bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiome and metabolome to discover pathogenic bacteria and probiotics in ankylosing spondylitis
Authors: Lai Yupeng , Tang Wenli , Luo Xiao , Zheng Huihui , Zhang Yanpeng , Wang Meiying , Yu Guangchuang , Yang Min
Published: April 2024

Objective

Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome–metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS.

Methods

To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites.

Results

A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored.

Conclusion

In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.
Cost-effectiveness of additional serplulimab to chemotherapy in metastatic squamous non-small cell lung cancer patients
Authors: Zheng Hanrui , Zeng Ya , Wen Feng , Hu Ming
Published: April 2024

Objective

To estimate the cost-effectiveness of adding serplulimab to chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC) patients in a first-line setting from a Chinese perspective.

Methods

A three-health state partitioned survival model was constructed to simulate disease development. The clinical data used in the model were derived from the ASTRUM-004 clinical trial. Only direct medical costs were included, and the utilities were derived from published literature. The quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were employed to evaluate health outcomes. Additionally, a sensitivity analysis was performed to verify the robustness of the results.

Results

Compared with chemotherapy alone, the addition of serplulimab resulted in an increase of 0.63 QALYs with an incremental cost of $5,372.73, leading to an ICER of $8,528.14 per QALY. This ICER was significantly lower than 3 times China’s per capita GDP. The one-way sensitivity analysis suggested that the utility of PFS was the most sensitive factor on ICERs, followed by the price of serplulimab.

Conclusion

The combination of serplulimab and chemotherapy has been shown to be a cost-effective initial treatment option for patients with metastatic squamous NSCLC with the commonly accepted willingness-to-pay threshold of 3 times the GDP per capita per QALY in China.
Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: a pilot study
Authors: Zamani Mahtab , Skagen Karolina , Lindberg Beate , Bjerkeli Vigdis , Aukrust Pål , Halvorsen Bente , Skjelland Mona
Published: April 2024

Background

Unstable atherosclerotic carotid plaques with intraplaque neovascularization (IPN) carry a substantial risk for ischemic stroke. Conventional ultrasound methods fall short in detecting IPN, where superb microvascular imaging (SMI) has emerged as a promising tool for both visualizing and quantification. High levels of fibroblast growth factor 23 (FGF-23) have, in observational studies, been suggested as related to cardiovascular morbidity and mortality. The association of FGF-23 to atherosclerotic carotid plaque instability remains relatively unexplored.

Methods

A cohort of twenty-nine patients with ≥50% atherosclerotic carotid stenosis underwent conventional carotid ultrasound, SMI, and blood tests, including measurement of FGF-23 in plasma. Nineteen patients were characterized as symptomatic and ten as asymptomatic.

Results

Our major findings were: i) Higher FGF-23 levels were strongly correlated with increased SMI-assessed IPN. ii) Neo-vessel count recorded by quantitative SMI was positively correlated to increased FGF-23 levels, but not with basic FGF levels. (iii) In contrast, traditional risk factors for plaque instability exhibited no noteworthy associations with SMI-assessed IPN or with FGF-23 levels.

Conclusion

This pilot study suggest the potential of FGF-23 as a valuable marker for neovascularization and atherosclerotic carotid plaque instability as a risk factor for ischemic stroke. Further research involving larger cohorts and prospective data is necessary to understand FGF-23’s role in this context comprehensively.
Machine learning and weighted gene co-expression network analysis identify a three-gene signature to diagnose rheumatoid arthritis
Authors: Wu Ying-Kai , Liu Cai-De , Liu Chao , Wu Jun , Xie Zong-Gang
Published: April 2024

Background

Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains unclear, and diagnostic markers with high sensitivity and specificity are needed urgently. This study aims to identify potential biomarkers in the synovium for diagnosing RA and to investigate their association with immune infiltration.

Methods

We downloaded four datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. Then, various enrichment analyses were conducted. Subsequently, weighted gene co-expression network analysis (WGCNA), random forest (RF), support vector machine–recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO) were used to identify the hub genes for RA diagnosis. Receiver operating characteristic curves and nomogram models were used to validate the specificity and sensitivity of hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profile and their relationship with the hub genes using single-sample gene set enrichment analysis.

