bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Effects
Authors: Antony Alexander K , Thompson William R
Published: July 2024

This chapter looks into how network structures influence the creation of rivalry and positive peace relationships that form the constitutive elements of zones of peace. It discusses the importance of dyadic versus neighborhood attributes in driving patterns of rivalry and positive peace. From a theoretical perspective, neighborhood industrialization should both prevent the formation of local rivalries and facilitate the formation of positive peaceful ties. The chapter details how network analysis techniques are uniquely positioned to provide a way to assess the relative contribution of dyadic attributes, regional attributes, and network structure on relations between states. It considers the Exponential Random Graph Model (ERGM) as the most common and well-developed inferential network model.
Morphology, immunophenotype, and suggested diagnostic criteria of TCL1 family–negative T-prolymphocytic leukemia
Authors: Fang Hong , Wang Sa A , Beird Hannah C , Tang Zhenya , You M James , Li Shaoying , Xu Jie , Hu Shimin , Yin C Cameron , El Hussein Siba , Lin Pei , Jelloul Fatima Zahra , Vega Francisco , Medeiros L Jeffrey , Wang Wei
Published: July 2024

Objectives

We sought to investigate the morphologic and immunophenotypic characteristics of TCL1 family–negative T-cell prolymphocytic leukemia (T-PLL)

Methods

Twenty cases of TCL1 family–negative T-PLL were studied.

Results

The doubling time of leukemic cells ranged from less than 2 days to more than 5 years, with a median of 5.5 months. Leukemic cells were small to medium-sized, with round to irregular nuclei, variably condensed chromatin, and small amounts of agranular cytoplasm. A visible nucleolus was identified in 11 (55%) cases. Cytoplasmic blebs/protrusions were identified in all cases, but their occurrence was highly variable from case to case. Bone marrow biopsy showed an interstitial pattern in 90% of cases and a diffuse pattern in the remaining 10% of cases. Flow cytometric immunophenotypic analysis showed that the leukemic cells in all cases were CD4 positive; 3 (15%) also showed concurrent CD8 expression. All cases were positive for CD2 and CD5. Surface CD3 and CD7 were positive in 19 of 20 (95%) cases, and all CD3-positive cases expressed the T-cell receptor αβ. Compared with prototypic T-PLL cases, these 2 groups shared many immunophenotypic findings, except CD8 and CD26, both of which were more commonly expressed in prototypic T-PLL cases.

Conclusions

TCL1 family–negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αβ phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL.
SFINN: inferring gene regulatory network from single-cell and spatial transcriptomic data with shared factor neighborhood and integrated neural network
Authors: Wang Yongjie , Zhou Fengfan , Guan Jinting
Published: July 2024

Motivation

The rise of single-cell RNA sequencing (scRNA-seq) technology presents new opportunities for constructing detailed cell type-specific gene regulatory networks (GRNs) to study cell heterogeneity. However, challenges caused by noises, technical errors, and dropout phenomena in scRNA-seq data pose significant obstacles to GRN inference, making the design of accurate GRN inference algorithms still essential. The recent growth of both single-cell and spatial transcriptomic sequencing data enables the development of supervised deep learning methods to infer GRNs on these diverse single-cell datasets.

Results

In this study, we introduce a novel deep learning framework based on shared factor neighborhood and integrated neural network (SFINN) for inferring potential interactions and causalities between transcription factors and target genes from single-cell and spatial transcriptomic data. SFINN utilizes shared factor neighborhood to construct cellular neighborhood network based on gene expression data and additionally integrates cellular network generated from spatial location information. Subsequently, the cell adjacency matrix and gene pair expression are fed into an integrated neural network framework consisting of a graph convolutional neural network and a fully-connected neural network to determine whether the genes interact. Performance evaluation in the tasks of gene interaction and causality prediction against the existing GRN reconstruction algorithms demonstrates the usability and competitiveness of SFINN across different kinds of data. SFINN can be applied to infer GRNs from conventional single-cell sequencing data and spatial transcriptomic data.

