bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered N6‐methyladenosine methylation level in spermatozoa messenger RNA of the male partners is related to unexplained recurrent pregnancy loss
Authors: Yang Tingting , Liu Yanyan , Lin Ziyuan , Chen Feng , Zhu Lin , Zhang Lin , Zhou Bin , Li Fuping , Sun Huaqin
Published: July 2024

Background

Understanding the pathogenesis of unexplained recurrent pregnancy loss is paramount for advancing effective treatments. Various biological processes, including spermatogenesis and embryo development, are tightly regulated by N6‐methyladenosine modifications. However, few studies have focused on the impact of sperm N6‐methyladenosine modifications on embryonic development. Therefore, we aimed to study altered N6‐methyladenosine‐mediated messenger RNA methylation modifications in the spermatozoa of male partners from couples experiencing unexplained recurrent pregnancy loss, to identify potential diagnostic markers and explore their potential molecular mechanisms in pregnancy loss and embryogenesis.

Methods

Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were conducted on the spermatozoa of men from couples in the ‘unexplained recurrent pregnancy loss’ group (n = 6), and the fertility control group (n = 6). To identify the role of the detected key genes, zebrafish model embryos were studied, and multi‐omics (transcriptomics, proteomics, and metabolomics) analyses helped to explore the molecular mechanism of abnormal embryogenesis.

Findings

Comparing unexplained recurrent pregnancy loss with the fertility control group, 217 N6‐methyladenosine peaks were significantly upregulated, and 40 were downregulated in the spermatozoa. The combined analyses of spermatozoa‐methylated RNA immunoprecipitation sequencing and RNA sequencing indicated that N6‐methyladenosine methylation and the expression of SEMA5A, MT‐ATP6, ZNF662, and KDM4C were significantly different. In zebrafish embryos, the altered expression of the four genes increased embryonic mortality and malformations by disturbing several key signaling pathways and zygotic genome activation.

Interpretation

This study highlights the paternal epigenome, which could be one of the reasons for faulty embryogenesis leading to pregnancy loss. The N6‐methyladenosine modification, the most prevalent RNA modification, contributes to the exploration and understanding of the paternal epigenome in the maintenance of pregnancy and fetal growth and development. The four genes identified in this study may serve as potential diagnostic markers and elucidate novel molecular mechanisms of embryogenesis.
Direct measurements of neurosteroid binding to specific sites on GABAA receptors
Authors: Chintala Satyanarayana M. , Tateiwa Hiroki , Qian Mingxing , Xu Yuanjian , Amtashar Fatima , Chen Zi‐Wei , Kirkpatrick Charles C. , Bracamontes John , Germann Allison L. , Akk Gustav , Covey Douglas F. , Evers Alex S.
Published: July 2024

Background and Purpose

Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady‐state binding affinities of various neurosteroids for specific sites on the GABAA receptor.

Experimental Approach

Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17‐methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC‐α1GABAAR, a chimeric receptor containing transmembrane domains of the α1‐GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions.

Key Results

Allopregnanolone (3α‐OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi‐allopregnanolone (3β‐OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site‐specific probe for the intersubunit site. The affinity and site‐specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites.

Conclusions and Implications

The affinity and specificity of neurosteroid binding to two sites in the ELIC‐α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate‐reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.
Word Forms Reflect Trade‐Offs Between Speaker Effort and Robust Listener Recognition
Authors: Meylan Stephan C. , Griffiths Thomas L.
Published: July 2024

How do cognitive pressures shape the lexicons of natural languages? Here, we reframe George Kingsley Zipf's proposed “law of abbreviation” within a more general framework that relates it to cognitive pressures that affect speakers and listeners. In this new framework, speakers' drive to reduce effort (Zipf's proposal) is counteracted by the need for low‐frequency words to have word forms that are sufficiently distinctive to allow for accurate recognition by listeners. To support this framework, we replicate and extend recent work using the prevalence of subword phonemic sequences (phonotactic probability) to measure speakers' production effort in place of Zipf's measure of length. Across languages and corpora, phonotactic probability is more strongly correlated with word frequency than word length. We also show this measure of ease of speech production (phonotactic probability) is strongly correlated with a measure of perceptual difficulty that indexes the degree of competition from alternative interpretations in word recognition. This is consistent with the claim that there must be trade‐offs between these two factors, and is inconsistent with a recent proposal that phonotactic probability facilitates both perception and production. To our knowledge, this is the first work to offer an explanation why long, phonotactically improbable word forms remain in the lexicons of natural languages.
Dual add‐on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study
Authors: Han Kyung Ah , Hwang You‐Cheol , Moon Shin Je , Cho Ho Chan , Yoo Hye Jin , Choi Sung Hee , Chon Suk , Kim Kyoung‐Ah , Kim Tae Nyun , Kang Jun Goo , Park Cheol‐Young , Won Jong Chul , Cho Eunjoo , Kim Jeongyun , Park Kyong Soo
Published: July 2024

Aim

To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add‐on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add‐on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin.

