bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic surveillance of SARS-CoV-2 using long-range PCR primers
Authors: Kandel Sangam , Hartzell Susanna L. , Ingold Ashton K. , Turner Grace A. , Kennedy Joshua L. , Ussery David W.
Published: February 2024

Introduction

Whole Genome Sequencing (WGS) of the SARS-CoV-2 virus is crucial in the surveillance of the COVID-19 pandemic. Several primer schemes have been developed to sequence nearly all of the ~30,000 nucleotide SARS-CoV-2 genome, using a multiplex PCR approach to amplify cDNA copies of the viral genomic RNA. Midnight primers and ARTIC V4.1 primers are the most popular primer schemes that can amplify segments of SARS-CoV-2 (400 bp and 1200 bp, respectively) tiled across the viral RNA genome. Mutations within primer binding sites and primer-primer interactions can result in amplicon dropouts and coverage bias, yielding low-quality genomes with ‘Ns’ inserted in the missing amplicon regions, causing inaccurate lineage assignments, and making it challenging to monitor lineage-specific mutations in Variants of Concern (VoCs).

Methods

In this study we used a set of seven long-range PCR primer pairs to sequence clinical isolates of SARS-CoV-2 on Oxford Nanopore sequencer. These long-range primers generate seven amplicons approximately 4500 bp that covered whole genome of SARS-CoV-2. One of these regions includes the full-length S-gene by using a set of flanking primers. We also evaluated the performance of these long-range primers with Midnight primers by sequencing 94 clinical isolates in a Nanopore flow cell.

Results and discussion

Using a small set of long-range primers to sequence SARS-CoV-2 genomes reduces the possibility of amplicon dropout and coverage bias. The key finding of this study is that long range primers can be used in single-molecule sequencing of RNA viruses in surveillance of emerging variants. We also show that by designing primers flanking the S-gene, we can obtain reliable identification of SARS-CoV-2 variants.
The causal correlation between gut microbiota abundance and pathogenesis of cervical cancer: a bidirectional mendelian randomization study
Authors: Yang Hua
Published: February 2024

Background

Observational studies and animal experiments suggested potential relevance between gut microbiota (GM) and cervical cancer (CC), but the relevance of this association remains to be clarified.

Methods

We performed a two-sample bidirectional Mendelian randomization (MR) analysis to explore whether there was a causal correlation between GM and CC, and the direction of causality.

Results

In primary outcomes, we found that a higher abundance of class Clostridia, family Family XI, genus Alloprevotella, genus Ruminiclostridium 9, and order Clostridiales predicted higher risk of CC, and a higher abundance of class Lentisphaeria, family Acidaminococcaceae, genus Christensenellaceae R7 group, genus Marvinbryantia, order Victivallales, phylum Actinobacteria, and phylum Lentisphaerae predicted lower risk of CC. During verifiable outcomes, we found that a higher abundance of class Methanobacteria, family Actinomycetaceae, family Methanobacteriaceae, genus Lachnospiraceae UCG 010, genus Methanobrevibacter, order Actinomycetales, and order Methanobacteriales predicted a higher risk of CC, and a higher abundance of family Streptococcaceae, genus Dialister, and phylum Bacteroidetes predicted a lower risk of CC, and vice versa.

Conclusion

Our study implied a mutual causality between GM and CC, which provided a novel concept for the occurrence and development of CC, and might promote future functional or clinical analysis.
Pharmaceutically active micropollutants: origin, hazards and removal
Authors: Gupta Anuradha , Kumar Sandeep , Bajpai Yashi , Chaturvedi Kavita , Johri Parul , Tiwari Rajesh K. , Vivekanand V. , Trivedi Mala
Published: February 2024

