bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Antioxidant Activity and Phenolic Composition of Different Monofloral and Polyfloral Brazilian Honey Extracts
Authors: Wisniewski Julie , Hacke Ana Carolina Mendes , Mazer Etto Rafael , Boligon Aline Augusti , Takeda Inês , Marques Jacqueline Aparecida , Pereira Romaiana Picada
Published: July 2024

This study aimed to evaluate the chemical composition and antioxidant activity of phenolic extracts from monofloral and polyfloral honey samples obtained from different Brazilian regions. The chemical composition (total content of phenolic compounds and flavonoids) of extracts were measured by using colorimetric assays and analyzed by high performance liquid chromatographic (HPLC‐DAD). The antioxidant activity was evaluated by chemical and biochemical assays (reducing power assay, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH⋅) and 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic) acid (ABTS⋅+) scavenger assays. It was also investigated the ability of extracts in attenuate lipid peroxidation induced by Fe2+ in phospholipids. The obtained results clearly demonstrated that the botanical origin and geographical region of honey collection influenced the chemical composition and antioxidant activity of extracts. Furthermore, the samples were constituted by phenolic acids and flavonoids, which p‐coumaric acid was predominant among the compounds identified. All samples were able to scavenge free radicals and inhibit lipid peroxidation, and good correlations were obtained between the flavonoid content and honey color. In conclusion, the obtained extracts were constituted by antioxidant compounds, which reinforce the usage of honey in human diets, and demonstrated that the region of honey collection strong influenced in the chemical composition and, consequently, its biological effect.
Left‐sided infective endocarditis presenting with pulmonary involvement and liver abscess: A case report
Authors: Basiri Reza , Shazdehahmadi Safieh , Boskabadi Amir Reza
Published: July 2024

Key Clinical Message

Infective endocarditis is an important differential diagnosis in patients with persistent fever and chills not responding to antibiotics and involvement of multiple organs. It can present without any specific signs such as valvular murmurs and no growth on blood cultures. Therefore, considering an echocardiography can be crucial and helpful in establishing the diagnosis.

Infective endocarditis (IE), a rare disease with high mortality, arises from microbial infection affecting the heart valves and endocardium. It exhibits diverse symptoms and can involve various organs, including the brain, lungs, spleen, and liver. Diagnosis is often intricate due to its polymorphic nature, and negative blood cultures can add complexity to the diagnostic process. In this report, we present an unusual case of IE in a 53‐year‐old male farmer with multi‐organ involvement, including liver abscesses and pulmonary infiltration with cavities. Echocardiography showed a nodular mass attached to his bicuspid aortic valve, thus, playing a crucial role in confirming the diagnosis. This atypical manifestation highlights the necessity for increased clinical vigilance and further research to improve diagnostic approaches for uncommon IE cases.
Optical Genome Mapping for Applications in Repeat Expansion Disorders
Authors: van der Sanden Bart , Neveling Kornelia , Pang Andy Wing Chun , Shukor Syukri , Gallagher Michael D. , Burke Stephanie L. , Kamsteeg Erik‐Jan , Hastie Alex , Hoischen Alexander
Published: July 2024

Short tandem repeat (STR) expansions are associated with more than 60 genetic disorders. The size and stability of these expansions correlate with the severity and age of onset of the disease. Therefore, being able to accurately detect the absolute length of STRs is important. Current diagnostic assays include laborious lab experiments, including repeat‐primed PCR and Southern blotting, that still cannot precisely determine the exact length of very long repeat expansions. Optical genome mapping (OGM) is a cost‐effective and easy‐to‐use alternative to traditional cytogenetic techniques and allows the comprehensive detection of chromosomal aberrations and structural variants >500 bp in length, including insertions, deletions, duplications, inversions, translocations, and copy number variants. Here, we provide methodological guidance for preparing samples and performing OGM as well as running the analysis pipelines and using the specific repeat expansion workflows to determine the exact repeat length of repeat expansions expanded beyond 500 bp. Together these protocols provide all details needed to analyze the length and stability of any repeat expansion with an expected repeat size difference from the expected wild‐type allele of >500 bp. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Genomic ultra‐high‐molecular‐weight DNA isolation, labeling, and staining

Basic Protocol 2: Data generation and genome mapping using the Bionano Saphyr® System

Basic Protocol 3: Manual De Novo Assembly workflow

Basic Protocol 4: Local guided assembly workflow

Basic Protocol 5: EnFocus Fragile X workflow

Basic Protocol 6: Molecule distance script workflow
Topology and modulation improvement of a dual‐output DC‐DC converter in order to minimize the output ports dependence
Authors: Farhadi‐Kangarlu Mohammad , Khiavi Abdolhamid Moallemi , Neyshabouri Yousef
Published: July 2024

