bluuebunny/crossref_metadata_2025 huggingface dataset:
Vericiguat combined with “new quadruple” therapy enhances cardiac function and life quality in patients with heart failure: a single-center prospective study
Authors: Zhao Di , Zhang Yanjuan , Yong Yonghong , Wang Liansheng , Liu Jiabao
Published: October 2024

Objective

To investigate the therapeutic effect of Vericiguat combined with “new quadruple” drugs on patients with heart failure (HF).

Methods

From December 1, 2022 to February 1, 2024, 103 patients with heart failure were consecutively enrolled from the cardiology clinic or ward of the First Affiliated Hospital of Nanjing Medical University. Before enrollment, the patients’ left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), liver and kidney function electrolytes, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and other indicators were measured. Patients diagnosed with reduced ejection fraction (HFrEF) and with heart failure with mildly reduced ejection fraction (HFmrEF) were treated with Vericiguat combined with “ARNI, BB, MRA, SGLT2i” therapy. Patients diagnosed with preserved ejection fraction (HFpEF) were treated with Vericiguat combined with “ARNI, BB, SGLT2i” therapy. The above indicators were rechecked after 1 month of treatment.

Results

For all patients, comparison after treatment: LVEF (38.1 ± 8.5% vs. 43.1 ± 8.5%, P < 0.01), LVEDD (60.5 ± 8.1 vs. 58.2 ± 7.3 mm, P < 0.01), NT-proBNP (4,567.8 ± 5,163.9 vs. 1,895.6 ± 2,702.1 ng/L, P < 0.01), MLHFQ (45.72 ± 11.09 vs. 32.29 ± 9.41, P < 0.01). Further subgroup analysis showed that Vericiguat combined with “ARNI, BB, SGLT2i or MRA” improved the LVEF and reduced NT-proBNP levels in patients with HFrEF, HFmrEF or HFpEF. and improved patients’ quality of life scores. The intergroup comparison showed the therapeutic effect of the combination was equivalent in HF caused by myocardial Infarction (MI), dilated cardiomyopathy (DCM) or Valvular Heart Disease (VHD).

Conclusion

Vericiguat combined with the “new quadruple” therapy has a significant therapeutic effect on patients with heart failure caused by MI, DCM or VHD.
Effect of double adhesive layer application on micro-tensile dentin bond strength of a universal adhesive
Authors: Al-Zain Afnan O. , Albuqayli Asrar , Albogami Abdulaziz , Alkudsi Abdulghani , Alwabiri Meshari , Koshak Abdullah T. , Alsefri Hattan , Munchow Eliseu A.
Published: October 2024

Introduction

Achieving optimal dentin bond strength is crucial for the long-term success of adhesive restorations. This study aims to evaluate the impact of double adhesive layer application, with and without light curing between applications, on the micro-tensile dentin bond strength (µ-TBS) of a universal adhesive, in comparison to the conventional single-layer application.

Methods

Intact human molars were divided into three groups (n = 15) according to the adhesive application technique using a universal self-etch adhesive (Tetric N-Bond Universal, Ivoclar) as follows: (1) according to the manufacturer's instructions, (2) double-layer application without light curing between layers, and (3) double-layer application with light curing between layers. Samples were immediately tested for µ-TBS, with failure types recorded as adhesive, cohesive, or mixed. Representative samples were observed by scanning electron microscopy. Data were analyzed using multiple-way ANOVA (α = 0.05).

Results

The double adhesive layer with and without light curing between layers showed similar μ-TBS to that of the control group (p > 0.05).

Discussion

From a clinical perspective, these findings suggest that the accurate application of a single layer of a universal adhesive can be as effective as more complex techniques. Additionally, the use of universal bonding agents may have contributed to the outcomes observed in this study. In conclusion, double adhesive layer application and light curing between adhesive layers did not increase the µ-TBS with the universal adhesive agent explored.
Child and adolescent social withdrawal predict adult psychosocial adjustment: A meta-analysis
Authors: Gazelle Heidi , Shafer Lundin Jessie K. , Lei Haochen , Cao Hongyuan , Litchfield Meghan
Published: October 2024