Results

Three hub genes, namely, ribonucleotide reductase regulatory subunit M2 (RRM2), DLG-associated protein 5 (DLGAP5), and kinesin family member 11 (KIF11), were identified through WGCNA, LASSO, SVM-RFE, and RF algorithms. These hub genes correlated strongly with T cells, natural killer cells, and macrophage cells as indicated by immune cell infiltration analysis.

Conclusion

RRM2, DLGAP5, and KIF11 could serve as potential diagnostic indicators and treatment targets for RA. The infiltration of immune cells offers additional insights into the underlying mechanisms involved in the progression of RA.
Shell shape polymorphism analysis of the Manila clam Ruditapes philippinarum across different geographical populations in China
Authors: Huo Zhongming , Wang Zixuan , Li Dongdong , Liu Kuo , Li Xiaotong , Fang Lei , Yan Xiwu
Published: April 2024

Morphology of bivalves, a kind of quantitative character, is closely connected with the ecological and physiological behaviors of bivalves, including growth, survival, metabolism and reproduction. In this study, a multivariate statistical method was used to analyze seven indices for shell shape evaluation of Ruditaps philippinarum (R. philippinarum). Polymorphism of R. philippinarum shell shape across seven geographical populations from the southern and northern regions of China was revealed, and decisive effect of shell shape in determining the trait of weight was discussed. In total, three types of R. philippinarum shell shape were observed: globular, flat, and lateral-view round. The Laizhou (LZ) population from the north of China displayed an approximately globular shell shape, with a shell-width-to-shell-length ratio of 0.5496 and an ellipse index ventral view (EIV) value of 0.9543. The Lianjiang (LJ) population from the south of China displayed a flat shell shape, with a shell-width-to-shell-length ratio of 0.4044, an ellipse index lateral view (EIL) value of 1.2518, and an EIV value of 0.7063. The Zhangzidao (ZZD) population from the north of China displayed a lateral view round shell shape, with a shell-width-to-shell-length ratio of 0.7476 and a circle index lateral view (CIL) value of 0.7195. According to the results of principal component analysis (PCA), discriminant analysis and cluster analysis on shell shape parameters, LJ population and LZ population could be grouped separately. However, despite the long geographical distance, Rongcheng (RC) population was highly similar with ZZD population in terms of shell shape traits, implying that these two populations might be more closely related. Lowest degree of divergence in shell shape was observed in Beihai (BH) population and Yingkou (YK) population, both of which belonged to Zuidong (ZD) population. Weight of globular Manila clams was significantly higher than that of flat clams (P < 0.05). This study not only lays a foundation for conservation of R. philippinarum germplasm resources, but also highlights the importance of considering shell morphology in the breeding and culture of R. philippinarum.
Protection pattern and driving mechanism of typical marine ecosystems: a case study of China-ASEAN countries
Authors: Chen Fenggui , Cui Zhiyi , Wu Jianwei , Jiang Yuhuan , Cai Feng
Published: April 2024

The protection pattern of typical marine ecosystems is an overall summary of the regional marine ecosystem protection, indicating the protection status of typical marine ecosystems. The coastal waters of China and ASEAN countries have a highly diverse range of ecosystem types, including mangroves, coral reefs, and seagrass beds. The need to protect these ecosystems is urgent, but establishing marine protected areas often involves conflicts with stakeholders highly dependent on these ecosystems. By constructing an analysis model of the protection pattern and driving mechanisms of typical marine ecosystems, with a focus on the China-ASEAN region, this study aimed to analyze the characteristics of typical marine ecosystems protection patterns in China-ASEAN, evaluate the current protection status of these ecosystems, discuss the driving factors, and derive a regression function to clarify the quantitative relationship between the protection pattern and driving factors of typical marine ecosystems in the China-ASEAN region. The results indicate that there are four main driving factors influencing the protection pattern of typical marine ecosystems in China-ASEAN countries. The most significant driving factor is the Natural Geographic and Resource Factor, followed by Urbanization, Industrial Structure, and Population Size and GDP Factor. Among these, the Natural Geographic and Resource Factor and the Industrial Structure Factor have a positive impact, while the others have a negative impact. In the future, it is crucial to fully consider the diversity and distribution of marine ecosystems to promote joint efforts among China-ASEAN countries in protecting marine ecosystems through international cooperation.
Reflections on the European Union’s participation in negotiations of the global plastic pollution instrument under international environmental law
Authors: Xu Qi , Zhang Mingyang , Han Shuli
Published: April 2024