Availability and implementation

SFINN can be accessed at GitHub: https://github.com/JGuan-lab/SFINN.
Reproductive biology of Santolina ligustica Arrigoni, a rare narrow-ranged species: implications for conservation
Authors: Bonifazio Chiara , Guerrina Maria , Armanino Filippo , Casazza Gabriele , Galli Loris , Varaldo Lucia , Zappa Elena , Minuto Luigi
Published: July 2024

Santolina ligustica is a rare narrow-ranged species endemic to Liguria (Italy) for which a likely trend of decline has been recorded. For this reason, it would be important to assess the reproductive biology of this endemic species. In this study, we investigated the plant–pollinator interactions, the reproductive mode of the plant, and we evaluated both reproductive efficiency and seeds’ germination performances. Santolina ligustica is an obligate cross-pollinating species with a generalist pollination system. The most frequent insects are Coleoptera belonging to the genus Oedemera. Seed set is low, but the seeds germinate under a wide range of temperatures. Taken together, our results indicate that S. ligustica is an insect pollinated and self-incompatible plant, in which low visitation rate, secondary pollen presentation and/or lack of compatible mate may cause a low seed set per capitulum. Nevertheless, the high number of capitula per plant and the high percentage of germination may assure high number of seedlings. Thus, the survival of S. ligustica is probably threatened by other factors such as fragmented distribution and habitat reduction because of land-use change. Under this scenario, we proved that species’ decline is not directly related to reproductive failure and different studies are desirable to provide suggestions for the species conservation.
Surgical outcomes of hidradenitis suppurativa: evaluating factors influencing recurrence and complications after 284 complete excisions
Authors: Chang Tsung-Hsien , Sheen Yi-Shuan , Liao Yi-Hua
Published: July 2024

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder associated with tunnel formation and scarring. Surgical excision is a potential curative therapy for HS.

Objectives

To characterize the surgical outcomes of patients with HS undergoing complete excision and to identify the risk factors associated with postoperative recurrence.

Methods

This retrospective 16-year cohort study enrolled patients ≥ 20 years who underwent complete excision for HS lesions at the National Taiwan University Hospital. We assessed the rates of postsurgical recurrence and complications and estimated the odds ratio (ORs) with 95% confidence intervals (CIs) of their association with potential risk factors using generalized estimating equations.

Results

In total, 136 patients with HS and the 284 corresponding complete excisions were identified. Recurrence developed in 88 of 284 (31.0%) operations and complications occurred in 102 (35.9%). Common types of complications included wound dehiscence, hypertrophic scars and surgical-site infection. Clinical factors associated with a lower risk of recurrence were male sex [adjusted OR (aOR) 0.48, 95% CI 0.23–0.98], surgery at atypical body sites (aOR 0.28, 95% CI 0.08–0.99) and wound repair by split-thickness skin graft (aOR 0.31, 95% CI 0.12–0.77). Wound dehiscence was associated with an increased risk of recurrence (aOR 2.55, 95% CI 1.21–5.42). No independent factors were identified as being associated with composite postoperative complications.

Conclusions

Complete excision alone can be effective in curing HS in Asian populations. Recurrence developed in about one-third of the complete excisions performed for HS. Sex, surgical body sites, methods of wound repair and wound dehiscence were major determinants for recurrence.
Conversion or Reversion of Interferon γ Release Assays for Mycobacterium tuberculosis Infection: A Systematic Review and Meta-analysis
Authors: Wang Mao-Shui , Li-Hunnam Jarrod , Chen Ya-Li , Gilmour Beth , Alene Kefyalew Addis , Zhang Yan-An , Nicol Mark P
Published: July 2024

Background

Interferon γ release assays (IGRAs) are widely used for diagnosis of latent tuberculosis infection. However, with repeated testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation.

Methods

We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and participant characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors.

Results

The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% confidence interval [CI], 6.1%–8.5%) or 22.8% (20.1%–25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (95% CI, 35.7%–56.4%) or 19.6% (9.2%–31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [95% CI, .1%–3.5%]). IGRA results in the borderline-positive or borderline-negative range were associated with increased risk of conversion or reversion (pooled odds ratio [OR] for conversion, 4.15 [95% CI, 3.00–5.30]; pooled OR for reversion, 4.06 [3.07–5.06]). BCG vaccination was associated with decreased risk of conversion (OR, 0.70 [95% CI, .56–.84]), cigarette smoking with decreased risk of reversion (0.44 [.06–.82]), and female sex with decreased risk of either conversion or reversion (OR for conversion, 0.66 [.58–.75]; OR for reversion, 0.46 [.31–.61]).