Pharmaceuticals, recognized for their life-saving potential, have emerged as a concerning class of micropollutants in the environment. Even at minute concentrations, chronic exposure poses a significant threat to ecosystems. Various pharmaceutically active micropollutants (PhAMP), including antibiotics, analgesics, and hormones, have been detected in underground waters, surface waters, seawater, sewage treatment plants, soils, and activated sludges due to the absence of standardized regulations on pharmaceutical discharge. Prolonged exposureof hospital waste and sewage treatment facilities is linked to the presence of antibiotic-resistant bacteria. Conventional water treatment methods prove ineffective, prompting the use of alternative techniques like photolysis, reverse osmosis, UV-degradation, bio-degradation, and nano-filtration. However, commercial implementation faces challenges such as incomplete removal, toxic sludge generation, high costs, and the need for skilled personnel. Research gaps include the need to comprehensively identify and understand various types of pharmaceutically active micropollutants, investigate their long-term ecological impact, develop more sensitive monitoring techniques, and explore integrated treatment approaches. Additionally, there is a gap in understanding the socio-economic implications of pharmaceutical pollution and the efficacy of public awareness campaigns. Future research should delve into alternative strategies like phagotherapy, vaccines, and natural substance substitutes to address the escalating threat of pharmaceutical pollution.
Metabolic dynamics in astrocytes and microglia during post-natal development and their implications for autism spectrum disorders
Authors: Cantando Iva , Centofanti Cristiana , D’Alessandro Giuseppina , Limatola Cristina , Bezzi Paola
Published: February 2024

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by elusive underlying mechanisms. Recent attention has focused on the involvement of astrocytes and microglia in ASD pathology. These glial cells play pivotal roles in maintaining neuronal homeostasis, including the regulation of metabolism. Emerging evidence suggests a potential association between ASD and inborn errors of metabolism. Therefore, gaining a comprehensive understanding of the functions of microglia and astrocytes in ASD is crucial for the development of effective therapeutic interventions. This review aims to provide a summary of the metabolism of astrocytes and microglia during post-natal development and the evidence of disrupted metabolic pathways in ASD, with particular emphasis on those potentially important for the regulation of neuronal post-natal maturation by astrocytes and microglia.
Substrate-bound and soluble domains of tenascin-C regulate differentiation, proliferation and migration of neural stem and progenitor cells
Authors: Glotzbach Kristin , Faissner Andreas
Published: February 2024

Introduction

The lack of regenerative capacity of the central nervous system is one of the major challenges nowadays. The knowledge of guidance cues that trigger differentiation, proliferation, and migration of neural stem and progenitor cells is one key element in regenerative medicine. The extracellular matrix protein tenascin-C (Tnc) is a promising candidate to regulate cell fate due to its expression in the developing central nervous system and in the adult neural stem cell niches. Of special interest are the alternatively spliced fibronectin type III (FnIII) domains of Tnc whose combinatorial diversity could theoretically generate up to 64 isoforms in the mouse. A total of 27 isoforms have already been discovered in the developing brain, among others the domain combinations A1D, CD, and A124BCD.

Methods

In the present study, these domains as well as the combination of the constitutively expressed FnIII domains 7 and 8 (78) were expressed in Chinese hamster ovary cells as pseudo-antibodies fused to the Fc-fragment of a human immunoglobulin G antibody. The fusion proteins were presented to primary mouse neural stem/progenitor cells (NSPCs) grown as neurospheres, either as coated culture substrates or as soluble additives in vitro. The influence of the domains on the differentiation, proliferation and migration of NSPCs was analyzed.

Results

We observed that the domain combination A124BCD promoted the differentiation of neurons and oligodendrocytes, whereas the domain A1D supported astrocyte differentiation. The constitutively expressed domain 78 had a proliferation and migration stimulating impact. Moreover, most effects were seen only in one of the presentation modes but not in both, suggesting different effects of the Tnc domains in two- and three-dimensional cultures.

Discussion

This knowledge about the different effect of the Tnc domains might be used to create artificial three-dimensional environments for cell transplantation. Hydrogels spiked with Tnc-domains might represent a promising tool in regenerative medicine.
Impact of alkaline phosphatase on clinical outcomes in patients with ischemic stroke: a nationwide registry analysis
Authors: Wang Zhaobin , Li Jing , Jing Jing , Zhang Zhe , Xu Qin , Liu Tao , Lin Jinxi , Jiang Yong , Wang Yongjun , Wang Anxin , Meng Xia
Published: February 2024

Background

Data on the association between serum alkaline phosphatase (ALP) levels and clinical outcomes in patients with ischemic stroke (IS) are inconsistent and limited. Therefore, this study aimed to investigate the correlation between ALP and prognosis in patients with IS.

