bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of On-Admission Anemia With 1-Year Mortality in Patients Hospitalized With Acute Heart Failure: Results From the HERO Study
Authors: Li Junlei , Jiang Chao , Lai Yiwei , Li Li , Zhao Xiaoyan , Wang Xiaofang , Li Ling , Du Xin , Ma Changsheng , Dong Jianzeng
Published: May 2022

Background

Anemia is common in patients with chronic heart failure (HF) and is associated with adverse outcomes. However, data regarding the prognostic value of on-admission anemia on mortality in patients hospitalized with acute HF were relatively limited and conflicting. This study aimed to investigate the association of on-admission anemia with 1-year mortality and evaluate whether anemia is an independent predictor of mortality in patients hospitalized with acute HF.

Methods

The present analysis included 4,244 patients hospitalized with acute HF from the HERO (Heart Failure Registry of Patient Outcomes) study. On-admission anemia was defined using the World Health Organization (WHO) criteria (hemoglobin <120 g/L in women and <130 g/L in men). Cox proportional hazards models were used to assess the association of anemia with 1-year all-cause and cardiovascular mortality.

Results

Of 4,244 patients, 2,206 (52.0%) patients had no anemia, 1,106 (26.1%) patients had mild anemia (men 110 ≤ hemoglobin < 130 g/L; women 110 ≤ hemoglobin < 120g/L), and 932 (22.0%) patients had moderate-to-severe anemia (hemoglobin < 110 g/L). After a median follow-up of 12.4 months (interquartile range: 11.9, 12.6), 867 (20.4%) patients died. Among the 742 (85.6%) deaths with confirmed causes, 664 (89.5%) were due to cardiovascular diseases. The mortality rates in patients with no anemia, mild anemia, and moderate-to-severe anemia were 16.6%, 20.4%, and 29.4%, respectively (p < 0.001). The association of anemia with increased all-cause mortality was significant in the unadjusted model (hazard ratio [HR]: 1.54, 95% confidential interval [CI]: 1.35–1.77, p < 0.001), and remained statistically significant after adjustment for most potential confounders (HR: 1.20, 95%CI: 1.03–1.40, p = 0.020), but no longer significant after additional adjustment for natriuretic peptides (HR: 1.02, 95%CI: 0.86–1.21, p = 0.843). When considering the degree of anemia, moderate-to-severe anemia was an independent predictor of all-cause mortality after full adjustment (HR:1.26, 95%CI: 1.03–1.54, p = 0.028), whereas mild anemia was not (HR: 0.84, 95%CI: 0.69–1.04, p = 0.104). A similar relationship was also found between anemia and cardiovascular mortality.

Conclusions

On-admission anemia, defined by the WHO criteria, is not an independent predictor of mortality in patients hospitalized with acute HF. Moderate-to-severe anemia in patients with acute HF is independently associated with increased mortality.
Long-Term Survival of Adult Patients With Atrial Septal Defect With Regards to Defect Closure and Pulmonary Hypertension
Authors: Rubáčková Popelová Jana , Tomková Markéta , Tomek Jakub , Živná Renata
Published: May 2022

Background

Atrial septal defect (ASD) is the most common congenital heart disease (CHD) in adults and pulmonary hypertension (PH) is an established risk factor. A decision whether to perform ASD closure, especially in elderly patients with PH, is a complex dilemma. The aim of our study was to compare long-term survival in patients with closed and open ASD.

Methods

A retrospective cohort study was performed on 427 patients with ASD (median age at diagnosis 38 years, IQR 18–56) out of which 186 patients (44%) manifested PH. ASD closure in patients with PH was only considered in patients without Eisenmenger syndrome with pulmonary vascular resistance < 5 WU. Median follow-up duration was 18 years (IQR 9–31 years). Kaplan-Meier and Cox proportional hazards survival analyses were performed to evaluate 12 potential predictors of survival.

Results

Defect closure was associated with improved long-term survival in ASD patients both with (P < 0.001) and without PH (P = 0.01) and this association was present also in patients over 40 years. The 20-year survival since diagnosis was significantly higher in patients with PH and closed ASD compared to those with PH and open ASD (65% vs. 41%). ASD closure was a significant independent predictor of long-term survival (P = 0.003) after accounting for age at diagnosis, PH, NYHA class, Eisenmenger syndrome, and mitral regurgitation. Significant negative independent predictors of survival were older age at diagnosis (P < 0.001), Eisenmenger syndrome (P < 0.001), and PH (P = 0.03).