Materials and Methods

In this randomized, double‐blind, double‐dummy, active‐controlled, parallel‐group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24.

Results

Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were −1.34% with GEMI + DAPA, −0.90% with GEMI (difference between GEMI + DAPA vs. GEMI −0.44% [95% confidence interval {CI}: −0.58% to −0.31%], P < .01) and −0.78% with DAPA (difference between GEMI + DAPA vs. DAPA −0.56% [95% CI: −0.69% to −0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection.

Conclusions

These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well‐tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.
The interaction effect between BMI, diabetes and age at diabetes onset on the risk of thyroid cancer: A population‐based cohort study in Shanghai, China
Authors: Hou Tianzhichao , Li Yanyun , Yan Qinghua , Zhou Yulin , Cheng Minna , Gu Kai , Wu Chunxiao , Pang Yi , Yu Pengcheng , Kain Khalil , Bloomgarden Zachary , Ning Guang , Li Qinyu , Tian Jingyan , Shi Yan
Published: July 2024

Aim

To determine the association of the presence of diabetes and, among persons with diabetes, the age at type 2 diabetes mellitus (T2DM) onset, BMI and the interactive effect with the subsequent thyroid cancer risk.

Materials and Methods

We conducted a population register‐based longitudinal cohort study in Shanghai, including 428 568 persons with new‐onset T2DM matched with the general population. The risk of thyroid cancer among subgroups was calculated based on standardized incidence ratio (SIR), hazard ratio (HR) and Cox proportional hazards models.

Results

In total, 1142 thyroid cancer cases were identified during 8 years of follow‐up, with an incidence rate of 59.01/100 000 person‐years and a higher risk (SIR = 1.21) compared with the general population. The earlier age at T2DM onset and higher BMI were associated with an increasing risk of thyroid cancer independently (onset age <50, SIR: 1.46; BMI ≥30.0 kg/m2, SIR: 1.93), with the highest risk in patients with both BMI ≥30.0 kg/m2 and onset age <50 years (SIR = 3.91, HR = 3.04). Among patients with T2DM onset age <60 years, SIR increased with higher BMI, while there were no trends when onset age ≥60 years. Among patients with BMI ≥25.0 kg/m2, SIR increased with an earlier onset age, whereas no trends were shown in the BMI <24.9 kg/m2 groups. Obese (BMI ≥30.0 kg/m2) patients had a significantly higher HR of thyroid cancer only when T2DM onset age <60 years.

Conclusions

Both earlier age of T2DM onset (<50 years) and higher BMI (≥30 kg/m2) contributed to the higher risk of thyroid cancer. Patients with young‐onset T2DM and obesity are considered more vulnerable to thyroid cancer development.
Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction‐associated steatotic liver disease but is not altered by 6 weeks of exercise training
Authors: Willis Scott A. , Malaikah Sundus , Bawden Stephen J. , Sherry Aron P. , Sargeant Jack A. , Coull Nicole A. , Bradley Christopher R. , Rowlands Alex , Naim Iyad , Ennequin Gaël , Yates Thomas , Waheed Ghazala , Gowland Penny , Stensel David J. , Webb David R. , Davies Melanie J. , Aithal Guruprasad P. , King James A.
Published: July 2024

Aims

To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction‐associated steatotic liver disease (MASLD).

Materials and Methods

In Part A (cross‐sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol−1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol−1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6‐week interventions: (1) exercise training (EX; 70%–75% maximum heart rate; four sessions/week; n = 13) or (2) non‐exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA‐IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin‐18 (CK18) M65, among others.

Results

In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA‐IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = −0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433).

Conclusions

Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate‐intensity exercise training.
Clinicopathological concordance of mucocutaneous manifestations in people living with HIV: A cross‐sectional study
Authors: Zajdman‐Faitelson Dalit , Cárdenas‐Hernández Miren Lorea , Guzmán‐Bucio Simón , Camiro‐Zuñiga Antonio , Vega Memije Maria Elisa
Published: July 2024

Objective

To describe the frequency and clinicopathological concordance of mucocutaneous manifestations in people living with HIV (PLWH) and its correlation with CD4+ T lymphocyte count and HIV viral load.

