bluuebunny/crossref_metadata_2025 huggingface dataset:
Permafrost trapped natural gas in Svalbard, Norway
Authors: Birchall Thomas , Jochmann Malte , Betlem Peter , Senger Kim , Hodson Andrew , Olaussen Snorre
Published: December 2023

Permafrost is widespread in the High Arctic, including the Norwegian archipelago of Svalbard. The uppermost permafrost intervals have been well studied, but the processes at its base and the impacts of the underlying geology have been largely overlooked. More than a century of coal, hydrocarbon, and scientific drilling through the permafrost in Svalbard shows that accumulations of natural gas trapped at the base of permafrost are common. These accumulations exist in several stratigraphic intervals throughout Svalbard and show both thermogenic and biogenic origins. The gas, combined with the relatively young permafrost age, is evidence of ongoing gas migration throughout Svalbard. The accumulation sizes are uncertain, but one case demonstrably produced several million cubic metres of gas over 8 years. Heavier gas encountered in two boreholes on Hopen may be situated in the gas hydrate stability zone. While permafrost is demonstrably ice-saturated and acting as seal to gas in lowland areas, in the highlands permafrost is more complex and often dry and permeable. Svalbard shares a similar geological and glacial history with much of the Circum-Arctic, suggesting that sub-permafrost gas accumulations are regionally common. With permafrost thawing in the Arctic, there is a risk that the impacts of releasing of methane trapped beneath permafrost will lead to positive climatic feedback effects.
The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease
Authors: Demir And , Böber Ece , Darcan Sükran , Aydın Adem , Stenman Ulf-Håkan , Büyükgebiz Atilla , Hero Matti
Published: December 2023

Objectives

Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies.

Methods

We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy.

Results

FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively).

Conclusion

FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.
Genetic variants of ERBB4 gene and risk of gestational diabetes mellitus: a susceptibility and diagnostic nomogram study
Authors: Li Ruiqi , Wang Yukun , Yang Lin , Zhong Ping , Huang Gongchen , Liang Qiulian , Yu Xiangyuan
Published: December 2023

Introduction

Gestational diabetes (GDM) is one of the common complications of female pregnancy, which seriously affects the health of mothers and their offspring. So far, the etiology has not been fully clarified.

Methods

A case-control study was conducted to clarify the relationship between Erb-b2 receptor tyrosine kinase 4 (ERBB4) functional tag genetic variants (rs1595064, rs1595065, rs1595066 and rs6719645) and the risk of GDM. Associations between variants and GDM risk were evaluated with the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Subsequently, the false-positive reporting probability (FPRP), multi-factor dimension reduction (MDR) and bioinformatics analysis were adopted to confirm the significant associations. A nomogram model was constructed to predict the risk of GDM.

Results

Association analysis demonstrated that rs1595066 TT genotype performed a protective effect on GDM risk among all subjects (TT vs. CC: adjusted OR = 0.60, 95% CI = 0.38 - 0.94, P = 0.026; TT vs. CC/CT: adjusted OR = 0.61, 95% CI = 0.40 - 0.95, P = 0.027). Meanwhile, stratified analysis showed that rs1595066 TT can also reduce the GDM risk in age > 30.09 years old, pre-pregnancy BMI > 22.23 Kg/m2, SBP ≤ 110.08 mmHg, etc subgroups. Interactions between rs1595066 and DBP (Pinteraction = 0.01), FPG (Pinteraction < 0.001) and HbA1c (Pinteraction < 0.001) were detected. The FPRP analysis confirmed that association between rs1595066 and GDM risk in subjects of FPG < 4.79 mmol/L (P = 0.199) is true. The MDR analysis showed that rs1595066 was the best single locus model while the 4-loci model was the best multiple factors model to predict GDM risk. Functional prediction revealed that rs1595066 may disturb the stability of miRNA-mRNA binding. The predictive nomogram model has a well consistence and acceptable discriminative ability with a diagnosed AUC of 0.813.

Discussion

ERBB4 variants can change an individual’s susceptibility to GDM via the interaction of gene-gene, gene-environment and changes in the regulatory effects of miRNAs on ERBB4 expression.
The effect of ovarian injection of autologous platelet rich plasma in patients with poor ovarian responder: a systematic review and meta-analysis
Authors: Li Xuanling , Liu Huicong , Lin Guangyao , Xu Lianwei
Published: December 2023

Objective

To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence.

Methods

According to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials.

