bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory activation of the FcγR and IFNγR pathways co-influences the differentiation and activity of osteoclasts
Authors: Groetsch Bettina , Schachtschabel Elisabeth , Tripal Philipp , Schmid Benjamin , Smith Ana-Suncana , Schett Georg , Bozec Aline
Published: September 2022

Osteoclasts are polykaryons formed by cell–cell fusion of highly motile progenitors of the myeloid lineage. Osteoclast activity can preserve skeletal strength and bone homeostasis. However, osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA). Fc receptors activated by IgG immune complexes (IC) can boost osteoclast differentiation and bone loss in the course of RA. In contrast, interferon (IFN) γ secreted by immune cells blocks osteoclast activation. Despite their hypothetical importance in the regulation of osteoclast differentiation in RA, the interconnection between the two pathways has not been described so far. Here, we show by total internal reflection fluorescence (TIRF) microscopy that FcγR3 and IFNγ receptor (IFNγR) locate at close vicinity to each other on the human osteoclast surface. Moreover, the average distance increases during the differentiation process. Interestingly, FcγR and IFNγR activation shapes the position of both receptors to each other. Surprisingly, the inhibitory action of IFNγ onin-vitrohuman osteoclast differentiation depends on the osteoclast differentiation stage. Indeed, IFNγR activation in early osteoclast precursors completely inhibits the formation of polynucleated osteoclasts, while in premature osteoclasts, it further enhanced their fusion. In addition, gene expression analyses showed that IFNγR activation on early precursor cells but not on premature osteoclasts could induce FcγR expression, suggesting a co-regulation of both receptors on human osteoclast precursors. Phosphokinase array data of precursor cells demonstrate that the observed divergence of IFNγR signaling is dependent on the mitogen−activated protein kinase (MAPK) downstream signaling pathway. Overall, our data indicate that FcγR and IFNγR signaling pathways co-influence the differentiation and activity of osteoclasts dependent on the differentiation state, which might reflect the different stages in RA.
Evidence of temperature control on mesopelagic fish and zooplankton communities at high latitudes
Authors: Chawarski Julek , Klevjer Thor A. , Coté David , Geoffroy Maxime
Published: September 2022

Across temperate and equatorial oceans, a diverse community of fish and zooplankton occupies the mesopelagic zone, where they are detectable as sound-scattering layers. At high latitudes, extreme day-night light cycles may limit the range of some species, while at lower latitudes communities are structured by dynamic ocean processes, such as temperature. Using acoustic and oceanographic measurements, we demonstrate that latitudinal changes in mesopelagic communities align with polar boundaries defined by deep ocean temperature gradients. At the transition to cold polar water masses we observe abrupt weakening and vertical dispersion of acoustic backscatter of mesopelagic organisms, thereby altering the structure of the mesopelagic zone. In the Canadian Arctic, we used biological sampling to show that this boundary is associated with a significant change in the pelagic fish community structure. Rapid ocean warming projected at mesopelagic depths could shift these boundaries with far-reaching effects on ecosystem function and biogeochemical cycles.
Body mass index, body fat percentage, and visceral fat as mediators in the association between health literacy and hypertension among residents living in rural and suburban areas
Authors: Nguyen Tham T. , Nguyen Minh H. , Nguyen Yen H. , Nguyen Thao T. P. , Giap Manh H. , Tran Tung D. X. , Pham Thu T. M. , Pham Khue M. , Nguyen Kien T. , Le Vinh-Tuyen T. , Su Chien-Tien , Duong Tuyen Van
Published: September 2022

Background

Hypertension is a major cause of death and disability worldwide. Enhancing health literacy (HL) may help to alleviate the risk of hypertension and its burden. However, evidence on the association between HL and hypertension and potential mechanisms remain to be explored.

Objectives

This study examined the association between HL and hypertension; and explored whether body mass index (BMI), body fat percentage (PBF), and visceral fat (VF) were mediators of this association in people who resided in rural and suburban areas in Vietnam.

Methods

A cross-sectional survey was conducted from 1st July to 31st December 2019, involving 1655 residents and exploring participants' sociodemographic characteristics, HL, health-related behaviors, comorbidities, body composition, and blood pressure (BP). People with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or using antihypertensive medication were classified as having hypertension. Multiple logistic regression and mediation analyses were used to explore associations.