Methods

Cross‐sectional study of patients diagnosed with HIV infection who underwent skin biopsy for histopathological study from 1992 to 2022. Skin diseases were categorized as opportunistic and sexually transmitted infections, inflammatory dermatoses, benign cutaneous neoplasms, and premalignant and malignant cutaneous neoplasms. Clinicopathological concordance was classified as complete, partial or discordant. Frequency of skin diseases are presented by category and according to lymphocyte CD4+ count and HIV viral load.

Results

A total of 659 patients were included of whom 88.5% (n = 583) were male. The most frequent diagnostic category was opportunistic or sexually transmitted infections in 34% (n = 224) and the most frequently found condition was Kaposi sarcoma in 17% (n = 112). Clinicopathological concordance was complete in 53.7% (n = 354) of cases, partial in 26.7% (n = 176) and discordant in 19.6% (n = 129). Among the 282 patients with available serological data, 58.9% (n = 166), 23.8% (n = 67) and 17.4% (n = 49) had CD4+ counts below 200, between 200 and 499, and above 500 cells/μl, respectively.

Conclusions

Although there is a high variability in skin conditions which people with HIV may present, there was a high rate of clinicopathological concordance (80.4%). We emphasize the importance of diagnostic skin biopsies due to their diverse morphological presentation. The frequency of skin diseases in PLWH depending on different clinical settings should aid the clinician in reaching an adequate diagnosis in this population.
Study on botulinum toxin in dermatology from 2000 to 2023: A CiteSpace‐based bibliometric analyses
Authors: Zhou Ziwenyan , Huang Fujun , Chen Jin
Published: July 2024

Objective

Using bibliometric methods, this study analyzed and summarized the current situation and development of the global application of botulinum toxin in dermatology.

Methods

Literature published in the Web of Science Core Collection database from January 1, 2000 to October 28, 2023 was searched for topics such as “Botulinum toxin,” “Dermatology,” and so forth. The number of publications, countries, institutions, journals, authors, cited literature, keywords, and so forth, were analyzed and a visual knowledge map was created using scientometric tools such as CiteSpace, VOSviewer, and Scimago Graphica.

Results

A total of 2039 documents were retrieved and 1877 documents were included after de‐duplication and transformation. The country with the highest number of published periodical articles was the United States; the main research institution was Yonsei University; the author with the highest number of published periodical articles was Kim, Hee Jin; and the high‐frequency keywords mainly related to indications, combination therapy, and safety optimization.

Conclusion

The results of this study provide information on the current status and trends in clinical studies of botulinum toxin in dermatology, which will help researchers identify hotspots and explore new research directions in this field.
Melatonin Protects Against Colistin‐Induced Intestinal Inflammation and Microbiota Dysbiosis
Authors: Jia Yuqian , Zhang Tingting , He Mengping , Yang Bingqing , Wang Zhiqiang , Liu Yuan
Published: July 2024

Colistin is renowned as a last‐resort antibiotic due to the emergence of multidrug‐resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as N‐acetyl‐5‐hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic‐induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of Erysipelotrichales and Bifidobacteriales, as well as an increase in Desulfovibrionales abundance, following colistin exposure. Remarkably, short‐chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin‐induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS‐induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF‐κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases.
The public's perception of the nursing profession: Validity and reliability of the Chinese version of the nursing image scale in Taiwan
Authors: Hu Shui‐Tao , Chou Pei‐Chun , Wu Li‐Min , Feng Jui‐Ying , Yeh Tzu‐Pei
Published: July 2024

The public's perception of the nursing image deeply influences nurses' work and professional development. However, the Taiwanese public's perception of nursing remains unclear. This study aimed to determine the validity and reliability of a Chinese version of the Nursing Image Scale (NIS) in Taiwan. This was a psychometric study using a cross‐sectional survey. Participants were recruited via the snowball sampling method through the online community software LINE from August 1 to 13, 2019. After data collection, the construction and validation of the NIS to measure public opinion were assessed, including content validity, corrected item‐total correlation, exploratory factor analysis (EFA), and reliability. A total of 1331 valid responses were included in the analysis. After EFA analysis, the 20 scale items were divided across the four domains of prudence and care, innovation and cooperation, efficiency and division, and professionalism and respect. The NIS (Chinese version) was valid and reliable for measuring public opinion and may be used to examine changes in public perceptions of nursing.
The dental management of patients with Brugada syndrome: A case series
Authors: Ahmed Zunera , Dungarwalla Mohammed , Jones Judith
Published: July 2024

Brugada syndrome is an inherited cardiovascular disorder, which can affect the rhythm of the heart. Dental treatment can often present as an obstacle for patients with Brugada syndrome as the use of local anaesthetic can have adverse effects on the electrical conduction system of the heart.