Results

Add up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p<0.0001). We compared the relevant data of patients before and after treatment after 2 months of intervention. It can be seen that ovarian injection of PRP treatment for 2 months has better effects in reducing FSH levels, increasing AMH levels, increasing antral follicle count, and increasing the number of oocytes and embryos (p<0.05). When the dose of PRP injected into each ovary was ≥ 4ml, there was also a significant correlation (p<0.05) with improving the number of AFC, oocytes and embryos. Significant heterogeneity existed among the studies.

Conclusion

The pooled results suggest that intra-ovarian injection of PRP can promote ovarian regeneration and improve the reproductive outcomes of patients with ovarian dysfunction. This therapy may have significant clinical potential in improving sex hormone levels, increasing AFC, oocyte count, and embryo count. However, this findings still requires more rigorous and extensive trials worldwide to determine the value of intra-ovarian injection of PRP in POR patients.

Systematic review registration

https://www.crd.york.ac.uk, Identifier CRD42023451232.
Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment
Authors: Cattoni Alessandro , Nicolosi Maria Laura , Capitoli Giulia , Gadda Alberto , Molinari Silvia , Louka Sotiris , Buonsante Andrea , Orlandi Simona , Salierno Gianluca , Bellani Iacopo , Vendemini Francesca , Ottaviano Giorgio , Gaiero Alberto , Fichera Graziella , Biondi Andrea , Balduzzi Adriana
Published: December 2023

Introduction

Impaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.

Methods

Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.

Results

Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT (p 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (p<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan (p 0.024). Chemo-only regimens were associated with statistically larger TV (p <0.001), higher testosterone (p 0.008) and lower gonadotropin levels (p <0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).

Conclusions

a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.
Non-linear association of triglyceride-glucose index with prevalence of prediabetes and diabetes: a cross-sectional study
Authors: Zhang Linhao , Zeng Ling
Published: December 2023

Background

The Triglyceride-glucose (TyG) index has been acknowledged as a convenient, cost-effective, and relatively simple marker for insulin resistance (IR). Meanwhile, prediabetes, described as an asymptomatic, moderately hyperglycemic state, tends to be more prevalent than diabetes. Thus, the objective of this study was to explore the relationship between the TyG index and the prevalence of both prediabetes and diabetes within the U.S. population.

Methods

This study utilized a cross-sectional dataset derived from the National Health and Nutrition Survey (NHANES) spanning 1999 to 2018. The subjects were individuals aged 18 years and above, who had available fasting glucose and fasting triglyceride information, permitting a diagnosis of prediabetes or diabetes. The TyG index was computed using laboratory data, and participants were subsequently categorized into quartiles based on this information. The relationship between the TyG index and the prevalence of prediabetes and diabetes was investigated using logistic regression analysis.

Results

Out of the 25,159 participants, 23.88% were found to have prediabetes, while 16.22% were diagnosed with diabetes. After adjusting for confounding factors, a linear increase in relative odds was observed in Q2 (OR: 1.69; 95% CI: 1.52, 1.89), Q3 (OR: 2.57; 95% CI: 2.30, 2.88), and Q4 (OR: 4.88; 95% CI: 4.33, 5.49) groups in comparison to the reference group, Q1. In addition, a non-linear relationship was observed between the TyG index and the prevalence of prediabetes and diabetes. Specifically, patients with a TyG index greater than 8.00 overall exhibited a significantly higher risk of prediabetes and diabetes, confirming that an increase in the TyG index is associated with a corresponding increase in risk. However, this shift showed gender-specific variations; the threshold was observed at 8.00 in males but shifted to 9.00 in females.

Conclusion

The TyG index demonstrated a non-linear positive correlation with both prediabetes and diabetes. This suggests that maintaining the TyG index at a certain, reduced level could potentially aid in preventing the onset of prediabetes and diabetes.
The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study
Authors: Zhang Ying , Li Hao , Zhu Shanshan , Jiang Shengfang , Zhao Wenxian , Wang Xiaoning , Tian Liu , Zhao Guangming , He Nongqiao , Diao Honglu , Cao Hong , Zhang Changjun
Published: December 2023

Objective

To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.

Design

A retrospective cohort study.

Setting

Tertiary-care academic medical center.

Population

A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.

Methods

A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.

Main outcome measures

The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.

Results

We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.

