bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol-mediated susceptibility to lung fibrosis is associated with group 2 innate lymphoid cells in mice
Authors: Chen Liang , Sun Rui , Lei Chao , Xu Zhishan , Song Yong , Deng Zhongbin
Published: June 2023

Chronic alcohol ingestion promotes acute lung injury and impairs immune function. However, the mechanisms involved are incompletely understood. Here, we show that alcohol feeding enhances bleomycin-induced lung fibrosis and inflammation via the regulation of type 2 innate immune responses, especially by group 2 innate lymphoid cells (ILC2s). Neuroimmune interactions have emerged as critical modulators of lung inflammation. We found alcohol consumption induced the accumulation of ILC2 and reduced the production of the neuropeptide calcitonin gene-related peptide (CGRP), primarily released from sensory nerves and pulmonary neuroendocrine cells (PNECs). CGRP potently suppressed alcohol-driven type 2 cytokine signals in vivo. Vagal ganglia TRPV1+ afferents mediated immunosuppression occurs through the release of CGRP. Inactivation of the TRPV1 receptor enhanced bleomycin-induced fibrosis. In addition, mice lacking the CGRP receptor had the increased lung inflammation and fibrosis and type 2 cytokine production as well as exaggerated responses to alcohol feeding. Together, these data indicate that alcohol consumption regulates the interaction of CGRP and ILC2, which is a critical contributor of lung inflammation and fibrosis.
Emerging roles of a chemoattractant receptor GPR15 and ligands in pathophysiology
Authors: Okamoto Yukari , Shikano Sojin
Published: June 2023

Chemokine receptors play a central role in the maintenance of immune homeostasis and development of inflammation by directing leukocyte migration to tissues. GPR15 is a G protein-coupled receptor (GPCR) that was initially known as a co-receptor for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), with structural similarity to other members of the chemoattractant receptor family. Since the discovery of its novel function as a colon-homing receptor of T cells in mice a decade ago, GPR15 has been rapidly gaining attention for its involvement in a variety of inflammatory and immune disorders. The recent identification of its natural ligand C10orf99, a chemokine-like polypeptide strongly expressed in gastrointestinal tissues, has established that GPR15-C10orf99 is a novel signaling axis that controls intestinal homeostasis and inflammation through the migration of immune cells. In addition, it has been demonstrated that C10orf99-independent functions of GPR15 and GPR15-independent activities of C10orf99 also play significant roles in the pathophysiology. Therefore, GPR15 and its ligands are potential therapeutic targets. To provide a basis for the future development of GPR15- or GPR15 ligand-targeted therapeutics, we have summarized the latest advances in the role of GPR15 and its ligands in human diseases as well as the molecular mechanisms that regulate GPR15 expression and functions.
The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism
Authors: Lang Marie B. , Leung Kit-Yi , Greene Nicholas D.E. , Malone Kerri M. , Saginc Gaye , Randi Anna M. , Kiprianos Allan , Maughan Robert T. , Pericleous Charis , Mason Justin C.
Published: June 2023

Objectives

The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium.

Methods

Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels.

Results

In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites.

Conclusion

We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium.
Maternal hepatic immunology during pregnancy
Authors: Yang Ling , Meng Yao , Shi Yuxiang , Fang Hongxu , Zhang Leying
Published: June 2023

The liver plays pivotal roles in immunologic responses, and correct hepatic adaptations in maternal immunology are required during pregnancy. In this review, we focus on anatomical and immunological maternal hepatic adaptations during pregnancy, including our recent reports in this area. Moreover, we summarize maternal pregnancy-associated liver diseases, including hyperemesis gravidarum; intrahepatic cholestasis of pregnancy; preeclampsia, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome; and acute fatty liver of pregnancy. In addition, the latest information about the factors that regulate hepatic immunology during pregnancy are reviewed for the first time, including human chorionic gonadotropin, estrogen, progesterone, growth hormone, insulin like growth factor 1, oxytocin, adrenocorticotropic hormone, adrenal hormone, prolactin, melatonin and prostaglandins. In summary, the latest progress on maternal hepatic anatomy and immunological adaptations, maternal pregnancy-associated diseases and the factors that regulate hepatic immunology during pregnancy are discussed, which may be used to prevent embryo loss and abortion, as well as pregnancy-associated liver diseases.
Multi-year molecular quantification and ‘omics analysis of Planktothrix-specific cyanophage sequences from Sandusky Bay, Lake Erie
Authors: McKindles Katelyn M. , Manes Makayla , Neudeck Michelle , McKay Robert Michael , Bullerjahn George S.
Published: June 2023

Introduction

Planktothrix agardhii is a microcystin-producing cyanobacterium found in Sandusky Bay, a shallow and turbid embayment of Lake Erie. Previous work in other systems has indicated that cyanophages are an important natural control factor of harmful algal blooms. Currently, there are few cyanophages that are known to infect P. agardhii, with the best-known being PaV-LD, a tail-less cyanophage isolated from Lake Donghu, China. Presented here is a molecular characterization of Planktothrix specific cyanophages in Sandusky Bay.