Aim

The aim of this series is to discuss the aetiopathogenesis, presentation and management of Brugada syndrome and its relevance to dentistry and the dental team.

Methods

The authors present a series of three Brugada syndrome patients who underwent dental intervention in a hospital setting.

Results and Conclusion

The series highlighted the importance of multidisciplinary care for patients with Brugada syndrome. Liaising with other teams, such as cariologists and GMPs, allows a patient centred approach and better understanding of patient management.
Perioperative management in pediatric domino liver transplantation for metabolic disorders: A narrative review
Authors: Uslu Ahmed , Çekmen Nedim , Torgay Adnan , Haberal Mehmet
Published: July 2024

Domino liver transplantation and domino‐auxiliary partial orthotopic liver transplantation are emerging techniques that can expand the liver donor pool and provide hope for children with liver disease. The innovative technique of domino liver transplantation has emerged as a pioneering strategy, capitalizing on structurally preserved livers from donors exhibiting single enzymatic defects within a morphologically normal context, effectively broadening the donor pool. Concurrently, the increasingly prevalent domino‐auxiliary partial orthotopic liver transplantation method assumes a critical role in bolstering available donor resources. These advanced transplantation methods present a unique opportunity for pediatric patients who, despite having structurally and functionally intact livers and lacking early signs of portal hypertension or extrahepatic involvement, do not attain priority on conventional transplant lists. Utilizing optimal clinical conditions enhances posttransplant outcomes, benefiting patients who would otherwise endure extended waiting periods for traditional transplantation. The perioperative management of children undergoing these procedures is complex and requires careful consideration of some factors, including clinical and metabolic conditions of the specific metabolic disorder, and the need for tailored perioperative management planning. Furthermore, the prudent consideration of de novo disease development in the recipient assumes paramount significance when selecting suitable donors for domino liver transplantation, as it profoundly influences prognosis, mortality, and morbidity. This narrative review of domino liver transplantation will discuss the pathophysiology, clinical evaluation, perioperative management, and prognostic expectations, focusing on perioperative anesthetic considerations for children undergoing domino liver transplantation.
Root surface biomodification in periodontal therapy: Biological rationale and clinical applications
Authors: Saleh Muhammad H. A. , Dias Debora R. , Ravida Andrea , Wang Hom‐Lay
Published: July 2024

Regenerative periodontal therapy aims to form new cementum, periodontal ligament, and alveolar bone, all sealed by gingival tissue. The root surface acts as the wound margin during this regeneration process. Root surface biomodification (root conditioning/root decontamination), therefore, seems instrumental in promoting surface decontamination and enhancing tissue attachment by removing the smear layer, exposing collagen fibrils, and facilitating blood clot formation and stabilization. This review attempted to provide an all‐encompassing, evidence‐based assessment of the role of root surface biomodification in regenerative periodontal therapy, particularly in intrabony defects, furcation defects, and root coverage procedures. The reviewed evidence suggested that root conditioning agents, whether used independently or in conjunction with bone graft materials, biological agents, membranes, or connective tissue grafts, do not offer any clinical advantage regarding clinical attachment gain. Thus, integrating chemical methods with the mechanical root instrumentation process does not necessarily contribute to superior clinical outcomes.
How do I implement pathogen reduced Cryoprecipitated fibrinogen complex in a tertiary Hospital's blood Bank
Authors: Aidikoff Jennifer , Trivedi Dhaval , Kwock Richard , Shafi Hedyeh
Published: July 2024

Background

Kaiser‐Permanente Los Angeles Medical Center (LAMC) is a 560 licensed bed facility that provides regional cardiovascular services, including 1200 open heart surgeries annually. In 2021, LAMC explored alternative therapies to offset the impact of pandemic‐driven cryo AHF shortages, and implemented Pathogen Reduced Cryoprecipitated Fibrinogen Complex (also known as INTERCEPT Fibrinogen Complex or IFC). IFC is approved to treat and control bleeding associated with fibrinogen deficiency. Unlike cryo AHF, IFC has 5‐day post‐thaw shelf life with potential operational and clinical benefits. The implementation steps and the operational advantages to the LAMC Blood Bank are described.