Conclusion

The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.
Burden of type 1 and type 2 diabetes and high fasting plasma glucose in Europe, 1990-2019: a comprehensive analysis from the global burden of disease study 2019
Authors: Liang Dong , Cai Xiuli , Guan Qing , Ou Yangjiang , Zheng Xiaoxin , Lin Xiuquan
Published: December 2023

Introduction

With population aging rampant globally, Europe faces unique challenges and achievements in chronic disease prevention. Despite this, comprehensive studies examining the diabetes burden remain absent. We investigated the burden of type 1 and type 2 diabetes, alongside high fasting plasma glucose (HFPG), in Europe from 1990-2019, to provide evidence for global diabetes strategies.

Methods

Disease burden estimates due to type 1 and type 2 diabetes and HFPG were extracted from the GBD 2019 across Eastern, Central, and Western Europe. We analyzed trends from 1990 to 2019 by Joinpoint regression, examined correlations between diabetes burden and Socio-demographic indices (SDI), healthcare access quality (HAQ), and prevalence using linear regression models. The Population Attributable Fraction (PAF) was used to described diabetes risks.

Results

In Europe, diabetes accounted for 596 age-standardized disability-adjusted life years (DALYs) per 100,000 people in 2019, lower than globally. The disease burden from type 1 and type 2 diabetes was markedly higher in males and escalated with increasing age. Most DALYs were due to type 2 diabetes, showing regional inconsistency, highest in Central Europe. From 1990-2019, age-standardized DALYs attributable to type 2 diabetes rose faster in Eastern and Central Europe, slower in Western Europe. HFPG led to 2794 crude DALYs per 100,000 people in 2019. Type 1 and type 2 diabetes burdens correlated positively with diabetes prevalence and negatively with SDI and HAQ. High BMI (PAF 60.1%) and dietary risks (PAF 34.6%) were significant risk factors.

Conclusion

Europe’s diabetes burden was lower than the global average, but substantial from type 2 diabetes, reflecting regional heterogeneity. Altered DALYs composition suggested increased YLDs. Addressing the heavy burden of high fasting plasma glucose and the increasing burden of both types diabetes necessitate region-specific interventions to reduce type 2 diabetes risk, improve healthcare systems, and offer cost-effective care.
Evolution and drivers of secondary suspended rivers in typical wandering sections of the lower Yellow River from 1960–2021
Authors: Xu Linjuan , Li Junhua , Xu Haifan , Zhang Xiangping , Lai Ruixun , Zhang Xiang , Gao Xiangyu
Published: December 2023

The secondary suspended river increases the probability of the occurrence of “Heng river”, “Xie river” and “Gun river” in the lower Yellow River, and is the main factor threatening the safety of human life and property in the Yellow River levee and beach area. Here, the Dongbatou–Gaocun section of the severe secondary suspended river in the lower Yellow River was taken as the research object. The trend and periodicity of the evolution characteristics of the secondary suspended river in the study area from 1960–2021 were systematically analyzed using the Theil-Sen estimator and wavelet analysis, and the factors influencing its development were quantitatively explored. Over the past 62 years, development of secondary suspended rivers can be divided into four stages: initial formation (1960–1973), slow development (1974–1986), rapid development (1987–1999) and stable (2000–2021) periods. The evolution period of the beach transverse gradient differed significantly before and after operation of Xiaolangdi Reservoir commenced, prior to which there was a first main period of 31 years followed by a second main period of 21 years. Development of secondary suspended rivers was primarily related to floodplain flooding and human activity. When the inflow sediment coefficient of a floodplain flood (ζ) was < 0.04 and the floodplain coefficient was < 1.29, the secondary suspended river was relieved; when ζ > 0.04 or ζ < 0.04 and the floodplain coefficient was > 1.29, the secondary suspended river was intensified. The production levees have exacerbated development of secondary suspended rivers to some extent.
Direct antigen presentation is the canonical pathway of cytomegalovirus CD8 T-cell priming regulated by balanced immune evasion ensuring a strong antiviral response
Authors: Büttner Julia K. , Becker Sara , Fink Annette , Brinkmann Melanie M. , Holtappels Rafaela , Reddehase Matthias J. , Lemmermann Niels A.
Published: December 2023