Results

The hypertension prevalence was 41.9% (694/1,655). In adjusted models, a higher HL score was associated with a lower hypertension likelihood (OR = 0.96; 95%CI = 0.95–0.97; p < 0.001). Factors associated with a higher odd of hypertension were overweight/obese (OR = 1.69; 95%CI = 1.24–2.29; p = 0.001), high PBF (OR = 2.35; 95%CI = 1.85–2.99; p < 0.001), and high VF (OR = 2.27; 95%CI = 1.63–3.16; p < 0.001). Notably, PBF significantly mediated the association between HL and hypertension (indirect effect, OR = 0.99; 95%CI = 0.98–0.99; p = 0.009; percent mediated = 8.56%). The mediating roles of BMI and VF were not found.

Conclusion

The prevalence of hypertension was relatively high. People with better HL were less likely to have hypertension. The association between HL and hypertension was partially explained by PBF. Strategic approaches are required to improve people's HL and body fat which further help to manage hypertension in rural and suburban areas.
Incidence of postpartum infections and outcomes associated with antibiotic prophylaxis after normal vaginal birth
Authors: Sirilak Thitipong , Kanjanarat Penkarn , Nochaiwong Surapon , Katip Wasan
Published: September 2022

Antibiotic consumption accounted for approximately 15–20% of total drug costs in Thailand. From 2017 to 2018, 24.86% of Thai women who experienced vaginal delivery during normal term labour received antibiotics for postpartum infection. The Thai national practice guidelines set the target use of antibiotic prophylaxis in women following vaginal delivery of normal term labour to be no more than 10%. This study aimed to determine the incidence of postpartum infections and the outcomes and factors associated with antibiotic prophylaxis in women following vaginal delivery. The prospective cohort study was collected from 909 eligible patients who delivered infants in 7 secondary hospitals in Chiang Mai from July 2020 to February 2021. Antibiotic prescribing data and infections in women experiencing vaginal delivery during normal term labour were collected. The incidence of postpartum infections was calculated at 2 periods, 48 h and 6 weeks, after labour. Factors associated with the prescription of antibiotic prophylaxis in vaginal delivery were analysed using multivariate logistic regression. The results showed that the prevalence of antibiotic prescribing was 12.87% in a cohort of 117 patients. Postpartum infection was reported in 3 of 117 patients with antibiotics prophylaxis and 11 of 792 without antibiotics, with no statistically significant difference (RR: 1.04, 95% CI: 0.26–4.14; p = 0.956). Postpartum hygiene self-care practices were collected in the 6th week. The results found that there were no statistical differences in mean scores for all questions on postpartum hygiene self-care practices between the infected and non-infected groups (p-value > 0.05). One of the factors associated with antibiotic prophylaxis was third to fourth degree of tear and episiotomy (OR: 7.72, 95% CI: 1.13–52.75; p = 0.037 and OR: 2.41, 95% CI: 1.24–4.70; p = 0.010, respectively). There was no significance difference in postpartum infection among patients receiving antibiotic and those who did not receive antibiotics. Third to fourth degree of tear and episiotomy were significantly factors related to antibiotic prophylaxis in women with vaginal delivery after labour. This study supports practice guidelines and helps healthcare team to be assured on the use of antibiotics in no more than 10% of women experiencing normal vaginal delivery.
Informing healthcare operations with integrated pathology, clinical, and epidemiology data: Lessons from a single institution in Kenya during COVID-19 waves
Authors: Njau Allan , Kimeu Jemimah , Gohil Jaimini , Nganga David
Published: September 2022

Pathology, clinical care teams, and public health experts often operate in silos. We hypothesized that large data sets from laboratories when integrated with other healthcare data can provide evidence that can be used to optimize planning for healthcare needs, often driven by health-seeking or delivery behavior. From the hospital information system, we extracted raw data from tests performed from 2019 to 2021, prescription drug usage, and admission patterns from pharmacy and nursing departments during the COVID-19 pandemic in Kenya (March 2020 to December 2021). Proportions and rates were calculated. Regression models were created, and a t-test for differences between means was applied for monthly or yearly clustered data compared to pre-COVID-19 data. Tests for malaria parasite, Mycobacterium tuberculosis, rifampicin resistance, blood group, blood count, and histology showed a statistically significant decrease in 2020, followed by a partial recovery in 2021. This pattern was attributed to restrictions implemented to control the spread of COVID-19. On the contrary, D-dimer, fibrinogen, CRP, and HbA1c showed a statistically significant increase (p-value <0.001). This pattern was attributed to increased utilization related to the clinical management of COVID-19. Prescription drug utilization revealed a non-linear relationship to the COVID-19 positivity rate. The results from this study reveal the expected scenario in the event of similar outbreaks. They also reveal the need for increased efforts at diabetes and cancer screening, follow-up of HIV, and tuberculosis patients. To realize a broader healthcare impact, pathology departments in Africa should invest in integrated data analytics, for non-communicable diseases as well.
Sarcoidosis and autoimmunity: In the depth of a complex relationship
Authors: Rizzi Luigi , Sabbà Carlo , Suppressa Patrizia
Published: September 2022