Conclusion

ASD closure appears to be associated with improved long-term survival independently of age, PH, and other clinical variables.
A New Fracture Parameter Optimization Method for the Horizontal Well Section of Shale Oil
Authors: Ma Chunxiao , Xing Yun , Qu Yiqian , Cheng Xin , Wu Hanning , Luo Pan , Xu Pengxiang
Published: May 2022

Hydraulic fracturing is the most prominently used technique for increasing well productivity in shale oil reservoirs. Therefore, studying the method for optimizing fracture parameters is essential in the development of shale oil. This study established a mathematical model of non-Darcy flow in the fractured horizontal well section of a shale oil reservoir which considered the influence of the threshold pressure gradient. The finite element method was used to solve the problem, and the calculation method of pressure field and productivity was given. This model is used to study the optimal number of clusters, optimal cluster spacing, optimal fracture length, and optimal fracture conductivity in a horizontal well section. Simulation shows that the optimal number of clusters in a horizontal well section is five when the permeability is 0.02 × 10–3 μm2–∼0.10 × 10–3 μm2, and the optimal number is four when the permeability range is 0.15 × 10–3 μm2–∼0.30 × 10–3 μm2. With the increase in the number of clusters, the stimulation effect is more sufficient, the interference effect between fractures is enhanced, and the loss of stratum energy is accelerated. The optimal cluster spacing is 30 m. Several cases of non-uniform cluster spacing have little effect on the stimulation effect. The cluster number and the sum of the cluster spacing are the determinant factors affecting the stimulation effect. The optimal fracture half-length is 140 m. Several cases of the non-uniform fracture length have little effect on the stimulation effect. The cluster number and the sum of the length of the fracture are the determinant factors affecting the stimulation effect. The optimal conductivity is 20 D•cm. At last, it proposed a fracture parameter optimization method considering the stratum energy loss and productivity.
Serum Exosomes MicroRNAs Are Novel Non-Invasive Biomarkers of Intrahepatic Cholestasis of Pregnancy
Authors: Dong Ruirui , Ye Ningzhen , Wang Jing , Zhao Shaojie , Wang Tiejun , Wang Gaoying , Shi Xinrui , Cheng Jing , Zhang Yan , Yao Tingting , Chen Minjian , Zhang Ting , Luo Liang
Published: May 2022

Background

Intrahepatic cholestasis of pregnancy (ICP) is closely related to the occurrence of adverse outcomes. Currently, total bile acids (TBAs) are the only diagnostic index for ICP, and its sensitivity and specificity have certain limitations. In this study, we aimed to develop potential biomarkers for the diagnosis of ICP.

Methods

Sixty pregnant women diagnosed with ICP and 48 healthy pregnant controls were enrolled in this study. We used the Agilent microRNA (miRNA) array followed by quantitative reverse transcriptase polymerase chain reaction assays to identify and validate the serum exosome miRNA profiles in ICP and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed serum exosome miRNAs.

Results

The expression levels of hsa-miR-4271, hsa-miR-1275, and hsa-miR-6891-5p in maternal serum exosomes were significantly lower in ICP patients compared to controls; the diagnostic accuracy of hsa-miR-4271, hsa-miR-1275, and hsa-miR-6891-5p was evaluated with the area under the receiver operating characteristic curve (AUC) values of 0.861, 0.886, and 0.838, respectively. Multiple logistic regression analysis showed that a combination of the levels of hsa-miR-4271and hsa-miR-1275 afforded a significantly higher AUC (0.982). The non-error rate of a combination of all three exosome miRNAs was the highest (95%), thus more reliable ICP diagnosis. The expression levels of all three exosome miRNAs were negatively associated with TBAs. Furthermore, according to bioinformatics analysis, the three exosome miRNAs were related to lipid metabolism, apoptosis, oxidative stress, and the Mitogen Activated Protein Kinase (MAPK) signaling pathway.

Conclusions

This study may identify the novel non-invasive biomarkers for ICP and provided new insights into the important role of the exosome miRNA regulation in ICP.
Adaptive Changes in Glucose Homeostasis and Islet Function During Pregnancy: A Targeted Metabolomics Study in Mice
Authors: Zhang Ziyi , Piro Anthony L. , Dai Feihan F. , Wheeler Michael B.
Published: May 2022

Objective

Pregnancy is a dynamic state involving multiple metabolic adaptions in various tissues including the endocrine pancreas. However, a detailed characterization of the maternal islet metabolome in relation to islet function and the ambient circulating metabolome during pregnancy has not been established.

Methods

A timed-pregnancy mouse model was studied, and age-matched non-pregnant mice were used as controls. Targeted metabolomics was applied to fasting plasma and purified islets during each trimester of pregnancy. Glucose homeostasis and islet function was assessed. Bioinformatic analyses were performed to reveal the metabolic adaptive changes in plasma and islets, and to identify key metabolic pathways associated with pregnancy.

Results

Fasting glucose and insulin were found to be significantly lower in pregnant mice compared to non-pregnant controls, throughout the gestational period. Additionally, pregnant mice had superior glucose excursions and greater insulin response to an oral glucose tolerance test. Interestingly, both alpha and beta cell proliferation were significantly enhanced in early to mid-pregnancy, leading to significantly increased islet size seen in mid to late gestation. When comparing the plasma metabolome of pregnant and non-pregnant mice, phospholipid and fatty acid metabolism pathways were found to be upregulated throughout pregnancy, whereas amino acid metabolism initially decreased in early through mid pregnancy, but then increased in late pregnancy. Conversely, in islets, amino acid metabolism was consistently enriched throughout pregnancy, with glycerophospholid and fatty acid metabolism was only upregulated in late pregnancy. Specific amino acids (glutamate, valine) and lipids (acyl-alkyl-PC, diacyl-PC, and sphingomyelin) were found to be significantly differentially expressed in islets of the pregnant mice compared to controls, which was possibly linked to enhanced insulin secretion and islet proliferation.

