: October 2023

Objectives

To determine the contribution of cerebral amyloid angiopathy to cognitive impairment in MCI and dementia.

Methods

Patients with subjective memory impairment (SMI), amnestic and non‐amnestic mild cognitive impairment ((n)aMCI), Alzheimer's disease (AD), mixed and vascular dementia (MD/VD) from our memory clinic were included in this retrospective analysis. Patients underwent neuropsychological testing and cranial magnetic resonance imaging (MRI). Magnetic resonance imaging data sets were analyzed regarding the presence of CAA‐related MRI biomarkers to determine CAA prevalence. ANOVAs were used to investigate the contribution of CAA to cognitive impairment within diagnostic groups and to determine whether differences in cognitive test performance between the diagnostic groups are mediated by total CAA burden.

Results

475 patients (222 male, 253 female) with SMI (n = 47), naMCI (n = 41), aMCI (n = 189), early AD (n = 9), AD (n = 114), MD (n = 71) and VD (n = 4) were included. Mean age was 73.2 (9.9) years. CAA prevalence was 14.9% in SMI, 14.6% in naMCI, 24.3% in aMCI, 22.2% in early onset AD, 18.4% in late onset AD, 46.5% in MD and 25% in VD. Patients with possible and probable CAA were older than patients without CAA. In particular, diagnosis of aMCI, early onset AD, MD and VD showed high CAA prevalence. In AD but not in aMCI, CAA diagnosis significantly influenced test performance in the CERAD word list recall (F (1,78) = 4505; p = 0.037; partial eta‐square = 0.055). Differences in cognitive test performance between the diagnostic groups of naMCI, aMCI, AD and MD were mediated by total CAA burden within AAT simply nouns subtest (F (2,39) = 4059; p = 0.025; partial eta‐square = 0.172) and in CERAD verbal fluency test (F (3,129) = 3533; p = 0.017; partial eta‐square = 0.076).

Conclusion

This retrospective analysis demonstrates high prevalence rates of CAA in cognitive diagnoses. Our data suggest that comorbid CAA independently impacts cognitive test performance in the course of AD with presumably stage‐dependent effects. Especially in patients with AD comorbid CAA additionally impairs memory function. Total CAA small vessel disease burden further modulates psychometric differences in cognitive test performance between diagnostic groups regarding word finding and word fluency capabilities.
Morphological connectivity differences in Alzheimer's disease correlate with gene transcription and cell‐type
Authors: Yu Huiying , Ding Yanhui , Wei Yongbin , Dyrba Martin , Wang Dong , Kang Xiaopeng , Xu Weizhi , Zhao Kun , Liu Yong ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2023

Alzheimer's disease (AD) is one of the most prevalent forms of dementia in older individuals. Convergent evidence suggests structural connectome abnormalities in specific brain regions are linked to AD progression. The biological basis underpinnings of these connectome changes, however, have remained elusive. We utilized an individual regional mean connectivity strength (RMCS) derived from a regional radiomics similarity network to capture altered morphological connectivity in 1654 participants (605 normal controls, 766 mild cognitive impairment [MCI], and 283 AD). Then, we also explored the biological basis behind these morphological changes through gene enrichment analysis and cell‐specific analysis. We found that RMCS probes of the hippocampus and medial temporal lobe were significantly altered in AD and MCI, with these differences being spatially related to the expression of AD‐risk genes. In addition, gene enrichment analysis revealed that the modulation of chemical synaptic transmission is the most relevant biological process associated with the altered RMCS in AD. Notably, neuronal cells were found to be the most pertinent cells in the altered RMCS. Our findings shed light on understanding the biological basis of structural connectome changes in AD, which may ultimately lead to more effective diagnostic and therapeutic strategies for this devastating disease.
Hierarchical task analysis as a systems mapping tool in complex health care environments: Emergency department response to chemical, biological, radiological, and nuclear events
Authors: Razak Saydia , Hignett Sue , Barnes Jo , Hancox Graham
Published: October 2023

The emergency department (ED) is at the forefront of the chemical, biological, radiological, and nuclear (CBRN) response. This study adopted a multilevel systems approach using the human factors/ergonomics (HFE) method of hierarchical task analysis (HTA) with document analyses of CBRN plans to represent work‐as‐Imagined. Work‐as‐imagined was compared with data from semistructured interviews using prompt cards for CBRN scenarios (n = 57) representing work‐as‐done. The aim was to provide methodological evidence for the use of HTA with an empirical synthesis of the ED in response to CBRN events. HTA was the preferred systems mapping tool because it aligns with a systems thinking approach, allows multiple‐level comparisons, highlights variability, and has an established usability track record. This study demonstrates the usability of HTA in the context of the ED responding to a CBRN event. The findings for core CBRN concepts included (1) liaise and communicate, (2) isolate and contain, and (3) personal protective equipment.
Inflammatory bowel disease and the risk of intracerebral hemorrhage: A Mendelian randomization study and meta‐analysis
Authors: Song Yanju , Zou Xuelun , Zeng Yi , Zhang Le , Mao Xinfa
Published: October 2023

Background

The link between inflammatory bowel disease (IBD) and intracerebral hemorrhage (ICH) is still unclear.