Methods and Results

Putative Planktothrix-specific viral sequences from metagenomic data from the bay in 2013, 2018, and 2019 were identified by two approaches: homology to known phage PaV-LD, or through matching CRISPR spacer sequences with Planktothrix host genomes. Several contigs were identified as having viral signatures, either related to PaV-LD or potentially novel sequences. Transcriptomic data from 2015, 2018, and 2019 were also employed for the further identification of cyanophages, as well as gene expression of select viral sequences. Finally, viral quantification was tested using qPCR in 2015–2019 for PaV-LD like cyanophages to identify the relationship between presence and gene expression of these cyanophages. Notably, while PaV-LD like cyanophages were in high abundance over the course of multiple years (qPCR), transcriptomic analysis revealed only low levels of viral gene expression.

Discussion

This work aims to provide a broader understanding of Planktothrix cyanophage diversity with the goals of teasing apart the role of cyanophages in the control and regulation of harmful algal blooms and designing monitoring methodology for potential toxin-releasing lysis events.
Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from pulmonary tuberculosis and tuberculous lymphadenitis patients in Northwest Ethiopia
Authors: Mekonnen Daniel , Munshea Abaineh , Nibret Endalkachew , Adnew Bethlehem , Herrera-Leon Silvia , Amor Aramendia Aranzazu , Benito Agustín , Abascal Estefanía , Jacqueline Camille , Aseffa Abraham , Herrera-Leon Laura
Published: June 2023

Background

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), is a chronic infectious disease with both pulmonary and extrapulmonary forms. This study set out to investigate and compare the genomic diversity and transmission dynamics of Mycobacterium tuberculosis (Mtb) isolates obtained from tuberculous lymphadenitis (TBLN) and pulmonary TB (PTB) cases in Northwest Ethiopia.

Methods

A facility-based cross-sectional study was conducted using two groups of samples collected between February 2021 and June 2022 (Group 1) and between June 2020 and June 2022 (Group 2) in Northwest Ethiopia. Deoxyribonucleic acid (DNA) was extracted from 200 heat-inactivated Mtb isolates. Whole-genome sequencing (WGS) was performed from 161 isolates having ≥1 ng DNA/μl using Illumina NovaSeq 6000 technology.

Results

From the total 161 isolates sequenced, 146 Mtb isolates were successfully genotyped into three lineages (L) and 18 sub-lineages. The Euro-American (EA, L4) lineage was the prevailing (n = 100; 68.5%) followed by Central Asian (CAS, L3, n = 43; 25.3%) and then L7 (n = 3; 2.05%). The L4.2.2.ETH sub-lineage accounted for 19.9%, while Haarlem estimated at 13.7%. The phylogenetic tree revealed distinct Mtb clusters between PTB and TBLN isolates even though there was no difference at lineages and sub-lineages levels. The clustering rate (CR) and recent transmission index (RTI) for PTB were 30 and 15%, respectively. Similarly, the CR and RTI for TBLN were 31.1 and 18 %, respectively.

Conclusion and recommendations

PTB and TBLN isolates showed no Mtb lineages and sub-lineages difference. However, at the threshold of five allelic distances, Mtb isolates obtained from PTB and TBLN form distinct complexes in the phylogenetic tree, which indicates the presence of Mtb genomic variation among the two clinical forms. The high rate of clustering and RTI among TBLN implied that TBLN was likely the result of recent transmission and/or reactivation from short latency. Hence, the high incidence rate of TBLN in the Amhara region could be the result of Mtb genomic diversity and rapid clinical progression from primary infection and/or short latency. To validate this conclusion, a similar community-based study with a large sample size and better sampling technique is highly desirable. Additionally, analysis of genomic variants other than phylogenetic informative regions could give insightful information. Combined analysis of the host and the pathogen genome (GXG) together with environmental (GxGxE) factors could give comprehensive co-evolutionary information.
Acoustic analysis in stuttering: a machine-learning study
Authors: Asci Francesco , Marsili Luca , Suppa Antonio , Saggio Giovanni , Michetti Elena , Di Leo Pietro , Patera Martina , Longo Lucia , Ruoppolo Giovanni , Del Gado Francesca , Tomaiuoli Donatella , Costantini Giovanni
Published: June 2023

Background

Stuttering is a childhood-onset neurodevelopmental disorder affecting speech fluency. The diagnosis and clinical management of stuttering is currently based on perceptual examination and clinical scales. Standardized techniques for acoustic analysis have prompted promising results for the objective assessment of dysfluency in people with stuttering (PWS).

Objective

We assessed objectively and automatically voice in stuttering, through artificial intelligence (i.e., the support vector machine – SVM classifier). We also investigated the age-related changes affecting voice in stutterers, and verified the relevance of specific speech tasks for the objective and automatic assessment of stuttering.

Methods

Fifty-three PWS (20 children, 33 younger adults) and 71 age−/gender-matched controls (31 children, 40 younger adults) were recruited. Clinical data were assessed through clinical scales. The voluntary and sustained emission of a vowel and two sentences were recorded through smartphones. Audio samples were analyzed using a dedicated machine-learning algorithm, the SVM to compare PWS and controls, both children and younger adults. The receiver operating characteristic (ROC) curves were calculated for a description of the accuracy, for all comparisons. The likelihood ratio (LR), was calculated for each PWS during all speech tasks, for clinical-instrumental correlations, by using an artificial neural network (ANN).