Conclusion

Beta cell proliferation and function are elevated during pregnancy, and this is coupled to the enrichment of islet metabolites and metabolic pathways primarily associated with amino acid and glycerophospholipid metabolism. This study provides insight into metabolic adaptive changes in glucose homeostasis and islet function seen during pregnancy, which will provide a molecular rationale to further explore the regulation of maternal metabolism to avoid the onset of pregnancy disorders, including gestational diabetes.
Effect of Comorbid Diabetes on Clinical Characteristics of COVID-19 Patients Infected by the Wild-Type or Delta Variant of SARS-CoV-2
Authors: Zhang Jianguo , Zhang Jinhui , Tao Zhimin
Published: May 2022

Background

Diabetes is one of the most common comorbidities in COVID-19 patients that pertains to disease severity, but the causal mechanism regarding its negative impact on COVID-19 outcome has yet been uncovered.

Methods

We retrospectively analyzed 459 COVID-19 patients admitted in early 2020 and 336 COVID-19 patients admitted in August 2021, with their demographic information, medical history, vaccination status (if applied), and laboratory data reported.

Results

Among COVID-19 patients, compared to the non-diabetic group, the diabetic group exhibited elder age, higher proportion of patients with other major comorbidities, more severe dysfunction of innate immune cells, more refractory blood coagulopathy and more detrimental organ damage. For the wild-type SARS-CoV-2 infection, diabetic comorbidity was associated with COVID-19 severity but not mortality, and the glycemic levels in the non-diabetic group upon infection experienced high and analogous to those in the diabetic group. Besides, infected by the delta variant of SARS-CoV-2, the non-diabetic patients did not demonstrate hyperglycemia, and despite different vaccination statuses, the diabetic patients exhibited comparable antibody responses to non-diabetic, showing the robustness of acquired immunity.

Conclusions

SARS-CoV-2 infection may superimpose the deterioration of innate immune systems in diabetic patients, which contributes to their worsened disease outcome, but timely COVID-19 immunization could provide adequate protection in diabetic population that leads to favored prognosis.
Thyroid Dysfunction and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Charoenngam Nipith , Rittiphairoj Thanitsara , Ponvilawan Ben , Prasongdee Klaorat
Published: May 2022

Objective

Studies have suggested that patients with thyroid dysfunction may have an increased risk of developing Parkinson’s disease (PD). However, the results from existing studies are inconsistent. Therefore, we aimed to investigate the association of hypothyroidism and hyperthyroidism with risk of PD using the method of systematic review and meta-analysis.

Methods

Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 2021 using search strategy that comprised of terms for “Thyroid” and “Parkinson’s Disease”. Eligible cohort study must consist of one cohort of patients with hypothyroidism/hyperthyroidism and another cohort of individuals without hypothyroidism/hyperthyroidism. Then, the study must report effect estimates with 95% confidence intervals (95% CIs) comparing incident PD between the groups. Eligible case-control studies must include cases with PD and controls without PD. Then, the study must explore their history of hypothyroidism/hyperthyroidism. Odds ratio (OR) with 95% CIs of the association between presence of hypothyroidism/hyperthyroidism and PD must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method.

Results

A total of 3,147 articles were identified. After two rounds of independent review by three investigators, 3 cohort studies and 6 case-control studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed an increased likelihood of PD in both patients with hypothyroidism (pooled OR 1.56; 95%CI, 1.38 – 1.77; with moderate heterogeneity, I2 66.9%) and patients with hyperthyroidism (pooled OR 1.57; 95%CI, 1.40 – 1.77; with insignificant heterogeneity, I2 0.0%). Funnel plots for both meta-analyses were fairly symmetric, which did not indicate presence of publication bias.

Conclusion

This systematic review and meta-analysis found a significant association of both hypothyroidism and hyperthyroidism with an increased risk of PD.
Brain Activation in Response to Low-Calorie Food Pictures: An Explorative Analysis of a Randomized Trial With Dapagliflozin and Exenatide
Authors: van Ruiten Charlotte C. , Veltman Dick J. , Nieuwdorp Max , IJzerman Richard G.
Published: May 2022

Background and Aim

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce less weight loss than expected. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, contributing to increased appetite and food intake. This hyperphagia may be specific to high-calorie foods. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with lower preferences for high-calorie foods, and with decreased activation in areas regulating satiety and reward in response to high-calorie food pictures, which may reflect this lower preference for energy-dense foods. To optimize treatment, we need a better understanding of how intake is controlled, and how [(un)healthy] food choices are made. The aim of the study was to investigate the effects of dapagliflozin, exenatide, and their combination on brain activation in response to low-calorie food pictures.

Methods

We performed an exploratory analysis of a larger, 16-week, double-blind, randomized, placebo-controlled trial. Sixty-eight subjects with obesity and type 2 diabetes were randomized to dapagliflozin, exenatide, dapagliflozin plus exenatide, or double placebo. Using functional MRI, the effects of treatments on brain responses to low-calorie food pictures were assessed after 10 days and 16 weeks.

