bluuebunny/crossref_metadata_2025 huggingface dataset:
TAGLN2-Regulated Trophoblast Migration, Invasion and Fusion are Impaired in Preeclampsia
Authors: Wang Hao , Zhang Xiaowei , Liu Chunfeng , Chen Shengfu , Liu Xinyang , Fan Shangrong
Published: February 2022

Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year and is closely related to abnormal trophoblast function. However, research on placental trophoblast functional abnormalities is insufficient, and the etiology of PE is unclear. Here, we report that the expression of transgelin-2 (TAGLN2) was downregulated in the placenta of patients with PE. In addition, a lack of TAGLN2 significantly reduced the ability of trophoblasts to migrate, invade and fuse. A co-immunoprecipitation (Co-IP) and microscale thermophoresis analysis showed that TAGLN2 bound directly to E-cadherin. A decrease in TAGLN2 expression led to a reduction in cleavage of the E-cadherin extracellular domain, thereby regulating the function of trophoblasts. In addition, we found that a reduction in soluble E-cadherin may also have an effect on blood vessel formation in the placenta, which is necessary for normal placental development. What’s more, the in vivo mouse model provided additional evidence of TAGLN2 involvement in the development of PE. By injecting pregnant mice with Ad-TAGLN2, we successfully generated a human PE-like syndrome that resulted in high blood pressure and some adverse pregnancy outcomes. Overall, the association between TAGLN2 and PE gives a new insight into PE diagnosis and treatment.
The Role of Keratin17 in Human Tumours
Authors: Zhang Hanqun , Zhang Yun , Xia Tingting , Lu Liang , Luo Min , Chen Yanping , Liu Yuncong , Li Yong
Published: February 2022

Keratins are a group of proteins that can constitute intermediate fibers. It is a component of the cytoskeleton and plays an important role in cell protection and structural support. Keratin 17, a Type I keratin, is a multifunctional protein that regulates a variety of biological processes, including cell growth, proliferation, migration, apoptosis and signal transduction. Abnormal expression of KRT17 is associated with a variety of diseases, such as skin diseases. In recent years, studies have shown that KRT17 is abnormally expressed in a variety of malignant tumours, such as lung cancer, cervical cancer, oral squamous cell carcinoma and sarcoma. These abnormal expressions are related to the occurrence, development and prognosis of malignant tumors. In this review, we summarized the expression patterns of KRT17 in a variety of malignant tumours, the role of KRT17 in the development and prognosis of different malignant tumors and its molecular mechanisms. We also discuss the potential clinical application of KRT17 as a valuable therapeutic target.
Adenosine Kinase Inhibition Prevents Severe Acute Pancreatitis via Suppressing Inflammation and Acinar Cell Necroptosis
Authors: Sun Shukun , Han Yu , Zhang Chuanxin , Liu Han , Wang Bailu , Cao Shengchuan , Yuan Qiuhuan , Wei Shujian , Chen Yuguo
Published: February 2022

Background: Inflammatory disorder and acinar cell death contribute to the initiation and progression of severe acute pancreatitis (SAP). Adenosine kinase (ADK) has potential effects on both inflammation and cell death. However, the role of ADK in SAP remains to be explored.

Methods: To establish an experimental SAP model, male C57BL/6 mice were intraperitoneally injected with cerulein (50 μg/kg, seven doses at hourly intervals) and LPS (10 mg/kg, at the last cerulein injection). For ADK inhibition, ABT702 (1.5 mg/kg) was intraperitoneally injected 1 h before cerulein treatment. The pancreas and serum were collected and analyzed to determine the severity of pancreatic injury and explore the potential pathophysiological mechanisms. Pancreatic acinar cells (AR42J) were used to explore the in vitro effects of ADK inhibition on cerulein–induced inflammation and necroptotic cell death.

Results: ADK inhibition notably attenuated the severity of SAP, as indicated by the decreased serum amylase (7,416.76 ± 1,457.76 vs. 4,581.89 ± 1,175.04 U/L) and lipase (46.51 ± 11.50 vs. 32.94 ± 11.46 U/L) levels and fewer pancreatic histopathological alterations (histological scores: 6.433 ± 0.60 vs. 3.77 ± 0.70). MOMA-2 and CD11b staining confirmed that ADK inhibition prevented the infiltration of neutrophils and macrophages. The phosphorylation of nuclear factor-κB (NF-κB) was also reduced by ADK inhibition. ADK inhibition markedly limited the necrotic area of the pancreas and prevented the activation of the necroptotic signaling pathway. Endoplasmic reticulum (ER) stress was activated in the pancreas using the SAP model and cerulein–treated AR42J cells whereas ADK inhibition reversed the activation of ER stress both in vivo and in vitro. Moreover, the alleviating effects of ADK inhibition on ER stress, inflammation, and cell necroptosis were eliminated by the adenosine A2A receptor antagonist.