This systematic review and set of five meta-analyses synthesized the results of prospective longitudinal publications on childhood and/or adolescent social withdrawal as a predictor of adult psychosocial adjustment. Meta-analyses were conducted with results for five adult outcomes from 31 publications derived from 14 longitudinal samples and a combined sample size of 19,806 adults (50% women, M = 38.88 years, 83% White) with childhood and/or adolescent ( ≤ 16 years) histories of social withdrawal and their offspring (N = 175). Dependency among publications derived from the same longitudinal samples was explicitly modeled in meta-analyses with clustering. Meta-analytic results support childhood and/or adolescent social withdrawal as a medium-sized risk factor for adult social anxiety and intergenerational difficulties in mothers and their offspring (both p < 0.0001); a small-size risk factor for delayed adult developmental milestones (p < 0.05), adult social withdrawal (p < 0.0001), other anxiety (p < 0.05), and depression (p < 0.01); and a small-size protective factor against adult substance use (p < 0.01). However, meta-analytic results did not support childhood and/or adolescent social withdrawal as a predictor of physical health, likely due to the heterogeneous nature of the investigated health outcomes. Consistent with a Developmental Science Model, results are interpreted as supporting interpersonal mechanisms (missing out, interpersonal stress, and poor relationship quality) and developmental cascades (cross domain-influences) in socially withdrawn children's life-course development. Because evidence for intergenerational difficulties was based on a single longitudinal sample, confidence in intergenerational effects would be increased by replication in other samples. Heterogeneity among effect sizes included in most meta-analyses suggests that the relation between childhood and/or adolescent social withdrawal and adult outcomes is likely to be moderated by other factors. Future directions in this area of research are discussed.
Adolescent close friendships, self-perceived social acceptance, and peer-rated likeability as predictors of wellbeing in young adulthood
Authors: Shah Emily N. , Szwedo David E. , Allen Joseph P.
Published: October 2024

Introduction

Links between interpersonal relationships and physical and psychological functioning have been well-established in the literature. During adolescence, success or distress in peer relationships may have distinct effects on different aspects of wellbeing. The present study aims to examine the ways in which different adolescent peer relationship contexts (i.e., close friendship quality, social acceptance, and likability from peers) can predict outcomes relevant to adult wellbeing (i.e., social anxiety, depression, aggression, social integration, romantic insecurity, job satisfaction, and physical health). Further, the study considers how different developmental stages of adolescence may impact links between peer relationships and wellbeing outcomes.

Method

Peer relationship contexts were assessed in early (ages 13–14) and late (ages 17–18) adolescence. Markers of wellbeing were measured in young adulthood (ages 28–30). A path analysis was used to examine whether the developmental timing of adolescent peer relationship contexts could predict wellbeing in young adulthood.

Results

Results suggest that, across adolescence, broader perceived social acceptance may be a more robust predictor of adult wellbeing compared to close friendship quality and peer likability. When examined at early and late adolescence separately, early adolescent social acceptance and late adolescent close friendship quality best predicted outcomes of adult wellbeing.

Discussion

Implications and considerations for future research are discussed.
Response characteristics of 3D tensor CSAMT in axis anisotropic media
Authors: Liu Xiao , Gao Shijie
Published: October 2024

Considering the significant impact of anisotropy on forward and inversion results, this paper presents a research study on tensor controlled-source audio magnetotellurics (CSAMT) forward modeling in axis anisotropic media. In this study, the tensor resistivity of axis anisotropic medium is introduced according to the control equation of electric field with sources. The total electric field is decomposed into primary and secondary fields, with the primary field obtained using Key’s algorithm and the secondary field calculated using the finite difference method. This approach enables three-dimensional (3D) modeling of tensor CSAMT in axis anisotropic media. The correctness of the algorithm is verified by comparing it with the results obtained using a two-dimensional (2D) finite element algorithm. Several sets of axis anisotropic 3D models are designed, and the response characteristics of anisotropic target bodies to plane waves and non-plane waves are summarized. The findings indicate that the Cagniard resistivity and tipper are sensitive to changes in the X and Y directions of the anomaly, but not sensitive to changes in resistivity in the Z direction. Additionally, in the near region, non-plane wave CSAMT signals may cause distortion in the Cagniard resistivity. The results highlight that tensor CSAMT has the capability to detect changes in resistivity in two-axis directions (X and Y), providing greater exploration advantages compared to scalar CSAMT. This study provides a foundation for the forward modeling and inversion of tensor CSAMT in arbitrary anisotropic media.
Multifactorial analysis of risk factors for foot ulcers in patients with neurovascular complications of diabetes
Authors: Fan Zibo , Huang Jinyan , Liu Yue , Xie Hao , Yang Qinfeng , Liang Yue , Ding Hong
Published: October 2024

Background

Diabetic foot ulcers (DFU) are a major complication associated with significant morbidity and mortality. While numerous studies have investigated risk factors for these ulcers in general, few have focused specifically on patients with Neurovascular Complications of Diabetes. This study aimed to evaluate the prevalence and risk factors for DFU in this specific population.