Results

Acoustic analysis based on machine-learning algorithm objectively and automatically discriminated between the overall cohort of PWS and controls with high accuracy (88%). Also, physiologic ageing crucially influenced stuttering as demonstrated by the high accuracy (92%) of machine-learning analysis when classifying children and younger adults PWS. The diagnostic accuracies achieved by machine-learning analysis were comparable for each speech task. The significant clinical-instrumental correlations between LRs and clinical scales supported the biological plausibility of our findings.

Conclusion

Acoustic analysis based on artificial intelligence (SVM) represents a reliable tool for the objective and automatic recognition of stuttering and its relationship with physiologic ageing. The accuracy of the automatic classification is high and independent of the speech task. Machine-learning analysis would help clinicians in the objective diagnosis and clinical management of stuttering. The digital collection of audio samples here achieved through smartphones would promote the future application of the technique in a telemedicine context (home environment).
A case report of Andersen-Tawil syndrome misdiagnosed with myodystrophy
Authors: Zhao Xiuqin , Zu Hengbing , Yao Kai
Published: June 2023

Andersen-Tawil syndrome (ATS) is a rare periodic paralysis caused by the KCNJ2 gene mutation. Here, we report on an ATS patient misdiagnosed with myodystrophy. A 66-year-old man presented with a 60-year history of episodic weakness in the proximal muscles of the upper and lower limbs. The man has been diagnosed with muscle pathology and has undergone genetic examinations in many hospitals since childhood. We conducted a correct diagnosis in combination with the patient’s history, electrical physiology, and genetic analysis and identified a heterozygous KCNJ2 gene variant (c.220A > G; p.T74A). Patients with ATS can develop permanent myasthenia characterized by chronic progressive myopathy. ATS patients should also pay special attention to the risks of anesthesia in surgery, including malignant hyperthermia (MH), muscle spasms affecting tracheal intubation or ventilation, and ventilator weakness. Early diagnosis and therapy could help delay the onset of myasthenia and prevent risks associated with anesthesia accidents.
Roles of sulfur-containing compounds in fermented beverages with 2-furfurylthiol as a case example
Authors: Zhang Guihu , Xiao Peng , Yuan Mengmeng , Li Youming , Xu Youqiang , Li Hehe , Sun Jinyuan , Sun Baoguo
Published: June 2023

Aroma is a critical component of the flavor and quality of beverages. Among the volatile chemicals responsible for fragrance perception, sulfur compounds are unique odorants due to their extremely low odor threshold. Although trace amounts of sulfur compounds can enhance the flavor profile of beverages, they can lead to off-odors. Sulfur compounds can be formed via Maillard reaction and microbial metabolism, imparting coffee aroma and altering the flavor of beverages. In order to increase the understanding of sulfur compounds in the field of food flavor, 2-furfurylthiol (FFT) was chosen as a representative to discuss the current status of their generation, sensory impact, enrichment, analytical methods, formation mechanisms, aroma deterioration, and aroma regulation. FFT is comprehensively reviewed, and the main beverages of interest are typically baijiu, beer, wine, and coffee. Challenges and recommendations for FFT are also discussed, including analytical methods and mechanisms of formation, interactions between FFT and other compounds, and the development of specific materials to extend the duration of aroma after release.
The immunomodulatory role of IDO1-Kynurenine-NAD+ pathway in switching cold tumor microenvironment in PDAC
Authors: Anu R. I. , Shiu Kai-Keen , Khan Khurum Hayat
Published: June 2023

Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically ‘non-inflamed’ tumor microenvironment in PDACs has proven to be challenging. Indolamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the catabolic pathway of L-Tryptophan, an essential amino acid, that gives rise to the immunosuppressive metabolite Kynurenine. IDO1, Indolamine 2,3-dioxygenase 2 (IDO2), and Tryptophan 2,3-dioxygenase (TDO) are the key enzymes in the tryptophan catabolic pathway but we focus on the role of the predominant enzyme form IDO1 in this review. Nicotinamide phosphoribosyl transferase (iNAMPT) regulates the intracellular concentration of NAD and is upregulated in the tumor. In light of the potential role of IDO1 as a driver of hostile TME in PDAC and NAD+ as a key coenzyme in anti-tumor immune response, this review urges focus on extensive research and initiation of clinical trials using IDO1 and NAMPT inhibitors in pancreatic cancer in the future.
SMARCB1/INI1 loss in skull base conventional chordomas: a clinicopathological and molecular analysis
Authors: Righi Alberto , Cocchi Stefania , Maioli Margherita , Zoli Matteo , Guaraldi Federica , Carretta Elisa , Magagnoli Giovanna , Pasquini Ernesto , Melotti Sofia , Vornetti Gianfranco , Tonon Caterina , Mazzatenta Diego , Asioli Sofia
Published: June 2023

Introduction

The loss of SMARCB1/INI1 protein has been recently described in poorly differentiated chordoma, an aggressive and rare disease variant typically arising from the skull base.