Methods

Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the Third China National Stroke Registry were divided into four groups according to the quartiles of serum ALP levels on admission. Cox proportional hazards and logistic regression models were used to evaluate the correlation between ALP and the risk of all-cause mortality, disability (modified Rankin Scale (mRS) score 3–5), and poor functional outcomes (mRS score 3–6).

Results

A total of 11,405 patients were included in the study. Higher levels of ALP were associated with all-cause mortality at 3 months (adjusted hazard ratio [HR] per standard deviation [SD]: 1.16; 95% confidence interval (CI): 1.07–1.27; p = 0.001) and 1 year (adjusted HR: 1.11; 95% CI: 1.03–1.20; p = 0.010). At the 3-month follow-up, each SD increase of ALP was associated with a 12 and 14% higher risk of disability (adjusted odds ratio (OR): 1.12; 95% CI: 1.06–1.18; p < 0.001) and poor functional outcomes (adjusted OR: 1.14; 95% CI: 1.08–1.20; p < 0.001). Similar results were observed at the 1-year follow-up. Higher ALP levels were associated with an increased risk of all-cause mortality, disability, and poor functional outcomes in patients with “others” subtypes (including other determined etiology and undetermined etiology) (p < 0.05).

Conclusion

Elevated ALP levels were associated with an increased risk of all-cause mortality, disability, and poor function outcomes in patients with IS. Heterogeneity was observed among the subtypes of different etiologies.
Identification of hub genes significantly linked to tuberous sclerosis related-epilepsy and lipid metabolism via bioinformatics analysis
Authors: Weiliang Wang , Yinghao Ren , Weiliang Hou , Xiaobin Zhang , Chenglong Yang , Weimiao An , Fei Xu , Fengpeng Wang
Published: February 2024

Background

Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Identifying differentially expressed lipid metabolism related genes (DELMRGs) is crucial for guiding treatment decisions.

Methods

We acquired tuberous sclerosis related epilepsy (TSE) datasets, GSE16969 and GSE62019. Differential expression analysis identified 1,421 differentially expressed genes (DEGs). Intersecting these with lipid metabolism related genes (LMRGs) yielded 103 DELMRGs. DELMRGs underwent enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and AUCell analysis.

Results

In TSE datasets, 103 DELMRGs were identified. Four diagnostic biomarkers (ALOX12B, CBS, CPT1C, and DAGLB) showed high accuracy for epilepsy diagnosis, with an AUC value of 0.9592. Significant differences (p < 0.05) in Plasma cells, T cells regulatory (Tregs), and Macrophages M2 were observed between diagnostic groups. Microglia cells were highly correlated with lipid metabolism functions.

Conclusions

Our research unveiled potential DELMRGs (ALOX12B, CBS, CPT1C and DAGLB) in TSE, which may provide new ideas for studying the psathogenesis of epilepsy.
Outcome of psychogenic non-epileptic seizures following diagnosis in the epilepsy monitoring unit
Authors: Abi-Nahed Rachelle , Li Jimmy , Carlier Jasmine , Birca Véronica , Bérubé Arline-Aude , Nguyen Dang Khoa
Published: February 2024

Objective

To study the outcome of patients with psychogenic non-epileptic seizures (PNES) after their diagnosis in the epilepsy monitoring unit (EMU).

Methods

Patients diagnosed in our EMU with definite PNES between January 2009 and May 2023 were contacted by phone, and those who agreed to participate were asked a set of predetermined questions. Comparative analyses were carried out on several variables before and after diagnosis: number of participants with daily PNES, number of visits to the emergency department, number of participants who consulted their general practitioner or a neurologist outside of a scheduled follow-up, number of participants who took antiseizure medications (ASMs) or psychotropic drugs, and employment status.