Conclusion: ADK inhibition reduced inflammation and necroptotic acinar cell death in SAP via the adenosine A2A receptor/ER stress pathway, suggesting that ADK might be a potential therapeutic target for SAP.
Recurrent Co-Option and Recombination of Cytokine and Three Finger Proteins in Multiple Reproductive Tissues Throughout Salamander Evolution
Authors: Wilburn Damien B. , Kunkel Christy L. , Feldhoff Richard C. , Feldhoff Pamela W. , Searle Brian C.
Published: February 2022

Reproductive proteins evolve at unparalleled rates, resulting in tremendous diversity of both molecular composition and biochemical function between gametes of different taxonomic clades. To date, the proteomic composition of amphibian gametes is largely a molecular mystery, particularly for Urodeles (salamanders and newts) for which few genomic-scale resources exist. In this study, we provide the first detailed molecular characterization of gametes from two salamander species (Plethodon shermani and Desmognathus ocoee) that are models of reproductive behavior. Long-read PacBio transcriptome sequencing of testis and ovary of both species revealed sex-specific expression of many genes common to vertebrate gametes, including a similar expression profile to the egg coat genes of Xenopus oocytes. In contrast to broad conservation of oocyte genes, major testis transcripts included paralogs of salamander-specific courtship pheromones (PRF, PMF, and SPF) that were confirmed as major sperm proteins by mass spectrometry proteomics. Sperm-specific paralogs of PMF and SPF are likely the most abundant secreted proteins in P. shermani and D. ocoee, respectively. In contrast, sperm PRF lacks a signal peptide and may be expressed in cytoplasm. PRF pheromone genes evolved independently multiple times by repeated gene duplication of sperm PRF genes with signal peptides recovered through recombination with PMF genes. Phylogenetic analysis of courtship pheromones and their sperm paralogs support that each protein family evolved for these two reproductive contexts at distinct evolutionary time points between 17 and 360 million years ago. Our combined phylogenetic, transcriptomic and proteomic analyses of plethodontid reproductive tissues support that the recurrent co-option and recombination of TFPs and cytokine-like proteins have been a novel driving force throughout salamander evolution and reproduction.
Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome
Authors: Spicher Barbara , Fischer Kady , Zimmerli Zoe A. , Yamaji Kyohei , Ueki Yasushi , Bertschinger Carina N. , Jung Bernd , Otsuka Tatsuhiko , Bigler Marius R. , Gräni Christoph , von Tengg-Kobligk Hendrik , Räber Lorenz , Eberle Balthasar , Guensch Dominik P.
Published: February 2022

Introduction

In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction.

Methods

A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain.

Results

In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (−5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone.

Conclusion

In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.
Effect of a Novel Pocket Compression Device on Hematomas Following Cardiac Electronic Device Implantation in Patients Receiving Direct Oral Anticoagulants
Authors: Fei Ye-Ping , Wang Lei , Zhu Chun-Yan , Sun Jing-Chao , Hu Hui-Lin , Zhai Chang-Lin , He Chao-Jie
Published: February 2022

Background

A pocket hematoma is a well-recognized complication that occurs after pacemaker or defibrillator implantation. It is associated with increased pocket infection and hospital stay. Patients suffering from atrial fibrillation and undergoing cardiovascular electronic implantable device (CIED) surgery are widely prescribed and treated with direct oral anticoagulants (DOACs). In this study, the use of a novel compression device was evaluated to examine its ability to decrease the incidence of pocket hematomas following device implantation with uninterrupted DOACs.

Methods

A total of 204 participants who received DOACs and underwent CIED implantation were randomized into an experimental group (novel compression device) and a control group (elastic adhesive tape with a sandbag). The primary outcome was pocket hematoma, and the secondary outcomes were skin erosions and patient comfort score. Grade 3 hematoma was defined as a hematoma that required anticoagulation therapy interruption, re-operation, or prolonged hospital stay.