Sarcoidosis is a chronic granulomatous disease that can virtually affect any organ. Its etiology is unknown, although it has been proposed that environmental or biological agents can act as triggers, ultimately leading to chronic inflammation in genetically predisposed individuals. The main component of sarcoid inflammation is represented by an exaggerated T- lymphocytic cellular response to a putative antigen that could not be efficiently cleared in the patient. However, several clinical and immunological observations, such as the association of sarcoidosis to autoimmune diseases or the presence of autoantibodies in the serum of patients with sarcoidosis, suggest that humoral-mediated immune response might also play a role in the pathogenesis of sarcoidosis. The aim of this review is to deepen the relationship between sarcoidosis and autoimmunity, by analyzing the most recent advances and proposing new fields of research.
Contribution of gut microbiota toward renal function in sepsis
Authors: Xu Yaya , Kong Xiangmei , Zhu Yueniu , Xu Jiayue , Mao Haoyun , Li Jiru , Zhang Jianhua , Zhu Xiaodong
Published: September 2022

Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut–kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.
Biological activity of galacto-oligosaccharides: A review
Authors: Mei Zhaojun , Yuan Jiaqin , Li Dandan
Published: September 2022

Galacto-oligosaccharides (GOS) are oligosaccharides formed by β-galactosidase transgalactosylation. GOS is an indigestible food component that can pass through the upper gastrointestinal tract relatively intact and ferment in the colon to produce short-chain fatty acids (SCFAs) that further regulate the body’s intestinal flora. GOS and other prebiotics are increasingly recognized as useful food tools for regulating the balance of colonic microbiota-human health. GOS performed well compared to other oligosaccharides in regulating gut microbiota, body immunity, and food function. This review summarizes the sources, classification, preparation methods, and biological activities of GOS, focusing on the introduction and summary of the effects of GOS on ulcerative colitis (UC), to gain a comprehensive understanding of the application of GOS.
Case report: Spontaneous carotid-cavernous fistula associated with persistent primitive trigeminal artery aneurysm rupture
Authors: Sun Peng , Chai Yuan , Fang Wei , Chen Hu , Long Qianfa , Zhao Zhenwei , Zhang Tao
Published: September 2022

Background

The incidence of carotid cavernous fistula (CCF) associated with persistent primitive trigeminal artery (PPTA) aneurysm rupture is extremely rare. We presented a case about a spontaneous CCF secondary to a ruptured PPTA aneurysm, which was successfully embolized with coils and onyx-18 by a trans-arterial approach.

Case presentation

A 55-year-old female suffered a sudden onset of headache, left orbital pain, and pulsatile exophthalmos for a month without any history of trauma. Angiography revealed a left-sided CCF associated with a ruptured PPTA aneurysm, with major drainage to the ipsilateral superior ophthalmic vein. Through a trans-arterial approach, the fistula and ruptured PPTA aneurysm were embolized with coils and onyx-18, while the cavernous sinus and PPTA were well-preserved. However, the preserved PPTA vanished at 4 month follow-up. The patient had no neurological deficit from hospitalization to 1 year follow-up period.

Conclusion

Trans-arterial approach was a reasonable choice for spontaneous CCF associated with ruptured PPTA aneurysm. The requirement for PPTA preservation depended on individual evaluation.
Neurons gating behavior—developmental, molecular and functional features of neurons in the Substantia Nigra pars reticulata
Authors: Partanen Juha , Achim Kaia
Published: September 2022