Conclusions

IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis-preventive treatment. Retesting of people with indeterminate results is probably not indicated, because indeterminate results seldom revert to positive.
The cytidine deaminase APOBEC3C has unique sequence and genome feature preferences
Authors: Brown Grant W
Published: July 2024

APOBEC proteins are cytidine deaminases that restrict the replication of viruses and transposable elements. Several members of the APOBEC3 family, APOBEC3A, APOBEC3B, and APOBEC3H-I, can access the nucleus and cause what is thought to be indiscriminate deamination of the genome, resulting in mutagenesis and genome instability. Although APOBEC3C is also present in the nucleus, the full scope of its deamination target preferences is unknown. By expressing human APOBEC3C in a yeast model system, I have defined the APOBEC3C mutation signature, as well as the preferred genome features of APOBEC3C targets. The APOBEC3C mutation signature is distinct from those of the known cancer genome mutators APOBEC3A and APOBEC3B. APOBEC3C produces DNA strand-coordinated mutation clusters, and APOBEC3C mutations are enriched near the transcription start sites of active genes. Surprisingly, APOBEC3C lacks the bias for the lagging strand of DNA replication that is seen for APOBEC3A and APOBEC3B. The unique preferences of APOBEC3C constitute a mutation profile that will be useful in defining sites of APOBEC3C mutagenesis in human genomes.
SE(3) Synchronization by eigenvectors of dual quaternion matrices
Authors: Hadi Ido , Bendory Tamir , Sharon Nir
Published: July 2024

In synchronization problems, the goal is to estimate elements of a group from noisy measurements of their ratios. A popular estimation method for synchronization is the spectral method. It extracts the group elements from eigenvectors of a block matrix formed from the measurements. The eigenvectors must be projected, or ‘rounded’, onto the group. The rounding procedures are constructed ad hoc and increasingly so when applied to synchronization problems over non-compact groups. In this paper, we develop a spectral approach to synchronization over the non-compact group $\mathrm{SE}(3)$, the group of rigid motions of $\mathbb{R}^{3}$. We based our method on embedding $\mathrm{SE}(3)$ into the algebra of dual quaternions, which has deep algebraic connections with the group $\mathrm{SE}(3)$. These connections suggest a natural rounding procedure considerably more straightforward than the current state of the art for spectral $\mathrm{SE}(3)$ synchronization, which uses a matrix embedding of $\mathrm{SE}(3)$. We show by numerical experiments that our approach yields comparable results with the current state of the art in $\mathrm{SE}(3)$ synchronization via the spectral method. Thus, our approach reaps the benefits of the dual quaternion embedding of $\mathrm{SE}(3)$ while yielding estimators of similar quality.
Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill
Authors: Wessel Rebecca J , Rivera Christina G , Ausman Sara E , Martin Nathaniel , Braga Shienna A , Hagy Natalie T , Moreland-Head Lindsay N , Abu Saleh Omar M , Gajic Ognjen , Jannetto Paul J , Barreto Erin F
Published: July 2024

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after “go-live,” 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.
Asymmetric relations and systemic misperceptions: Why and how Australia and China talk past each other
Authors: Pan Guangyi
Published: July 2024

Caught by conflicts, both Australia and China exhibited confused attitudes towards each other’s motives. For China, despite the common interests of strong economic and trade complementarities, Australia acts as a vassal state of the USA, campaigning against China for no reason. For Canberra, it has been frustrated by China’s ignorance of Australia’s independent position and concerns. This article explores the fundamental cause behind this misperception, arguing that asymmetric relationships lead two countries to put their attention on different levels, generating misinterpretations from both sides. As a great power, China concentrates on worldwide competition with the USA and prioritizes its global strategy while underplaying concerns of Australia. However, in Australia’s agenda, regional security and China’s expansion deepened its anxiety, so its over-attention spotlighted Beijing’s moves in a sensitive scenario. The asymmetry exacerbates each other’s threats. The article provides a systematic explanation of the China–Australia tension and clarifies the mechanism behind asymmetric relations.
The first step is the hardest: pitfalls of representing and tokenizing temporal data for large language models
Authors: Spathis Dimitris , Kawsar Fahim
Published: July 2024