Results

Out of the 103 patients with a definite diagnosis of PNES, 61 patients (79% female) accepted to participate in our study. The median age at PNES onset was 35 years, and the median delay to diagnosis was 3 years. Almost two-thirds (62%) were receiving ASMs and 40% psychotropic drugs. The mean stay at the EMU was 5 days. PNES diagnosis was explained to almost all patients (97%) by the end of their EMU stay and was well-accepted by most (89%). When contacted, 46% of participants no longer had PNES; 32% mentioned that their PNES had ceased immediately upon communication of the diagnosis. The median follow-up duration was 51 months. Fewer patients had daily seizures after the diagnosis (18 vs. 38%; p < 0.0455). Similarly, the median number of emergency department visits was significantly lower (0 vs. 2; p < 0.001). Only 17 patients consulted their general practitioner (vs. 40, p < 0.001) and 20 a neurologist (vs. 55, p < 0.001) after a PNES attack outside of a scheduled follow-up. The use of ASMs was also significantly reduced from 70 to 33% (p < 0.01), with only one still taking an ASM for its antiseizure properties. Significantly more participants were working at last follow-up than at PNES diagnosis (49 vs. 25%; p < 0.001).

Conclusion

Our study revealed a relatively favorable long-term outcome of definite PNES diagnosed in the EMU that translated in significant reductions in PNES frequency, health care utilization and ASM use, as well as a significant increase in employment rate.
Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization
Authors: Liao Yin-Chun , Yang Ching-Ju , Yu Hsin-Yen , Huang Chiu-Jung , Hong Tzu-Yi , Li Wei-Chi , Chen Li-Fen , Hsieh Jen-Chuen
Published: February 2024

Introduction

The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP).

Methods

The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions.

Results

Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule.

Discussion

PG’s rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.
Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes
Authors: Zhang Zhi-Ling , Wu Zi-Yang , Liu Feng-Yu , Hang-YuChen  , Zhai Suo-Di
Published: February 2024

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.
Premature Infant Gut Microbiome relationships with childhood behavioral scales: preliminary insights
Authors: Ozorio Dutra Samia Valeria , Sarkar Anujit , Yoo Ji Youn , Shaffer-Hudkins Emily , Groer Maureen
Published: February 2024

Introduction

Very Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants’ gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models.

Methods

Parents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin).

Results

Nineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such asVeillonella dispar, Enterococcus, Escherichia coli, andRumincococcusto later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years.

Discussion

These preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).
Research progress on the mechanism of probiotics regulating cow milk allergy in early childhood and its application in hypoallergenic infant formula
Authors: Lin Mao , Yanjun Cong
Published: February 2024

Some infants and young children suffer from cow's milk allergy (CMA), and have always mainly used hypoallergenic infant formula as a substitute for breast milk, but some of these formulas can still cause allergic reactions. In recent years, it has been found that probiotic nutritional interventions can regulate CMA in children. Scientific and reasonable application of probiotics to hypoallergenic infant formula is the key research direction in the future. This paper discusses the mechanism and clinical symptoms of CMA in children. This review critically ex- amines the issue of how probiotics use intestinal flora as the main vector to combine with the immune system to exert physiological functions to intervene CMA in children, with a particular focus on four mechanisms: promoting the early establishment of intestinal microecological balance, regulating the body's immunity and alleviating allergic response, enhancing the intestinal mucosal barrier function, and destroying allergen epitopes. Additionally, it overviews the development process of hypoallergenic infant formula and the research progress of probiotics in hypoallergenic infant formula. The article also offers suggestions and outlines potential future research directions and ideas in this field.
Risk factors for immune-related adverse effects during CPI therapy in patients with head and neck malignancies – a single center study
Authors: Jungbauer Frederic , Affolter Annette , Brochhausen Christoph , Lammert Anne , Ludwig Sonja , Merx Kirsten , Rotter Nicole , Huber Lena
Published: February 2024

Introduction

Checkpoint inhibitors, such as PD1 inhibitors, represent an important pillar in the therapy of advanced malignancies of the head and neck region. The most relevant complications are immune-related adverse effects (irAEs), which represent an immense burden for patients. Currently, no sufficient stratification measures are available to identify patients at increased risk of irAEs. The aim of this retrospective study was to examine whether demographic, histopathological, clinical, or laboratory values at the start of CPI therapy represent a risk factor for the later occurrence of autoimmune complications.