Methods

Retrospective study aimed at 1) examining the differential immunohistochemical expression of SMARCB1/INI1 in conventional skull base chordomas, including the chondroid subtype; 2) evaluating SMARCB1 gene deletions/copy number gain; and 3) analyzing the association of SMARCB1/INI1 expression with clinicopathological parameters and patient survival.

Results

65 patients (35 men and 30 women) affected by conventional skull base chordoma, 15 with chondroid subtype, followed for >48 months after surgery were collected. Median age at surgery was 50 years old (range 9-79). Mean tumor size was 3.6 cm (range 2-9.5). At immunohistochemical evaluation, a partial loss of SMARCB1/INI1 (>10% of neoplastic examined cells) was observed in 21 (32.3%) cases; the remaining 43 showed a strong nuclear expression. Fluorescence in situ hybridization (FISH) analysis was performed in 15/21 (71.4%) cases of the chordomas with partial SMARCB1/INI1 loss of expression. Heterozygous deletion of SMARCB1 was identified in 9/15 (60%) cases and was associated to copy number gain in one case; no deletion was found in the other 6 (40%) cases, 3 of which presenting with a copy number gain. No correlations were found between partial loss of SMARCB1/INI1 and the clinicopathological parameters evaluated (i.e., age, tumor size, gender, tumor size and histotype). Overall 5-year survival and 5-year disease-free rates were 82% and 59%, respectively. According to log-rank test analysis the various clinico-pathological parameters and SMARCB1/INI1 expression did not impact on overall and disease free-survival.

Discussion

Partial loss of SMARCB1/INI1, secondary to heterozygous deletion and/or copy number gain of SMARCB1, is not peculiar of aggressive forms, but can be identified by immunohistochemistry in a significant portion of conventional skull base chordomas, including the chondroid subtype. The variable protein expression does not appear to correlate with clinicopathological parameters, nor survival outcomes, but still, it could have therapeutic implications.
Case Report: Advanced pulmonary sarcomatoid carcinoma with adrenal gland metastasis after sintilimab combined with anlotinib treatment
Authors: Dai Gangyi , He Lang , Yan Qin , Li Yamao , Huang Yuandong , Li Bin , Wang Guoping
Published: June 2023

Background

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to conventional chemotherapy and radiotherapy with a poor prognosis. The MET inhibitor may be effective for the patients with MET exon 14 skipping mutation. This mutation was not detected in this patient. However, the PD-L1 TPS 60%, KRAS and TP53 mutations were detected in this patient could benefited from immunotherapy. The anlotinib is a novel multitarget antiangiogenic drug that could be effective for advanced non-small-cell lung cancer and some sarcoma patients. We report a patient with advanced pulmonary sarcomatoid carcinoma successfully treated with immunotherapy combined with antiangiogenic drugs.

Case summary

A 75-year-old male was admitted to the hospital in July 2020 because of productive cough for more than three months. The patient was diagnosed with advanced pulmonary sarcomatoid carcinoma with adrenal gland metastasis (cT4N3M1b, stage IVA) was treated in our hospital. Genetic testing revealed KRAS P.L19F mutation (abundance 19.12%) and NFEE2L2 P.E82G mutation (abundance 14.84%); TP53 P.S183 mutation (abundance 26.97%), TMB(Tumor Mutational Burden) 30.91 muts/Mb, MSS, and PD-L1 (Daco 22C3) TPS 60% were also detected. We administrated sintilimab combined with anlotinib treatment, a PD-1 inhibitor with antiangiogenic drug. The patient achieved a favorable outcome with tolerable adverse effects.

Conclusion

Sintilimab combined with anlotinib treatment may lead to a favorable outcome for patients with advanced pulmonary sarcomatoid carcinoma.
Site-specific performance of 68Ga-DOTATATE PET/CT in detecting tumors with ectopic adrenocorticotropic hormone secretion
Authors: Wang Junhu , Luan Zhonghua , Li Ting , Guan Xiaodong
Published: June 2023

Objective

The aim of this study was to assess the detection ability of 68Ga-DOTATATE in pulmonary versus extrapulmonary tumors with ectopic adrenocorticotropic hormone secretion (EAS).

Methods

Images of 68Ga-DOTATATE PET/CT from 74 patients with suspected EAS were retrospectively reviewed. EAS tumors were confirmed in 39 patients through surgical resection or biopsy. Image findings were compared with the histopathological results.

Results

EAS tumors were pathologically confirmed via surgery or biopsy in 39 patients. Among those 39 patients, 25 were with pulmonary neuroendocrine tumors (NETs), and the remaining 14 were with extrapulmonary NETs. 68Ga-DOTATATE PET/CT correctly identified the tumor in 26 patients, rendering an overall detection rate of 66.7%. On a site-based analysis, 68Ga-DOTATATE PET/CT correctly identified the EAS tumor in 13 of 25 patients with pulmonary NETs, yielding a detection rate of 52%; for the 14 patients with extrapulmonary NETs, 68Ga-DOTATATE PET/CT correctly identified the EAS tumor in 13, yielding a detection rate of 92.9%. The detection rate of 68Ga-DOTATATE was significantly higher in extrapulmonary NETs than in pulmonary NETs (92.9%% vs. 52%, P = 0.013). For the 13 patients with positive pulmonary NETs, the tumor SUVmax ranged from 1.1 to 7.4 with an average SUVmax of 3.1 ± 2.1. For the 13 patients with positive extrapulmonary NETs, the tumor SUVmax ranged from 2.7 to 21.8 with an average SUVmax of 9.9 ± 6.3. The tumor SUVmax was significantly higher in extrapulmonary tumors than pulmonary tumors (P = 0.015). The tumor size was smaller in pulmonary tumors than in extrapulmonary tumors, while the difference was not significant (P = 0.516).