Increasing plastic pollution is looming worldwide, damaging biodiversity, marine ecosystems, and human health. At the global level, no overarching normative framework sets out the specific rules and principles of general application in international environmental law, leading to difficulties in compliance and enforcement of plastic pollution governance. Developing an effective and legally binding instrument to tackle this emerging issue is imperative. The United Nations Environment Assembly (UNEA) has called for developing an international legally binding instrument on plastic pollution, including in the marine environment, based on plastic’s full lifecycle approach. As one of the active participants in the negotiations, the European Union (EU) has discussed various aspects of the instrument in detail and sought to introduce the EU governance experience at the international level. This article develops a framework that considers contextual, actor, and process factors to assess the extent of achieving EU targets. On this basis, we argue that the EU’s objectives for the international instrument may be achieved at a high level. However, how the EU responds to challenges will also impact subsequent development, which may require the EU to adopt a more moderate stance and compromise on some controversial issues.
Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel
Authors: Rudnicka Lidia , Trzeciak Magdalena , Alpsoy Erkan , Arenberger Petr , Alper Sibel , Benáková Nina , Bobko Svetlana , Borlu Murat , Czarnecka Operacz Magdalena , Engin Burhan , Ergun Tülin , Sağduyu Ilgen Ertam , Filipovská Olga , Gadzhigoroeva Aida , Kojanová Martina , Lesiak Aleksandra , Michenko Anna , Murashkin Nikolay , Onsun Nahide , Owczarek Witold , Plzakova Zuzana , Reich Adam , Selerová Marie , Gürbüz Burcu Aybike
Published: April 2024

Objectives

This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions.

Methods

A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata.

Results

The study revealed that moderate-to-severe AA significantly impacts patients’ and their families’ QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need.

Conclusion

The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.
Acute and chronic eosinophilic pneumonia: an overview
Authors: Carbone Roberto G. , Puppo Francesco , Mattar Eduardo , Roden Anja C. , Hirani Nikhil
Published: April 2024

Acute and chronic eosinophilic pneumonia (AEP and CEP) include a group of rare interstitial lung diseases characterized by peripheral blood eosinophilia, increased eosinophils in bronchoalveolar lavage fluid, or eosinophilic infiltration of lung parenchyma. AEP is characterized by rapid onset, fast response to steroid treatment, and no relapse. CEP is characterized by marked tissue and peripheral blood eosinophilia, rapid response to steroid therapy, and tendency to disease recurrence. In addition, we briefly describe other eosinophilic lung diseases that must be considered in differential diagnosis of AEP and CEP. Eosinophilic pneumonias may be idiopathic or due to known causes such as medications or environmental exposure. At variance with previous reviews on this topic, a particular look in this overview was directed at pathological findings and radiological patterns.
The role of zyxin in signal transduction and its relationship with diseases
Authors: Wu Zelan , Wu Daiqin , Zhong Qin , Zou Xue , Liu Zhongjing , Long Hehua , Wei Jing , Li Xia , Dai Fangjie
Published: April 2024

This review highlighted the pivotal role of zyxin, an essential cell focal adhesions protein, in cellular biology and various diseases. Zyxin can orchestrate the restructuring and dynamic alterations of the cellular cytoskeleton, which is involved in cell proliferation, adhesion, motility, and gene transcription. Aberrant zyxin expression is closely correlated with tumor cell activity and cardiac function in both tumorigenesis and cardiovascular diseases. Moreover, in fibrotic and inflammatory conditions, zyxin can modulate cellular functions and inflammatory responses. Therefore, a comprehensive understanding of zyxin is crucial for deciphering signal transduction networks and disease pathogenesis. Investigating its role in diseases holds promise for novel avenues in early diagnosis and therapeutic strategies. Nevertheless, targeting zyxin as a therapeutic focal point presents challenges in terms of specificity, safety, drug delivery, and resistance. Nonetheless, in-depth studies on zyxin and the application of precision medicine could offer new possibilities for personalized treatment modalities.
Global study of anti-NMDA encephalitis: a bibliometric analysis from 2005 to 2023
Authors: Song Xinyue , Luo Zixin , Huang Duoqin , Lv Jialian , Xiao Li , Liang Ting , Zou Kang
Published: April 2024