Single‐input multioutput (SIMO) DC‐DC converters are used to provide several DC voltages in systems that require different voltage levels. In this paper, a modified single‐input double‐output (SIDO) boost DC‐DC converter is proposed with reduced coupling of the output ports voltages. Also, the switching sequence is selected in a way that the coupling of the output ports is minimized. In the proposed SIDO converter, only two active switches are used and the passive elements requirement is low while the input current ripple is reduced in comparison with the comparable converters. Moreover, it has higher efficiency and requires lower rated power semiconductor devices. The common‐emitter arrangement of the switches makes the driver circuit of the switches to be simple and cost effective. The converter is designed to provide two nonisolated series output ports that can be used, for example, in photovoltaic (PV) energy systems. The large‐signal modeling and design procedure of the proposed converter is presented in details. The experimental results of a 300‐W prototype are presented to verify the performance of the proposed converter.
Condition monitoring and fault diagnosis of flyback switching power supply
Authors: Tang Shengxue , Tan Liqiang , Cheng Lixiang , Wang Weiwei , Wang Hongfan , Zhao Jinze
Published: July 2024

This paper presents a fault diagnosis method for flyback switching power supply. The proposed method integrates input current and output voltage information to improve fault diagnosis accuracy. The flyback switching power supply's signal characteristics and fault separability are analyzed. Time domain features and frequency band wavelet packet dispersion entropy features are constructed to form multidimensional feature vectors that fuse time and frequency information, which enhances fault separability. Then, the MIV algorithm is used to screen the features to reduce the redundant information. Additionally, the diagnostic method of the NGO‐SVM model is proposed to optimize the multiclass SVM model by using NGO to improve the diagnosis model generalization performance. The experimental results show that the method proposed in this paper has good diagnostic effect for both single and multiple faults, and the diagnostic accuracy is up to 98.3% under ideal conditions, and up to 96.8% in the presence of noise interference.
Endogenous bystander killing mechanisms enhance the activity of novel FAP‐specific CAR‐T cells against glioblastoma
Authors: Yu Wenbo , Truong Nga TH , Polara Ruhi , Gargett Tessa , Tea Melinda N , Pitson Stuart M , Cockshell Michaelia P , Bonder Claudine S , Ebert Lisa M , Brown Michael P
Published: July 2024

Objectives

CAR‐T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR‐T cells targeting FAP have never been investigated as a therapy for glioblastoma.

Methods

We generated a novel FAP targeting CAR with CD3ζ and CD28 signalling domains and tested the resulting CAR‐T cells for their lytic activity and cytokine secretion function in vitro (using real‐time impedance, flow cytometry, imaging and bead‐based cytokine assays), and in vivo (using a xenograft mimicking the natural heterogeneity of human glioblastoma).

Results

FAP‐CAR‐T cells exhibited target specificity against model cell lines and potent cytotoxicity against patient‐derived glioma neural stem cells, even when only a subpopulation expressed FAP, indicating a bystander killing mechanism. Using co‐culture assays, we confirmed FAP‐CAR‐T cells mediate bystander killing of antigen‐negative tumor cells, but only after activation by FAP‐positive target cells. This bystander killing was at least partially mediated by soluble factors and amplified by IL‐2 which activated the non‐transduced fraction of the CAR‐T product. Finally, a low dose of intravenously administered FAP‐CAR‐T cells controlled, without overt toxicity, the growth of subcutaneous tumors created using a mixture of antigen‐negative and antigen‐positive glioblastoma cells.

Conclusions

Our findings advance FAP as a leading candidate for clinical CAR‐T therapy of glioblastoma and highlight under‐recognised antigen nonspecific mechanisms that may contribute meaningfully to the antitumor activity of CAR‐T cells.
A novel method of reliable data transmission for Internet of Vehicles based on crowd sensing strategy
Authors: Zhang Ting , Zhang Degan , Zhang Ping , Zhang Jie , Tian Shuhua
Published: July 2024

The Internet of Vehicles (IoV) is a hot research topic in intelligent transportation, and the research on new methods of intelligent data transmission is one of the key contents. Aiming at the application scenario of urban air quality monitoring data collection and transmission based on IoV, a new reliable data transmission method (Vehicular Grouping‐Communicated Data [VGCD]) based on crowd sensing strategy is proposed. This method is designed to utilize the intelligent perception and collaborative monitoring of vehicle to collect data, avoiding redundancy and overload of information; a reliable data transmission minimum delay hybrid routing method is proposed in the data transmission part, which combines encoding mechanism with routing design, integrates routing switching ideas, predicts vehicle adaptive connectivity based on fuzzy logic, and makes probability based routing decisions to minimize delay, achieving reliable and efficient data collection and transmission. The proposed new method has important theoretical significance and practical value for various applications such as dynamic remote perception monitoring based on the IoV in intelligent transportation.
Characteristics and outcome of hospitalized patients with heart failure stratified for chronic kidney disease
Authors: König Sebastian , Pellissier Vincent , Hohenstein Sven , Leiner Johannes , Schanner Carolin , Kwast Stefan , Müller Marlena , Kuhlen Ralf , Bollmann Andreas
Published: July 2024