CD8 T cells are important antiviral effectors in the adaptive immune response to cytomegaloviruses (CMV). Naïve CD8 T cells can be primed by professional antigen-presenting cells (pAPCs) alternatively by “direct antigen presentation” or “antigen cross-presentation”. In the case of direct antigen presentation, viral proteins are expressed in infected pAPCs and enter the classical MHC class-I (MHC-I) pathway of antigen processing and presentation of antigenic peptides. In the alternative pathway of antigen cross-presentation, viral antigenic material derived from infected cells of principally any cell type is taken up by uninfected pAPCs and eventually also fed into the MHC class-I pathway. A fundamental difference, which can be used to distinguish between these two mechanisms, is the fact that viral immune evasion proteins that interfere with the cell surface trafficking of peptide-loaded MHC-I (pMHC-I) complexes are absent in cross-presenting uninfected pAPCs. Murine cytomegalovirus (mCMV) models designed to disrupt either of the two presentation pathways revealed that both are possible in principle and can substitute each other. Overall, however, the majority of evidence has led to current opinion favoring cross-presentation as the canonical pathway. To study priming in the normal host genetically competent in both antigen presentation pathways, we took the novel approach of enhancing or inhibiting direct antigen presentation by using recombinant viruses lacking or overexpressing a key mCMV immune evasion protein. Against any prediction, the strongest CD8 T-cell response was elicited under the condition of intermediate direct antigen presentation, as it exists for wild-type virus, whereas the extremes of enhanced or inhibited direct antigen presentation resulted in an identical and weaker response. Our findings are explained by direct antigen presentation combined with a negative feedback regulation exerted by the newly primed antiviral effector CD8 T cells. This insight sheds a completely new light on the acquisition of viral immune evasion genes during virus-host co-evolution.
Trafficking and effect of released DNA on cGAS-STING signaling pathway and cardiovascular disease
Authors: Zhou Zimo , Ou-yang Changhan , Chen Qingjie , Ren Zhanhong , Guo Xiying , Lei Min , Liu Chao , Yang Xiaosong
Published: December 2023

Evidence from clinical research and animal studies indicates that inflammation is an important factor in the occurrence and development of cardiovascular disease (CVD). Emerging evidence shows that nucleic acids serve as crucial pathogen-associated molecular patterns (PAMPs) or non-infectious damage-associated molecular patterns (DAMPs), are released and then recognized by pattern recognition receptors (PRRs), which activates immunological signaling pathways for host defense. Mechanistically, the released nucleic acids activate cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING) to promote type I interferons (IFNs) production, which play an important regulatory function during the initiation of an innate immune response to various diseases, including CVD. This pathway represents an essential defense regulatory mechanism in an organism’s innate immune system. In this review, we outline the overall profile of cGAS-STING signaling, summarize the latest findings on nucleic acid release and trafficking, and discuss their potential role in CVD. This review also sheds light on potential directions for future investigations on CVD.
Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events
Authors: Altan Mehmet , Li Quan-Zhen , Wang Qi , Vokes Natalie I. , Sheshadri Ajay , Gao Jianjun , Zhu Chengsong , Tran Hai T. , Gandhi Saumil , Antonoff Mara B. , Swisher Stephen , Wang Jing , Byers Lauren A. , Abdel-Wahab Noha , Franco-Vega Maria C. , Wang Yinghong , Lee J. Jack , Zhang Jianjun , Heymach John V.
Published: December 2023

The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were associated with the subsequent development of organ-specific irAEs. Notably, ACHRG IgM was associated with pneumonitis, anti-cytokeratin 19 IgM with dermatitis, and anti-thyroglobulin IgG with hepatitis. These antibodies merit further investigation as potential biomarkers for identifying high-risk populations for irAEs and/or monitoring irAEs during immunotherapy treatment.

Trial registration

ClinicalTrials.gov identifier: NCT03391869.
MGFGNet: an automatic underwater acoustic target recognition method based on the multi-gradient flow global feature enhancement network
Authors: Chen Zhe , Tang Jianxun , Qiu Hongbin , Chen Mingsong
Published: December 2023

The recognition of underwater acoustic targets plays a crucial role in marine vessel monitoring. However, traditional underwater target recognition models suffer from limitations, including low recognition accuracy and slow prediction speed. To address these challenges, this article introduces a novel approach called the Multi-Gradient Flow Global Feature Enhancement Network (MGFGNet) for automatic recognition of underwater acoustic targets. Firstly, a new spectrogram feature fusion scheme is presented, effectively capturing both the physical and brain-inspired features of the acoustic signal. This fusion technique enhances the representation of underwater acoustic data, resulting in more accurate recognition results. Moreover, MGFGNet utilizes the multi-gradient flow network and incorporates a multi-dimensional feature enhancement technique to achieve fast and precise end-to-end recognition. Finally, a loss function is introduced to mitigate the influence of unbalanced data sets on model recognition performance using Taylor series. This further enhances model recognition performance. Experimental evaluations were conducted on the DeepShip dataset to assess the performance of our proposed method. The results demonstrate the superiority of MGFGNet, achieving a recognition rate of 99.1%, which significantly surpasses conventional methods. Furthermore, MGFGNet exhibits improved efficiency compared to the widely used ResNet18 model, reducing the parameter count by 51.28% and enhancing prediction speed by 33.9%. Additionally, we evaluated the generalization capability of our model using the ShipsEar dataset, where MGFGNet achieves a recognition rate of 99.5%, indicating its superior performance when applied to unbalanced data. The promising results obtained in this study highlight the potential of MGFGNet in practical applications.
Pulmonary tuberculosis and multidrug-resistant Mycobacterium tuberculosis in northwestern Ethiopia: a hospital-based cross-sectional study among presumptive pulmonary tuberculosis patients
Authors: Wubu Birhanu , Jemal Mohabaw , Million Yihenew , Gizachew Mucheye
Published: December 2023