The Substantia Nigra pars reticulata (SNpr) is the major information output site of the basal ganglia network and instrumental for the activation and adjustment of movement, regulation of the behavioral state and response to reward. Due to both overlapping and unique input and output connections, the SNpr might also have signal integration capacity and contribute to action selection. How the SNpr regulates these multiple functions remains incompletely understood. The SNpr is located in the ventral midbrain and is composed primarily of inhibitory GABAergic projection neurons that are heterogeneous in their properties. In addition, the SNpr contains smaller populations of other neurons, including glutamatergic neurons. Here, we discuss regionalization of the SNpr, in particular the division of the SNpr neurons to anterior (aSNpr) and posterior (pSNpr) subtypes, which display differences in many of their features. We hypothesize that unique developmental and molecular characteristics of the SNpr neuron subtypes correlate with both region-specific connections and notable functional specializations of the SNpr. Variation in both the genetic control of the SNpr neuron development as well as signals regulating cell migration and axon guidance may contribute to the functional diversity of the SNpr neurons. Therefore, insights into the various aspects of differentiation of the SNpr neurons can increase our understanding of fundamental brain functions and their defects in neurological and psychiatric disorders, including movement and mood disorders, as well as epilepsy.
Next-generation sequencing based detection of BRCA1 and BRCA2 large genomic rearrangements in Chinese cancer patients
Authors: Hua Dingchao , Tian Qiuhong , Wang Xue , Bei Ting , Cui Lina , Zhang Bei , Bao Celimuge , Bai Yuezong , Zhao Xiaochen , Yuan Peng
Published: September 2022

BRCA1/2 mutation is a biomarker for guiding multiple solid tumor treatment. However, the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in Chinese cancer patients has not been well revealed partially due to technical difficulties in LGR detection. This study utilized next-generation sequencing (NGS) to analyze the BRCA1/2 mutation profile, including LGR, in 56126 Chinese cancer patients. We also reported that two ovarian and breast cancer patients with NGS-determined BRCA1/2 LGR benefited from PARP inhibitors (PARPi). DNA sequencing identified BRCA1/2 variants (including LGR, pathogenic and likely-pathogenic variants) in 2108 individuals. Seventy patients were discovered to harbor germline LGRs in BRCA1 and 14 had germline LGRs in BRCA2. Among the LGRs detected, exon 1-2 deletion was the predominant LGR (14/70) in BRCA1, and exon 22-24 deletion was the most frequent LGR (3/14) in BRCA2. Notably, the BRCA1 exon 7 deletion was a novel LGR and was identified in six patients, suggesting a specific LGR in Chinese cancer patients. The prevalence analysis of BRCA1 and BRCA2 LGRs across multiple cancers revealed that BRCA1 LGR more frequently occurred in ovarian cancer (1.31%, 33/2526), and BRCA2 LGR was more commonly seen in cholangiocarcinoma (0.47%, 2/425). Two ovarian and breast cancer patients with BRCA1/2 LGR benefited from PARPi therapy. This is the first study to reveal the BRCA1/2 LGR profile of a Chinese pan-cancer cohort by using an NGS-based assay. Two breast and ovarian cancer patients harboring NGS-determined BRCA1/2 LGR benefited from PARPi, indicating that NGS-based detection of BRCA1/2 LGR has the potential to guide PARPi treatment.
Myoferlin disturbs redox equilibrium to accelerate gastric cancer migration
Authors: Shi Hailong , Cheng Yuanyuan , Shi Qimei , Liu Wenzhi , Yang Xue , Wang Shuang , Wei Lin , Chen Xiangming , Fang Hao
Published: September 2022

Objective

In contrast to normal cells, in which reactive oxygen species (ROS) are maintained in redox equilibrium, cancer cells are characterized by ectopic ROS accumulation. Myoferlin, a newly identified oncogene, has been associated with tumor metastasis, intracellular ROS production, and energy metabolism. The mechanism by which myoferlin regulates gastric cancer cell migration and ROS accumulation has not been determined.

Methods

Myoferlin expression, intracellular ROS levels, the ratios of reduced to oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) and migratory ability were measured in gastric cancer cells in vitro and in the TCGA and GEO databases in silico.

Results

Myoferlin was found to be more highly expressed in tumor than in normal tissues of gastric cancer patients, with higher expression of Myoferlin associated with shorter survival time. Myoferlin was associated with significantly higher intracellular ROS levels and enhanced migration of gastric cancer cells. N-acetyl-L-cysteine (NAC), a potent inhibitor of ROS, inhibited Myoferlin-induced ROS accumulation and cell migration.

Conclusions

Myoferlin is a candidate prognostic biomarker for gastric cancer and plays an essential role in regulating redox equilibrium and gastric cancer cell migration. Myoferlin may also be a new target for treatment of patients with gastric cancer.
Endoglin (CD105) and proliferation index in recurrent glioblastoma treated with anti-angiogenic therapy
Authors: Bastos António G. P. , Carvalho Bruno , Silva Roberto , Leitão Dina , Linhares Paulo , Vaz Rui , Lima Jorge
Published: September 2022

Introduction

CD105 is an angiogenic biomarker that is useful to determine the microvessel density (MVD) within a tumor, namely, in highly vascularized tumors like glioblastoma (GBM). However, its expression has shown inconsistent associations with the prognosis of GBM patients. The aim of this study was to evaluate the value of MVD-CD105 (microvessel density assessed with anti-CD105 antibody) and Ki-67 (proliferation index marker) as prognostic and therapy response biomarkers, specifically in primary tumors and in recurrent tumoral specimens of a cohort of GBM patients treated with bevacizumab upon recurrence.