Material and methods

Data from 35 patients between 2018 and 2021 who received therapy with nivolumab or pembrolizumab for head and neck malignancy were analyzed and assessed for any associations with the subsequent occurrence of irAEs.

Results

IrAE developed in 37% of patients, with pneumonitis being the most common form (14%). Pneumonitis was found in patients with an average significantly lower T-stage of primary tumors. An increase in basophilic leukocytes was found in patients with dermatitis later in the course. When thyroiditis developed later, the patients had a higher CPS score and lower monocyte levels.

Discussion

Even though individual laboratory values at the beginning of therapy might show a statistical association with the later occurrence of irAEs, neither demographic, histopathological, nor laboratory chemistry values seem to be able to generate a sound and reliable risk profile for this type of complication. Therefore, patients need to be educated and sensitized to irAEs, and regular screening for irAEs should be carried out.
Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway
Authors: Iida Yasushi , Yanaihara Nozomu , Yoshino Yuki , Saito Misato , Saito Ryosuke , Tabata Junya , Kawabata Ayako , Takenaka Masataka , Chiba Natsuko , Okamoto Aikou
Published: February 2024

PARP inhibitors have changed the management of advanced high-grade epithelial ovarian cancer (EOC), especially homologous recombinant (HR)-deficient advanced high-grade EOC. However, the effect of PARP inhibitors on HR-proficient (HRP) EOC is limited. Thus, new therapeutic strategy for HRP EOC is desired. In recent clinical study, the combination of PARP inhibitors with anti-angiogenic agents improved therapeutic efficacy, even in HRP cases. These data suggested that anti-angiogenic agents might potentiate the response to PARP inhibitors in EOC cells. Here, we demonstrated that anti-angiogenic agents, bevacizumab and cediranib, increased the sensitivity of olaparib in HRP EOC cells by suppressing HR activity. Most of the γ-H2AX foci were co-localized with RAD51 foci in control cells. However, most of the RAD51 were decreased in the bevacizumab-treated cells. RNA sequencing showed that bevacizumab decreased the expression of CRY1 under DNA damage stress. CRY1 is one of the transcriptional coregulators associated with circadian rhythm and has recently been reported to regulate the expression of genes required for HR in cancer cells. We found that the anti-angiogenic agents suppressed the increase of CRY1 expression by inhibiting VEGF/VEGFR/PI3K pathway. The suppression of CRY1 expression resulted in decrease of HR activity. In addition, CRY1 inhibition also sensitized EOC cells to olaparib. These data suggested that anti-angiogenic agents and CRY1 inhibitors will be the promising candidate in the combination therapy with PARP inhibitors in HR-proficient EOC.
Knowledge mapping of anaplastic thyroid cancer treatments: a bibliometric analysis (2000-2023)
Authors: Liu Shiqiang , Yan Xingmin , Yang Yalong , Xia Yun , Zhang Panshi
Published: February 2024

Context

Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.

Methodology

A systematic search was conducted on the WoSCC database to identify publications pertaining to ATC treatment between the years 2000 and 2023. In this bibliometric investigation, the tools VOSviewers, CiteSpace, and the R package “bibliometrix” were employed to investigate the general attributes, developmental framework, and academic frontiers of the subject matter.

Results

1223 publications in total, written by 6937 scholars from 53 areas and 1402 institutions and published in 358 scholarly journals, were analyzed. There has been a gradual increase in the quantity of publications pertaining to ATC treatment. The United States and China emerged as the most prominent nations. The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Counseling Center are prominent research institutions in highly productive countries. The journal Thyroid holds a prominent position within its discipline, being widely recognized as both the most popular and highly co-cited publication. According to the available data, Maria Cabanillas has authored the highest number of published articles, while RC Smallridge has received the highest number of co-citations. It turned out that the prevailing keywords encompassed expression, therapy, apoptosis, survival, activation, proliferation, metastasis, and other related terms. Immunotherapy, targeted therapy, and prognostic factors are the emerging research hotspots and trends.