Background

Autoimmune diseases have always been one of the difficult diseases of clinical concern. Because of the diversity and complexity of its causative factors, unclear occurrence and development process and difficult treatment, it has become a key disease for researchers to study. And the disease explored in this paper, anti-NMDA encephalitis, belongs to a common type of autoimmune encephalitis. However, the quality of articles and research hotspots in this field are not yet known. Therefore, in this field, we completed a bibliometric and visualization analysis from 2005 to 2023 in order to understand the research hotspots and directions of development in this field.

Materials and methods

We searched the SCI-expanded databases using Web of Science’s core databases on January 22, 2024 and used tools such as VOS viewer, Cite Space, and R software to visualize and analyze the authors, countries, journals, institutions, and keywords of the articles.

Results

A total of 1,161 literatures were retrieved and analyzed in this study. China was the country with the most total publications, and USA and Spain were the most influential countries in the field of anti-NMDA encephalitis. University of Pennsylvania from USA was the institution with the highest number of publications. While Dalmau Josep is the most prolific, influential and contributing author who published one of the most cited articles in Lancet Neurology, which laid the foundation for anti-NMDA encephalitis research, the top three appearances of keyword analysis were: “antibodies”, “diagnosis”, and “autoimmune encephalitis.”

Conclusion

Bibliometric analysis shows that the number of studies on anti-NMDA encephalitis is generally increasing year by year, and it is a hot disease pursued by researchers. USA and Spain are leading in the field of anti-NMDA encephalitis, while China should continue to improve the quality of its own research. The suspected causes of anti-NMDA encephalitis other than ovarian teratoma and herpes simplex, the specific clinical manifestations that are not masked by psychiatric symptoms, the diagnostic modalities that are faster and more accurate than antibody tests, and the improvement of treatment modalities by evaluating prognosis of various types of patients are the hotspots for future research.
Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions
Authors: O’Shea Deirdre M. , Arkhipenko Alexander , Galasko Douglas , Goldman Jennifer G. , Sheikh Zulfiqar Haider , Petrides George , Toledo Jon B. , Galvin James E.
Published: April 2024

Background

Diagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake—a key biomarker in DLB diagnosis—could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management.

Methods

This review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches.

Results

The radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan’s diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities.

Conclusion

123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer’s Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.
First clinical implementation of insertion force measurement in cochlear implantation surgery
Authors: Rau Thomas S. , Böttcher-Rebmann Georg , Schell Viktor , Cramer Jakob , Artukarslan Eralp , Baier Claas , Lenarz Thomas , Salcher Rolf
Published: April 2024

Purpose

The significance of atraumatic electrode array (EA) insertion in cochlear implant (CI) surgery is widely acknowledged, with consensus that forces due to EA insertion are directly correlated with insertion trauma. Unfortunately, the manual perception of these forces through haptic feedback is inherently limited, and techniques for in vivo force measurements to monitor the insertion are not yet available. Addressing this gap, we developed of a force-sensitive insertion tool capable of capturing real-time insertion forces during standard CI surgery.

Methods

This paper describes the tool and its pioneering application in a clinical setting and reports initial findings from an ongoing clinical study. Data and experiences from five patients have been evaluated so far, including force profiles of four patients.

Results

The initial intraoperative experiences are promising, with successful integration into the conventional workflow. Feasibility of in vivo insertion force measurement and practicability of the tool’s intraoperative use could be demonstrated. The recorded in vivo insertion forces show the expected rise with increasing insertion depth. Forces at the end of insertion range from 17.2 mN to 43.6 mN, while maximal peak forces were observed in the range from 44.8 mN to 102.4 mN.