Materials and methods

We conducted a retrospective study of 102 consecutive GBM patients treated with bevacizumab upon recurrence at CHUSJ between 2010 and 2017. Demographic, clinical, and survival data of all patients were collected and analyzed. The tissue expression of MVD-CD105 and Ki-67 in primary and recurrent specimens was correlated with progression-free survival after temozolomide (PFS-1), progression-free survival after bevacizumab (PFS-2), and overall survival (OS).

Results

The immunohistochemical expression score for MVD-CD105 was similar in primary and recurrent tumoral specimens (mean scores of 15 and 16, respectively). Likewise, the mean Ki-67 expression was similar in primary (mean of 31% of tumor cells) and recurrent tumoral specimens (mean of 29% of tumor cells). MVD-CD105 expression in primary tumors had no impact on PFS-1, PFS-2, or OS. At recurrence, patients whose tumors showed increased MVD-CD105 had worse median PFS-2 (2 vs. 8 months, p = 0.045) and OS (17 vs. 26 months, p = 0.007) compared to those whose tumors showed lower MVD-CD105. CD105 tumoral pattern and localization had no impact on prognosis. Ki-67 expression was not associated with differences in survival outcomes.

Conclusion

In this study, higher MVD-CD105 expression in recurrent GBM patients seems to be associated with a worse PFS-2 and OS while portending no prognostic significance in the primary tumors. This highlights the importance of keeping track of the molecular evolution of the tumor over the course of the disease.
Advances in the research of the mechanism of secondary resistance to imatinib in gastrointestinal stromal tumors
Authors: Hu Xiangchen , Wang Zhe , Su Peng , Zhang Qiqi , Kou Youwei
Published: September 2022

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. At present, surgery is the first-line treatment for primary resectable GISTs; however, the recurrence rate is high. Imatinib mesylate (IM) is an effective first-line drug used for the treatment of unresectable or metastatic recurrent GISTs. More than 80% of patients with GISTs show significantly improved 5-year survival after treatment; however, approximately 50% of patients develop drug resistance after 2 years of IM treatment. Therefore, an in-depth research is urgently needed to reveal the mechanisms of secondary resistance to IM in patients with GISTs and to develop new therapeutic targets and regimens to improve their long-term prognoses. In this review, research on the mechanisms of secondary resistance to IM conducted in the last 5 years is discussed and summarized from the aspects of abnormal energy metabolism, gene mutations, non-coding RNA, and key proteins. Studies have shown that different drug-resistance mechanism networks are closely linked and interconnected. However, the influence of these drug-resistance mechanisms has not been compared. The combined inhibition of drug-resistance mechanisms with IM therapy and the combined inhibition of multiple drug-resistance mechanisms are expected to become new therapeutic options in the treatment of GISTs. In addition, implementing individualized therapies based on the identification of resistance mechanisms will provide new adjuvant treatment options for patients with IM-resistant GISTs, thereby delaying the progression of GISTs. Previous studies provide theoretical support for solving the problems of drug-resistance mechanisms. However, most studies on drug-resistance mechanisms are still in the research stage. Further clinical studies are needed to confirm the safety and efficacy of the inhibition of drug-resistance mechanisms as a potential therapeutic target.
Sacral Ewing sarcoma with rib, lung, and multifocal skull metastases: A rare case report and review of treatments
Authors: Ye Chen , Wei Wei , Tang Xuebin , Li Feng , Xin Baoquan , Chen Qianqian , Wei Haifeng , He Shaohui , Xiao Jianru
Published: September 2022

Ewing sarcoma (ES) rarely derives from the sacrum or mobile spine. The discovery of primary ES with multimetastatic involvements is exceedingly less frequent in clinical practice. A 23-year-old man with initial primary sacral ES developed metastases of rib, lung, and multifocal skull after receiving surgical intervention and series of adjuvant therapies. We provide this very rare case consisting of its clinical features, imaging findings, treatments, and outcomes. Therapeutic modalities of ES are also reviewed in previous published articles. The prognosis of metastatic ES remains dismal; effective therapeutic modalities for ES require multidisciplinary collaboration, with more high-quality clinical trials to promote the optimal protocols.
The immune escape signature predicts the prognosis and immunotherapy sensitivity for pancreatic ductal adenocarcinoma
Authors: Lu Hao , Zheng Li-Yan , Wu Ling-Yan , Chen Jun , Xu Na , Mi Sui-Cai
Published: September 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide. Immune escape is considered to be a reason for immunotherapy failure in PDAC. In this study, we explored the correlation between immune escape-related genes and the prognosis of PDAC patients.