Aims

We conducted a Mendelian randomization research and meta‐analysis to explore the impact of IBD and its subtypes (Crohn's disease [CD], ulcerative colitis [UC]) on the risk of ICH.

Methods

Two large genome‐wide association analysis studies of International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) and International Stroke Genetics Consortium as exposure (IBD, UC, and CD) and outcome (ICH) in the initial stage. IBD, CD, UC GWAS data from the FinnGen consortium were adopted for the replication phase, and ultimately, the results of the initial stage and replication phase data were combined in a meta‐analysis to evaluate the causal association between IBD and its subtypes and the risk of ICH.

Results

In the initial stage, we found that in the IVW (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.71–0.96, p = .01), MR‐PRESSO (OR = 0.85, 95% CI: 0.75–0.97, p = .02) and MR.RAPS (OR = 0.86, 95% CI: 0.76–0.98, p = .02) method showed that UC is associated with the risk of ICH. The causal relationship between IBD, CD, and the risk of ICH cannot be found by the IVW method. IBD and its subtypes UC, CD, and risk of ICH cannot find the presence of heterogeneity and pleiotropy. In replication stage, IBD (OR = 0.74, 95% CI: 0.59–0.94, p = .0135) related to ICH, while the IVW approach did not establish a causal link in UC and CD. The meta‐analysis still indicated that UC (OR = 0.83, 95% CI: 0.72–0.93, p < .05) would lessen the risk of ICH while the causality between IBD, CD, and ICH was unable to be established.

Conclusion

UC was causally related to ICH, but IBD and CD are not associated with ICH. The precise pathophysiological mechanism needs to be thoroughly investigated in more detail.
A Quantitative Sequencing Method for 5‐Formylcytosine in RNA
Authors: Lyu Ruitu , Pajdzik Kinga , Sun Hui‐Lung , Zhang Linda , Zhang Li‐Sheng , Wu Tong , Yang Lei , Pan Tao , He Chuan , Dai Qing
Published: October 2023

5‐Formylcytosine (f5C) modification is present in human mitochondrial methionine tRNA (mt‐tRNAMet) and cytosolic leucine tRNA (ct‐tRNALeu), with their formation mediated by NSUN3 and ALKBH1. f5C has also been detected in yeast mRNA and human tRNA, but its transcriptome‐wide distribution in mammals has not been studied. Here we report f5C‐seq, a quantitative sequencing method to map f5C transcriptome‐wide in HeLa and mouse embryonic stem cells (mESCs). We show that f5C in RNA can be reduced to dihydrouracil (DHU) by pic‐borane, and DHU can be exclusively read as T during reverse transcription (RT) reaction, allowing the detection and quantification of f5C sites by a unique C‐to‐T mutation signature. We validated f5C‐seq by identifying and quantifying the two known f5C sites in tRNA, in which the f5C modification fractions dropped significantly in ALKBH1‐depleted cells. By applying f5C‐seq to chromatin‐associated RNA (caRNA), we identified several highly modified f5C sites in HeLa and mouse embryonic stem cells (mESC).
A mixed‐methods study of the quality of parental support during adolescents' information‐related Internet use as a co‐construction process
Authors: Kurock Ricarda , Teichert Jeannine , Meister Dorothee M. , Gerhardts Lara , Buhl Heike M. , Bonanati Sabrina
Published: October 2023

Introduction

In Europe, most Internet searches for school‐related tasks are situated at home, where parents can support adolescents. Although the frequency (quantity) of parental support has already been analyzed, a research gap exists concerning the quality of parental support in adolescents' information‐related Internet use. The quality of parental support in the field of homework involvement is known to be a predictor of adolescents' learning motivation and academic achievement, often discussed with regard to self‐determination theory (SDT) in terms of autonomy support, structure, emotional support, and control. These categories were adapted in this study to analyze parents' support in adolescents' Internet searching activities.

Methods

Using a mixed‐methods approach, we combined quantitative questionnaires and qualitative observations to analyze joint information‐related Internet uses. Therefore, 243 parent–adolescent dyads were surveyed and six parent–adolescent dyads were observed by videography in 2019/2020 in Germany. The adolescents were 11 years old, on average.