Methods

We analyzed data from the National Institutes of Health (NIS) database for the years 2017-2019, involving a cohort of 161,834 patients aged over 18 who were diagnosed with neurovascular complications of diabetes. Demographic characteristics (age, gender, ethnicity), hospital characteristics, comorbidities, and other relevant data were included for analysis. A binary logistic regression model was generated to identify independent risk factors for DFU.

Results

The prevalence of DFU among patients with neurovascular complications of diabetes was 29.4% during the period from 2017 to 2019. Compared to patients without DFU, those with DFU had longer hospitalization times and higher costs. The multiple regression analysis revealed that Iron-deficiency anemia (OR, 1.10; 95% CI, 1.01-1.11; P=0.019), Hypertension (OR, 1.07; 95% CI, 1.03-1.11; P=0.001), Obesity (OR, 1.08; 95% CI, 1.06-1.11; P<0.001), Peripheral vascular disorders (PVD) (OR, 1.69; 95% CI, 1.65-1.74; P<0.001), Osteomyelitis (OR, 7.10; 95% CI, 6.89-7.31; P<0.001), Tinea pedis (OR, 1.89; 95% CI, 1.59-2.26; P<0.001), Sepsis (OR, 1.24; 95% CI, 1.20-1.28; P<0.001), and onychomycosis (OR, 1.26; 95% CI, 1.13-1.42; P<0.001) were independent predictors for DFU in this population.

Conclusion

The study found a high prevalence of DFU in patients with neurovascular complications of diabetes. Identifying and addressing risk factors such as deficiency anemia, hypertension, obesity, PVD, infections, and foot conditions may contribute to reducing the prevalence of DFU in this vulnerable population.
Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients
Authors: Chen Yuezhou , Xie Minyu , Wu Siyun , Deng Zehua , Tang Yan , Guan Yiqing , Ye Yun , He Qiandong , Li Lei
Published: October 2024

Background

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence.

Methods

A total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential).

Results

Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2’-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle.

Conclusions

We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.
Bad data identification method considering the on-load tap changer model
Authors: Hu Shiyao , Rong Chunyan , Zhang Mengnan , Chai Linjie , Ma Yuxuan , Zhang Tianlei
Published: October 2024

With the connection and integration of renewable energy, the on-load tap-changer (OLTC) has become an important device for regulating voltage in distribution networks. However, due to non-smooth and non-linear characteristics of OLTC, traditional bad data identification and state estimation methods for transmission network are limited when applied to the distribution network. Therefore, the nonlinearity and droop control constraints of the OLTC model are considered in this paper. At the same time, the quadratic penalty function is introduced to realize the fast normalization of the tap position. It proposes a two-stage bad data identification method based on mixed-integer linear programming. In the first stage, suspicious measurements are identified using projection statistics and maximum normalized residual methods for preprocessing the measurement data. In the second stage, a linearization approach utilizing hyhrid data-physical driven is applied to handle nonlinear constraints, leading to the development of a bad data identification model based on mixed-integer linear programming. Finally, the proposed methodology is validated using a modified IEEE-33 node test feeder example, demonstrating the accuracy and efficiency of bad data identification.
Innovation and application of inter-provincial carbon emission transfer accounting model in China’s domestic production network
Authors: YANG Puhang , YANG Yong
Published: October 2024

The New Development Paradigm will result in the significant development of domestic production networks and the accelerated growth of carbon transfers among provinces in China. However, the existing value chain or the trade of intermediate goods decomposition method cannot completely account for the carbon content of intermediate goods. So the paper developed a accounting model for inter-regional intermediate goods trade based on input-output model. The most significant advantage of this accounting model is that by further decomposing final output into three components—final consumption within the region, final consumption flowing to other regions, and final output flowing to other regions as intermediate goods that are not returned to the region—it achieves a more comprehensive decomposition of the value chain in comparison to the established models. This approach allows for the tracking of longer value chains and the accounting for intermediate goods inflows and outflows simultaneously. Furthermore, the accounting of trade in intermediate goods can be conducted for any number of countries, regions, and sectors within the input-output system, thereby providing a foundation for the comprehensive accounting of inter-regional carbon transfers within production networks. With the input-output tables and carbon emission inventories from the CEADs (the China Carbon Emissions Accounting Database), the paper has calculated the changes of the carbon transfer among provinces in the China’s domestic production network from 2012 to 2017 and find that the inter-provincial intermediate goods trade and carbon transfer among provinces is increasing significantly. Each province has a strong incentive to overuse the carbon embodied in the intermediate goods from others, but lacks the motivation to reduce their own carbon emission. In the inter-provincial transfer of the carbon content of intermediate goods in China’s domestic production network, the difference between the average value of the ratio of the carbon content of intermediate goods from other provinces used by each province and that supplied for use by other provinces to the ratio of the carbon content of intermediate goods produced by itself increased by 13.6% between 2012 and 2017. Only a few provinces are evolving towards a win-win between economic and environmental benefits, while most are still facing the evolutionary dilemma in choosing between economic and environmental benefits. In the future, we should comprehensively explore the cooperative governance of carbon emission reduction in the domestic production network, including establishing a national standard for calculating the carbon transfer in domestic production network, improving the carbon emission responsibility sharing mechanism and carbon emission reduction compensation systems.
The impact of sleep problems on cerebral aneurysm risk is mediated by hypertension: a mediated Mendelian randomization study
Authors: Yan Xiaofei , Li Hongwu
Published: October 2024