Conclusions

This paper presents a complete overview of research trends and advancements in the treatment of ATC using bibliometric analysis. The acquisition of information will offer vital insights for funding and potential creative strategies in researching the treatment of ATC, which indicates the research frontiers as well as prevalent directions in recent years.
Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy
Authors: Xing Hui-Lin , Ma Dong-Hong , Li Jin , Xu Qing-Yu , Ji Li-Ke , Zhu Qiong-Jie , Luo Yu-Qing , Guo Ming-Hao
Published: February 2024

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy.

Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed.

Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05).

Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.
The impact of level of documentation on the accessibility and affordability of new drugs in Norway
Authors: Fagereng Gro Live , Morvik Anne Marit , Reinvik Ulimoen Sara , Ringerud Anne Marthe , Dahlen Syversen Iselin , Sagdahl Erik
Published: February 2024

Introduction: Over the preceding decade, an increasing number of drugs have been approved by the European Medicines Agency (EMA) with limited knowledge of their relative efficacy. This is due to the utilization of non-randomized, single-arm studies, surrogate endpoints, and shorter follow-up time. The impact of this trend on the accessibility and affordability of newly approved drugs in Europe remains uncertain. The primary objective of this study is to provide insights into the issues of accessibility and affordability of new drugs in the Norwegian healthcare system.

Method: The presented study entails an analysis of all reimbursement decisions for hospital drugs in Norway spanning 2021–2022. The included drugs were approved by the EMA between 2014 and 2022, with the majority (91%) receiving approval between 2018 and 2022. The drugs were categorized based on the level of documentation of relative efficacy. Approval rates and costs (confidential net-prices) were compared.

Results: A total of 35% (70/199) of the reimbursement decisions were characterized by limited certainty regarding relative efficacy and as a consequence the Norwegian Health Technology Assessment (HTA) body did not present an incremental cost-effectiveness ratio (ICER) in the HTA report. Within this category, a lower percentage of drugs (47%) gained reimbursement approval compared to those with a higher certainty level, which were presented with an ICER (58%). On average, drugs with an established relative efficacy were accepted with a 4.4-fold higher cost (confidential net-prices). These trends persisted when specifically examining oncology drugs.

Conclusion: Our study underscores that a substantial number of recently introduced drugs receive reimbursement regardless of the level of certainty concerning relative efficacy. However, the results suggest that payers prioritize documented over potential efficacy. Given that updated information on relative efficacy may emerge post-market access, a potential solution to address challenges related to accessibility and affordability in Europe could involve an increased adoption of market entry agreements. These agreements could allow for price adjustments after the presentation of new knowledge regarding relative efficacy, potentially resolving some of the current challenges.
Hybrid quantum sensing in diamond
Authors: Wang Ning , Cai Jianming
Published: February 2024

Quantum sensing is a quantum technology for ultrasensitive detection, which is particularly useful for sensing weak signals at the nanoscale. Nitrogen vacancy centers in diamond, thanks to their superb quantum coherence under ambient conditions and the stability of the material in extreme and complicated environments, have been demonstrated as promising quantum probes in multi-parameter sensing. Their spin properties make them particularly sensitive to magnetic fields, but they are insensitive to temperature, electric field, pressure, etc., and even immune to some bio-parameters (e.g., pH and glucose concentration). Recently, hybrid quantum sensing has emerged as a promising avenue for further enhancing the capabilities of diamond sensors. Different techniques can potentially improve the sensitivity, range of detectable parameters, and sensing frequencies of diamond sensors. This review provides an overview of hybrid quantum sensing using diamond. We first give a brief introduction to quantum sensing using diamond, and then review various hybrid sensing schemes that have been developed to enhance the sensing capabilities of diamond sensors. Finally, the potential applications and challenges associated with hybrid quantum sensing in diamond are discussed.
Nitrate nitrogen enhances the efficiency of photoprotection in Leymus chinensis under drought stress
Authors: Wei Xiaowei , Han Lin , Xu Nan , Sun Mingyue , Yang Xuechen
Published: February 2024