Methods

1163 PDAC patients from four public databases, including The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Array-express, and Gene Expression Omnibus (GEO), were included in our study. Cox regression analysis was used to identify the 182 immune genes which were significantly associated with overall survival (OS). And then we established an immune escape-related gene prognosis index (IEGPI) score using several datasets as the training cohort and validated it using the validation cohort. Kaplan-Meier (KM) and Cox regression analysis were used to detect the relationship of IEGPI score with OS. We further explored the relationship between the IEGPI and immune indexes. And the prediction value of response for immunotherapy in Tumor Immune Dysfunction and Exclusion (TIDE) dataset.

Results

We establish an IEGPI score based on 27 immune escape genes which were significantly related to the prognosis of OS in PDAC patients. Patients in the high-IEGPI group had a significantly worse overall survival rate compared with that in the low-IEGPI groups by KM curves and cox-regression. 5 of the 32 cancer types in TCGA could be significantly distinguished in survival rates through the low- and high-IEGPI groups. Moreover, the correlation between the IEGPI score was negatively correlated with an immune score in several datasets. And higher IEGPI better recurrence-free survival (RFS) and OS in the patients after patients were treated with both PD-1 and CTLA4 in the public datasets (P<0.05). Intriguingly, by using RT-PCR, we verified that the gene of PTPN2, CEP55, and JAK2 were all higher in the BxPC-3 and PANC-1 than HPDE5 cells. Lastly, we found that the IEGPI score was higher in K-rasLSL.G12D/+, p53LSL.R172H/+, Pdx1Cre (KPC) mice model with anti-PD-L1 than that without anti-PD-L1.

Conclusion

Using the immune escape-related genes, our study established and validated an IEGPI score in PDAC patients from the public dataset. IEGPI score has the potential to serve as a prognostic marker and as a tool for selecting tumor patients suitable for immunotherapy in clinical practice.
Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs
Authors: Rowlison de Ortiz Avery , Belda Beatriz , Hash Jon , Enomoto Masataka , Robertson James , Lascelles B. Duncan X.
Published: September 2022

Background

Accelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain.

Methods

This was an observational, non-interventional study in healthy dogs and dogs with OA-pain. All dogs were outfitted with the PetPace collar and the Actical monitor simultaneously for 14 days. Output from these devices was compared (correlations), and output from the PetPace device was used to explore differences between groups across the activity and vital sign outputs (including calculated heart rate variability indices).

Results

There was moderate correlation between the PetPace collar and Actical monitor output (R2= 0.56,p< 0.001). Using data generated by the PetPace collar, OA-pain dogs had lower overall activity counts and spent less time standing than healthy dogs. Healthy dogs spent more time at higher activity levels than OA-pain dogs. Certain heart rate variability indices in OA-pain dogs were lower than in healthy dogs.

Conclusions and clinical relevance

The results of this study suggest that the PetPace collar can detect differences between healthy dogs and those with OA-pain, and that OA-pain negatively impacts overall activity levels in dogs, and especially higher intensity activity.
Detection of a novel SETBP1 variant in a Chinese neonate with Schinzel–Giedion syndrome
Authors: Yang Hansong , Liu Zhiyong , Chen Dongmei , Lin Weiru , Wang Lin , Chen Tianfeng , Wang Ruiquan , Yan Xialin
Published: September 2022