Introduction

Border areas are important sites for disseminating Mycobacterium tuberculosis among individuals living in such areas. This study examined patients with suspected pulmonary tuberculosis (PTB) visiting the Abrihajira and Metema hospitals in northwest Ethiopia to investigate the prevalence of rifampicin-resistant Mycobacterium tuberculosis (RR-MTB), multidrug-resistant Mycobacterium tuberculosis (MDR-MTB), and risk factors related to Mycobacterium tuberculosis infection.

Methods

A hospital-based cross-sectional study was conducted from February to August 2021 among 314 PTB presumptive patients. Xpert MTB/RIF and line probe assays (LPA) were used to process sputum samples. Data were imported into the Epi-Data 3.1 program and exported to Statistical Package for the Social Sciences (SPSS) version 20.0 (SPSS, Chicago, IL, United States) to conduct the analysis. A logistic regression analysis was used to investigate the relationship between the dependent and independent variables. A value of p of <0.05 denoted statistical significance.

Results

Of the total (314) PTB presumptive patients who participated in this study, 178 (56.69%) were men, and 165 (52.5%) were from 25 to 50 years of age with a median age of 35.00 (inter-quartile: 25–45 years). Among all patients, 12.7% had PTB by Gene Xpert and 7/314 (2.23%) were resistant to rifampicin. Among patients enrolled, 4/314 (1.27%) had MDR-MTB (resistant to RIF and INH) by LPA. Regarding the risk factors assessed, primary level of education, sputum production, night sweating, respiratory disorder, contact history of TB, history of MDR-MTB infection, history of alcohol use, and cigarette smoking showed statistical significance with the prevalence of PTB (p ≤ 0.05).

Discussion

This study observed a high prevalence of PTB, RR-MTB, and MDR-MTB compared with many other previous studies conducted in Ethiopia. Among the assessed risk factors that could be associated with the prevalence of PTB, eight were statistically significant. This prevalence, resistance, and statistically significant variables are the evidence to which more emphasis should be given to the country’s border areas.
Distributed team processes in healthcare services: a scoping review
Authors: Eid Jarle , Brattebø Guttorm , Jacobsen Johan K. , Espevik Roar , Johnsen Bjørn Helge
Published: December 2023

Objective

High-quality healthcare services is delivered by teams rather than individuals and depends heavily on multidisciplinary cooperation between dispersed healthcare professionals. The aim of this scoping review is to identify common barriers and innovative applications of technology supporting team processes and patient safety, in geographically dispersed healthcare services.

Methods

Studies were identified from searches in APA PsychINFO, Epistemonikos and Medline databases, from 2010 to 2023. A detailed search strategy was performed, and studies were included, based on prior established criteria.

Results

Among the 19 studies that fulfilled our inclusion criteria, the majority (85%) were from Europe or North America, and most studies (53%) were quantitative, with a cross-sectional study design. Several reported observed distributed team processes in training and education. Most studies described barriers and detailed how innovative approaches and technological solutions were introduced to improve communication, coordination, and shared mental models in distributed healthcare settings. A small proportion of studies (16%) used health services data to examine interpersonal exchange and team processes.