Conclusion

68Ga-DOTATATE showed site-specific difference in detecting tumors with EAS secretion. Specifically, 68Ga-DOTATATE performed better in the extrapulmonary EAS tumors than in pulmonary ones with both higher detection rate and uptake. Combination of anatomic imaging techniques are necessary for the correct diagnosis of pulmonary EAS tumors.
Case report: Molecular characterisation of adipose-tissue derived cells from a patient with ROHHAD syndrome
Authors: Biernacka Kalina M. , Giri Dinesh , Hawton Katherine , Segers Francisca , Perks Claire M. , Hamilton-Shield Julian P.
Published: June 2023

There have been over 100 cases of Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome reported, but there is currently no curative treatment for children with this condition. We aimed to better characterise adipose cells from a child with ROHHAD syndrome. We isolated pre-adipocytes from a 4 year-old female patient with ROHHAD syndrome and assessed proliferation rate of these cells. We evaluated levels of DLP-Pref-1(pre-adipocyte marker) using western blotting, and concentrations of interleukin-6(IL-6) using ELISA. We performed next-generation sequencing (NGS) and bioinformatic analyses on these cells compared to tissue from an age/sex-matched control. The two most up-/down-regulated genes were validated using QPCR. We successfully isolated pre-adipocytes from a fat biopsy, by confirming the presence of Pref-1 and differentiated them to mature adipocytes. Interleukin 6, (Il-6) levels were 5.6-fold higher in ROHHAD cells compared to a control age/sex-matched biopsy. NGS revealed 25,703 differentially expressed genes (DEGs) from ROHHAD cells vs. control of which 2,237 genes were significantly altered. The 20 most significantly up/down-regulated genes were selected for discussion. This paper describes the first transcriptomic analysis of adipose cells from a child with ROHHAD vs. normal control adipose tissue as a first step in identifying targetable pathways/mechanisms underlying this condition with novel therapeutic interventions.
Joint effect of overweight/obesity and tobacco exposure on hypertension in children aged 6–17 years: a cross-sectional study
Authors: Gu Huan , Hao Long , Li Mingxi , Li Ji
Published: June 2023

Aim

To assess the individual effects of overweight/obesity and tobacco exposure, and their combined effects on hypertension in children.

Methods

This cross-sectional study included 6,339 children aged 6–17 years from National Health and Nutrition Examination Surveys 1999–2018. Participants’ height, weight and blood pressure (BP) were measured by trained technicians. Hypertension was defined as: mean systolic BP (SBP) and/or diastolic BP (DBP) ≥ 90th percentile for sex, age, and height (for children aged 1–13 years), and SBP ≥120 mmHg and/or a DBP ≥80 mmHg (for adolescents aged 13–17 years); or self-reported having been diagnosed with hypertension or taking antihypertensive medication. Gender- and age-specific body mass index (BMI) cut-points were used to define overweight/obesity: “overweight” was defined as a BMI > 1 standard deviation (SD); “obesity” was defined as BMI > 2SD; and “thinness” was defined as BMI < −2SD. Tobacco exposure was defined as having serum cotinine levels >0.05 µg/L or reporting the presence of at least one smoker in the household. Weighted univariate and multivariate logistic regression models were used to assess overweight/obesity and tobacco exposure with the odds of hypertension, and the combined effects of overweight/ obesity and tobacco exposure on hypertension, followed by strata-specific analyses. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

The prevalence of overweight/obesity and tobacco exposure was significantly higher in the hypertension group than in the non-hypertension group. Overweight/obesity (OR = 1.67, 95%CI: 1.26–2.21/ OR = 2.38, 95%CI: 1.67–3.39) and tobacco exposure (OR = 1.58, 95%CI: 1.16–2.14) were associated with a higher odd of hypertension in children, respectively. Additionally, we also observed the combined effect between overweight (OR = 3.05, 95%CI: 1.96–4.75)/obesity (OR = 3.68, 95%CI: 2.24–6.03) and tobacco exposure were related to hypertension odds in children, with a significant effect in different populations.

Conclusion

There may exist joint effect of overweight/obesity and tobacco exposure on the odds of hypertension in American children. These findings offer an insight that early weight control and reduction of tobacco exposure may be important to reduce odds of hypertension in children.
Cost-effectiveness of empagliflozin for the treatment of heart failure: a systematic review
Authors: Liu Jinyu , Liu Dong , Gong Xuepeng , Wei Anhua , You Ruxu
Published: June 2023

Objective: This study aims to synthesize evidence on the cost-effectiveness of empagliflozin for heart failure (HF).