Schinzel–Giedion syndrome (SGS) is a multiple malformation syndrome characterized by typical facial features, severe neurodevelopmental delay, and multiple congenital abnormalities. SGS is associated with de novo pathogenic variants in the SETBP1 gene. In specific, SETBP1 variants in over 50 patients with classical or non-classical SGS were clustered within exon 4. A male Chinese neonate with dysmorphic facial features, nervous system disorders, and organ malformations at birth was examined in this study and long-term followed-up. Whole-exome sequencing was performed to identify any underlying pathogenic variants in the proband. Additionally, we reviewed the literature that documents the main clinical features and underlying variants of all patients genetically diagnosed with SGS. The neonate had a characteristic midface retraction, abnormal electroencephalogram waveforms, and genital abnormalities. The patient did not initially develop hydronephrosis or undergo a comprehensive skeletal assessment. Six months after birth, the patient had an epileptic seizure and experienced persistent neurodevelopmental delay with auditory and visual abnormalities. Color Doppler ultrasonography at 18 months revealed hydronephrosis and bilateral widening of the lateral ventricles. The patient died suddenly 20.5 months after birth. Whole-exome sequencing revealed a heterozygous de novo variant (c.2605A > G:p.S869G) in exon 4 degradation sequence in SETBP1. The reported de novo heterozygous variant in SETBP1 (c.2605A > G:p.S869G) broadens the knowledge of the scientific community's on the possible SGS genetic alterations. To the best of our knowledge, this is the first report of SETBP1 variant (c.2605A > G:p.S869G) in SGS. The clinical manifestations of neonatal SGS are atypical, and genetic testing is crucial for diagnosis. Long-term follow-up should be conducted after diagnosis to optimize the therapeutic interventions.
Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study
Authors: Suzuki Hiromi , Yasuda Saneyuki , Htun Yinmon , Aye Nant San San , Oo Hnin , Oo Thet Paing , Htut Zaw Lin , Koyano Kosuke , Nakamura Shinji , Kusaka Takashi
Published: September 2022

Background

Neonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET).

Methods

This retrospective cohort study was conducted at the Central Women’s Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer’s rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth.

Results

Groups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8–67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively).

Conclusion

The management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.
Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism
Authors: Wang Shan , Hao Hui-feng , Jiao Yan-na , Fu Jia-lei , Guo Zheng-wang , Guo Yang , Yuan Yuan , Li Ping-ping , Han Shu-yan
Published: September 2022

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.
Functional characterization of cannabidiol effect on the serotonergic neurons of the dorsal raphe nucleus in rat brain slices
Authors: Mendiguren Aitziber , Aostri Erik , Alberdi Elena , Pérez-Samartín Alberto , Pineda Joseba
Published: September 2022

Cannabidiol (CBD), the main non-psychoactive cannabinoid found in the cannabis plant, elicits several pharmacological effects via the 5-HT1A receptor. The dorsal raphe nucleus (DRN) is the main serotonergic cluster in the brain that expresses the 5-HT1A receptor. To date, the effect of CBD on the neuronal activity of DRN 5-HT cells and its interaction with somatodendritic 5-HT1A autoreceptors have not been characterized. Our aim was to study the effect of CBD on the firing activity of DRN 5-HT cells and the 5-HT1A autoreceptor activation by electrophysiological and calcium imaging techniques in male Sprague–Dawley rat brain slices. Perfusion with CBD (30 μM, 10 min) did not significantly change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (50–100 μM, 1 min). However, in the presence of CBD (30 μM, 10 min), the inhibitory effects of 8-OH-DPAT (10 nM) and ipsapirone (100 nM) were reduced by 66% and 53%, respectively. CBD failed to reverse ipsapirone-induced inhibition, whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30 nM) completely restored by 97.05 ± 14.63% the firing activity of 5-HT cells. Administration of AM251 (1 µM), MDL100907 (30 nM), or picrotoxin (20 μM) did not change the blockade produced by CBD (30 μM) on ipsapirone-induced inhibition. Our study also shows that CBD failed to modify the KCl (15 mM, 4 min)-evoked increase in [Ca2+]i or the inhibitory effect of ipsapirone (1 μM, 4 min) on KCl-evoked [Ca2+]i. In conclusion, CBD does not activate 5-HT1A autoreceptors, but it hindered the inhibitory effect produced by selective 5-HT1A receptor agonists on the firing activity of DRN 5-HT cells through a mechanism that does not involve CB1, 5-HT2A, or GABAA receptors. Our data support a negative allosteric modulation of DRN somatodendritic 5-HT1A receptor by CBD.
Global research trends on maternal exposure to methylmercury and offspring health outcomes
Authors: Nascimento Priscila Cunha , Ferreira Maria Karolina Martins , Bittencourt Leonardo Oliveira , Martins-Júnior Paulo Antônio , Lima Rafael Rodrigues
Published: September 2022