Conclusion

The scoping review offer recommendations to enhance future research on distributed team processes in healthcare services.
Rosacea pathogenesis and therapeutics: current treatments and a look at future targets
Authors: Fisher Garrett W. , Travers Jeffrey B. , Rohan Craig A.
Published: December 2023

Rosacea is a chronic inflammatory skin condition associated with a significant health and economic burden from costs and loss of productivity due to seeking medical treatment. The disease encompasses multiple phenotypic manifestations involving a complex and multi-variate pathogenesis. Although the pathophysiology of rosacea is not completely understood, ongoing research is continually elucidating its mechanisms. In this review, current concepts of rosacea pathogenesis will be addressed which involve skin barrier and permeability dysfunction, the innate and adaptive immune systems, and the neurovascular system. More specifically, the cathelicidin pathway, transient potential receptor channels, mast cells, and the NLRP3 inflammasome pathway are various targets of current pharmacologic regimens. Future therapies may seek different mechanisms to act on current treatment targets, like the potential use of JAK/STAT inhibitors in ameliorating skin barrier dysfunction or TLR antagonists in alleviating cathelicidin mediated inflammation. Other potential treatments aim for entirely different molecular targets such as microvesicle particle mediated local and systemic inflammation. Ultimately rosacea is associated with a significant health and economic burden which warrants deeper research into its pathogenesis and resultant new treatment discovery.
CRISPR/Cas12a toolbox for genome editing in Methanosarcina acetivorans
Authors: Zhu Ping , Somvanshi Tejas , Bao Jichen , Scheller Silvan
Published: December 2023

Methanogenic archaea play an important role in the global carbon cycle and may serve as host organisms for the biotechnological production of fuels and chemicals from CO2 and other one-carbon substrates. Methanosarcina acetivorans is extensively studied as a model methanogen due to its large genome, versatile substrate range, and available genetic tools. Genome editing in M. acetivorans via CRISPR/Cas9 has also been demonstrated. Here, we describe a user-friendly CRISPR/Cas12a toolbox that recognizes T-rich (5′-TTTV) PAM sequences. The toolbox can manage deletions of 3,500 bp (i.e., knocking out the entire frhADGB operon) and heterologous gene insertions with positive rates of over 80%. Cas12a-mediated multiplex genome editing was used to edit two separate sites on the chromosome in one round of editing. Double deletions of 100 bp were achieved, with 8/8 of transformants being edited correctly. Simultaneous deletion of 100 bp at one site and replacement of 100 bp with the 2,400 bp uidA expression cassette at a separate site yielded 5/6 correctly edited transformants. Our CRISPR/Cas12a toolbox enables reliable genome editing, and it can be used in parallel with the previously reported Cas9-based system for the genetic engineering of the Methanosarcina species.
Bacterial extracellular vesicles: towards realistic models for bacterial membranes in molecular interaction studies by surface plasmon resonance
Authors: Bril’kov Maxim S. , Stenbakk Victoria , Jakubec Martin , Vasskog Terje , Kristoffersen Tone , Cavanagh Jorunn Pauline , Ericson Johanna U. , Isaksson Johan , Flaten Gøril Eide
Published: December 2023

One way to mitigate the ongoing antimicrobial resistance crisis is to discover and develop new classes of antibiotics. As all antibiotics at some point need to either cross or just interact with the bacterial membrane, there is a need for representative models of bacterial membranes and efficient methods to characterize the interactions with novel molecules -both to generate new knowledge and to screen compound libraries. Since the bacterial cell envelope is a complex assembly of lipids, lipopolysaccharides, membrane proteins and other components, constructing relevant synthetic liposome-based models of the membrane is both difficult and expensive. We here propose to let the bacteria do the hard work for us. Bacterial extracellular vesicles (bEVs) are naturally secreted by Gram-negative and Gram-positive bacteria, playing a role in communication between bacteria, as virulence factors, molecular transport or being a part of the antimicrobial resistance mechanism. bEVs consist of the bacterial outer membrane and thus inherit many components and properties of the native outer cell envelope. In this work, we have isolated and characterized bEVs from one Escherichia coli mutant and three clinical strains of the ESKAPE pathogens Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The bEVs were shown to be representative models for the bacterial membrane in terms of lipid composition with speciesstrain specific variations. The bEVs were further used to probe the interactions between bEV and antimicrobial peptides (AMPs) as model compounds by Surface Plasmon Resonance (SPR) and provide proof-of-principle that bEVs can be used as an easily accessible and highly realistic model for the bacterial surface in interaction studies. This further enables direct monitoring of the effect induced by antibiotics, or the response to host-pathogen interactions.
Severe central nervous system demyelination in Sanfilippo disease
Authors: Taherzadeh Mahsa , Zhang Erjun , Londono Irene , De Leener Benjamin , Wang Sophie , Cooper Jonathan D. , Kennedy Timothy E. , Morales Carlos R. , Chen Zesheng , Lodygensky Gregory A. , Pshezhetsky Alexey V.
Published: December 2023

Introduction

Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC HgsnatP304L and post-mortem brain samples of MPS III patients.