Results

Dapagliflozin versus placebo decreased activity in response to low-calorie food pictures, in the caudate nucleus, insula, and amygdala after 10 days, and in the insula after 16 weeks. Exenatide versus placebo increased activation in the putamen in response to low-calorie food pictures after 10 days, but not after 16 weeks. Dapagliflozin plus exenatide versus placebo had no effect on brain responses, but after 10 days dapagliflozin plus exenatide versus dapagliflozin increased activity in the insula and amygdala in response to low-calorie food pictures.

Conclusion

Dapagliflozin decreased activation in response to low-calorie food pictures, which may reflect a specific decreased preference for low-calorie foods, in combination with the previously found increased activation in response to high-calorie foods, which may reflect a specific preference for high-calorie foods, and may hamper SGLT2i-induced weight loss. Exenatide treatment increased activation in response to low-calorie foods. Combination treatment may lead to more favorable brain responses to low-calorie food cues, as we observed that the dapagliflozin-induced decreased response to low-calorie food pictures had disappeared.
Novel Glycemic Index Based on Continuous Glucose Monitoring to Predict Poor Clinical Outcomes in Critically Ill Patients: A Pilot Study
Authors: Ha Eun Yeong , Chung Seung Min , Park Il Rae , Lee Yin Young , Choi Eun Young , Moon Jun Sung
Published: May 2022

Aim

We explored the prospective relationship between continuous glucose monitoring (CGM) metrics and clinical outcomes in patients admitted to the intensive care unit (ICU).

Materials and Methods

We enrolled critically ill patients admitted to the medical ICU. Patients with an Acute Physiology and Chronic Health Evaluation (APACHE) score ≤9 or ICU stay ≤48 h were excluded. CGM was performed for five days, and standardized CGM metrics were analyzed. The duration of ICU stay and 28-day mortality rate were evaluated as outcomes.

Results

A total of 36 patients were included in this study (age [range], 49–88 years; men, 55.6%). The average APACHE score was 25.4 ± 8.3; 33 (91.7%) patients required ventilator support, and 16 (44.4%) patients had diabetes. The duration of ICU stay showed a positive correlation with the average blood glucose level, glucose management indicator (GMI), time above range, and GMI minus (-) glycated hemoglobin (HbA1c). Eight (22.2%) patients died within 28 days, and their average blood glucose levels, GMI, and GMI-HbA1c were significantly higher than those of survivors (p<0.05). After adjustments for age, sex, presence of diabetes, APACHE score, and dose of steroid administered, the GMI-HbA1c was associated with the risk of longer ICU stay (coefficient=2.34, 95% CI 0.54-4.14, p=0.017) and higher 28-day mortality rate (HR=2.42, 95% CI 1.01-5.76, p=0.046).

Conclusion

The acute glycemic gap, assessed as GMI-HbA1c, is an independent risk factor for longer ICU stay and 28-day mortality rate. In the ICU setting, CGM of critically ill patients might be beneficial, irrespective of the presence of diabetes.
Follow-Up of Thyroid Function in Children With Neonatal Hyperthyroidism
Authors: Pyrżak Beata , Rumińska Małgorzata , Witkowska-Sędek Ewelina , Kucharska Anna
Published: May 2022

Introduction

Neonatal hyperthyroidism mainly occurring in the children born to mothers with Graves’ disease (GD). The influence of maternal GD on the newborn’s thyroid function includes not only hyperthyroidism, but also various forms of hypothyroidism. Maternally transferred thyrotropin receptor antibodies (TRAb), the antithyroid drug (ATD) administration during pregnancy and previous definitive treatment of GD (radioactive iodine therapy or thyroidectomy) in the mother impact the function of the fetal/neonatal thyroid. Some newborns born to mothers with GD may present central hypothyroidism (CeH) due to impaired regulation of the fetal hypothalamic-pituitary-thyroid axis. The aim of this study was to evaluate different types of thyroid dysfunction in babies with neonatal hyperthyroidism.

Materials and Methods

Medical records of 14 infants with neonatal hyperthyroidism (13 born to mothers with GD, and one born to mother with Hashimoto thyroiditis) were analyzed.

Results

Transient hyperthyroidism was the main thyroid dysfunction in our study group. Overt hyperthyroidism with highly increased TRAb levels (mean 13.0 ± 7.0 IU/L) was diagnosed in 6 (43%) neonates. Another 6 (43%) babies presented hyperthyroidism with slightly increased fT4 and/or fT3 levels and TSH levels in the lower limit of the normal range coinciding with positive TRAb levels (mean 3.8 ± 1.6 IU/L). Normal thyroid hormone levels with TSH levels below the lower limit of the range were observed in 2 (14%) neonates. Four babies in the study group (28.5%) required further levothyroxine (L-T4) supplementation due to CeH or, in one case, due to primary hypothyroidism.