Objectives

Large language models (LLMs) have demonstrated remarkable generalization and across diverse tasks, leading individuals to increasingly use them as personal assistants due to their emerging reasoning capabilities. Nevertheless, a notable obstacle emerges when including numerical/temporal data into these prompts, such as data sourced from wearables or electronic health records. LLMs employ tokenizers in their input that break down text into smaller units. However, tokenizers are not designed to represent numerical values and might struggle to understand repetitive patterns and context, treating consecutive values as separate tokens and disregarding their temporal relationships. This article discusses the challenges of representing and tokenizing temporal data. It argues that naively passing timeseries to LLMs can be ineffective due to the modality gap between numbers and text.

Materials and methods

We conduct a case study by tokenizing a sample mobile sensing dataset using the OpenAI tokenizer. We also review recent works that feed timeseries data into LLMs for human-centric tasks, outlining common experimental setups like zero-shot prompting and few-shot learning.

Results

The case study shows that popular LLMs split timestamps and sensor values into multiple nonmeaningful tokens, indicating they struggle with temporal data. We find that preliminary works rely heavily on prompt engineering and timeseries aggregation to “ground” LLMs, hinting that the “modality gap” hampers progress. The literature was critically analyzed through the lens of models optimizing for expressiveness versus parameter efficiency. On one end of the spectrum, training large domain-specific models from scratch is expressive but not parameter-efficient. On the other end, zero-shot prompting of LLMs is parameter-efficient but lacks expressiveness for temporal data.

Discussion

We argue tokenizers are not optimized for numerical data, while the scarcity of timeseries examples in training corpora exacerbates difficulties. We advocate balancing model expressiveness and computational efficiency when integrating temporal data. Prompt tuning, model grafting, and improved tokenizers are highlighted as promising directions.

Conclusion

We underscore that despite promising capabilities, LLMs cannot meaningfully process temporal data unless the input representation is addressed. We argue that this paradigm shift in how we leverage pretrained models will particularly affect the area of biomedical signals, given the lack of modality-specific foundation models.
Mutation of mpv17 results in loss of iridophores due to mitochondrial dysfunction in tilapia
Authors: Xu Jia , Li Peng , Xu Mengmeng , Wang Chenxu , Kocher Thomas D , Wang Deshou
Published: July 2024

Mpv17 (mitochondrial inner membrane protein MPV17) deficiency causes severe mitochondrial DNA depletion syndrome in mammals and loss of pigmentation of iridophores and a significant decrease of melanophores in zebrafish. The reasons for this are still unclear. In this study, we established an mpv17 homozygous mutant line in Nile tilapia. The developing mutants are transparent due to the loss of iridophores and aggregation of pigment granules in the melanophores and disappearance of the vertical pigment bars on the side of the fish. Transcriptome analysis using the skin of fish at 30 dpf (days post fertilization) revealed that the genes related to purine (especially pnp4a) and melanin synthesis were significantly downregulated. However, administration of guanine diets failed to rescue the phenotype of the mutants. In addition, no obvious apoptosis signals were observed in the iris of the mutants by TUNEL staining. Significant downregulation of genes related to iridophore differentiation was detected by qPCR. Insufficient ATP, as revealed by ATP assay, α-MSH treatment, and adcy5 mutational analysis, might account for the defects of melanophores in mpv17 mutants. Several tissues displayed less mtDNA and decreased ATP levels. Taken together, these results indicated that mutation of mpv17 led to mitochondrial dTMP deficiency, followed by impaired mtDNA content and mitochondrial function, which in turn, led to loss of iridophores and a transparent body color in tilapia.
Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration
Authors: Feng Kuan , Ye Gengfan , Wang Hongcai , Li Shiwei , Wen Xuebin , Chen Maosong
Published: July 2024

Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.
Origin of extended main-sequence turn-off in open cluster NGC 2355
Authors: Maurya Jayanand , Samal M R , Amard Louis , Zhang Yu , Niu Hubiao , Kim Sang Chul , Joshi Y C , Kumar B
Published: July 2024