Aims

Heart failure (HF) and chronic kidney disease (CKD) place significant challenges on the healthcare system, and their co‐existence is associated with shared adverse outcomes. The multinational CaReMe project was initiated to provide contemporary, real‐world epidemiological data on cardiovascular and reno‐metabolic diseases. Utilizing data from the German CaReMe cohort, we characterize a multicentric HF population and describe in‐hospital outcomes stratified for co‐morbid CKD.

Methods and results

This retrospective, observational study analysed administrative data from inpatient cases hospitalized in 87 German Helios hospitals between 1 January 2016 and 31 August 2022. The first hospitalization of patients aged ≥18 years with a primary discharge diagnosis of HF, based on ICD‐10 codes, were considered the index cases, and subsequent hospitalizations were considered as readmissions. Baseline characteristics and outcomes were stratified for co‐morbid CKD using ICD‐10‐encoding from the index cases. Cox regression was utilized for readmission endpoints and in‐hospital mortality. In total, 174 829 index cases (mean age 79 ± 15 years, 49.9% female) were included; of these, 55.0% had coexisting CKD. Patients with CKD were older, suffered from worse HF‐related symptoms, had a higher co‐morbidity burden, and in‐hospital mortality was increased at index and during follow‐up. Prevalent CKD was associated with higher rehospitalization rates and was an independent predictor for in‐hospital death.

Conclusions

Within this HF inpatient cohort from a multicentric German database, CKD was diagnosed in more than half of the patients and was associated with increased in‐hospital mortality at baseline and during follow‐up. Rehospitalizations were observed earlier and more frequently in patients with HF and co‐morbid CKD.
Long‐term outcomes of phenoclusters in preclinical heart failure with preserved and mildly reduced ejection fraction
Authors: Fazzini Luca , Ghirardi Arianna , Limonta Raul , Calabrese Alice , D'Elia Emilia , Canova Paolo , Fontana Alessandra , Grosu Aurelia , Iacovoni Attilio , Ferrari Paola , De Maria Renata , Gavazzi Antonello , Montisci Roberta , Senni Michele , Gori Mauro
Published: July 2024

Aims

The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID‐Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification.

Methods

The DAVID‐Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death.

Results

The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and the largest left atrium. During a median follow‐up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log‐rank test: Cluster 3 vs. 1 P < 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24–4.90].

Conclusions

Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF > 40% who deserve more efforts to prevent clinical HF.
Can Loss and Damage Fund Strike a Responsive Chord in Global Climate Finance?
Authors: South David W. , Alpay Savas
Published: July 2024

The June 2023 column “COP27 Loss and Damage Fund—financial band aid or effective mechanism?” outlined the definition, evolution and potential establishment of a Loss and Damage Fund (LDF) to financially aid least developing countries (LDCs) and small island developing states (SIDS) and others countries impacted by sea level rise from climate change, while the January 2024 column “Loss and Damage Fund—operationalized at COP28 but funding and allocation process unresolved” outlined the initial funding and allocation process challenges. Since COP28 both the LDF Board and World Bank have been addressing elements required to operationalize the Fund. A key challenge is that only $661 million has been pledged to the Fund, while up to $400 billion is needed annually to address economic and non‐economic loss and damage. While it is recognized that the initial pledges are “financial resources for commencing operationalization of the Fund,” they are “by no means enough for an initial resource mobilization effort.”
Outcomes of SWI/SNF complex‐deficient sinonasal carcinomas in a Southeast Asian cohort
Authors: Xu Xinni , Wu Bingcheng , Loh Kwok Seng , Lim Wei Sian , Tan Charmaine Si Min , Low Terese Huiying , Ong Yew Kwang , Tan Jeng Swan , Eu Donovan Kum Chuen
Published: July 2024

Background

SWI/SNF complex‐deficient sinonasal carcinomas are rare, genetically distinct, and aggressive entities.

Methods

SMARCB1 and SMARCA4 immunohistochemistry was retrospectively performed on a cohort of undifferentiated, poorly differentiated, and poorly defined sinonasal carcinomas. Survival outcomes were compared between SMARCB1/SMARCA4 (SWI/SNF complex)‐deficient and ‐retained groups.