Conclusion

We hypothesize that this novel method holds the potential to assist surgeons in monitoring the insertion forces and, thus, minimizing insertion trauma and ensuring better preservation of residual hearing. Future data recording with this tool can form the basis of ongoing research into the causes of insertion trauma, paving the way for new and improved prevention strategies.
Studying m6A in the brain: a perspective on current methods, challenges, and future directions
Authors: Tegowski Matthew , Meyer Kate D.
Published: April 2024

A major mechanism of post-transcriptional RNA regulation in cells is the addition of chemical modifications to RNA nucleosides, which contributes to nearly every aspect of the RNA life cycle. N6-methyladenosine (m6A) is a highly prevalent modification in cellular mRNAs and non-coding RNAs, and it plays important roles in the control of gene expression and cellular function. Within the brain, proper regulation of m6A is critical for neurodevelopment, learning and memory, and the response to injury, and m6A dysregulation has been implicated in a variety of neurological disorders. Thus, understanding m6A and how it is regulated in the brain is important for uncovering its roles in brain function and potentially identifying novel therapeutic pathways for human disease. Much of our knowledge of m6A has been driven by technical advances in the ability to map and quantify m6A sites. Here, we review current technologies for characterizing m6A and highlight emerging methods. We discuss the advantages and limitations of current tools as well as major challenges going forward, and we provide our perspective on how continued developments in this area can propel our understanding of m6A in the brain and its role in brain disease.
Orthorexic tendency and its association with weight control methods and dietary variety in Polish adults: a cross-sectional study
Authors: Plichta Marta , Kowalkowska Joanna
Published: April 2024

The methods for controlling weight play a central role in formally diagnosed eating disorders (EDs) and appear to be important in the context of other nonformally recognized disorders, such as orthorexia nervosa (ON). These methods also have an impact on eating behaviors, including dietary variety. Our study aimed to: (i) assess the intensity of ON tendency by sex and BMI groups, (ii) evaluate the associations between ON tendency, weight control methods, and dietary variety, and (iii) determine the extent to which weight control methods and dietary variety contribute to the ON tendency among both females and males. Data were gathered from a sample of 936 Polish adults (463 females and 473 males) through a cross-sectional quantitative study conducted in 2019. Participants were requested to complete the ORTO-6, the Weight Control Methods Scale, and the Food Intake Variety Questionnaire (FIVeQ). Multiple linear regression analysis was employed to evaluate associations between ON tendency, weight control methods, and dietary variety. Females exhibited a higher ON tendency than males (14.4 ± 3.4 vs. 13.5 ± 3.7, p < 0.001, d = 0.25). In the regression model, the higher ON tendency was predicted by more frequent use of weight control methods, such as restricting the amount of food consumed, using laxatives, and physical exercise among both females and males as well as following a starvation diet in females, and drinking teas to aid bowel movements among males. Moreover, the higher ON tendency was predicted by higher dietary variety, lower age in both sexes, and higher level of education among males. However, there were no differences in ON tendency across BMI groups. In conclusion, the findings showed that ON tendency was predicted by a higher frequency of weight control methods commonly used by individuals with anorexia nervosa (AN) and bulimia nervosa (BN). The resemblance to these two EDs is also suggested by the higher intensity of ON tendency among females and younger people. However, the prediction of ON tendency by dietary variety indicates that the obsessive preoccupation with healthy eating may not be advanced enough to observe a decrease in the dietary variety among these individuals.
Managing potential adverse events during treatment with enfortumab vedotin + pembrolizumab in patients with advanced urothelial cancer
Authors: Brower Blaine , McCoy Asia , Ahmad Hiba , Eitman Cheryl , Bowman I. Alex , Rembisz Jennifer , Milowsky Matthew I.
Published: April 2024