Results

The parents rated all qualities higher than the adolescents. Emotional support was rated highest by both groups, whereas structure was rated lowest. Adolescents' and parents' view on parental support differ. The qualitative study revealed parents' often interfering behavior, whereas emotional support was low. Further, the active role of adolescents was highlighted in both quantitative and qualitative data.

Conclusions

By combining quantitative and qualitative approaches, we demonstrated a fruitful application of SDT in analyzing the quality of parental support during adolescents' Internet searches at home and shed light on the co‐construction of joint Internet searches.
Carbon and nitrogen dynamics in agricultural soil after application of cattle manure and eastern redcedar wood chips
Authors: Olivo Agustin J. , Henning Eric , Schott Linda , Schmidt Amy Millmier
Published: October 2023

Uncontrolled proliferation of eastern redcedar tree (Juniperus virginiana) in the Midwest United States requires new alternatives for utilization of waste wood, such as mulching, that promotes efficient tree management by landowners. Similarly, efficient use of manure from animal feeding operations in cropping systems can reduce negative environmental impacts and increase cropland productivity. The objectives of this study were to quantify the nitrogen (N) and carbon (C) decomposition rates, availability, and effects on soil chemical properties of eastern redcedar wood chips (WC), cattle manure (CM), and the combination of cattle manure and wood chips (MW). A 120‐day incubation and a 12‐month field experiment were conducted in Nebraska. In the incubation study, CM decomposed the fastest, followed by MW and WC. At the end of the experiment, WC induced N immobilization. In the field experiment, most decomposition for all amendments occurred during the period between May and August (spring/summer). Decomposition was most rapid for CM and WC with 44% and 55% organic‐C loss by mass, respectively. Approximately, 40% of the organic N in CM mineralized during the 1‐year field study. Wood chips induced N immobilization after 6 months for shallow soil layers compared to control (no amendment) but did not induce N immobilization when combined with manure. Changes in soil organic matter concentration due to amendment application were not observed at any stages of the field experiment, likely due to the length of the experiment. However, consecutive applications of comingled MW may provide benefits of C contribution to the soil without inducing N limitations.
Uniformly 3‐connected graphs
Authors: Xu Liqiong
Published: October 2023

Let be a positive integer. A graph is said to be uniformly ‐connected if between any pair of vertices the maximum number of independent paths is exactly . Dawes showed that all minimally 3‐connected graphs can be constructed from such that every graph in each intermediate step is also minimally 3‐connected. In this paper, we generalize Dawes' result to uniformly 3‐connected graphs. We give a constructive characterization of the class of uniformly 3‐connected graphs which differs from the characterization provided by Göring et al., where their characterization requires the set of all 3‐connected and 3‐regular graphs as a starting set, the new characterization requires only the graph . Eventually, we obtain a tight bound on the number of edges in uniformly 3‐connected graphs.
Datamining approaches for examining the low prevalence of N‐acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes
Authors: Caldovic Ljubica , Ahn Julie J. , Andricovic Jacklyn , Balick Veronica M. , Brayer Mallory , Chansky Pamela A. , Dawson Tyson , Edwards Alex C. , Felsen Sara E. , Ismat Karim , Jagannathan Sveta V. , Mann Brendan T. , Medina Jacob A. , Morizono Toshio , Morizono Michio , Salameh Shatha , Vashist Neerja , Williams Emily C. , Zhou Zhe , Morizono Hiroki
Published: October 2023

Ammonia, which is toxic to the brain, is converted into non‐toxic urea, through a pathway of six enzymatically catalyzed steps known as the urea cycle. In this pathway, N‐acetylglutamate synthase (NAGS, EC 2.3.1.1) catalyzes the formation of N‐acetylglutamate (NAG) from glutamate and acetyl coenzyme A. NAGS deficiency (NAGSD) is the rarest of the urea cycle disorders, yet is unique in that ureagenesis can be restored with the drug N‐carbamylglutamate (NCG). We investigated whether the rarity of NAGSD could be due to low sequence variation in the NAGS genomic region, high NAGS tolerance for amino acid replacements, and alternative sources of NAG and NCG in the body. We also evaluated whether the small genomic footprint of the NAGS catalytic domain might play a role. The small number of patients diagnosed with NAGSD could result from the absence of specific disease biomarkers and/or short NAGS catalytic domain. We screened for sequence variants in NAGS regulatory regions in patients suspected of having NAGSD and found a novel NAGS regulatory element in the first intron of the NAGS gene. We applied the same datamining approach to identify regulatory elements in the remaining urea cycle genes. In addition to the known promoters and enhancers of each gene, we identified several novel regulatory elements in their upstream regions and first introns. The identification of cis‐regulatory elements of urea cycle genes and their associated transcription factors holds promise for uncovering shared mechanisms governing urea cycle gene expression and potentially leading to new treatments for urea cycle disorders.