Study Design and Methods

Eighteen months post‐implementation, the institution reviewed their product implementation experience and compared IFC with cryo AHF with a retrospective review of transfusion service and cardiac post‐op data.

Results

IFC significantly decreased product wastage rates and order‐to‐issue time. It did not significantly impact post‐op product utilization or hospital length of stay (LOS) in cardiac surgery patients when compared with cryo AHF.

Discussion

Implementation of IFC provides improved product supply stability, shorter turnaround times, and reduced wastage.
Anisotropy and Mechanical Characteristics of Ultra-High Performance Concrete and Its Interpenetrating Phase Composite With Triply Periodic Minimal Surface Architectures
Authors: Le Ba-Anh , Tran Bao-Viet , Vu Thai-Son , Nguyen Quoc-Bao , Nguyen Hoang-Quan , Chateau Xavier
Published: July 2024

This work numerically explores the anisotropy, impact phase wave propagation, buckling resistance, and natural vibration of ultra-high performance concrete (UHPC) and UHPC-steel interpenetrating phase composite (IPC) with triply periodic minimal surfaces (TPMSs), including sheet and solid gyroid, primitive, diamond, and the Schoen I-graph-wrapped package (I-WP). The experiment is conducted to verify the accuracy of the numerical model in terms of Young's modulus of polylactic acid (PLA)-based TPMS lattices and PLA-cement IPCs with TPMS cores, with the highest percent difference of 15% found for IPCs and 17% found for lattice. The results indicate that UHPC material with sheet gyroid exhibits the least extreme anisotropy in response to the varying orientation among other lattices regardless of the change of solid density, making it the ideal candidate for construction materials. Interestingly, compared to UHPC-based TPMS lattice, IPCs possess a much smaller anisotropy and exhibit almost isotropy regardless the variation of solid density and TPMS topology, offering a free selection of TPMS type to fabricate IPCs without much care of anisotropy. The phase wave velocity and buckling resistance of UHPC- and IPC-based beams with TPMSs nonlinearly decrease with a drop of TPMS solid density, but it is the almost linear pattern for the case of natural vibration frequency. UHPC material and IPC with sheet gyroid lattice are found to possess the lowest phase wave velocity and exhibit the least anisotropy of wave propagation, showing it as an ideal candidate for UHPC material to suppress the destructive energy induced by the external impact.
Topology Optimization of Hard-Magnetic Soft Phononic Structures for Wide Magnetically Tunable Band Gaps
Authors: Alam Zeeshan , Sharma Atul Kumar
Published: July 2024

Hard-magnetic soft materials, which exhibit finite deformation under magnetic loading, have emerged as a promising class of soft active materials for the development of phononic structures with tunable elastic wave band gap characteristics. In this paper, we present a gradient-based topology optimization framework for designing the hard-magnetic soft materials-based two-phase phononic structures with wide and magnetically tunable anti-plane shear wave band gaps. The incompressible Gent hyperelastic material model, along with the ideal hard-magnetic soft material model, is used to characterize the constitutive behavior of the hard-magnetic soft phononic structure phases. To extract the dispersion curves, an in-house finite element model in conjunction with Bloch’s theorem is employed. The method of moving asymptotes is used to iteratively update the design variables and obtain the optimal distribution of the hard-magnetic soft phases within the phononic structure unit cell. Analytical sensitivity analysis is performed to evaluate the gradient of the band gap maximization function with respect to each one of the design variables. Numerical results show that the optimized phononic structures exhibit a wide band gap width in comparison to a standard hard-magnetic soft phononic structure with a central circular inclusion, demonstrating the effectiveness of the proposed numerical framework. The numerical framework presented in this study, along with the derived conclusions, can serve as a valuable guide for the design and development of futuristic tunable wave manipulators.
A magnetic phantom technique for investigating structural effects on quantitative ultrasound parameters
Authors: Malinet Cyril , Muleki-Seya Pauline , Liebgott Hervé , Mamou Jonathan
Published: July 2024