Results

Eight SWI/SNF complex‐deficient (six SMARCB1‐deficient, two SMARCA4‐deficient) cases were identified among 47 patients over 12 years. Triple‐modality treatment was more frequently utilized in SWI/SNF complex‐deficient carcinomas than in SWI/SNF complex‐retained carcinomas (71.4% vs. 11.8%, p = 0.001). After a median follow‐up of 21.3 (IQR 9.9–56.0) months, SWI/SNF complex‐deficient sinonasal carcinomas showed comparable recurrence rates (57.1% vs. 52.9%, p = 0.839), time‐to‐recurrence (7.3 [IQR 6.6–8.3] vs. 9.1 [IQR 3.9–17.4] months, p = 0.531), and overall survival (17.7 [IQR 11.8–67.0] vs. 21.6 [IQR 8.9–56.0] months, p = 0.835) compared to SWI/SNF complex‐retained sinonasal carcinomas.

Conclusion

Triple‐modality treatment may improve survival in SWI/SNF complex‐deficient sinonasal carcinomas.
The development and validation of a conceptual definition of avoidable transitions from long‐term care to the emergency department: A mixed methods study
Authors: Cummings Greta G. , Tate Kaitlyn , Spiers Jude , El‐Bialy Rowan , McLane Patrick , Park Claire Su‐Yeon , Penconek Tatiana , Cummings Garnet , Robinson Carole A. , Reid Robert Colin , Estabrooks Carole A. , Rowe Brian H. , Anderson Carol
Published: July 2024

Background/Objectives

Transitions to and from Emergency Departments (EDs) can be detrimental to long‐term care (LTC) residents and burden the healthcare system. While reducing avoidable transfers is imperative, various terms are used interchangeably including inappropriate, preventable, or unnecessary transitions. Our study objectives were to develop a conceptual definition of avoidable LTC‐ED transitions and to verify the level of stakeholder agreement with this definition.

Methods

The EXamining Aged Care Transitions study adopted an exploratory sequential mixed‐method design. The study was conducted in 2015–2016 in 16 LTC facilities, 1 ED, and 1 Emergency Medical Service (EMS) in a major urban center in western Canada. Phase 1 included 80 participants, (healthcare aides, licensed practical nurses, registered nurses, LTC managers, family members of residents, and EMS staff). We conducted semistructured interviews (n = 25) and focus groups (n = 19). In Phase 2, 327 ED staff, EMS staff, LTC staff, and medical directors responded to a survey based on the qualitative findings.

Results

Avoidable transitions were attributed to limited resources in LTC, insufficient preventive care, and resident or family wishes. The definition generated was: A transition of an LTC resident to the ED is considered avoidable if: (a) Diagnostic testing, medical assessment, and treatment can be accessed in a timely manner by other means; (b) the reasons for a transfer are unclear and the transition would increase the disorientation, pain, or discomfort of a resident, outweighing a clear benefit of a transfer; and (c) the transition is against the wishes expressed by the resident over time, including through informal and undocumented conversations. There was a high level of agreement with the definition across the four participant groups.

Conclusions and Implications

To effectively reduce LTC resident avoidable transitions, stakeholders must share a common definition. Our conceptual definition may significantly contribute to improved care for LTC residents.
Prevalence and associated factors of overweight in Chinese adolescents: A cross‐sectional study
Authors: Huang Junjie , Keung Vera M. W. , Cheung Calvin K. M. , Lo Amelia S. C. , Chan Sze C. , Wong Yuet Y. , Mui Lancelot W. H. , Lee Albert , Wong Martin C. S.
Published: July 2024

Background and Aim

Obesity has been a global public health issue due to the increasing mortality rate and prevalence among children. However, there are scarce studies on obesity prevalence in Hong Kong children. The study aims to identify the risk factors of obesity among primary and secondary school students by assessing the relationship between sociodemographic factors, health‐related behaviors, and social relationships.

Methods

Self‐administrated surveys were collected from 30 primary schools and 25 secondary schools participating in the “Quality Education Fund Thematic Network on Health Schools” project. Descriptive analysis was conducted to examine the proportions of different characteristics and to compare the disparity between primary and secondary school students with obesity.

Results

A total of 4884 responses were collected. A larger proportion of primary school students with obesity were male (adjusted odds ratio [aOR]: 2.55, 95% confidence interval [CI]: 1.77–3.67, p < 0.001) and actively gamed (aOR: 1.64, 95% CI: 1.07–2.51, p = 0.024). Secondary school students with obesity were male (aOR: 1.61, 95% CI: 1.21–2.13, p = 0.001), had poor self‐perceived academic performance (aOR:1.51, 95% CI: 1.10–2.08, p = 0.011) and expressed higher life satisfaction (family) (aOR: 1.13, 95% CI: 1.01–1.26, p = 0.032). There were negative associations found between obesity and physical activity, high consumption of sugary drinks, chocolate or candies, and insufficient consumption of vegetables.