Introduction

Cerebral aneurysm (CA) is a common vascular disease. The risk factors of CA include hypertension, smoking, and a family history of genetic predisposition. Although sleep-related problems have been found to have a strong association with cardiovascular disease, there is a lack of research regarding the causal relationship with cerebral aneurysms.

Methods

In this study, we investigated the causal relationship between four sleep-related problems, including snoring, insomnia, narcolepsy, and napping during the day, and CA using a two-sample Mendelian randomization (MR) analysis. Moreover, the potential confounders before sleep problems and CA were further analyzed by multivariate MR (MVMR).

Results

The causal relationship between insomnia and CA was obtained analytically by means of six MR analyses. There was a strong causal effect relationship between insomnia and CA, which suggests this as a potential risk factor [odds ratio (OR) = 8.35, 95% confidence interval (CI) = 2.422–28.791, p = 7.772e-04]. On this basis, hypertension was identified as a mediator between insomnia and CA by MVMR, with a mediating effect of 52.538% (OR = 3.05, 95% CI = 1.549–4.55, p = 0.015).

Conclusion

The causal relationship between insomnia and CA was predicted using genetic variance data, and insomnia was found to be a potential risk factor. Furthermore, hypertension is a mediator between insomnia and CA. Therefore, focusing on sleep problems and improving sleep quality may be an active and effective strategy to prevent CA.
Protein kinase D1 in myeloid lineage cells contributes to the accumulation of CXCR3+CCR6+ nonconventional Th1 cells in the lungs and potentiates hypersensitivity pneumonitis caused by S. rectivirgula
Authors: Snyder John D. , Yoon Tae Won , Lee Sangmin , Halder Priyanka , Fitzpatrick Elizabeth Ann , Yi Ae-Kyung
Published: October 2024

Introduction

Hypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula-induced HP.

Methods

Mice were exposed intranasally to S. rectivirgula once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected.

Results

Compared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula.

Discussion

Our results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs.
Case report: Progressive multifocal leukoencephalopathy co-occurring with neurosarcoidosis: early brain biopsy and appropriate therapy for PML resulted in a favorable prognosis
Authors: Wang Qiannan , Tsuboguchi Shintaro , Okamoto Kouichirou , Tada Mari , Kakita Akiyoshi , Nakamichi Kazuo , Oishi Makoto , Kanazawa Masato , Onodera Osamu
Published: October 2024

Progressive multifocal leukoencephalopathy (PML) is a rare central nervous system disease caused by JC virus (JCV) infection. Human immunodeficiency virus (HIV) infection is the greatest risk factor for PML. Other immunological diseases, including systemic sarcoidosis, have also been reported as risk factors for PML. Herein, we report a case of PML co-occurring with neurosarcoidosis. Early diagnosis using brain biopsy and appropriate therapeutic interventions achieved favorable outcomes. PML in patients with active intracranial neurosarcoidosis is extremely rare. We believe that it is important to perform brain biopsy at an early stage to allow diagnosis, even for central nervous system involvement with a progressive parenchymal lesion in patients with sarcoidosis, if PML is possible.
Circulatory microRNAs and proinflammatory cytokines as predictors of lupus nephritis
Authors: ElFeky Dalia Saad , Omar Noha Mohamed , Shaker Olfat Gamil , Abdelrahman Walaa , Gheita Tamer A. , Nada Mona Gamal
Published: October 2024

Introduction

Lupus nephritis (LN) is one of the most prevalent severe organ manifestations of systemic lupus erythematosus (SLE), impacting 70% of SLE patients. MicroRNAs (miRNAs), are small non-coding RNA molecules which influence the expression of approximately one-third of human genes after the process of transcription. Dysregulation of miRNAs was documented in numerous disorders, including SLE and LN. Cytokines are the orchestrators of the immune response in autoimmune diseases. Our study aims to explore the variation in the levels of circulating miRNAs and proinflammatory cytokines as potential diagnostic biomarkers among LN and SLE patients without LN in comparison to controls.