Cisplatin-based chemotherapy has been the standard of care for patients with locally advanced or metastatic urothelial cancer (la/mUC). Enfortumab vedotin, an antibody-drug conjugate directed to Nectin-4, and pembrolizumab, an immune checkpoint inhibitor, are two therapies that have individually provided a survival benefit in patients with la/mUC. The combination regimen of enfortumab vedotin plus pembrolizumab was evaluated in EV-302 (KEYNOTE-A39; NCT0422385), a phase 3 study that showed statistically significant and clinically meaningful improvement in overall survival, progression-free survival, and a key secondary endpoint of overall response rate versus chemotherapy. Based on these results and those from the EV-103 (KEYNOTE-869; NCT03288545) Dose Escalation cohort, Cohort A, and Cohort K, enfortumab vedotin plus pembrolizumab was granted approval from the US Food and Drug Administration for the treatment of adults with la/mUC. While guidelines and recommendations for the management of adverse events (AEs) have been developed for immune checkpoint inhibitor monotherapy and enfortumab vedotin monotherapy, additional guidance is needed for managing AEs that occur with enfortumab vedotin plus pembrolizumab. As monotherapies, enfortumab vedotin and pembrolizumab are both associated with some of the AEs observed with the combination, such as skin reactions, pneumonitis, and diarrhea, which may confound the attribution of the AE to a specific agent and thereby complicate clinical management. In this manuscript, we aim to provide recommendations for best practice for patient care and the management of AEs of clinical interest for patients with la/mUC receiving enfortumab vedotin plus pembrolizumab, including skin reactions, peripheral neuropathy, hyperglycemia, and pneumonitis. These recommendations were developed based on published guidelines, expert opinions, and the clinical experience of the authors, which include oncologist, advanced practice provider, nursing, and pharmacy perspectives. In addition, guidance on patient education and communication is provided. With vigilant monitoring, early detection, and prompt intervention of treatment-emergent AEs based on recommended approaches described herein, it is the authors’ experience that most AEs can be managed with supportive therapy and dose modification/interruptions, allowing patients to continue treatment.
Efficacy and safety of levetiracetam vs. oxcarbazepine in the treatment of children with epilepsy: a systematic review and meta-analysis
Authors: Liu Yuanyuan , Wang Yanxu , Li Xingzhou , Wu Xiaomin
Published: April 2024

Background

Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy.

Objective

The present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy.

Methods

We conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results.

Results

This meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], P > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), P > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), P > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), P > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = −0.144, 95% CI [−0.613, 0.325], P > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], P < 0.05).

Conclusion

The efficacy of LEV and OXC monotherapy in treating children with epilepsy is similar. However, OXC having a more significant effect on the thyroid than that of LEV. Therefore, LEV may be safer for children with epilepsy who are predisposed to thyroid disease than OXC.

Systematic Review Registration

https://www.crd.york.ac.uk/, PROSPERO (CRD42024514016)
Management of cognitive impairment associated with post-COVID-19 syndrome: recommendations for primary care
Authors: Zifko Udo , Guendling Katja , Seet Raymond , Kasper Siegfried
Published: April 2024

Introduction: Although post-COVID-19 syndrome (PCS) with cognitive impairment is increasingly encountered in primary care, evidence-based recommendations for its appropriate management are lacking.

Methods: A systematic literature search evaluating the diagnosis and treatment of cognitive impairment associated with PCS was conducted. Practical recommendations for the management of PCS-associated cognitive impairment in primary care are summarized, based on an evaluation of pharmacological plausibility and clinical applications.

Results: Currently, the pathology of cognitive impairment associated with PCS remains unclear with no high-quality data to support targeted interventions. Existing treatment approaches are directed towards symptom relief where counseling on the chronicity of the disease and regular reassessments at 4- to 8-week intervals is considered reasonable. Patients should be informed and encouraged to adopt a healthy lifestyle that centers around balanced nutrition and appropriate physical activities. They may also benefit from the intake of vitamins, micronutrients, and probiotics. The administration of Ginkgo biloba extract could offer a safe and potentially beneficial treatment option. Other non-pharmacological measures include physiotherapy, digitally supported cognitive training, and, if indicated, ergotherapy or speech therapy. In most patients, symptoms improve within 8 weeks. If serious, ambiguous, or when new symptoms occur, specialized diagnostic measures such as comprehensive neurocognitive testing or neuroimaging should be initiated. Very few patients would require inpatient rehabilitation.