Conclusion

Male sex, physical inactivity, low self‐perecived academic performance, and poor dietary behaviors were the risk factors for obesity among primary and secondary school students. The findings highlighted the importance of identifying younger individuals who were at risk of becoming clinically obese. Further studies should explore the effectiveness of various interventions through longitudinal study.
Bibliometric analysis of T‐cells immunity in pulmonary hypertension from 1992 to 2022
Authors: Chen Xian , Yan Zhe , Pan Qing , Zhang Chunxia , Chen Yakun , Liang Xuzhi , Li Shaomei , Wang Lei
Published: July 2024

Background

Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T‐cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T‐cells research in PH pathogenesis and to lay a solid foundation for further studies.

Methods

The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords.

Results

Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that “Pulmonary hypertension” was the most usually appeared keyword in the relevant literature, and included “T‐cells”, “Regulatory T cells”, and “Activated T cell.” “miRNA” of reference co‐citation clustering analysis demonstrated the possible T‐cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is “gene expression” and terms such as “vascular remodeling,” “growth,” “proliferation,” and “fibrosis” are among the list, indicating that T‐cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is “Galie N, 2016.”

Conclusions

T‐cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T‐cell immunity activation mechanisms in PH need to be investigated further.
Wogonin ameliorates the proliferation, inflammatory response, and pyroptosis in keratinocytes via NOD‐like receptor family pyrin domain containing 3/Caspase‐1/Gasdermin‐D pathway
Authors: Ma Jun , Ji Chen , Sun Yanhong , Liu Danqing , Pan Kai , Wei Yuegang
Published: July 2024

Background

Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood.

Aim

The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism.

Methods

Cell counting kit‐8 (CCK‐8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK‐8 and 5‐Ethynyl‐2′‐deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme‐linked immunosorbent assay. Immunofluorescence staining tested nucleotide‐binding oligomerization domain (NOD)‐like receptor family pyrin domain containing 3 (NLRP3) and Caspase‐1 expressions. Western blot examined the protein expressions of proliferation‐, inflammation‐, pyroptosis‐associated factors, and NLRP3.

Results

Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase‐1/Gasdermin‐D (GSDMD)‐mediated pyroptosis in M5‐challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5‐induced proliferation, inflammatory response, and NLRP3/caspase‐1/GSDMD‐mediated pyroptosis in HaCaT cells.

Conclusion

In a word, Wogonin might exert anti‐proliferation, anti‐inflammatory and anti‐pyroptosis activities in M5‐induced cell model of psoriasis and the blockade of NLRP3/Caspase‐1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti‐psoriasis drug.
Enhancing electrical conductivity and mechanical properties of decellularized umbilical cord arteries using graphene coatings
Authors: Karimi Fateme , Alizadeh Morteza , Bitaraf Fateme Sadat , Shirshahi Vahid
Published: July 2024

Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time‐dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation.
Key risk factors and adverse outcomes in metachronous vertebral osteomyelitis following periprosthetic joint infection: A 5‐year retrospective study
Authors: Lin Yu‐Chih , Luo An‐Jhih , Kao Fu‐Cheng , Tai An‐Shun , Chang Yuhan , Hsieh Pang‐Hsin , Lee Sheng‐Hsun , Lin Sheng‐Hsuan
Published: July 2024

Purpose

Periprosthetic joint infection (PJI) is a leading cause of joint arthroplasty failure, potentially leading to critical complications like vertebral osteomyelitis (VO). The factors contributing to VO after PJI and the outcomes for these patients are not well understood. Our study aims to (1) identify risk factors for VO following PJI and (2) assess the clinical outcomes in these cases.

Methods

We included PJI patients treated surgically at our centre from January 2006 to December 2020, excluding those with simultaneous VO post‐PJI. Our focus was on patients with VO occurring after PJI, monitored for at least 5 years. Analysis included patient comorbidities, PJI treatment approaches, pathogen identification and clinical outcomes.

Results

Of 1701 PJI cases, 21 (1.23%) developed VO. Key risk factors for VO post‐PJI were identified: systemic inflammatory response syndrome, substance misuse, polymicrobial infection and undergoing at least three stages of resection arthroplasty (odds ratios: 1.86, 54.28, 52.33 and 31.88, respectively). Adverse outcomes were noted in VO patients, with recurrent VO in 6/21 and repeated PJIs in 18/21 cases.

Conclusions

Patients with PJI, especially those with certain risk factors, have an increased likelihood of developing VO and encountering negative outcomes. The potential role of bacteremia in the development of VO after PJI needs further exploration.