Methods: MEDLINE, Embase, the Cochrane Library, EconLit, CNKI, Wanfang Data and Chongqing VIP were searched to identify original articles on cost-effectiveness of empagliflozin for HF, and literature surveillance ended on 20 November 2022. The reporting quality of the included articles was determined using the Consolidated Health Economic Evaluation Reporting Standards statement.

Results: Of 97 articles identified, 11 studies published from 2020 to 2022 met the inclusion criteria, and the overall quality was accepted. The studies were conducted in 8 countries (China, Japan, Korea, Singapore, Thailand, Australia, United States, and United Kingdom). This body of evidence suggested that add-on empagliflozin was cost effective for HF with reduced ejection fraction (HFrEF) patients compared to standard of care alone in all the related studies including China, Japan, Korea, Singapore, Thailand, and Australia. For HF with preserved ejection fraction (HFpEF) patients, add-on empagliflozin was cost effective in China and Australia, but not in United States and Thailand. For HF with diabetes, add-on empagliflozin was cost effective in United Kingdom. Moreover, the incremental cost-effectiveness ratios (ICER) were lower for patients with diabetes than without in subgroup analysis. In the uncertainty analysis of all included studies, the ICERs were most sensitive to the cost of empagliflozin and cardiovascular mortality, followed by the cost of the standard treatment, hazard ratio of HF hospitalization.

Conclusion: add-on empagliflozin for HFrEF might be cost-effective or dominant compared with standard of care alone. However, for HFpEF patients, add-on empagliflozin might be cost-effective in China and Australian, but not cost-effective in United States and Thailand.
Analysis of leaf forage value and screening of different populations of Pteroceltis tatarinowii, a rare and endemic species in China
Authors: Gao Yun , Cheng Tian-Tian , Zhang Chun-Xiang , Yan Yu , Zhang Lin , Liu Qing-Zhong , Liu Yan , Qiao Qian
Published: June 2023

To fully exploit the economic value of the Chinese endemic species Pteroceltis tatarinowii and provide new resources for forage production, the forage nutritional value of P. tatarinowii leaves from different populations was analyzed and evaluated. The results were as follows: 1) There were significant differences in the forage nutrient indices of leaves from different populations. The crude protein content was 10.77%–18.65%, with an average of 14.58%, and the SDJN population had the highest crude protein content. The average crude fat, crude fiber content was 7.62%; the average neutral detergent fiber content was 25.33%; and the average acid detergent fiber contents were 6.79%, 7.62%, 25.33%, and 17.52%, respectively. The average phosphorus and calcium content in the leaves was 0.785 g·kg−1 and 58.01 g·kg−1, respectively. The tannin content was much lower than the antifeedant standard, at an average of 4.97 g·kg−1. The average total amounts of hydrolyzed and free amino acids in the leaves were 108.20 mg·g−1 and 47.87 mg·g−1, respectively. Thus, P. tatarinowii leaves have high crude protein, crude fat, and calcium contents, and low fiber, tannin contents, and are protein-rich. These results provide evidence that this species can be developed into an excellent woody forage tree. 2) There were significant differences in the forage quality evaluation indices among the populations. The forage indices of NDP, ADP, DMI, DDM, and RFV of 21 populations all met the super standard of the American Grass and Grassland Association (AFGC) for hay, two crude protein indices met the grade 1 standard, and 12 crude protein indices met the grade 2 standard. Four high-protein and high-RFV forage populations (SDJN, SDZZ, SXLQ, and AHXX) were selected. 3) The results of the correlation analysis showed that there was no significant correlation between the forage characteristics of P. tatarinowii leaves and latitude and longitude, indicating no significant geographical variation. However, the forage characteristics were strongly correlated with elevation, average annual temperature, and annual precipitation. Thus, high elevation, low temperatures, and rainy weather can improve the forage value of the leaves. P. tatarinowii can be planted to provide leaf forage in cold and wet areas at a specific elevation. Moreover, the forage value of P. tatarinowii leaves can be further improved by increasing nitrogen fertilizer and reducing K and Ca fertilizers during cultivation. 4) Cluster analysis revealed obvious regionalism. Taking the Yangtze River Basin as the limit, cluster analysis divided the species into four population groups: the Yangtze River Basin and northern, southwestern, and eastern coastal populations.
Impact of deeper groundwater depth on vegetation and soil in semi-arid region of eastern China
Authors: Zhao Siteng , Zhao Xueyong , Li Yulin , Chen Xueping , Li Chengyi , Fang Hong , Li Wenshuang , Guo Wei
Published: June 2023

Introduction

Understanding the impact of deep groundwater depth on vegetation communities and soil in sand dunes with different underground water tables is essential for ecological restoration and the conservation of groundwater. Furthermore, this understanding is critical for determining the threshold value of groundwater depth that ensures the survival of vegetation.

Method

This paper was conducted in a semi-arid region in eastern China, and the effects of deep groundwater depth (6.25 m, 10.61 m, and 15.26 m) on vegetation communities and soil properties (0–200 cm) across three dune types (mobile, semi-fixed, and fixed dunes) were evaluated in a sand ecosystem in the Horqin Sandy Land.