Results

The baseline characteristics of both groups had no significant differences. The incidence of grades 1 and 2 hematomas was significantly lower in the compression device group than in the conventional pressure dressing group (7.8 vs. 23.5 and 2.0 vs. 5.9%, respectively; P < 0.01). Grade 3 hematoma occurred in 2 of 102 patients in the experimental group and 7 of 102 patients in the control group (2.0 vs. 6.9%; P = 0.03). The incidence rates of skin erosion were significantly lower, and the patient comfort score was much higher in the compression device group than in the control group (P < 0.01). Multivariable logistic regression analysis showed that the use of novel compression device was a significant protective factor for pocket hematoma (OR = 0.42; 95% CI, 0.29–0.69, P = 0.01).

Conclusions

The incidence of pocket hematomas and skin erosions significantly decreases when the proposed compression device is used for patients undergoing device implantation with uninterrupted DOACs. Thus, the length of hospital stay and re-operation rate can be reduced, and patient comfort can be improved.

Clinical Trial Registration

http://www.chictr.org.cn, identifier: ChiCTR2100049430.
Predictors and Mortality for Worsening Left Ventricular Ejection Fraction in Patients With HFpEF
Authors: Chen Liling , Huang Zhidong , Zhao Xiaoli , Liang Jingjing , Lu Xiaozhao , He Yibo , Kang Yu , Xie Yun , Liu Jin , Liu Yong , Yang Jin , Yu Weixu , Deng Wanling , Pan Yuxiong , Lu Jin , Yang Yanfang , Xie Xujing , Qian Xiaoxian , Xu Qingbo , Chen Longtian , Chen Kaihong , Chen Shiqun
Published: February 2022

Background

Definitions of declined left ventricular ejection fraction (LVEF) vary across studies and research results concerning the association of mortality with declined LVEF are inconsistent. Thus, this study aimed to assess the impact of early worsening LVEF on mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to establish independent predictors of early worsening LVEF.

Methods and Results

A total of 1,418 consecutive patients with HFpEF with LVEF remeasurement from the Cardiorenal Improvement registry were included in this study. Worsening LVEF was defined as an absolute decline ≥ 5% from baseline LVEF within 3 to 12 months after discharge. The Cox and logistic regression analyses were performed to assess prognostic effects and predictors for worsening LVEF, respectively. Among 1,418 patients with HFpEF, 457 (32.2%) patients exhibited worsening LVEF. During a median follow-up of 3.2 years (interquartile range: 2.3–4.0 years), 92 (6.5%) patients died. Patients with HFpEF with worsening LVEF had higher mortality relative to those with nonworsening LVEF [9.2 vs. 5.2%; adjusted hazard ratio (aHR): 2.18, 95% CI: 1.35–3.52]. In the multivariate binary logistic regression analysis, baseline left ventricular end-diastolic dimension (LVEDD), LVEF, high-density lipoprotein cholesterol (HDL-C), atrial fibrillation (AF), and diabetes mellitus (DM) emerged as predictive factors of worsening LVEF.

Conclusion

This study demonstrated that about one out of three patients with HFpEF experiences worsening LVEF during follow-up, which is associated with 2.2-fold increased mortality. Increased LVEDD and LVEF, low HDL-C levels, AF, and DM were predictors of worsening LVEF. Further studies are needed to prospectively assess the efficacy of early active management on prognosis in patients with HF with worsening LVEF.

Registration

ClinicalTrials.gov, identifier NCT04407936.
Significant Prediction of In-hospital Major Adverse Events by D-Dimer Level in Patients With Acute Type A Aortic Dissection
Authors: Feng Weiqi , Wang Qiuji , Li Chenxi , Wu Jinlin , Kuang Juntao , Yang Jue , Fan Ruixin
Published: February 2022

Background

Acute type A aortic dissection (ATAAD) is a rare, life-threatening condition affecting the aorta. This study explores the relationship between the level of admission D-dimer, which was assessed during the first 2 h from admission, and in-hospital major adverse events (MAE) with ATAAD.