Conclusion

Our study highlights the need for prolonged monitoring of thyroid function in children born to mothers with GD. Diagnosis of CeH could be delayed due to its masking by transient hyperthyroidism. Prolonged thyroid-stimulating hormone suppression after TRAb elimination should be considered as a signal announcing CeH.
The Foundation for Engineering a Pancreatic Islet Niche
Authors: Patel Smit N. , Mathews Clayton E. , Chandler Rachel , Stabler Cherie L.
Published: May 2022

Progress in diabetes research is hindered, in part, by deficiencies in current experimental systems to accurately model human pathophysiology and/or predict clinical outcomes. Engineering human-centric platforms that more closely mimic in vivo physiology, however, requires thoughtful and informed design. Summarizing our contemporary understanding of the unique and critical features of the pancreatic islet can inform engineering design criteria. Furthermore, a broad understanding of conventional experimental practices and their current advantages and limitations ensures that new models address key gaps. Improving beyond traditional cell culture, emerging platforms are combining diabetes-relevant cells within three-dimensional niches containing dynamic matrices and controlled fluidic flow. While highly promising, islet-on-a-chip prototypes must evolve their utility, adaptability, and adoptability to ensure broad and reproducible use. Here we propose a roadmap for engineers to craft biorelevant and accessible diabetes models. Concurrently, we seek to inspire biologists to leverage such tools to ask complex and nuanced questions. The progenies of such diabetes models should ultimately enable investigators to translate ambitious research expeditions from benchtop to the clinic.
Central Diabetes Insipidus Following Immunization With BNT162b2 mRNA COVID-19 Vaccine: A Case Report
Authors: Bouça Bruno , Roldão Marisa , Bogalho Paula , Cerqueira Luís , Silva-Nunes José
Published: May 2022

Introduction

Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines potential adverse effects may mimetize some of these complications.

Case Report

Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician.

Blood Analysis

creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0’ – Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60’ - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed, and started therapy with desmopressine. A report of potential adverse effect was addressed to national health authorities.

Conclusion

In hypophysitis MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following administration of a COVID-19 vaccine.
Sellar Glomus Tumor Misdiagnosed as Pituitary Adenoma: A Case Report and Review of the Literature
Authors: Cheng Yijun , Tang Hao , Wu Zhe Bao
Published: May 2022

Glomus tumor is a rare mesenchymal tumor with an organ-like structure. Sellar glomus tumors are extremely rare with only six reported cases in the literature. Because of the lack of special clinical manifestations and imaging features, the disorder may be easily misdiagnosed as other sellar tumors, especially pituitary adenomas. Here, the present study showed a case of a 69-year-old male with hypopituitarism who was preliminarily misdiagnosed as non-functional pituitary adenoma.
Updates in Sertoli Cell-Mediated Signaling During Spermatogenesis and Advances in Restoring Sertoli Cell Function
Authors: Ruthig Victor A. , Lamb Dolores J.
Published: May 2022

Since their initial description by Enrico Sertoli in 1865, Sertoli cells have continued to enchant testis biologists. Testis size and germ cell carrying capacity are intimately tied to Sertoli cell number and function. One critical Sertoli cell function is signaling from Sertoli cells to germ cells as part of regulation of the spermatogenic cycle. Sertoli cell signals can be endocrine or paracrine in nature. Here we review recent advances in understanding the interplay of Sertoli cell endocrine and paracrine signals that regulate germ cell state. Although these findings have long-term implications for treating male infertility, recent breakthroughs in Sertoli cell transplantation have more immediate implications. We summarize the surge of advances in Sertoli cell ablation and transplantation, both of which are wedded to a growing understanding of the unique Sertoli cell niche in the transitional zone of the testis.
Flow Field and Particle Flow of Two-Stage Deep-Sea Lifting Pump Based on DEM-CFD
Authors: Yuanwen Li , Zhiming Guo , Liu Shaojun , Xiaozhou Hu
Published: May 2022

Through discrete element method-computational fluid dynamics, the internal flow field and particle motion law of a two-stage deep-sea lifting pump at different rotational speeds were analyzed in this work. In addition, the physical phenomena, such as flow field velocity, secondary flow, and particle flow, were studied. The relationship between the rotational speed of the lifting pump and solid–liquid two-phase flow was investigated. An experiment on the hydraulic performance of the lift pump showed that the resulting lift and efficiency were consistent with the numerical simulation data. When the rotational speed was 1,450 rpm, the particles can obtain a higher kinetic energy from the flow field, the flow was more stable, and particle deposition was reduced.
Rapid Identification of Interwell Fracture-Cavity Combination Structure in Fracture-Cavity Reservoir Based on Tracer-Curve Morphological Characteristics
Authors: Jing Cheng , Zhang Shaowei , Li Lu , Wang Jian , Chen Bo , Tian Bo , Dai Zhiyuan , Gao Le
Published: May 2022