Level of Evidence

Level III.
Effects of acute hypoxia exposure and acclimation on the thermal tolerance of an imperiled Canadian minnow
Authors: Reemeyer Jessica E. , Chapman Lauren J.
Published: July 2024

Elevated water temperatures and low dissolved oxygen (hypoxia) are pervasive stressors in aquatic systems that can be exacerbated by climate change and anthropogenic activities, and there is growing interest in their interactive effects. To explore this interaction, we quantified the effects of acute and long‐term hypoxia exposure on the critical thermal maximum (CTmax) of Redside Dace (Clinostomus elongatus), a small‐bodied freshwater minnow with sparse populations in the Great Lakes Basin of Canada and designated as Endangered under Canada's Species at Risk Act. Fish were held at 18°C and acclimated to four levels of dissolved oxygen (>90%, 60%, 40%, and 20% air saturation). CTmax was measured after 2 and 10 weeks of acclimation and after 3.5 weeks of reoxygenation, and agitation behavior was quantified during CTmax trials. Aquatic surface respiration behavior was also quantified at 14 weeks of acclimation to oxygen treatments. Acute hypoxia exposure decreased CTmax in fish acclimated to normoxia (>90% air saturation), but acclimation to hypoxia reduced this effect. There was no effect of acclimation oxygen level on CTmax when measured in normoxia, and there was no effect of exposure time to hypoxia on CTmax. Residual effects of hypoxia acclimation on CTmax were not seen after reoxygenation. Agitation behavior varied greatly among individuals and was not affected by oxygen conditions. Fish performed aquatic surface respiration with low frequency, but performed it earlier when acclimated to higher levels of oxygen. Overall, this work sheds light on the vulnerability of fish experiencing acute hypoxia and heat waves concurrently.
Icariside II in NSCLC and COVID‐19: Network pharmacology and molecular docking study
Authors: Kong Qing , Zhu Huahe , Dong Jingcheng , Liu Baojun
Published: July 2024

Background

Patients with non‐small cell lung cancer (NSCLC) are susceptible to coronavirus disease‐2019 (COVID‐19), but current treatments are limited. Icariside II (IS), a flavonoid compound derived from the plant epimedin, showed anti‐cancer,anti‐inflammation and immunoregulation effects. The present study aimed to evaluate the possible effect and underlying mechanisms of IS on NSCLC patients with COVID‐19 (NSCLC/COVID‐19).

Methods

NSCLC/COVID‐19 targets were defined as the common targets of NSCLC (collected from The Cancer Genome Atlas database) and COVID‐19 targets (collected from disease database of Genecards, OMIM, and NCBI). The correlations of NSCLC/COVID‐19 targets and survival rates in patients with NSCLC were analyzed using the survival R package. Prognostic analyses were performed using univariate and multivariate Cox proportional hazards regression models. Furthermore, the targets in IS treatment of NSCLC/COVID‐19 were defined as the overlapping targets of IS (predicted from drug database of TMSCP, HERBs, SwissTarget Prediction) and NSCLC/COVID‐19 targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of these treatment targets were performed aiming to understand the biological process, cellular component, molecular function and signaling pathway. The hub targets were analyzed by a protein–protein interaction network and the binding capacity with IS was characterized by molecular docking.

Results

The hub targets for IS in the treatment of NSCLC/COVID‐19 includes F2, SELE, MMP1, MMP2, AGTR1 and AGTR2, and the molecular docking results showed that the above target proteins had a good binding degree to IS. Network pharmacology showed that IS might affect the leucocytes migration, inflammation response and active oxygen species metabolic process, as well as regulate the interleukin‐17, tumor necrosus factor and hypoxia‐inducible factor‐1 signaling pathway in NSCLC/COVID‐19.

Conclusions

IS may enhance the therapeutic efficacy of current clinical anti‐inflammatory and anti‐cancer therapy to benefit patients with NSCLC combined with COVID‐19.
Long‐acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project
Authors: Nguyen Nadia , Lane Benjamin , Golub Sarit A. , Chastain Cody , Zucker Jason , King Katherine , Terry Marvell , Burdge Jennifer , Carnevale Caroline , Muscarella Anahit , Castor Delivette , Kutner Bryan , Meyers Kathrine
Published: July 2024

Introduction

Approval of the first long‐acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The “Accelerating Implementation of Multilevel Strategies to Advance Long‐Acting Injectable for Underserved Populations (ALAI UP Project)” aims to accelerate the systematic and equitable delivery of LAI ART.

Methods

We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short‐answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023.

Results

Thirty‐eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient‐facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics’ LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38).