Methods

Brain and spinal cord tissues of human MPS III patients, 6-month-old HgsnatP304L mice and age- and sex-matching wild type mice were analyzed by immunofluorescence to assess levels of myelin-associated proteins, primary and secondary storage materials, and levels of microgliosis. Corpus callosum (CC) region was studied by transmission electron microscopy to analyze axon myelination and morphology of oligodendrocytes and microglia. Mouse brains were analyzed ex vivo by high-filed MRI using Diffusion Basis Spectrum Imaging in Python-Diffusion tensor imaging algorithms.

Results

Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains of MPS IIIC mice and human MPS IIIC patients compared to healthy controls. Oligodendrocytes (OLs) in the CC of MPS IIIC mice were scarce, while examination of the remaining cells revealed numerous enlarged lysosomes containing heparan sulfate, GM3 ganglioside or “zebra bodies” consistent with accumulation of lipids and myelin fragments. In addition, OLs contained swollen mitochondria with largely dissolved cristae, resembling those previously identified in the dysfunctional neurons of MPS IIIC mice. Ex vivo Diffusion Basis Spectrum Imaging revealed compelling signs of demyelination (26% increase in radial diffusivity) and tissue loss (76% increase in hindered diffusivity) in CC of MPS IIIC mice.

Discussion

Our findings demonstrate an important role for white matter injury in the pathophysiology of MPS III. This study also defines specific parameters and brain regions for MRI analysis and suggests that it may become a crucial non-invasive method to evaluate disease progression and therapeutic response.
Utilizing MRI, [18F]FDG-PET and [89Zr]Zr-DFO-28H1 FAP-PET tracer to assess inflammation and fibrogenesis in a reproducible lung injury rat model: a multimodal imaging study
Authors: Boswinkel Milou , Raavé René , Veltien Andor , Scheenen Tom WJ , Fransén Petterson Nina , in ‘t Zandt René , Olsson Lars E. , von Wachenfeldt Karin , Heskamp Sandra , Mahmutovic Persson Irma
Published: December 2023

Objective

Accurate imaging biomarkers that indicate disease progression at an early stage are highly important to enable timely mitigation of symptoms in progressive lung disease. In this context, reproducible experimental models and readouts are key. Here, we aim to show reproducibility of a lung injury rat model by inducing disease and assessing disease progression by multi-modal non-invasive imaging techniques at two different research sites. Furthermore, we evaluated the potential of fibroblast activating protein (FAP) as an imaging biomarker in the early stage of lung fibrosis.

Methods

An initial lung injury rat model was set up at one research site (Lund University, Lund, Sweden) and repeated at a second site (Radboudumc, Nijmegen, The Netherlands). To induce lung injury, Sprague-Dawley rats received intratracheal instillation of bleomycin as one single dose (1,000 iU in 200 µL) or saline as control. Thereafter, longitudinal images were acquired to track inflammation in the lungs, at 1 and 2 weeks after the bleomycin challenge by magnetic resonance imaging (MRI) and [18F]FDG-PET. After the final [18F]FDG-PET scan, rats received an intravenous tracer [89Zr]Zr-DFO-28H1 (anti-FAP antibody) and were imaged at day 15 to track fibrogenesis. Upon termination, bronchoalveolar lavage (BAL) was performed to assess cell and protein concentration. Subsequently, the biodistribution of [89Zr]Zr-DFO-28H1 was measured ex vivo and the spatial distribution in lung tissue was studied by autoradiography. Lung sections were stained and fibrosis assessed using the modified Ashcroft score.

Results

Bleomycin-challenged rats showed body weight loss and increased numbers of immune cells and protein concentrations after BAL compared with control animals. The initiation and progression of the disease were reproduced at both research sites. Lung lesions in bleomycin-exposed rats were visualized by MRI and confirmed by histology. [18F]FDG uptake was higher in the lungs of bleomycin-challenged rats compared with the controls, similar to that observed in the Lund study. [89Zr]Zr-DFO-28H1 tracer uptake in the lung was increased in bleomycin-challenged rats compared with control rats (p = 0.03).