Results

For vegetation community, variations in the same species are more significant at different groundwater depths. For soil properties, groundwater depth negatively influences soil moisture, total carbon, total nitrogen, available nitrogen, available phosphorus concentrations, and soil pH. Besides, groundwater depth also significantly affected organic carbon and available potassium concentrations. In addition, herb species were mainly distributed in areas with lower groundwater depth, yet arbor and shrub species were sparsely distributed in places with deeper groundwater depth.

Discussion

As arbor and shrub species are key drivers of ecosystem sustainability, the adaptation of these dominant species to increasing groundwater depth may alleviate the negative effects of increasing groundwater depth; however, restrictions on this adaptation were exceeded at deeper groundwater depth.
Pseudomonas forestsoilum sp. nov. and P. tohonis biocontrol bacterial wilt by quenching 3-hydroxypalmitic acid methyl ester
Authors: Wang Si , Hu Ming , Chen Huilin , Li Chuhao , Xue Yang , Song Xinyue , Qi Yuqing , Liu Fan , Zhou Xiaofan , Zhang Lian-hui , Zhou Jianuan
Published: June 2023

Bacterial wilt caused by Ralstonia solanacearum ranks the second top important bacterial plant disease worldwide. It is also the most important bacterial disease threatening the healthy development of Casuarina equisetifolia protection forest. 3-hydroxypalmitic acid methyl ester (3-OH PAME) functions as an important quorum sensing (QS) signal regulating the expression of virulence genes in R. solanacearum, and has been regarded as an ideal target for disease prevention and control. To screen native microorganisms capable of degrading 3-OH PAME, samples of C. equisetifolia branches and forest soil were collected and cultured in the medium containing 3-OH PAME as the sole carbon source. Bacteria with over 85% degradation rates of 3-OH PAME after 7-day incubation were further separated and purified. As a result, strain Q1-7 isolated from forest soil and strain Q4-3 isolated from C. equisetifolia branches were obtained and identified as Pseudomonas novel species Pseudomonas forestsoilum sp. nov. and P. tohonis, respectively, according to whole genome sequencing results. The degradation efficiencies of 3-OH PAME of strains Q1-7 and Q4-3 were 95.80% and 100.00% at 48 h, respectively. Both strains showed high esterase activities and inhibited R. solanacearum exopolysaccharide (EPS) and cellulase production. Application of strains Q1-7 and Q4-3 effectively protects C. equisetifolia, peanut and tomato plants from infection by R. solanacearum. Findings in this study provide potential resources for the prevention and control of bacterial wilt caused by R. solanacearum, as well as valuable materials for the identification of downstream quenching genes and the research and development of quenching enzymes for disease control.
Targeted system approach to ethylene biosynthesis and signaling of a heat tolerant tomato cultivar; the impact of growing season on fruit ripening
Authors: Nguyen Thao Minh Viet , Hertog Maarten L. A. T. M. , Van de Poel Bram , Tran Dinh Thi , Nicolaï Bart
Published: June 2023

Growing tomato in hot weather conditions is challenging for fruit production and yield. Tomato cv. Savior is a heat-tolerant cultivar which can be grown during both the Vietnamese winter (mild condition) and summer (hot condition) season. Understanding the mechanisms of ethylene biosynthesis and signaling are important for agriculture, as manipulation of these pathways can lead to improvements in crop yield, stress tolerance, and fruit ripening. The objective of this study was to investigate an overview of ethylene biosynthesis and signaling from target genes to proteins and metabolites and the impact of growing season on a heat tolerant tomato cultivar throughout fruit ripening and postharvest storage. This work also showed the feasibility of absolute protein quantification of ethylene biosynthesis enzymes. Summer fruit showed the delayed peak of ethylene production until the red ripe stage. The difference in postharvest ethylene production between winter and summer fruit appears to be regulated by the difference in accumulation of 1-aminocyclopropane-1-carboxylic acid (ACC) which depends on the putative up-regulation of SAM levels. The lack of differences in protein concentrations between winter and summer fruit indicate that heat stress did not alter the ethylene biosynthesis-related protein abundance in heat tolerant cultivar. The analysis results of enzymatic activity and proteomics showed that in both winter and summer fruit, the majority of ACO activity could be mainly contributed to the abundance of ACO5 and ACO6 isoforms, rather than ACO1. Likewise, ethylene signal transduction was largely controlled by the abundance of ethylene receptors ETR1, ETR3, ETR6, and ETR7 together with the constitute triple response regulator CTR1 for both winter and summer grown tomatoes. Altogether our results indicate that in the heat tolerant tomato cv. Savior, growing season mainly affects the ethylene biosynthesis pathway and leaves the signaling pathway relatively unaffected.
RoseAP: an analytical platform for gene function of Rosa rugosa
Authors: Da Lingling , Li Jiande , Zhao Fan , Liu Huilin , Shi Pengxia , Shi Shaoming , Zhang Xinxin , Yang Jiaotong , Zhang Hui
Published: June 2023