The presence of extended Main-Sequence Turn-Off (eMSTO) in the open clusters has been attributed to various factors, such as spread in rotation rates, binary stars, and dust-like extinction from stellar excretion discs. We present a comprehensive analysis of the eMSTO in the open cluster NGC 2355. Using spectra from the Gaia–European Southern Observatory (ESO) archives, we find that the stars in the red part of the eMSTO have a higher mean v sin i value of 135.3 $\pm$ 4.6 km s$^{-1}$ compared to the stars in the blue part that have an average v sin i equal to 81.3 $\pm$ 5.6 km s$^{-1}$. This suggests that the eMSTO in NGC 2355 is possibly caused by the spread in rotation rates of stars. We do not find any substantial evidence of the dust-like extinction from the eMSTO stars using ultraviolet data from the Swift survey. The estimated synchronization time for low-mass ratio close binaries in the blue part of the eMSTO suggests that they would be mostly slow-rotating if present. However, the stars in the blue part of the eMSTO are preferentially located in the outer region of the cluster indicating that they may lack low-mass ratio close binaries. The spread in rotation rates of eMSTO stars in NGC 2355 is most likely caused by the star-disc interaction mechanism. The stars in the lower main sequence beyond the eMSTO region of NGC 2355 are slow rotating (mean v sin i = 26.5 $\pm$ 1.3 km s$^{-1}$) possibly due to the magnetic braking of their rotations.
Hydrodynamic simulation of Cygnus OB2: the absence of a cluster wind termination shock
Authors: Vieu T , Larkin C J K , Härer L , Reville B , Sander A A C , Ramachandran V
Published: July 2024

We perform a large-scale hydrodynamic simulation of a massive star cluster whose stellar population mimics that of the Cygnus OB2 association. The main-sequence stars are first simulated during 1.6 Myr, until a quasi-stationary state is reached. At this time, the three Wolf–Rayet stars observed in Cygnus OB2 are added to the simulation, which continues to 2 Myr. Using a high-resolution grid in the centre of the domain, we can resolve the most massive stars individually, which allows us to probe the kinetic structures at small (parsec) scales. We find that, although the cluster excavates a spherical ‘superbubble’ cavity, the stellar population is too loosely distributed to blow a large-scale cluster wind termination shock, and that collective effects from wind–wind interactions are much less efficient than usually assumed. This challenges our understanding of the ultra-high energy emission observed from the region.
Challenges and opportunities in access to care for systemic lupus erythematosus patients across Europe and worldwide
Authors: Mosca Marta , Bruce Ian N , Andersen Jeanette , Ugarte-Gil Manuel F , Arnaud Laurent
Published: July 2024

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve.
Could tocilizumab be used in familial Mediterranean fever? A systematic review
Authors: Mertz Philippe , Hentgen Véronique , Georgin-Lavialle Sophie
Published: July 2024

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as IL-1β, TNF-α and IL-6 inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.

Objective

To evaluate the efficacy and safety of TCZ in the treatment of FMF.

Methods

Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF.

Results

After selection, 14 articles were included: two double-blind RCTs, two retrospective studies and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in paediatric FMF.

Conclusion

This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.
Exploring the therapeutic potential of Caralluma fimbriata for antioxidant and diabetes management: a 28-day rat model study
Authors: Arif Aleena , Sultan M Tauseef , Nazir Fahid , Ahmad Khalil , Kashif Muhammad , Ahmad Muhammad Mahboob , Shehzad Farooq Khurum , Nazir Muhammad Altaf , Mushtaq Shehla , Khalid Muhammad Usman , Noman Ahmad Mujtaba , Raza Hassan , Israr Muhammad , Sohail Hira , Rocha João Miguel
Published: July 2024