Rapid and effective identification of interwell fracture-cavity composite structures is a necessary prerequisite for a detailed and in-depth understanding of interwell connectivity in fracture-cavity reservoirs. Current identification methods and technologies have the problems of being large-scale and low-resolution; in view of these problems, a method is proposed for rapidly identifying interwell fracture-cavity combination structures using tracer-curve morphological characteristics (peak number and characteristics of two wings). Based on concentration models of tracer curves for an interwell single fracture/pipe/cavity, the morphological characteristics of tracer curves were researched in five different series-parallel combination modes consisting of fractures, pipes, and cavities. The tracer curves of fracture-cavity reservoirs are categorized into three types: single sharp peak, single slow peak, and multipeak. Furthermore, a matching relationship between different fracture-cavity combination structures and the morphological characteristics of tracer curves is clarified. The single-sharp-peak curve with basically symmetrical wings reflects that of an interwell single fracture/pipe; the single-slow-peak curve with a steep ascending branch and a slow descending branch (obvious trailing phenomenon) reflects that of an interwell single cavity or fracture/pipe series cavity; the multipeak curve reflects that of an interwell multifracture/pipe/cavity in parallel; according to the flow difference of each branch flow channel, they can be divided into independent multipeak and continuous multipeak forms. Taking tracer monitoring results from a well group in the Tahe oilfield as an example, field application analysis and verification were carried out. The results show that this method is simple and reliable and can provide a fast and effective means for identifying interwell fracture-cavity combination structures. Meanwhile, the research results can lay a foundation for quantitative interpretation modeling of interwell tracers in fracture-cavity reservoirs considering fracture-cavity configuration.
Characterization of Montmorillonite–Biochar Composite and Its Application in the Removal of Atrazine in Aqueous Solution and Soil
Authors: Wang Pingping , Stenrød Marianne , Wang Liang , Yuan Shankui , Mao Liangang , Zhu Lizhen , Zhang Lan , Zhang Yanning , Jiang Hongyun , Zheng Yongquan , Liu Xingang
Published: May 2022

Atrazine is a widely used triazine herbicide, which poses a serious threat to human health and aquatic ecosystem. A montmorillonite–biochar composite (MMT/BC) was prepared for atrazine remediation. Biochar samples were characterized by using scanning electron microscope (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Structural and morphological analysis of raw biochar (BC) and MMT/BC showed that MMT particles have been successfully coated on the surface of biochar. Sorption experiments in aqueous solution indicated that the MMT/BC has higher removal capacity of atrazine compared to BC (about 3.2 times). The sorption of atrazine on the MMT/BC was primarily controlled by both physisorption and chemisorption mechanisms. The amendment of MMT/BC increased the sorption capacity of soils and delayed the degradation of atrazine. Findings from this work indicate that the MMT/BC composite can effectively improve the sorption capacity of atrazine in aquatic environment and farmland soil and reduce the environmental risk.
The Impacts of Carbon Emissions and Energy Consumption on Life Satisfaction: Evidence From China
Authors: Li Jiaying , Chen Fuzhong
Published: May 2022

This study investigates how carbon emissions and energy consumption related to the life satisfaction of Chinese households over the 2010–2018 period. The China Family Panel Studies (CFPS) data from 25 Chinese provinces shows that the effect of provincial carbon emissions on life satisfaction is positive, and increases in fuel and electricity consumption also predict a higher life satisfaction level. Fuel consumption, especially, has a greater impact on life satisfaction among older people with lower income or education levels. In addition, an increase in relative energy consumption negatively affects Chinese households’ life satisfaction. Heterogeneity analysis demonstrates that the relative fuel consumption change has a larger negative life satisfaction effect for younger, less educated or rural people. In developed regions (including Beijing and Shanghai), a strong inverse relationship between carbon emissions and the residents’ life satisfaction exists in China, but the effects of residents’ own and relative energy consumption are insignificant or slight.
Single-Cell Transcriptomics Uncovers Cellular Heterogeneity, Mechanisms, and Therapeutic Targets for Parkinson’s Disease
Authors: Huang Jianjun , Liu Li , Qin Lingling , Huang Hehua , Li Xue
Published: May 2022

Objective: This study aimed to exploit cellular heterogeneity for revealing mechanisms and identifying therapeutic targets for Parkinson’s disease (PD) via single-cell transcriptomics.

Methods: Single-cell RNA sequencing (scRNA-seq) data on midbrain specimens from PD and healthy individuals were obtained from the GSE157783 dataset. After quality control and preprocessing, the principal component analysis (PCA) was presented. Cells were clustered with the Seurat package. Cell clusters were labeled by matching marker genes and annotations of the brain in the CellMarker database. The ligand–receptor networks were established, and the core cell cluster was selected. Biological functions of differentially expressed genes in core cell clusters were analyzed. Upregulated marker genes were identified between PD and healthy individuals, which were measured in 18 PD patients’ and 18 healthy individuals’ blood specimens through RT-qPCR and Western blotting.

Results: The first nine PCs were determined, which can better represent the overall change. Five cell clusters were identified, including oligodendrocytes, astrocytes, neurons, microglial cells, and endothelial cells. Among them, endothelial cells were the core cell cluster in the ligand–receptor network. Marker genes of endothelial cells possessed various biological functions. Among them, five marker genes (ANGPT2, APOD, HSP90AA1, HSPA1A, and PDE1C) were upregulated in PD patients’ than in healthy individuals’ endothelial cells, which were confirmed in PD patients’ than in healthy individuals’ blood specimens.

Conclusion: Our findings revealed that the cellular heterogeneity of PD and endothelial cells could play a major role in cell-to-cell communications. Five upregulated marker genes of endothelial cells could be underlying therapeutic targets of PD, which deserve more in-depth clinical research.
Computational Analysis Reveals the Characteristics of Immune Cells in Glomerular and Tubulointerstitial Compartments in IgA Nephropathy Patients
Authors: Li Bin , Li Suchun , Fan Yuting , Diao Hui , Ye Siyang , Peng Huajing , Chen Wei
Published: May 2022

Objective: The commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments of IgA nephropathy (IgAN) remains largely undetermined. We aim to perform bioinformatic analysis for providing a comprehensive insight into the characteristics of immune cells and associated molecular mechanisms in IgAN.