Media that contain ultrasound scatterers arranged in a regular spatial distribution can be considered as structured. Structural effects affect quantitative ultrasound parameters that reflect the microstructure properties. Prior studies examined structural effects using simulations or phantoms with fixed microarchitecture, focusing on a limited set of ultrasound parameters, with limited attention given to their underlying physical significance. This study aims to investigate the concordance of the physical interpretations of multiple quantitative ultrasound parameters experimentally by introducing a phantom type with an adjustable microarchitecture. The phantom consists of an aqueous solution containing superparamagnetic microspheres, acting as scatterers. The spatial arrangement of the magnetic particles is modified by applying an external magnetic field, therefore changing the degree of structure of the phantom. Quantitative ultrasound parameters are estimated in three different configurations: the magnetic field intensity is varied over time, strength, and orientation. In each experiment, the backscatter coefficient and the envelope quantitative ultrasound parameters are successfully extracted (R2 ≈ 0.94). Their physical interpretations are supported by microphotographs and geometrical considerations through concordant hypotheses. This study paves the way for the use of magnetic phantoms. This methodology could be followed to validate theoretical scattering models and the physical meanings of quantitative ultrasound parameters.
Zero-shot classification of small target on sea bottom using model-agnostic meta-learning
Authors: You Heewon , Choo Youngmin
Published: July 2024

A model-agnostic meta-learning (MAML)-based active target classifier to identify small targets (e.g., mines) on the sea bottom in different ocean environments from those present in the training data is proposed. To better classify the targets deviating from those in the training set, MAML is applied to the out-of-distribution samples. Frequency-domain target and clutter scattering signals from various tasks with varying bottom types (silt/clay) and incident angles (low/moderate/high) are utilized as training data samples. MAML significantly outperforms conventional neural networks during the test. The improved generalization of MAML is explained using loss landscape in the form of a smooth convex curve.
Principal dimensions of voice production and their role in vocal expression
Authors: Zhang Zhaoyan
Published: July 2024

How we produce and perceive voice is constrained by laryngeal physiology and biomechanics. Such constraints may present themselves as principal dimensions in the voice outcome space that are shared among speakers. This study attempts to identify such principal dimensions in the voice outcome space and the underlying laryngeal control mechanisms in a three-dimensional computational model of voice production. A large-scale voice simulation was performed with parametric variations in vocal fold geometry and stiffness, glottal gap, vocal tract shape, and subglottal pressure. Principal component analysis was applied to data combining both the physiological control parameters and voice outcome measures. The results showed three dominant dimensions accounting for at least 50% of the total variance. The first two dimensions describe respiratory-laryngeal coordination in controlling the energy balance between low- and high-frequency harmonics in the produced voice, and the third dimension describes control of the fundamental frequency. The dominance of these three dimensions suggests that voice changes along these principal dimensions are likely to be more consistently produced and perceived by most speakers than other voice changes, and thus are more likely to have emerged during evolution and be used to convey important personal information, such as emotion and larynx size.
A metabolic regulator for parietal cells
Authors: VanHook Annalisa M.
Published: July 2024

The orphan nuclear receptor ERRγ directs the differentiation of acid-secreting gastric cells.
The type II secretion system as an underappreciated and understudied mediator of interbacterial antagonism
Authors: Cianciotto Nicholas P.
Published: July 2024

Interbacterial antagonism involves all major phyla, occurs across the full range of ecological niches, and has great significance for the environment, clinical arena, and agricultural and industrial sectors. Though the earliest insight into interbacterial antagonism traces back to the discovery of antibiotics, a paradigm shift happened when it was learned that protein secretion systems (e.g., types VI and IV secretion systems) deliver toxic “effectors” against competitors. However, a link between interbacterial antagonism and the Gram-negative type II secretion system (T2SS), which exists in many pathogens and environmental species, is not evident in prior reviews on bacterial competition or T2SS function. A current examination of the literature revealed four examples of a T2SS or one of its known substrates having a bactericidal activity against a Gram-positive target or another Gram-negative. When further studied, the T2SS effectors proved to be peptidases that target the peptidoglycan of the competitor. There are also reports of various bacteriolytic enzymes occurring in the culture supernatants of some other Gram-negative species, and a link between these bactericidal activities and T2SS is suggested. Thus, a T2SS can be a mediator of interbacterial antagonism, and it is possible that many T2SSs have antibacterial outputs. Yet, at present, the T2SS remains relatively understudied for its role in interbacterial competition. Arguably, there is a need to analyze the T2SSs of a broader range of species for their role in interbacterial antagonism. Such investigation offers, among other things, a possible pathway toward developing new antimicrobials for treating disease.
Deciphering the interplay of gut microbiota and metabolomics in retinal vein occlusion
Authors: Ai Jing , Cao Yunbo , Zhang Cong , Sun Jun-Hui , Dong Feng , Jing Li , Wang Jianyong , Cui Hongguang
Published: July 2024