This study aimed to analyze the landscape of maternal methylmercury exposure and its offspring consequences based on knowledge mapping of the 100 most-cited papers about this theme. A search was performed using the Web of Science, without any restriction of language or publication year. Data bibliometrics, such as the number of citations, citation density, corresponding author’s country, year of publication, study design, and keywords, were extracted from each paper and analyzed. VOSviewer software was used to create graphical bibliometric maps. Of a total of 1,776 studies on this theme, the 100 most-cited papers rendered the number of citations ranged from 110 to 1,356 citations. The non-systematic reviews and cohort studies from Anglo-Saxon countries published in the first decade of the 2000s were the most frequent. Clarkson, Grandjean, and Myers were the authors with higher citation density. A total of 520 keywords represented the evolution of the theme, from classic episodes of MeHg intoxication, as well as main the health changes until the different forms of exposure and, in recent years, biomonitoring studies were highlighted. Our findings provide the global research trends highlighting the network of most influential authors and a better understanding of the evolution and future scenarios of this theme.
Enoxacin ameliorates polycystic ovary syndrome by promoting the browning of white adipose tissue and restoring gut dysbiosis
Authors: Zhu Wanlong , Fu Liya , Xu Changjing , Peng Ke , Liu Yuanzhi , Tang Hui , Huang Yilan , Yang Xuping
Published: September 2022

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder syndrome characterized by polycystic ovary, ovulation disorder and hyperandrogenemia, and is often accompanied by metabolic disorders. Enoxacin has been reported to protect against diet-induced obesity and insulin resistance by promoting fat thermogenesis. However, the function of enoxacin in PCOS remains unknown. This study aimed to investigate the impact of the enoxacin on the regulation of PCOS mouse model induced by dehydroepiandrosterone (DHEA). Here, we found that reproductive endocrine disorder, glucose intolerance, and ovarian dysfunction in PCOS mice induced by DHEA were attenuated by enoxacin treatment. Mechanistically, we identified that enoxacin can promote white fat browning and improve metabolic disorders, thus ameliorating DHEA-induced reproductive dysfunction. Moreover, these beneficial effects might be associated with the restoration of gut dysbiosis. These findings provide a novel therapeutic target for enoxacin in the treatment of PCOS.
Jian-Ti-Kang-Yi decoction alleviates poly(I:C)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism
Authors: Cui Huantian , Wang Yuming , Yu Bolun , Wu Yulin , Zhang Gaijun , Guo Junli , Luo Junyu , Li Qin , Li Xiaojuan , He Wenju , Wen Weibo , Liao Jiabao , Wang Dongqiang
Published: September 2022

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86+/CD206+ macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b+Ly6G+ neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung.
Self-supervised neural network improves tri-exponential intravoxel incoherent motion model fitting compared to least-squares fitting in non-alcoholic fatty liver disease
Authors: Troelstra Marian A. , Van Dijk Anne-Marieke , Witjes Julia J. , Mak Anne Linde , Zwirs Diona , Runge Jurgen H. , Verheij Joanne , Beuers Ulrich H. , Nieuwdorp Max , Holleboom Adriaan G. , Nederveen Aart J. , Gurney-Champion Oliver J.
Published: September 2022

Recent literature suggests that tri-exponential models may provide additional information and fit liver intravoxel incoherent motion (IVIM) data more accurately than conventional bi-exponential models. However, voxel-wise fitting of IVIM results in noisy and unreliable parameter maps. For bi-exponential IVIM, neural networks (NN) were able to produce superior parameter maps than conventional least-squares (LSQ) generated images. Hence, to improve parameter map quality of tri-exponential IVIM, we developed an unsupervised physics-informed deep neural network (IVIM3-NET). We assessed its performance in simulations and in patients with non-alcoholic fatty liver disease (NAFLD) and compared outcomes with bi-exponential LSQ and NN fits and tri-exponential LSQ fits. Scanning was performed using a 3.0T free-breathing multi-slice diffusion-weighted single-shot echo-planar imaging sequence with 18 b-values. Images were analysed for visual quality, comparing the bi- and tri-exponential IVIM models for LSQ fits and NN fits using parameter-map signal-to-noise ratios (SNR) and adjusted R2. IVIM parameters were compared to histological fibrosis, disease activity and steatosis grades. Parameter map quality improved with bi- and tri-exponential NN approaches, with a significant increase in average parameter-map SNR from 3.38 to 5.59 and 2.45 to 4.01 for bi- and tri-exponential LSQ and NN models respectively. In 33 out of 36 patients, the tri-exponential model exhibited higher adjusted R2 values than the bi-exponential model. Correlating IVIM data to liver histology showed that the bi- and tri-exponential NN outperformed both LSQ models for the majority of IVIM parameters (10 out of 15 significant correlations). Overall, our results support the use of a tri-exponential IVIM model in NAFLD. We show that the IVIM3-NET can be used to improve image quality compared to a tri-exponential LSQ fit and provides promising correlations with histopathology similar to the bi-exponential neural network fit, while generating potentially complementary additional parameters.