This study evaluated the anti-oxidant and anti-diabetic potential of Caralluma fimbriata (CF) in 28-days rat modelling trial. Diabetes is a chronic disorder characterized by elevated blood glucose levels and insulin resistance and cause microvascular and macrovascular issues. Caralluma fimbriata was evaluated for its nutritional composition along with anti-oxidant potential of CF powder (CFP) and CF extract (CFE) using total phenolic contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Furthermore, anti-diabetic potential was computed by dividing rats into four groups of 5 individuals each. Rats of Group I was non-diabetic and no supplementation was given while rats of group II were diabetic and no supplementation was given. While group III and group IV rats were diabetic and received CFP and CFE supplementation respectively. CF powder’s TPC, and DPPH and FRAP activity were observed maximum at 44.17 ± 0.006 (μgFe/g) in water, 68.75 ± 0.49 (μgFe/g) in acetone and 800.81 ± 0.99 (μgFe/g) in hexane. Supplementation of CFP and CFE reduced blood glucose effectively i.e. (125.00 ± 4.04 and 121.00 ± 4.49 mg/dL, respectively). Moreover, the consumption of C. fimbriata can be helpful in the management of diabetes mellitus due to its glucose lowering potential, anorexic effects, anti-oxidant potential and α-amylase inhibition.
Comparative genomics reveals the evolutionary history of the unicellular eukaryote class Litostomatea and its adaptive evolution based on biochemical metabolic capacity
Authors: Zhang Ying , Fu Yu , Vďačný Peter , Liang Fasheng , Dou Huan , Warren Alan , Li Lifang
Published: July 2024

Ciliated protists are unicellular eukaryotic organisms characterized by their morphological diversity, ubiquitous distribution, and the important roles they play in a wide range of biological studies. The class Litostomatea is a morphologically diverse ciliate group that comprises hundreds of free-living and endosymbiotic species. Here, we sequenced 14 predatory litostomateans, i.e. 12 haptorians and two rhynchostomatians. A comparative analysis was performed with other published omics’ data on litostomateans. Our first phylogenomic analysis of litostomateans showed the monophyly of the subclasses Trichostomatia and Rhynchostomatia, the non-monophyly of the subclass Haptoria, and the monophyly of all orders and families that were analysed. Evolutionary history analysis suggested that Litostomatea diverged during the Late Neoproterozoic, the family Chaeneidae was the earliest diverging haptorian lineage, and the Rhynchostomatia probably separated from the order Lacrymariida (subclass Haptoria) during the Early Palaeozoic. Stop codon usage analysis of 28 litostomateans showed that they use TAA as the biased stop codon and reassign the other two stop codons (TAG and TGA) to code for amino acids. In addition, the preferred codons in the 14 newly sequenced litostomateans are strongly biased towards A/U bases in the third position, very probably due to the comparatively low GC content. Genes encoding carbohydrate-active enzymes (CAZymes) are more diversified in the endosymbiotic Trichostomatia than in the free-living predatory Rhynchostomatia and Haptoria, suggesting that trichostomes have the strongest capability of carbohydrate utilization. Notably, we found that three free-living litostomateans (Didinium sp.1, Myriokaryon sp., and Apodileptus visscheri) exhibit substantial differences from other free-living ciliates in terms of their number of CAZymes. Considering the potency and versatility of CAZymes in the degradation and biotransformation of carbohydates, we propose that the multifarious CAZymes in these three ciliates could be a survival strategy for nutrient acquisition and niche adaptation. Finally, the functional annotation of significantly expanded gene families in these three ciliates revealed their vigorous potency in biochemical metabolism. These findings will facilitate wider omic-scale phylogenetic analyses of Litostomatea and deepen our understanding of this group from an evolutionary standpoint.
Mechanisms of triple‐negative breast cancer extravasation: Impact of the physical environment and endothelial glycocalyx
Authors: Okorafor Chinedu C. , Shastri Sanjana , Wen Ke , Ebong Eno E.
Published: July 2024

Cancer metastasis is the leading cause of death for those afflicted with cancer. In cancer metastasis, the cancer cells break off from the primary tumor, penetrate nearby blood vessels, and attach and extravasate out of the vessels to form secondary tumors at distant organs. This makes extravasation a critical step of the metastatic cascade. Herein, with a focus on triple‐negative breast cancer, the role that the prospective secondary tumor microenvironment's mechanical properties play in circulating tumor cells' extravasation is reviewed. Specifically, the effects of the physically regulated vascular endothelial glycocalyx barrier element, vascular flow factors, and subendothelial extracellular matrix mechanical properties on cancer cell extravasation are examined. The ultimate goal of this review is to clarify the physical mechanisms that drive triple‐negative breast cancer extravasation, as these mechanisms may be potential new targets for anti‐metastasis therapy.
Automatic electrocardiograph diagnosis of myocardial ischemia with support vector machine
Authors: Zhong Dacheng , Huang Lingbin , Jin Shengxi , An Yukun , Zhu Songsheng , Li Jianqing
Published: July 2024