Methods

The study involved 20 LN patients, 20 SLE patients without LN, and 10 healthy controls. Serum levels of IL-12 and IL-21 in addition to miR-124, miR-146a, miR-199a, and miR-21 were assessed using the enzyme-linked immunosorbent assay (ELISA) for cytokines and quantitative real-time PCR for miRNAs.

Results

A significant downregulation in miR-124 (p<0.001) and a significant overexpression of miR-146a (p=0.005) were found in SLE patients without LN in comparison to controls. In comparison to SLE patients without LN and the control group, miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients (p=<0.001) with high diagnostic values of these miRNAs in discriminating LN from SLE patients without LN according to Receiver operating curve (ROC) analysis. Logistic regression analysis revealed that only miR-199a is an independent predictor of LN (OR 1.69; 95% CI: 1.1-2.6). The expression of miR-124 was reduced in LN patients in comparison to the control but increased in LN patients in comparison to SLE patients without LN. However, there was no statistically significant difference in either scenario. In comparison to both SLE patients without LN and controls, LN patients exhibited the highest serum levels of IL-12 and IL-21, with no statistically significant difference. Regression analysis revealed that only miR-146a was associated with creatinine levels and SLEDAI score (p= 0.009 and 0.03, respectively), while miR-124 was associated with hemoglobin level (p=0.03).

Conclusion

MiR-199a is an independent predictor for LN and might be used as a diagnostic biomarker for this disease. MiR-146a might play an important role in LN pathophysiology.
Clinical associations of complement-activating collectins, collectin-10, collectin-11 and mannose-binding lectin in preterm neonates
Authors: Gajek Gabriela , Hansen Soren W. K. , Jarych Dariusz , Kufelnicka-Babout Maja , Świerzko Anna S. , Kobiela Paulina , Szala-Poździej Agnieszka , Chojnacka Karolina , Sobczuk Katarzyna , Domżalska-Popadiuk Iwona , Mazela Jan , Kalinka Jarosław , Thiel Steffen , Cedzyński Maciej
Published: October 2024

Introduction

Premature and low-birthweight infants are at especially high risk of perinatal complications, including impaired thermoregulation, infections and respiratory distress. Such adverse effects and the need for invasive procedures are associated with high mortality among preterms. This study focused on the influence of the innate immune system and tested the levels of collectins, collectin-10 (CL-10), collectin-11 (CL-11) and mannose-binding lectin (MBL) in preterm neonates.

Methods

Cord blood was collected from 535 preterms (born at gestational age ≤37 weeks). COLEC10 and COLEC11 polymorphisms were analyzed by real-time PCR and those of MBL2 by PCR/PCR-RFLP. The concentrations of collectins in sera from cord blood were determined with ELISA.

Findings

Low concentrations of CL-10 in cord sera (<462 ng/ml corresponding to the 10th percentile) were significantly associated with births at GA ≤32 weeks. Median levels of both CL-10 and CL-11 were significantly lower in preterms with very low birthweight (<1500 g), low Apgar 1’ score and those who needed prolonged hospitalisation. Lower median CL-10 was also observed in fetal growth restriction cases. An important finding was the decreased concentrations of CL-10, CL-11 and MBL in respiratory distress syndrome (RDS). For CL-10 and CL-11, that relationship was confined to infants born at GA ≥33 weeks and/or with body mass at birth ≥1500 g. Only CL-10 was found to influence susceptibility to early-onset infections. COLEC11 heterozygosity for the activity-decreasing polymorphism (rs7567833, +39618 A>G, His219Arg) was more common in preterm premature rupture of membranes (pPROM) cases, compared with corresponding reference groups. Furthermore, C/T or T/T genotypes at COLEC11 at rs3820897 (-9570 C>T) as well as MBL deficiency-associated MBL2 gene variants were more common in preterms diagnosed with RDS than among unaffected newborns.