Conclusions

Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities.
Effectiveness of HIV self‐testing when offered within assisted partner services in Western Kenya (APS‐HIVST Study): a cluster randomized controlled trial
Authors: Roy Paladhi Unmesha , Katz David A. , Otieno George , Hughes James P. , Lagat Harison , Masyuko Sarah , Sharma Monisha , Macharia Paul , Bosire Rose , Mugambi Mary , Kariithi Edward , Farquhar Carey
Published: July 2024

Introduction

Assisted partner services (APS) is an effective strategy for increasing HIV testing, new diagnosis, and linkage to care among sexual partners of people living with HIV (PLWH). APS can be resource intensive as it requires community tracing to locate each partner named and offer them testing. There is limited evidence for the effectiveness of offering HIV self‐testing (HIVST) as an option for partner testing within APS.

Methods

We conducted a cluster randomized controlled trial comparing provider‐delivered HIV testing (Standard APS) versus offering partners the option of provider‐delivered testing or HIVST (APS+HIVST) at 24 health facilities in Western Kenya. Facilities were randomized 1:1 and we conducted intent‐to‐treat analyses using Poisson generalized linear mixed models to estimate intervention impact on HIV testing, new HIV diagnoses, and linkage to care. All models accounted for clustering at the clinic level and new diagnoses and linkage models were adjusted for individual‐level age, sex, and income a priori.

Results

From March to December 2021, 755 index clients received APS and named 5054 unique partners. Among these, 1408 partners reporting a prior HIV diagnosis were not eligible for HIV testing and were excluded from analyses. Of the remaining 3646 partners, 96.9% were successfully contacted for APS and tested for HIV: 2111 (97.9%) of 2157 in the APS+HIVST arm and 1422 (95.5%) of 1489 in the Standard APS arm. In the APS+HIVST arm, 84.6% (1785/2111) tested via HIVST and 15.4% (326/2111) received provider‐delivered testing. Overall, 16.7% of the 3533 who tested were newly diagnosed with HIV (APS+HIVST = 357/2111 [16.9%]; Standard APS = 232/1422 [16.3%]). Of the 589 partners who were newly diagnosed, 90.7% were linked to care (APS+HIVST = 309/357 [86.6%]; Standard APS = 225/232 [97.0%]). There were no significant differences between the two arms in HIV testing (relative risk [RR]: 1.02, 95% CI: 0.96–1.10), new HIV diagnoses (adjusted RR [aRR]: 1.03, 95% CI: 0.76–1.39) or linkage to care (aRR: 0.88, 95% CI: 0.74–1.06).

Conclusions

There were no differences between APS+HIVST and Standard APS, demonstrating that integrating HIVST into APS continues to be an effective strategy for identifying PLWH by successfully reaching and HIV testing >95% of elicited partners, newly diagnosing with HIV one in six of those tested, >90% of whom were linked to care.

Clinical Trial Number

NCT04774835
Acid sphingomyelinase deficiency and Gaucher disease in adults: Similarities and differences in two macrophage storage disorders
Authors: Eskes Eline C. B. , van Dussen Laura , Aerts Johannes M. F. G. , van der Lienden Martijn J. C. , Maas Mario , Akkerman Erik M. , van Kuilenburg André B. P. , Sjouke Barbara , Hollak Carla E. M.
Published: July 2024

The lysosomal storage diseases chronic visceral acid sphingomyelinase deficiency (ASMD) and Gaucher disease type 1 (GD1) are both macrophage storage disorders with overlapping clinical manifestations. We compared cross‐sectional data on visceral, hematological, and biochemical manifestations of untreated adult patients with chronic visceral ASMD (n = 19) and GD1 (n = 85). Spleen volume, liver volume, and bone marrow fat fraction did not significantly differ between the two disease groups (p >0.05 for all). Chitotriosidase activity was higher in GD1 (GD1: median 30 940 nmol/(mL.h), range 513–201 352, ASMD: median 1693 nmol/(mL.h), range 326–6620, p <0.001), whereas platelet levels were lower (GD1: median 102 109/L, range 16–726, ASMD: median 154 109/L, range 86–484, p <0.010), as were hemoglobin levels (GD1: median 7.8 mmol/L, range 5.0–10.4, ASMD: median 9.0 mmol/L, range 7.0–10.4, p <0.001). No bone complications were reported for ASMD, compared to 33% in GD1 (p <0.005). In ASMD pulmonary disease was more severe as evidenced by a median diffusion capacity of the lungs for carbon monoxide of 73% of predicted (range 26–104), compared to 85% (range 53–126) in GD1 (p = 0.029). In conclusion, bone complications, hematological abnormalities, chitotriosidase activity, and CCL18 levels were more prominent in GD1, while pulmonary manifestations were more common in AMSD. Different secondary pathophysiological processes surrounding sphingomyelin and glucosylceramide accumulation might explain these differences.
Genital ulcers in hospitalized patients: How often is genital herpes the culprit?
Authors: Bermúdez‐Rodríguez S. P. , Malagón‐Liceaga A. , Figueroa‐Ramos G. , Estrada‐Caraveo Y. V. , Gatica‐Torres M. , Domínguez‐Cherit J.
Published: July 2024

Background

Genital herpes (GH) is the main infectious cause of genital ulcers worldwide. Clinical diagnosis alone may be misleading, especially in immunocompromised patients in whom atypical presentations are common.