Background:

Myocardial ischemia is a severe cardiac disease and it happens when the heart's blood flow is insufficient, which impairs its capacity to operate correctly and causes several systemic issues. A standard auxiliary for the clinical diagnosis of myocardial ischemia is an electrocardiograph (ECG). However, the typical static ECG cannot record the myocardial ischemia paroxysmal fragments quickly and accurately. The information contained in long-term ECG recordings is more abundant, but the large volume of data makes manual processing costly. Our aim is to propose an automated method for handling ECG signals and diagnosing myocardial ischemia.

Methods:

To get evidence of myocardial ischemia, dynamic ECG is frequently employed. This paper suggests a machine learning technique to create a classification model using support vector machine (SVM), automatically identifying the existence of myocardial ischemia fragments. This study comprises waveform identification, feature extraction, creation of data sets, model training, and classification. The Long Term ST Database, made available by PhysioNet, is used as the database for this research.

Result:

According to the final test results, the classification accuracy is 97.98%. The ECG signals can be automatically segmented, and the automated diagnosis of myocardial ischemia can achieve an accuracy rate of 97.98%.

Conclusion:

The results suggest that the method proposed in this paper can more precisely and practically identify myocardial ischemia pieces.
A 3D reconstruction imaging study of the effect of anterior disk displacement on the bony structural relationship of the temporomandibular joint
Authors: Li Chenxi , Shao Bo , Fang Chang , Pataer Parekejiang , Gong Zhongcheng
Published: July 2024

Background:

The objective of this study was to measure the association between the status of anterior disk displacement (ADD) and the alterations of the mandibular condyle and articular fossa among patients diagnosed with temporomandibular joint (TMJ) ADD.

Patients and Methods:

A retrospective cross sectional study was designed, dividing into 4 groups: normal articular disk position (NADP) of unilateral ADD patients (n = 10), ADD with reduction (ADDwR, n = 16), ADD without reduction (ADDwoR, n = 24), and healthy volunteers (HV, n = 30) based on magnetic resonance imaging and cone beam computed tomography. After morphological parameters were calculated from three dimensional reconstructive images, differences in parameters with respect to TMJ ADD status were tested with analysis of variance and Fisher's least significant difference multiple comparisons were performed.

Results:

Patients were with a female to male ratio of 6.75:1 (21 females, 4 males) and an average age of 29.10 ± 8.94 years (ranging from 16 to 51). Condylar volume (CV) of the ADDwR, ADDwoR, NADP, and HVs was 1768.29 ± 404.19 mm, 1467.13 ± 438.20 mm, 1814.48 ± 753.60 mm, and 1914.66 ± 476.48 mm, respectively, showing a significant downward trend from healthy disk to a displaced one (P < 0.05). The same trend also found in condylar superficial area (CSA), with the CSA of the ADDwR, ADDwoR, NADP, and HVs, was 842.56 ± 138.78 mm, 748.52 ± 157.42 mm, 842.87 ± 263.00 mm, and 892.73 ± 164.19 mm, respectively. From NADP to ADDwR to ADDwoR, superior joint space (SJS) was declined (SJS
[NADP]
[2.10 ± 0.91 mm] > SJS
(ADDwR)
[1.85 ± 0.61 mm] > SJS
[ADDwoR]
[1.50 ± 0.50 mm], P = 0.034); medial joint space (MJS) was significantly associated with the different disk displacement types (P

[HV ADDwR]
= 0.001; P

[HV ADDwoR]
= 0.021; P

[NADP ADDwR]
= 0.022; P

[ADDwR ADDwoR]
= 0.001).