Conclusion: PCS with cognitive impairment is a debilitating condition that could affect daily functioning and reduce work productivity. Management in primary care should adopt a multidisciplinary approach, centering around physical, cognitive, and pharmacological therapies.
A deep learning framework for noninvasive fetal ECG signal extraction
Authors: Wahbah Maisam , Zitouni M. Sami , Al Sakaji Raghad , Funamoto Kiyoe , Widatalla Namareq , Krishnan Anita , Kimura Yoshitaka , Khandoker Ahsan H.
Published: April 2024

Introduction: The availability of proactive techniques for health monitoring is essential to reducing fetal mortality and avoiding complications in fetal wellbeing. In harsh circumstances such as pandemics, earthquakes, and low-resource settings, the incompetence of many healthcare systems worldwide in providing essential services, especially for pregnant women, is critical. Being able to continuously monitor the fetus in hospitals and homes in a direct and fast manner is very important in such conditions.

Methods: Monitoring the health of the baby can potentially be accomplished through the computation of vital bio-signal measures using a clear fetal electrocardiogram (ECG) signal. The aim of this study is to develop a framework to detect and identify the R-peaks of the fetal ECG directly from a 12 channel abdominal composite signal. Thus, signals were recorded noninvasively from 70 pregnant (healthy and with health conditions) women with no records of fetal abnormalities. The proposed model employs a recurrent neural network architecture to robustly detect the fetal ECG R-peaks.

Results: To test the proposed framework, we performed both subject-dependent (5-fold cross-validation) and independent (leave-one-subject-out) tests. The proposed framework achieved average accuracy values of 94.2% and 88.8%, respectively. More specifically, the leave-one-subject-out test accuracy was 86.7% during the challenging period of vernix caseosa layer formation. Furthermore, we computed the fetal heart rate from the detected R-peaks, and the demonstrated results highlight the robustness of the proposed framework.

Discussion: This work has the potential to cater to the critical industry of maternal and fetal healthcare as well as advance related applications.
Acute physiological and psychological responses during an incremental treadmill test wearing a new upper-body sports garment with elastomeric technology
Authors: Janicijevic Danica , Saez-Berlanga Angel , Babiloni-Lopez Carlos , Martin-Rivera Fernando , Jiménez-Martínez Pablo , Silvestre-Herrero Alejandro , Martínez-Puente Javier , Ferradás-Nogueira Pablo , Juesas Alvaro , Gene-Morales Javier , Chulvi-Medrano Iván , Colado Juan C.
Published: April 2024

Background: The use of elastomeric technology in sports garments is increasing in popularity; however, its specific impact on physiological and psychological variables is not fully understood. Thus, we aimed to analyze the physiological (muscle activation of the pectoralis major, triceps brachii, anterior deltoid, and rectus abdominis, capillary blood lactate, systolic and diastolic blood pressure, and heart rate) and psychological (global and respiratory rating of perceived exertion [RPE]) responses during an incremental treadmill test wearing a new sports garment for the upper body that incorporates elastomeric technology or a placebo garment.

Methods: Eighteen physically active young adults participated in two randomized sessions, one wearing the elastomeric garment and the other wearing a placebo. Participants performed in both sessions the same treadmill incremental test (i.e., starting at 8 km/h, an increase of 2 km/h each stage, stage duration of 3 min, and inclination of 1%; the test ended after completing the 18 km/h Stage or participant volitional exhaustion). The dependent variables were assessed before, during, and/or after the test. Nonparametric tests evaluated differences.

Results: The elastomeric garment led to a greater muscle activation (p < 0.05) in the pectoralis major at 16 km/h (+33.35%, p = 0.01, d = 0.47) and 18 km/h (+32.09%, p = 0.02, d = 0.55) and in the triceps brachii at 10 km/h (+20.28%, p = 0.01, d = 0.41) and 12 km/h (+34.95%, p = 0.04, d = 0.28). Additionally, lower lactate was observed at the end of the test (−7.81%, p = 0.01, d = 0.68) and after 5 min of recovery (−13.71%, p < 0.001, d = 1.00) with the elastomeric garment. Nonsignificant differences between the garments were encountered in the time to exhaustion, cardiovascular responses, or ratings of perceived exertion.