Conclusion

The complement-activating collectins investigated here could be important for maintaining homeostasis in preterm neonates. Despite similar structure and specificity, MBL, CL-10 and CL-11 manifest a different spectrum of clinical associations.
Assessment of daily altimeter-based open ocean water level with hindcast and forecast efficiency
Authors: Voukouvalas Evangelos , Papazoglou Michail , Almar Rafael , Synolakis Costas , Salamon Peter
Published: October 2024

Satellite altimetry water level measurements are valuable in episodic and climate change related hydrodynamic impact studies, despite their sparse temporal distribution over the global ocean. This study presents the spatiotemporal characteristics of the open-ocean satellite derived water level measurements globally for the period 31/12/1992-15/10/2019 and evaluates their efficacy to represent the water level even during intense atmospheric conditions. Water level measurements from 23 different satellite missions are compared with tide gauge records and hydrodynamic simulations. The satellite measurements reproduce the water-level variations with good to excellent skill for ~60% of the areas considered. Additionally, satellite measurements and local atmospheric conditions are utilized in order to examine whether statistical data driven models can contribute to decreasing the temporal sparseness of the water level data over the global ocean. The suitability of this low computational-cost method is demonstrated by deriving a 63-year hindcast of the daily maximum water level for the global ocean, and for a medium-term 15-day ensemble forecast. The publicly available long-term water-level hindcast and the parameters of the data-driven statistical model derived can serve as a tool for designing and facilitating local and global coastal risk-assessment studies.
Case report: A case of cutaneous anthrax guided by metagenomic next-generation sequencing technology
Authors: Wang Lu , Wen Danli , Qu Yuanqing , Wang Qin , Liu Yuan
Published: October 2024

Anthrax is an acute zoonotic infectious disease caused by Bacillus anthracis. It is categorized as a Class B (reported within 24 h of onset, including pulmonary anthrax, which is managed as a Class A infectious disease and reported within 2 h of onset) infectious disease in China. Human anthrax infection primarily occurs through direct or indirect contact with infected animals. This study reports a case of cutaneous anthrax where typical anthrax colonies were observed in conventional microbial cultures, and large Gram-positive rods with squared ends were visible under the microscope. The results from metagenomic next-generation sequencing (mNGS) suggested the presence of Bacillus anthracis. This research explores the value of combining traditional microbiology with mNGS technology for the early diagnosis and therapy of infectious diseases.
Estimation of skin surface roughness in vivo based on optical coherence tomography combined with convolutional neural network
Authors: Zhang Zhiqun , Chen Zhida , Li Zhenqian , Zou Jian , Guo Jian , Chen Kaihong , Guo Yong , Li Zhifang
Published: October 2024

The texture of human skin is influenced by both external and internal factors, and changes in wrinkles can most directly reflect the state of the skin. Skin roughness is primarily used to quantify the wrinkle features of the skin. Therefore, effective and accurate quantification of skin roughness is essential in skincare, medical treatment, and product development. This study proposes a method for estimating the skin surface roughness using optical coherence tomography (OCT) combined with a convolutional neural network (CNN). The proposed algorithm is validated through a roughness standard plate. Then, the experimental results revealed that skin surface roughness including arithmetic mean roughness and depth of roughness depends on age and gender. The advantage of the proposed method based on OCT is that it can reduce the effect of the skin surface’s natural curvature on roughness. In addition, the method is combined with the epidermal thickness and dermal attenuation coefficient for multi-parameter characterization of skin features. It could be seen as a potential tool for understanding the aging process and developing strategies to maintain and enhance skin health and appearance.
IgG4 serologic elevation in a patient with severe hidradenitis suppurativa: a case report and review of the literature
Authors: Gauger Andrew J. , Fritz Mike , Burgin Callie B.
Published: October 2024

Hidradenitis suppurativa (HS) is a chronic cutaneous and systemic inflammatory condition. Increasingly, reports have found that immunoglobulins play a role in the exaggerated immune response occurring in severe HS. It is important to recognize these implications as HS patients may present with laboratory abnormalities relating to chronic inflammation and immune activation. If these laboratory abnormalities are mistakenly associated with another disease process, it could lead to invasive workup and treatment, causing harm to patients. We describe the case of a 23-year-old woman with Hurley stage III HS who was hospitalized and found to have persistent immunoglobulin-G4 (IgG4) elevation. Upon discharge, the patient was diagnosed with IgG4-related disease (IgG4-RD) and started treatment with azathioprine. However, the biopsy ultimately was negative for IgG4-RD, and she presented to our clinic several months later with worsening HS disease during an active flare. Physical examination revealed actively draining nodules and sinus tracts in the bilateral axillae, inguinal folds, and mons pubis region. A confusing laboratory marker with HS was observed in this case. IgG4 has the potential to inhibit or activate inflammation depending on the context, and so IgG4 elevation has been noted in varying disease states. IgG4 elevation is observed in chronic inflammatory states and may represent a compensatory response by the body. While no other cases have reported the association between HS and IgG4 elevation, IgG levels have been found to reflect HS disease severity. Therefore, IgG4 could play a potential role in HS disease monitoring, and awareness of this association is important for providers when managing patients with HS.
Case report: Neoadjuvant-intent pembrolizumab resulted in complete response in a xeroderma pigmentosum patient with locally advanced resectable cutaneous squamous cell carcinoma of the nose
Authors: Zalaquett Nader G. , Kreidieh Lara , Youssef Bassem , Mourad Marc , Kreidieh Firas
Published: October 2024