Materials and Methods: We performed integrated bioinformatic analyses by using IgAN-related datasets from the Gene Expression Omnibus database. First, the differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, CIBERSORT was employed to determine the landscape of infiltrating immune cells in both glomerular and tubulointerstitial compartments of IgAN patients, followed by Pearson’s correlation analysis and principal component analysis (PCA). Finally, commonly shared DEGs between glomerular and tubulointerstitial entities were recognized, followed by correlation analyses to identify the dominant commonly shared DEGs associated with immune cell infiltration in IgAN.

Results: GO and KEGG enrichment analyses showed apparently distinct biological processes in the glomerular and tubulointerstitial compartments of IgAN. In addition, CIBERSORT analyses revealed a clear trend of increasing proportions of M1 macrophage and M2 macrophage in the glomerular compartment while noticeably higher proportions of resting CD4+ memory T cells and M2 macrophages in the tubulointerstitial compartments. The PCA analyses showed that the varying composition of immune cells in both glomerular and tubulointerstitial entities was compelling to distinguish IgAN patients from healthy living controls. In addition, 21 commonly shared DEGs between glomerular and tubulointerstitial entities were recognized as key regulators in the pathogenesis of IgAN, among which the enhanced hemoglobin subunit beta (HBB) gene expression was found to be positively associated with M2 macrophage in the glomerular compartment and resting CD4+ memory T cells in the tubulointerstitial compartment. Most importantly, FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene deficiency was recognized as the dominant alteration in promoting M2 macrophage infiltration in the glomerular compartment of IgAN.

Conclusion: The findings from our current study for the first time reveal commonalities and differences regarding immune states between glomerular and tubulointerstitial compartments, as well as decode the essential role of M2 macrophages and associated molecular patterns within the microenvironments of IgAN.
Comprehensive Analysis of N6-Methyladenosine-Related Long Noncoding RNA Prognosis of Acute Myeloid Leukemia and Immune Cell Infiltration
Authors: Zheng Guowei , Liu Mengying , Chang Xinyu , Cao Xiting , Dong Ani , Zhu Huili , Hu Wanli , Xie Junna , Zhao Yang , Hu Dongsheng , Jia Xiaocan , Yang Yongli , Shi Xuezhong , Lu Jie
Published: May 2022

N6-Methyladenosine-related long noncoding RNAs play an essential role in many cancers’ development. However, the relationship between m6A-related lncRNAs and acute myelogenous leukemia (AML) prognosis remains unclear. We systematically analyzed the association of m6A-related lncRNAs with the prognosis and tumor immune microenvironment (TME) features using the therapeutically applicable research to generate effective treatment (TARGET) database. We screened 315 lncRNAs associated with AML prognosis and identified nine key lncRNAs associated with m6A by the LASSO Cox analysis. A model was established based on these nine lncRNAs and the predictive power was explored in The Cancer Genome Atlas (TCGA) database. The areas under the ROC curve of TARGET and TCGA databases for ROC at 1, 3, and 5 years are 0.701, 0.704, and 0.696, and 0.587, 0.639, and 0.685, respectively. The nomogram and decision curve analysis (DCA) showed that the risk score was more accurate than other clinical indicators in evaluating patients’ prognoses. The clusters with a better prognosis enrich the AML pathways and immune-related pathways. We also found a close correlation between prognostic m6A-related lncRNAs and tumor immune cell infiltration. LAG3 expression at the immune checkpoint was lower in the worse prognostic cluster. In conclusion, m6A-related lncRNAs partly affected AML prognosis by remodeling the TME and affecting the anticarcinogenic ability of immune checkpoints, especially LAG3 inhibitors. The prognostic model constructed with nine key m6A-related lncRNAs can provide a method to assess the prognosis of AML patients in both adults and children.
Secondary Traumatic Stress and Moral Injury in Maternity Care Providers: A Narrative and Exploratory Review
Authors: Kendall-Tackett Kathleen , Beck Cheryl Tatano
Published: May 2022

Introduction

A significant percentage of maternity providers have experienced secondary traumatic stress following a traumatic birth. Previous studies identified it as an issue, but this literature review is 5–9 years old. In addition, the construct of moral injury has significantly increased our understanding of secondary trauma for military veterans. In the wake of COVID-19, this construct also applies to healthcare providers.

Objectives

The present article updates these reviews and compares findings for three groups: labor and delivery nurses, midwives, and obstetricians. The second portion of this review re-examines previously published qualitative research to determine whether moral injury might more accurately describe the experiences of maternity personnel.

Methods

A comprehensive review of PubMed, Scopus, Web of Science, PsychINFO, and CINAHL was conducted in June 2021 using search terms such as compassion fatigue, secondary trauma, moral injury, labor and delivery, nurses, midwives, and obstetricians. Forty articles were identified, but only 16 focused on secondary trauma or moral injury.