Introduction

Global climate change exerts a significant impact on the nitrogen supply and photosynthesis ability in land-based plants. The photosynthetic capacity of dominant grassland species is important if we are to understand carbon cycling under climate change. Drought stress is one of the major factors limiting plant photosynthesis, and nitrogen (N) is an essential nutrient involved in the photosynthetic activity of leaves. The regulatory mechanisms responsible for the effects of ammonium (NH4+) and nitrate (NO3-) on the drought-induced photoinhibition of photosystem II (PSII) in plants have yet to be fully elucidated. Therefore, there is a significant need to gain a better understanding of the role of electron transport in the photoinhibition of PSII.

Methods

In the present study, we conducted experiments with normal watering (LD), severe drought (MD), and extreme drought (HD) treatments, along with no nitrogen (N0), ammonium (NH4), nitrate (NO3), and mixed nitrogen (NH4NO3) treatments. We analyzed pigment accumulation, reactive oxygen species (ROS) accumulation, photosynthetic enzyme activity, photosystem activity, electron transport, and O-J-I-P kinetics.

Results

Analysis showed that increased nitrate application significantly increased the leaf chlorophyll content per unit area (Chlarea) and nitrogen content per unit area (Narea) (p< 0.05). Under HD treatment, ROS levels were lower in NO3-treated plants than in N0 plants, and there was no significant difference in photosynthetic enzyme activity between plants treated with NO3 and NH4NO3. Under drought stress, the maximum photochemical efficiency of PSII (Fv/Fm), PSII electron transport rate (ETR), and effective quantum yield of PSII (φPSII) were significant higher in NO3-treated plants (p< 0.05). Importantly, the K-band and G-band were higher in NO3-treated plants.

Discussion

These results suggest that drought stress hindered the formation of NADPH and ATP in N0 and NH4-treated L. chinensis plants, thus damaging the donor side of the PSII oxygen-evolving complex (OEC). After applying nitrate, higher photosynthetic enzyme and antioxidant enzyme activity not only protected PSII from photodamage under drought stress but also reduced the rate of damage in PSII during the growth of L. chinensis growth under drought stress.
A quasi-experimental mixed-method pilot study to check the efficacy of the “SOUND” active and passive music-based intervention on mental wellbeing and residual cognition of older people with dementia and dementia professionals’ burnout: a research protocol
Authors: Sara Santini  , Merizzi Alessandra , Caciula Ioana , Azevedo Maria Joao , Hera Albert , Napradean Lena , Di Rosa Mirko , Quattrini Sabrina
Published: February 2024

Purpose

The SOUND method offers an innovative blended intervention based on music circle-activities and cognitive stimulation approaches which was co-designed by musicians, health professionals, older people with dementia, family caregivers and researchers, for its application in dementia settings. The purpose of the paper is to describe the detailed procedure of the quasi-experimental pilot study.

Method

The experimental phase of SOUND uses a mixed-method design encompassing qualitative and quantitative observations, cognitive testing, self-report and interviewer-assisted questionnaires to investigate the effectiveness of the intervention for 45 people with dementia and 45 professionals (15 in every study country: Italy, Portugal, Romania).

Results

The pilot study will be the first implementation of the SOUND intervention aiming to investigate the feasibility and preliminary effects of the method.

Conclusion

The novelty of SOUND is its multicomponent method, including the most evidenced features for improving the wellbeing of participants.
Empowering young people—the impact of camp experiences on personal resources, well-being, and community building
Authors: Kirchhoff Esther , Keller Roger , Blanc Barbara
Published: February 2024

Introduction

Personal resources and resources of the sociocultural environment help children and adolescents to successfully cope with challenges in everyday life, which is associated with better individual well-being. SCOUT, the ‘Study on Competence development in OUT-of-school settings’, investigated whether participation in a summer camp enhanced adolescents’ personal resources, well-being, and readiness to contribute to the community.