Background

Anti-PD1 antibodies have gained popularity in the treatment of skin cancers. These drugs have been FDA approved for treatment of cutaneous melanoma and unresectable/metastatic squamous cell carcinoma of the skin. However, the use of anti-PD1 antibodies is not established for resectable cutaneous squamous cell carcinoma, as the mainstay treatment is surgical excision.

Case

A 49-year-old female with Xeroderma Pigmentosum presented with an ulcerating lateral nasal mass causing obstruction. Biopsy confirmed cutaneous squamous cell carcinoma and was staged as IVA (T2N2cM0) based on PET-CT findings, which showed a 2.7 × 2.3 cm left nasal mass and radiotracer-avid cervical lymph nodes. Despite surgical recommendations, the patient declined surgery due the expected morbidity and disfigurement. Instead, she received neoadjuvant Pembrolizumab (200 mg IV every 3 weeks). After two cycles, PET-CT and MRI showed significant reduction in the nasal mass and decreased cervical lymph node involvement. On physical exam, the nasal lesion had resolved. Multidisciplinary tumor board discussion recommended radiation therapy instead of neck dissection, considering the patient's clinical response and potential surgical morbidity. After a third Pembrolizumab cycle, she received 66 Gy in 33 fractions, followed by continued adjuvant immunotherapy.
A metagenomic approach to demystify the anaerobic digestion black box and achieve higher biogas yield: a review
Authors: Ostos Iván , Flórez-Pardo Luz Marina , Camargo Carolina
Published: October 2024

The increasing reliance on fossil fuels and the growing accumulation of organic waste necessitates the exploration of sustainable energy alternatives. Anaerobic digestion (AD) presents one such solution by utilizing secondary biomass to produce biogas while reducing greenhouse gas emissions. Given the crucial role of microbial activity in anaerobic digestion, a deeper understanding of the microbial community is essential for optimizing biogas production. While metagenomics has emerged as a valuable tool for unravelling microbial composition and providing insights into the functional potential in biodigestion, it falls short of interpreting the functional and metabolic interactions, limiting a comprehensive understanding of individual roles in the community. This emphasizes the significance of expanding the scope of metagenomics through innovative tools that highlight the often-overlooked, yet crucial, role of microbiota in biomass digestion. These tools can more accurately elucidate microbial ecological fitness, shared metabolic pathways, and interspecies interactions. By addressing current limitations and integrating metagenomics with other omics approaches, more accurate predictive techniques can be developed, facilitating informed decision-making to optimize AD processes and enhance biogas yields, thereby contributing to a more sustainable future.
Integrated gut microbiome and metabolomic analyses elucidate the therapeutic mechanisms of Suanzaoren decoction in insomnia and depression models
Authors: Zhang Hongxiong , Gao Taixiang , Zhao Feng , Wang Nan , Li Zhixuan , Qin Xuemei , Liu Ying , Wang Rui
Published: October 2024

Insomnia and depression are psychiatric disorders linked to substantial health burdens. The gut microbiome and metabolomic pathways are increasingly recognized as key contributors to these conditions’ pathophysiology. Suanzaoren Decoction (SZRD), a traditional Chinese herbal formulation, has demonstrated significant therapeutic benefits for both insomnia and depression. This study aims to elucidate the mechanistic effects of SZRD on insomnia and depression by integrating gut microbiome and metabolomic analyses and to assess the differential impacts of SZRD dosages. Using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC–MS), we identified 66 chemical constituents within SZRD. Behavioral assays indicated that low-dose SZRD (LSZRD) significantly ameliorated insomnia symptoms in rat models, whereas high-dose SZRD (HSZRD) markedly improved depressive behaviors. 16S rRNA sequencing revealed that SZRD modulated gut microbiome dysbiosis induced by insomnia and depression, characterized by an increased abundance of short-chain fatty acid (SCFA)-producing genera. Metabolomic profiling demonstrated reduced plasma amino acid metabolites and disrupted γ-aminobutyric acid (GABA) and L-glutamic acid metabolism in the hippocampus of affected rats. SZRD administration restored fecal SCFA levels and ameliorated metabolic imbalances in both plasma and hippocampal tissues. These findings underscore the pivotal role of gut microbiome modulation and metabolic regulation in the therapeutic effects of SZRD, providing a scientific basis for its use in treating insomnia and depression.
Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children’s cancer group ALL-2015 protocol: a single center results
Authors: Chen Xia , Yu Jie
Published: October 2024

Introduction

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children’s Cancer Group ALL-2015 protocol at the Children’s Hospital of Chongqing Medical University.