This study aims to explore the link between retinal vein occlusion (RVO), a blinding ocular condition, and alterations in gut microbiota composition, to offer insights into the pathogenesis of RVO. Fecal samples from 25 RVO patients and 11 non-RVO individuals were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Significant differences in the abundance of gut microbial species were noted between RVO and non-RVO groups. At the phylum level, the RVO group showed an elevation in the ratio of Firmicutes to Bacteroidetes. At the genus level, the RVO group showed higher abundance in
Escherichia_Shigella
(
P
< 0.05) and less abundance in
Parabacteroides
(
P
< 0.01) than the non-RVO group. Functional predictions indicated reduced folate synthesis, biotin metabolism, and oxidative phosphorylation, with an increase in butyric acid metabolism in the RVO group. LC-MS analysis showed significant differences in purine metabolism, ABC transporters, and naphthalene degradation pathways, especially purine metabolism. Pearson correlation analysis revealed significant associations between bacterial genera and fecal metabolites. Enrichment analysis highlighted connections between specific metabolites and bacterial genera. The findings showed that the dysregulation of gut microbiota was observed in RVO patients, suggesting the gut microbiota as a potential therapeutic target. Modulating the gut microbiota could be a novel strategy for managing RVO and improving patient outcomes. Furthermore, the study findings suggest the involvement of gut microbial dysbiosis in RVO development, underscoring the significance of understanding its pathogenesis for effective treatment development.

IMPORTANCE

Retinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.
A comparative study of sampling methods in the detection of esophageal cancer-related microbiota
Authors: Xue Xia , Wang Siyu , Li Yi , Liu Zhenzhen , Zhang Jun , Hu Ziqing , Fan Chengcheng , Zhang Xiaojuan , Li Hongle , Li Jun
Published: July 2024

Esophageal cancer (EC) is a multifaceted disease. Our understanding of the involvement of esophageal microbiota in its pathogenesis and progression is limited, which is due to the lack of proper endoscopic sampling methods. Hereby, we conducted a comparative analysis of paired samples obtained through endoscopic brushing and cytosponge, aiming at assessing the feasibility of using cytosponge as a minimally invasive sampling way for studying esophageal microbiota. Our findings suggest that cytosponge sampling yielded significantly superior community richness and diversity compared to endoscopic brushing in both controls (non-cancerous) and EC individuals. The analysis of beta-diversity revealed distinct microbial community pattern in the genus diversity between the two sampling methods, underscoring the importance of selecting appropriate sampling methods to effectively characterize the esophageal microbiota. Specifically,
Lactococcus
and
Serratia
showed higher abundance in the samples collected by endoscopic brushing, while
Alloprevotella
and
Leptotrichia
were more enriched in the samples collected by cytosponge. These differences in dominant microbes were associated with metabolic pathways that particularly were related to host inflammation, such as pyruvate and glucose metabolisms. Notably, the phylogenetic levels of the microbiota indicated varied explanatory power for different detection purposes. This study underscores the substantial impact of sampling method selection on the acquisition of esophageal microbiota associated with the EC development, encompassing considerations of both abundance and diversity. This highlights the significance of selecting an appropriate sampling method for investigating the esophageal microbial status and studying the micro-environment in EC-related individuals.

IMPORTANCE

This study addresses a critical issue in esophageal cancer study by comparing two different sampling methods, endoscopic brushing and cytosponge, for investigating the esophageal microbiota. Our work highlights the suitability of the cytosponge technique as a minimally invasive sampling method for studying the esophageal microbiota and emphasizes the importance of selecting an appropriate sampling method to characterize the microbial community. Our findings have significant implications for advancing the understanding of the role of the esophageal microbiota in cancer development and will inform future research and clinical approaches in this field.
Comparison of
Bordetella
species identification among differing rt-PCR assays in the United States
Authors: Cole Matthew , Simon Ashley K. , Faulkner Amanda , Skoff Tami , Tondella Maria L. , Montero Clemente , Nye Melinda B. , Williams Margaret
Published: July 2024