Conclusion: These findings suggest that elastomeric garments enhance physiological responses (muscle activation and blood lactate) during an incremental treadmill test without impairing physical performance or effort perception.
Immune niches for hair follicle development and homeostasis
Authors: Kiselev Artem , Park Sangbum
Published: April 2024

The hair follicle is a dynamic mini-organ that has specialized cycles and architectures with diverse cell types to form hairs. Previous studies for several decades have investigated morphogenesis and signaling pathways during embryonic development and adult hair cycles in both mouse and human skin. In particular, hair follicle stem cells and mesenchymal niches received major attention as key players, and their roles and interactions were heavily revealed. Although resident and circulating immune cells affect cellular function and interactions in the skin, research on immune cells has mainly received attention on diseases rather than development or homeostasis. Recently, many studies have suggested the functional roles of diverse immune cells as a niche for hair follicles. Here, we will review recent findings about immune niches for hair follicles and provide insight into mechanisms of hair growth and diseases.
Religion would be a missing link in the case formulation of adolescents with conduct problems: an eclectic approach
Authors: Goker Zeynep
Published: April 2024

Psychiatry is concerned with mental health. Cognition is one of the key mental functions and manifests itself primarily as behavior. A behavior exhibited in response to a stimulus is influenced by biological (inherited), psychological (individual), and social (environmental) factors. During consolidation of an exhibited behavior, the factors affecting the individual’s cognitive structure and personality play crucial roles. Underlying factors for a problematic behavior, and their weakness/strength levels are determined via the Biopsychosocial model. Empirically effective current practices to intervene the problematic behaviors do not always result in success. One of the reasons may be other elements that were omitted during the case formulation process. This article aims to stress the idea that whatever the underlying factor of a problematic behavior is, the most crucial determinant and/or pre-emptive factor in developing or maintaining that behavior might actually be the religion as a governing and directive philosophy on how to conduct oneself. In this instance, the key is in the hands of the parents or caregivers.
A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia
Authors: Selvan Panneer , Devkare Prashant , Shetty Arthik , Dharmadhikari Shruti , Khandhedia Chintan , Mane Amey , Mehta Suyog , Andrade Chittaranjan
Published: April 2024

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India’s Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.
Nurses’ perception of the impact of professional development sessions on their pre-hospital clinical practice with trauma victims
Authors: Mota Mauro , Pires Regina , Cunha Madalena , Santos Margarida Reis
Published: April 2024

Background

Continuing education is important for the quality of clinical practice because it complements it and focuses primarily on producing qualified pre-hospital nurses with operationally defined competence in nursing standards. The objective of this study was to assess pre-hospital nurses’ opinion of the impact of professional development sessions on their clinical practice.

Method

A descriptive and quantitative study was carried out involving Portuguese pre-hospital nurses. Six professional development sessions were presented in 2020 to pre-hospital registered nurses in four of Portugal’s main cities. To collect the data, at the end of each session, we apply a questionnaire designed specifically for this study. This data collection instrument consists of 11 questions, six designed to evaluate the session and five designed to evaluate the trainer responsible for the session. A five-point Likert scale was used for each question, where 1 corresponds to very dissatisfied and 5 to extremely satisfied.

Results

Two hundred and two nurses, which represents 55% of all Portuguese pre-hospital nurses, took part in the assessment of the professional development sessions. The nurses were from the Northern region of Portugal (51%; n = 102), the Centre region (29%; n = 59) and the Southern region of Portugal (20%; n = 41). Nurses found the session extremely satisfactory. All the assessment scores ranged between 4.4 and 4.7 points, on a scale of 1 to 5. 76.2% of the participants considered that the knowledge acquired could have a major impact [score = 5] on their future clinical practice. The majority of pre-hospital nurses (96.5%) felt that the session could have a major impact [score = 5; 76.2%, n = 154] or a very important impact [score = 4; 20.3%, n = 41] on their clinical practice.

Conclusion

The professional development sessions provide pre-hospital nurses with the latest research findings and the majority of nurses considered that the training had a huge impact on their clinical practice. However, it is important that future research aims to explore the cause-effect relationship between training and improved clinical practice.