Rosa rugosa, a perennial shrub belonging to family Rosaceae, is a well-known ornamental plant. Its petals contain an abundance of essential oils and anthocyanins with enormous economic and health benefits when used as edible or cosmetic ingredients. The whole genome of R. rugosa was sequenced in 2021, which provided opportunities and challenges for gene regulation. However, many gene functions remain unknown. Therefore, an analytical platform named RoseAP (http://www.gzybioinformatics.cn/RoseAP/index.php) for the functional analysis of R. rugosa genes was constructed. It improved the gene annotation rate by integrating and analyzing genomic and transcriptomic datasets. First, 38,815 genes, covering 97.76% of the coding genes, were annotated functionally and structurally using a variety of algorithms and rules. Second, a total of 33 transcriptome samples were integrated, including 23 samples from our lab and 10 samples from the SRA database. A co-expression network containing approximately 29,657 positive or negative gene pairs, covering 74.7% of the coding genes, was constructed based on PCC and MR algorithms. Network analysis revealed that the DFR function was closely related to anthocyanin metabolism. It demonstrated the reliability of the network. Several SAUR genes of R. rugosa shared similar expression patterns. RoseAP was used to determine the sequence, structure, functional annotation, expression profile, regulatory network, and functional modules at the transcriptional and protein levels by inputting gene IDs. In addition, auxiliary analytical tools, including BLAST, gene set enrichment, orthologue conversion, gene sequence extraction, gene expression value extraction, and JBrowse, were utilized. Regular updates to RoseAP are expected to facilitate mining of gene function and promote genetic improvement in R. rugosa.
Pathways to the therapist paragon: a decolonial grounded theory
Authors: Bergkamp Jude , O’Leary Sloan Maeve , Krizizke Jack , Lash Malea , Trantel Noah , Vaught Jason , Fulmer Tessa , Waite Ilana , Martin Abigail M. , Scheiderer Cynthia , Olson Lindsay
Published: June 2023

Introduction

While many professional associations within clinical and counseling psychology have made an aspirational call for clinician awareness of social position, there is a lack of research into how socially-conferred privilege impacts psychotherapy. Specifically of interest is the differences in race and gender within the therapeutic dyad, in which there is a BIPOC (Black, Indigenous, and Persons of Color)/white1 or male/female-identified dynamic.

Method

The authors utilized a Grounded Theory approach to analyze qualitative interviews with practicing psychologists to construct a process model regarding how socially-conferred privileged identity domains impact the therapeutic relationship and the participants’ professionalization process.

Results

The analysis identified the core conceptual theme of the Therapist Paragon, representing an idealized version of what a perfect therapist should be. This replicated the foundational figures of our field - primarily older, white men. The process model consisted of two distinct pathways toward the Therapist Paragon, one for BIPOC psychologists and one for white psychologists. The female BIPOC pathway consisted of imposter syndrome, persistent feelings of inadequacy, and tendencies to over-credential their professional identity to seek credibility in the eyes of clients and colleagues. The white pathway consisted of down-playing whiteness and attempting to initially modify behavior toward client cultural norms.

Discussion

The results point to a distinct professionalization and practice process for BIPOC psychologists compared to white counterparts. This dynamic may have implications beyond increasing support for BIPOC clinicians specifically, but instead indicate a lack of acknowledgement of the psychological impact of socially-conferred privilege in the psychotherapy enterprise overall. Recommendations are offered for revisions to training models, continuing education, and supervision/consultation.
Deep brain stimulation programming for intractable obsessive–compulsive disorder using a long pulse width
Authors: Beydler Emily , Katzell Lauren , Putinta Kevin , Holbert Richard , Carr Brent
Published: June 2023

Introduction

Around 25% of patients with obsessive–compulsive disorder (OCD) do not respond to medication or psychotherapy, producing significant impairment and treatment challenges. Deep Brain Stimulation (DBS) has been shown in multiple blinded trials to be a safe and durable emerging option for treatment-refractory OCD. Intraoperative device interrogation offers a theoretical anchor for starting outpatient DBS programming; however, no definitive post-operative programming algorithm for psychiatrists exists currently.

Case

Here we present a 58-year-old female with childhood-onset, severe, intractable OCD with multiple failed trials of psychotherapy, medication, and electroconvulsive therapy. After interdisciplinary evaluation, she underwent bilateral electrode implantation targeting the anterior limb of the internal capsule, nucleus accumbens (ALIC/NAc). Intraoperative interrogation afforded sparse information about a preferred lead contact or current density target. Subsequent outpatient interrogation consisted of systematic and independent mapping using monopolar cathodic stimulation with constant current. Modulating bipolar and triple monopolar configurations, amplitude, and pulse width all failed to induce observable effects. Given negligible interrogation feedback, we created an electrical field through the ALIC bilaterally, using the three most ventral contacts to create triple monopoles, with a long pulse width and moderate amperage.

Conclusion

Three months post-programming, the patient reported significant improvement in OCD symptoms, particularly checking behaviors, with response sustained over the next several months. As with our case, the majority of DBS lead contacts do not induce affective or physiological markers in patients, complicating programming optimization. Here, we discuss an approach to titrating various stimulation parameters and purported mechanisms of physiological markers in DBS for OCD.