In the United States, the general laboratory method for diagnosing pertussis, caused by
Bordetella pertussis,
is real-time PCR (rt-PCR) targeting insertion sequence 481 (IS
481
). Other
Bordetella
species (
parapertussis, holmesii
, and
bronchiseptica
) can also cause a pertussis-like syndrome, and some commercial laboratory assays include the insertion sequence 1001 (pIS
1001
) that can detect
B. parapertussis
/
B. bronchiseptica (BppBb
). Because IS
481
exists in
B. pertussis
and
B. holmesii
, current commercial assays cannot differentiate these two species. We used a multiplex rt-PCR assay containing species-specific targets to
Bordetella
to evaluate clinical specimens detected as
B. pertussis
/
B. holmesii
(
BpBh
) or
BppBb
by commercial laboratories. A sample of 3,984 clinical specimens positive for IS
481
or pIS
1001
from two commercial laboratories during 2012–2019 were re-tested at CDC. Agreement of
Bordetella
species between the CDC and commercial laboratory assays, and the proportion of commercial laboratory specimens that were non-
B
.
pertussis
by CDC’s assay was assessed. Overall agreement in
Bordetella
species detection and identification between the CDC and commercial lab assays was 85%. Agreement for identifying
B. pertussis
was 87% for 3,663
BpBh
specimens and 98% for identifying
B. parapertussis
in 310
BppBb
specimens. CDC’s assay detected
B. holmesii
in 55/3,984 (1.4%) specimens. Most discrepant results (410/490, 82%) were
BpBh
specimens interpreted as indeterminate
B. pertussis
at CDC. We found a small portion of
B. holmesii
in a sample of IS
481
-positive clinical specimens originally identified by commercial laboratory rt-PCR assays, suggesting that commercial PCR assays are a reliable diagnostic tool for correctly identifying
Bordetella
species in most patients with suspected pertussis.

IMPORTANCE

When testing specimens collected from patients with suspected pertussis, large-scale commercial laboratories in the United States employ an IS
481
-based assay that cannot differentiate between
Bordetella pertussis
and
Bordetella holmseii
. The level of
B. holmesii
causing pertussis-like illness in the United States is not well-understood given that only
B. pertussis
is nationally notifiable. After re-testing with a multiplex, species-specific rt-PCR assay, our data show low levels of
B. holmesii
identified in a sample of IS
481
-positive clinical specimens originally identified by commercial laboratory rt-PCR assays. These results reinforce the validity of large-scale commercial rt-PCR testing as a reliable diagnostic tool for pertussis in the United States.
The role of MNK1-mTORC1 pathway in modulating macrophage responses to
Vibrio vulnificus
infection
Authors: Lou Yong-Liang , Xie Dan-Li , Huang Xian-Hui , Zheng Meng-Meng , Chen Na , Xu Ji-Ru
Published: July 2024

Vibrio vulnificus
(
Vv
) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during
Vv
infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or
Vv
, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of
Vv
, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in
Vv
-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with
Vv
. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following
Vv
infection. In summary, our findings suggest that MNK promotes the
Vv
-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in
Vv
-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to
Vv
infection.

IMPORTANCE

Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during
Vibrio vulnificus
(
Vv
) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in
Vv
-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to
Vv
infection.
High rates of respiratory illnesses upon arrival: lessons from Team USA at the Santiago 2023 Pan American and Parapan American Games
Authors: Post Eric G , Anderson Travis , Samson Olivia , Triplett Ashley N , Gidley Alexis D , Isono Steven S , Watters Jennifer , Donaldson Amber T , Finnoff Jonathan T , Adams William M
Published: July 2024

Objective

To describe the incidence and characteristics of injuries and illnesses among Team USA athletes competing at the Santiago 2023 Pan American Games (PAG) and Parapan American Games (PPAG), with a particular focus on the incidence of respiratory illnesses and on injuries for sports new to the Olympic and Paralympic programmes.

Methods

Illnesses and injuries occurring among the 870 Team USA athletes competing in the Santiago 2023 PAG or PPAG were documented within Team USA’s Injury and Illness Surveillance system. Illness and injury incidence per 1000 athlete-days (ADs) and incidence ratios (IR) were calculated, both with 95% CIs.

Results

Illness (IR 2.5, 95% CI 1.6, 3.9) and injury (IR 1.8, 95% CI 1.3, 2.5) rates were greater during PPAG compared with PAG. Illness rates were higher in the pre-opening ceremony period compared with the competition period for both PAG (IR 2.7, 95% CI 1.1, 5.9) and PPAG (IR 1.9, 95% CI 0.9, 3.8). Respiratory illness was the most common illness with 3.2% and 8.9% of all Team USA athletes reporting a respiratory illness during the PAG and PPAG, respectively. Sports that are relatively new to the Olympic/Paralympic programmes exhibited the highest injury rates during the Games: breaking (250.0 (91.7, 544.2) per 1000 ADs), Para taekwondo (93.8 (19.3, 274.0) per 1000 ADs) and surfing (88.9 (24.2, 227.6) per 1000 ADs).

Conclusion

Respiratory illness rates were the most common type of illness during both PAG and PPAG and were more likely to occur prior to competition starting. Our data have identified high injury risk populations (breaking, surfing, Para taekwondo) and timing (pre-opening ceremony period) for further risk factor analysis.