Methods

The research took place during the Swiss National Jamboree of the Swiss Guide and Scout Movement, a two-week event in the summer of 2022, with a paper-pencil pretest (beginning of the camp – T1) and posttest (end of the camp – T2) survey (N = 607, aged 14–17). Confirmatory factor analyses were used to examine whether personal resources, well-being, and readiness to contribute to the community changed over time, and structural equation models were applied to test the direct and indirect effects of caring support from group leaders on the development of these variables.

Results

In less than two weeks, camp participants demonstrated increased empathy, emotional self-control, optimism, and assertiveness. Furthermore, the adolescents reported more positive emotions, higher self-esteem, and stronger readiness to contribute to the community. Group leaders played a crucial role by influencing the positive development of well-being and readiness to contribute to the community both directly and indirectly through the promotion of personal resources.

Discussion

The findings indicate that young people benefit not only from participating in collaborative activities in a stimulating environment, but also from caring support provided by their group leaders.
The role of emotional similarity and emotional accuracy in belonging and stress among first-generation and continuing-generation students
Authors: Lawrie Smaranda Ioana , Kim Heejung S.
Published: February 2024

Extensive research has documented the psychological, social, and academic predicament of first-generation college students. However, basic psychological mechanisms underlying the challenges experienced by these students have been understudied. Taking a cultural psychology perspective, the present research considers the role of emotional (mis)match as a key mechanism for explaining first-generation students’ lowered well-being. A sample of 344 American undergraduate students completed a survey designed to measure two aspects of emotional processing: (1) Emotional Accuracy – how accurately students perceive emotional reactions of majority-culture students (continuing-generation junior and senior students who have been socialized into college culture), and (2) Emotional Similarity –how similar students’ emotions are to the emotions experienced by majority-culture students. Emotional Accuracy predicted positive outcomes, in general, but was lower among first-generation students. Unexpectedly, Emotional Similarity predicted negative student outcomes. As one of the first studies addressing basic psychological mechanisms in college adjustment, these findings underscore the importance of understanding the roles that specific emotional processes play in social adjustment.
Complex executive functions assessed by the trail making test (TMT) part B improve more than those assessed by the TMT part A or digit span backward task during vagus nerve stimulation in patients with drug-resistant epilepsy
Authors: Lähde Niina , Basnyat Pabitra , Raitanen Jani , Kämppi Leena , Lehtimäki Kai , Rosti-Otajärvi Eija , Peltola Jukka
Published: February 2024

Introduction

There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years.

Methods

The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes.

Results

On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p = 0.036 and 0.028 units/month, p = 0.003, respectively). TMT-A z scores improved the most in patients taking 1–2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p = 0.002 and p = 0.003, respectively).

Conclusion

Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities.
Visual communication design: a neglected factor in nutrition promotion via packaged food labels
Authors: Kelly Meghan , McCann Jennifer R. , Chapple Celeste I. , Woods Julie , Russell Catherine G.
Published: February 2024

Packaging design is a communication device and a critical component in branding strategy, and has relevance for food policy. Presently, packaging-related nutrition policy initiatives focus on the role of regulated claims, nutrition information panels and front-of-pack nutrition labels to help guide consumer food choices and address high prevalences of discretionary and ultra-processed food consumption in many countries. However, these nutrition labelling systems are not optimized as public health policy tools as many consumers do not use them to inform their food choices. Visual communication design theory posits that a designer orders the elements and principles of design into hierarchies that prioritize certain elements over others, and that some of these elements are more dominant and given more emphasis than others. The overall design of the package thereby directs consumer attention to some aspects of pack design (e.g., characters, contents of the package) and away from others (e.g., nutrition details). Dual processing frameworks propose that food decisions are made with the interplay between automatic and rational thinking processes. Packaging designs affect whether consumers rely predominantly on automatic or rational thinking to select a food. This narrative review outlines the role of food packaging design and how it impacts the clear communication of nutrition aspects of food products and how the use of nutrition information by consumers to make decisions may depend upon design structures in packaging. This article attests that nutrition scientists and policy makers should incorporate visual communication design into research on the food packaging as a public health promotion tool. A stronger focus on the communication of regulated front-of-pack nutrition information can be made with a re-evaluation of the hierarchy of elements in the front-of-pack design enabling consumers to make healthier decisions.