Conclusion

Here, we demonstrate a reproducible lung injury model and monitored disease progression using conventional imaging biomarkers MRI and [18F]FDG-PET. Furthermore, we showed the first proof-of-concept of FAP imaging. This reproducible and robust animal model and imaging experimental set-up allows for future research on new therapeutics or biomarkers in lung disease.
Changes in pain perception during pregnancy after one-time maximal physical exertion and an 8-week high-intensity interval training
Authors: Leźnicka Katarzyna , Gasiorowska Agata , Pawlak Maciej , Jażdżewska Aleksandra , Maciejewska-Skrendo Agnieszka , Chudecka Monika , Szumilewicz Anna
Published: December 2023

Background: Pain, a subjective sensation, poses a great challenge to the human body as a stressor. There is empirical evidence that moderate to intense physical activity increases pain tolerance and this may be critical during pregnancy for optimal pregnancy, fetal development, and delivery. To the best of our knowledge, it is the first study examining the changes in pain perception in pregnant women after a maximal progressive exercise test and after 8 weeks of high-intensity interval training (HIIT).

Methods: Thirty-five women with uncomplicated singleton pregnancies between 13 and 28 weeks of gestation participated in the study. The HIIT intervention was developed in accordance with the recommendations and available data on HIIT during pregnancy. The maximal progressive cardiopulmonary exercise test was performed on a cycle ergometer with an electronically controlled load. Pressure pain threshold and pressure pain tolerance were measured with an algometer.

Results: We found significant effects of the maximal exercise test and high-intensity interval training, such that the pregnant women had higher pain tolerance after the maximal exercise test than before and after the high-intensity interval training than the baseline.

Conclusion: Our results suggest that post-exercise analgesia may be important in pregnant women and that high-intensity interval training appears to be beneficial for pregnant women to improve their pain tolerance while being obstetrically safe. Increased pain tolerance before labor could lead to better management of pain during labor and in the postpartum and lactation periods. Increasing pregnant women’s awareness of this issue can improve their wellbeing and provide more comfort during labor.
Integrated comparative transcriptome and physiological analysis reveals the metabolic responses underlying genotype variations in NH4+ tolerance
Authors: Chen Haifei , Lv Wei , Zhang Wenqi , Zhao Jie , Zhang Quan , Zhang Zhenhua
Published: December 2023

Several mechanisms have been proposed to explain NH4+ toxicity. However, the core information about the biochemical regulation of plants in response to NH4+ toxicity is still lacking. In this study, the tissue NH4+ concentration is an important factor contributing to variations in plant growth even under nitrate nutrition and NH4+ tolerance under ammonium nutrition. Furthermore, NH4+ led to the reprogramming of the transcriptional profile, as genes related to trehalose-6-phosphate and zeatin biosynthesis were downregulated, whereas genes related to nitrogen metabolism, camalexin, stilbenoid and phenylpropanoid biosynthesis were upregulated. Further analysis revealed that a large number of genes, which enriched in phenylpropanoid and stilbenoid biosynthesis, were uniquely upregulated in the NH4+- tolerant ecotype Or-1. These results suggested that the NH4+-tolerant ecotype showed a more intense response to NH4+ by activating defense processes and pathways. Importantly, the tolerant ecotype had a higher 15NH4+ uptake and nitrogen utilization efficiency, but lower NH4+, indicating the tolerant ecotype maintained a low NH4+ level, mainly by promoting NH4+ assimilation rather than inhibiting NH4+ uptake. The carbon and nitrogen metabolism analysis revealed that the tolerant ecotype had a stronger carbon skeleton production capacity with higher levels of hexokinase, pyruvate kinase, and glutamate dehydrogenase activity to assimilate free NH4+, Taken together, the results revealed the core mechanisms utilized by plants in response to NH4+, which are consequently of ecological and agricultural importance.
Contrasting patterns of genetic and phenotypic divergence of two sympatric congeners, Phragmites australis and P. hirsuta, in heterogeneous habitats
Authors: Qiu Tian , Liu Zhiyuan , Li Haiyan , Yang Ji , Liu Bao , Yang Yunfei
Published: December 2023

Habitat heterogeneity leads to genome-wide differentiation and morphological and ecological differentiation, which will progress along the speciation continuum, eventually leading to speciation. Phragmites hirsuta and Phragmites australis are sympatric congeners that coexist in saline-alkaline meadow soil (SAS) and sandy soil (SS) habitats of the Songnen Meadow. The results provided genetic evidence for two separate species of reeds. Genetic diversity and spatial genetic structure supported the specialist-generalist variation hypothesis (SGVH) in these two sympatric reed species, suggesting that P. australis is a generalist and P. hirsuta is a habitat specialist. When we compared these different species with respect to phenotypic and genetic variation patterns in different habitats, we found that the phenotypic differentiation of P. australis between the two habitats was higher than that of P. hirsuta. Multiple subtle differences in morphology, genetic background, and habitat use collectively contribute to ecological success for similar congeners. This study provided evidence of the two reed congeners, which should contribute to their success in harsh environments.