Results

Secondary trauma is a significant concern affecting at least 25% of maternity staff. However, some countries have very low rates, which correspond to low rates in childbirth-related trauma in mothers. Secondary trauma can lead to several symptoms, including re-experiencing, avoidance, negative changes in mood and cognitions, and hyperarousal, which can cause significant impairment. As a result, many providers decide to leave the field in the wake of a traumatic birth. The incidence of moral injury is unknown, but a re-examination of previously published qualitative data suggests that this construct, generally used to describe combat veterans, does describe some of what providers have reported. Acts of omission, i.e., failure to stop the harmful acts of others had long-term negative effects on labor and delivery nurses, consistent with data from military samples. Two possible mediators were proposed: hierarchical and gendered relationships in hospitals and agency of care.

Conclusion

The effects of traumatic birth on providers can be severe, including possible psychological sequelae, impaired job performance, and leaving the field. Moral injury expands upon the construct of secondary traumatic stress. This construct better describes the experiences of maternity staff in non-primary roles who witness traumatic births and are often haunted by events that they could not prevent, but often question whether they should have.
Homogeneous Polyporus Polysaccharide Inhibit Bladder Cancer by Resetting Tumor-Associated Macrophages Toward M1 Through NF-κB/NLRP3 Signaling
Authors: Liu Chunping , He Dongyue , Zhang Shihui , Chen Huiqi , Zhao Jie , Li Xiong , Zeng Xing
Published: May 2022

Bladder cancer(BC)is one of the most common urinary system tumors, which characterized by a high incidence. Polyporus polysaccharide is the main active component of polyporus, which is clinically used in the treatment of bladder cancer, but the mechanism is not clear. In previous study, we isolated homogeneous polyporus polysaccharide(HPP) with high purity from polyporus. The goal of this study was to assess the polarization of macrophages induced by HPP in the bladder tumor microenvironment and explored its anti-bladder cancer mechanism through BBN bladder cancer rat model and Tumor associated macrophages(TAM). The results suggested that HPP regulates TAM polarization to improve the tumor inflammatory microenvironment, possibly through the NF-κB/NLRP3 signaling pathway. Our results suggested that HPP may be a potential therapeutic agent for bladder tumors.
Generation of a High-Affinity Nanobody Against CD147 for Tumor Targeting and Therapeutic Efficacy Through Conjugating Doxorubicin
Authors: Li Rifei , Zhu Xinjie , Zhou Peng , Qiao Yuehua , Li Yinqian , Xu Yice , Shi Xi
Published: May 2022

CD147, a glycosylated transmembrane protein in the immunoglobulin superfamily, is overexpressed on the surfaces of various tumor cells and promotes cancer cell proliferation, invasion, and metastasis. Nanobodies, characterized by small sizes, high affinities and specificities, and low immunogenicities, are promising diagnostic and therapeutic tools. However, there are few reports on nanobodies that specifically target CD147. In this work, a specific anti-CD147 nanobody has been successfully identified using phage display technology. The tumor target and antitumor effects have also been detected in different CD147-positive tumors in in vitro and in vivo assays, respectively. Meanwhile, it has a synergistic effect for inhibiting 4T1-bearing mice through conjugating doxorubicin. It may afford new strategies for cancer therapies.
A Case Study to Dissect Immunity to SARS-CoV-2 in a Neonate Nonhuman Primate Model
Authors: Fovet Claire-Maëlle , Pimienta Camille , Galhaut Mathilde , Relouzat Francis , Nunez Natalia , Cavarelli Mariangela , Sconosciuti Quentin , Dhooge Nina , Marzinotto Ilaria , Lampasona Vito , Tolazzi Monica , Scarlatti Gabriella , Ho Tsong Fang Raphaël , Naninck Thibaut , Dereuddre-Bosquet Nathalie , Van Wassenhove Jérôme , Gallouët Anne-Sophie , Maisonnasse Pauline , Le Grand Roger , Menu Elisabeth , Seddiki Nabila
Published: May 2022

Most children are less severely affected by coronavirus-induced disease 2019 (COVID-19) than adults, and thus more difficult to study progressively. Here, we provide a neonatal nonhuman primate (NHP) deep analysis of early immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood and mucosal tissues. In addition, we provide a comparison with SARS-CoV-2-infected adult NHP. Infection of the neonate resulted in a mild disease compared with adult NHPs that develop, in most cases, moderate lung lesions. In concomitance with the viral RNA load increase, we observed the development of an early innate response in the blood, as demonstrated by RNA sequencing, flow cytometry, and cytokine longitudinal data analyses. This response included the presence of an antiviral type-I IFN gene signature, a persistent and lasting NKT cell population, a balanced peripheral and mucosal IFN-γ/IL-10 cytokine response, and an increase in B cells that was accompanied with anti-SARS-CoV-2 antibody response. Viral kinetics and immune responses coincided with changes in the microbiota profile composition in the pharyngeal and rectal mucosae. In the mother, viral RNA loads were close to the quantification limit, despite the very close contact with SARS-CoV-2-exposed neonate. This pilot study demonstrates that neonatal NHPs are a relevant model for pediatric SARS-CoV-2 infection, permitting insights into the early steps of anti-SARS-CoV-2 immune responses in infants.