Conclusion:

The CV and superficial area and superior and MJS are significantly associated with different disk displacement types. The mandibular condyle and articular fossa in TMJ ADD exhibited altered dimensions. These could be promising biometric markers for assessing ADD.
Detection of an 8p23.1 Inversion Using High-Resolution Optical Genome Mapping
Authors: Zhou Chunxiang , Li Huijun , Shi Yiyan , He Linlin , Duan Honglei , Li Jie
Published: July 2024

Objective

To evaluate the performance of optical genome mapping (OGM) in identifying an inversion located in the short arm of chromosome 8 (8p, 8p23.1), flanked by regions of complex segmental duplication (SD), using the GRCh38 and telomere-to-telomere (T2T) genome references.

Methods

We investigated a couple suspected of carrying the 8p23.1 inversion due to a terminal deletion combined with an interstitial duplication of 8p found in their abortus. OGM was performed on both individuals. The data were mapped to the current GRCh38 and the updated T2T genome references, respectively.

Results

The 8p23.1 inversion was observed in the female when mapping OGM data to the T2T assembly. In contrast, under the GRCh38 reference, the orientation between the suspected breakpoints within the SD regions could not be distinguished. Additional variants of uncertain significance were also identified in both individuals.

Conclusion

Our findings highlight the superiority of the T2T reference in recognizing structural variations involving SD regions. The enhanced SV detection using the T2T reference may contribute to a better understanding of genome instability and human diseases.
Unique Ultrastructural Alterations in the Placenta Associated With Macrosomia Induced by Gestational Diabetes Mellitus
Authors: Wei Junxiang , Dong Tianyu , Chen Mingxia , Luo Xiao , Mi Yang
Published: July 2024

Objective

To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)–induced macrosomia, term nondiabetic macrosomia, and normal pregnancies.

Methods

Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively.

Results

The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs. 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane.

Conclusion

Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.
Updates in the Management of HIV During Pregnancy
Authors: Benson Jemma , Pierre Cassandra , Joseph Naima T.
Published: July 2024

Human immunodeficiency virus in pregnant people remains a significant public health issue worldwide. The rate of perinatal transmission is 15% to 40% but can be decreased to less than 1% with appropriate antenatal management. Previous recommendations included a protease inhibitor-based antiretroviral therapy, infant prophylaxis, performance of cesarean section for uncontrolled viremia, and the use of formula for infant feeding. However, recent updates include first line of integrase inhibitor-based regimens and supporting parental choices for safe lactation. In this review, we summarize and provide updated recommendations for the care of people living with human immunodeficiency virus during pregnancy.
Predictors of Patient-Initiated Discharge From an Inpatient Withdrawal Management Service
Authors: Ling Sara , Sproule Beth , Puts Martine , Cleverley Kristin
Published: July 2024

Objectives

The purpose of this study was to examine sex-stratified independent predictors of patient-initiated discharge from an inpatient withdrawal management service and to determine whether those predictors differed by sex.

Methods

This study compared people who had self-initiated versus planned discharges and used sex-stratified generalized estimating equations models to identify independent predictors of patient-initiated discharge. Predictors examined included age, ethnicity, substance of concern, tobacco use, mental health comorbidities, day of discharge, referral source, children, and social assistance funds.

Results

Among females, there were 722 discharges, 116 of which were patient initiated. Among females, increasing age was associated with lower odds of patient-initiated discharge (OR = 0.97, 95% CI [0.95, 0.98]). Racialized females were nearly 2 times more likely to experience patient-initiated discharge compared with White females (OR = 1.8, 95% CI [1.09, 3.00]). Compared with weekdays, weekends were associated with over 4 times the odds of patient-initiated discharge (OR = 4.77, 95% CI [2.66, 8.56]). Having one or more mental health comorbidities was associated with lower odds of patient-initiated discharge compared with having no mental health comorbidities (OR = 0.51, 95% CI [0.32, 0.82]). Among males, there were 1,244 discharges, 185 of which were patient initiated. Among males, increasing age was associated with decreased odds of patient-initiated discharge (OR = 0.97, 95% CI [0.95, 0.98]). Compared with weekdays, weekends were associated with nearly 15 times the odds of patient-initiated discharge (OR = 14.9, 95% CI [9.11, 24.3]).

Conclusions

Males and females have shared and unique predictors of patient-initiated discharge. Future studies should continue to examine the influence of sex and gender on engagement with addictions care.