Objectives

To assess the herpetic etiology of genital ulcers in immunocompromised and immunocompetent hospitalized adults, and to identify the most frequent differential diagnoses within each patient group.

Methods

We conducted a retrospective transverse study at a third‐level center in Mexico City using PCR testing (HSV‐1, HSV‐2, VZV) in hospitalized patients with genital ulcers to diagnose GH. When negative, biopsy and tissue cultures were taken to establish the final diagnosis. Data from a 2‐year period (March 2021 to April 2023), including demographic characteristics, comorbidities, initial clinical suspicion, PCR test results, skin tissue biopsy results, cultures results, and final diagnosis, were collected from May 2023 to June 2023.

Results

A total of 59 hospital patients with genital ulcers underwent PCR testing due to clinical suspicion of GH, of which 39 (66%) were immunocompromised. The diagnosis was confirmed in 32/59 cases (54%), of which 22/32 (69%) were immunocompromised and 10/32 (31%) immunocompetent. In the 17 immunocompromised adults in whom GH was excluded, other viral (34%) or bacterial (23%) infections were the next most frequent etiologies. Meanwhile, among the 10 immunocompetent patients without GH, noninfectious causes, such as incontinence‐associated dermatitis (15%) and trauma or pressure ulcers (15%), were the most prevalent.

Conclusions

Genital ulcers in hospitalized adults should raise the suspicion of infectious etiologies, particularly of GH. Diagnostic confirmation with tests such as PCR is crucial given the uncertainty of its clinical diagnosis. Once GH diagnosis is excluded, immunocompromised patients should be evaluated for other infectious etiologies, while noninfectious causes should be considered first in immunocompetent patients.
An efficient computational approach and its analysis for the Caputo time‐fractional convection reaction–diffusion equation in two‐dimensional space
Authors: Roul Pradip , Yadav Jyoti , Kumari Trishna
Published: July 2024

This work concerns with a novel computational approach to solve a two‐dimensional Caputo time‐fractional convection reaction–diffusion (CTFCRD) equation with the weak singularity at the initial time. In this method, the
‐scheme on graded mesh is used to approximate the Caputo temporal derivative, while the spatial derivatives are approximated by using a compact finite difference method (CFDM) coupled with alternating direction implicit (ADI) scheme. We present a methodology to examine the optimal error estimates of the proposed scheme, in terms of
‐norm. Convergence and stability results are proved. It is shown that the suggested method yields an optimal order, that is, min(2‐
,
, 2
+1) in time direction, where
is the order of time fractional derivative and
is the grading parameter and has a fourth‐order of convergence in space direction. Finally, two numerical examples are provided to verify the theoretical estimates and to illustrate the accuracy and efficiency of the method.
Comparing the metabolic signatures of obesity defined by waist circumference, waist‐hip ratio, or BMI
Authors: Al Hariri Moustafa , Al‐Sulaiti Haya , Anwardeen Najeha , Naja Khaled , A. Elrayess Mohamed
Published: July 2024

Objective

Measuring obesity is crucial for assessing health risks and developing effective prevention and treatment strategies. The most common methods used to measure obesity include BMI, waist circumference, and waist‐hip ratio. This study aimed to determine the metabolic signatures associated with each measure of obesity in the Qatari population.

Methods

Metabolomics profiling was conducted to identify, quantify, and characterize metabolites in serum samples from the study participants. Inverse rank normalization, principal component analysis, and orthogonal partial least square‐discriminant analysis were used to analyze the metabolomics data.

Results

This study revealed significant differences in metabolites associated with obesity based on different measurements. In men, phosphatidylcholine and phosphatidylethanolamine metabolites were significantly enriched in individuals classified as having obesity based on the waist‐hip ratio. In women, significant changes were observed in leucine, isoleucine, and valine metabolism metabolites. Unique metabolites were found in the different categorization groups that could serve as biomarkers for assessing many obesity‐related disorders.

Conclusions

This study identified unique metabolic signatures associated with obesity based on different measurements in the Qatari population. These findings contribute to a better understanding of the molecular pathways involved in obesity and may have implications for developing personalized prevention and treatment strategies.