Methods

The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS.

Results

As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse.

Discussion

Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children’s Cancer Group ALL-2015 protocol at the Children’s Hospital of Chongqing Medical University.
The cardiopulmonary benefits of physiologically based cord clamping persist for at least 8 hours in lambs with a diaphragmatic hernia
Authors: Riddington Paige J. , DeKoninck Philip L. J. , Thio Marta , Roberts Calum T. , Bhatia Risha , Dekker Janneke , Kashyap Aidan J. , Amberg Benjamin J. , Rodgers Karyn A. , Thiel Alison M. , Nitsos Ilias , Zahra Valerie A. , Hodges Ryan J. , Hooper Stuart B. , Crossley Kelly J.
Published: October 2024

Introduction

Infants with congenital diaphragmatic hernia can suffer severe respiratory insufficiency and pulmonary hypertension after birth. Aerating the lungs before removing placental support (physiologically based cord clamping, PBCC) increases pulmonary blood flow (PBF) and reduces pulmonary vascular resistance (PVR) in lambs with a diaphragmatic hernia (DH). We hypothesized that these benefits of PBCC persist for at least 8 h after birth.

Methods

At ∼138 days of gestation age (dGA), 21 lambs with a surgically induced left-sided DH (∼86 dGA) were delivered via cesarean section. The umbilical cord was clamped either before ventilation onset (immediate cord clamping, ICC, n = 9) or after achieving a tidal volume of 4 ml/kg, with a maximum delay of 10 min (PBCC, n = 12). The lambs were ventilated for 8 h, initially with conventional mechanical ventilation, but were switched to high-frequency oscillatory ventilation after 30 min if required. Ventilatory parameters, cardiopulmonary physiology, and arterial blood gases were measured throughout the study.

Results

PBF increased after ventilation onset in both groups and was higher in the PBCC DH lambs than the ICC DH lambs at 8 h (5.2 ± 1.2 vs. 1.9 ± 0.3 ml/min/g; p < 0.05). Measured over the entire 8-h ventilation period, PBF was significantly greater (p = 0.003) and PVR was significantly lower (p = 0.0002) in the PBCC DH lambs compared to the ICC DH lambs. A high incidence of pneumothoraces in both the PBCC (58%) and ICC (55%) lambs contributed to a reduced sample size at 8 h (ICC n = 4 and PBCC n = 4).

Conclusion

Compared with ICC, PBCC increased PBF and reduced PVR in DH lambs and the effects were sustained for at least 8 h after ventilation onset.
Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354
Authors: Rees Tayla A. , Buttle Benjamin J. , Tasma Zoe , Yang Sung-Hyun , Harris Paul W. R. , Walker Christopher S.
Published: October 2024

Type 2 diabetes (T2D) and obesity are prevalent metabolic disorders affecting millions of individuals worldwide. A new effective therapeutic drug called tirzepatide for the treatment of obesity and T2D is a dual agonist of the GIP receptor and GLP-1 receptor. Tirzepatide is clinically more effective than GLP-1 receptor agonists but the reasons why are not well understood. Tirzepatide reportedly stimulates the GIP receptor more potently than the GLP-1 receptor. However, tirzepatide signaling has not been thoroughly investigated at the E354 (wildtype) or Q354 (E354Q) GIP receptor variants. The E354Q variant is associated increased risk of T2D and lower body mass index. To better understand GIP receptor signaling we characterized the activity of endogenous agonists and tirzepatide at both GIP receptor variants. Using Cos7 cells we examined wildtype and E354Q GIP receptor signaling, analyzing cAMP and IP1 accumulation as well as AKT, ERK1/2 and CREB phosphorylation. GIP(1-42) and GIP(1-30)NH2 displayed equipotent effects on these pathways excluding CREB phosphorylation where GIP(1-30)NH2 was more potent than GIP(1-42) at the E354Q GIP receptor. Tirzepatide favored cAMP signaling at both variants. These findings indicate that tirzepatide is a biased agonist towards Gαs signaling and suggests it equally activates the wildtype and E354Q GIP receptor variants. We also observed differences between the pharmacology of the GIP receptor variants with endogenous peptides, which may help to explain differences in phenotype. These findings contribute to a comprehensive understanding of GIP receptor signaling, and will aid development of therapies combating T2D and obesity.