Methods

A total of 470 patients with enhanced computed tomography (CT) confirmed diagnosis of ATAAD who underwent operation treatment in Guangdong Provincial People's hospital between September 2017 and June 2021 were enrolled in the present study. The X-tile program was used to determine the optimal D-dimer thresholds for risk. Restricted cubic spline (RSC) was performed to assess the association between D-dimer and endpoint. The perioperative data were compared between the two groups, univariate and multivariate analyses were used to investigate the risk factors of major adverse events (in-hospital mortality, gastrointestinal bleeding, paraplegia, acute kidney failure, reopen the chest, low cardiac output syndrome, cerebrovascular accident, respiratory insufficiency, MODS, gastrointestinal bleeding, and severe infection).

Results

Among 470 patients, 151 (32.1%) had MAE. In-hospital mortality was 7.44%. The patients with D-dimer >14,500 ng/ml were more likely to present with acute kidney failure, low cardiac output, cerebrovascular accident, multiple organ dysfunction syndromes (MODS), gastrointestinal bleeding, and severe infection. D-dimer level was an independent risk factor for acute kidney failure (OR 2.09, 95% CI: 1.25–3.51, p = 0.005), MODS (OR 6.40, 95% CI: 1.23–33.39, p = 0.028), gastrointestinal bleeding (OR 17.76, 95% CI: 1.99–158.78, p = 0.010) and mortality (OR 3.17, 95% CI: 1.32–7.63, p = 0.010). Multivariate regression analysis of adverse events also suggested that D-dimer >14,500 ng/ml (OR 1.68, 95% CI: 1.09–2.61, p = 0.020) was the independent risk factor of major adverse events.

Conclusions

Increasing D-dimer levels were independently associated with the in-hospital MAE and thus can be used as a useful prognostic biomarker before the surgery.
Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis
Authors: Wang Zuoxiang , Xia Qingyue , Su Wenxing , Cao Mingqiang , Sun Yunjuan , Zhang Mingyang , Chen Weixiang , Jiang Tingbo
Published: February 2022

Background

Cardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis.

Methods

Six datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)–mRNA–microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM.

Results

We found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM.

Conclusion

The identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.
Therapeutic Effect of His-Purkinje System Pacing Proportion on Persistent Atrial Fibrillation Patients With Heart Failure
Authors: Tong Fei , Sun Zhijun
Published: February 2022

Background

His-Purkinje system pacing (HPSP) combined with atrioventricular node ablation is an effective therapy for atrial fibrillation (AF) patients with heart failure (HF). However, atrioventricular node ablation has some limitations and disadvantages. HPSP combined with β -blockers reduces intrinsic heart rate and increases pacing proportion, which may be an alternative to HPSP combined with atrioventricular node ablation. This study was to assess the therapeutic effect of different HPSP proportion on AF patients with HF.

Methods

The study enrolled 30 consecutive persistent AF patients with HF who underwent HPSP. Heart rate was controlled by medical therapy. NYHA class, NT-proBNP, echocardiographic parameters were assessed at follow-up. MACE was defined as the composite endpoint of readmission for HF and cardiac mortality.

Results

The AUC of pacing proportion for predicting MACE was 0.830 (SE = 0.140, 95%CI:0.649–0.941, p = 0.018), the optimal cut-off point of pacing proportion to predict MACE by ROC analysis was 71% (sensitivity:83.3%, specificity: 91.7%). In high pacing proportion group (>71%), there were significant improvements of NYHA class, NT-proBNP, LVEF and LVEDD from the baseline in wide QRS complex (QRSd>120 ms) patients and HFrEF patients at half year follow-up, and there were significant improvements in NYHA class, NT-proBNP from baseline in narrow QRS complex (QRSd ≤ 120 ms) patients and HFpEF patients at half year follow-up, moderate but no significant improvements of LVEF and LVEDD were observed in these patients. In low pacing proportion group (≤ 71%), there were no significant improvements of NT-proBNP, LVEDD or LVEF regardless of baseline QRS duration or LVEF (p > 0.05).

Conclusion

High pacing proportion (>71%) of HPSP can improve clinical outcomes and echocardiographic parameters in persistent AF patients with wide QRS complex or HFrEF, and clinical outcomes in persistent AF patients with narrow QRS complex or HFpEF. High pacing proportion of HPSP has a beneficial effect on the prognosis of persistent AF patients with HF.
Quantitative Evaluation of Post-stenotic Blood Flow Disturbance in Canine Femoral Artery Stenosis Model: An Early Experience With Vector Flow Imaging
Authors: Zhao Rui , Zheng Haining , Wang Wei , Du Yigang , Tong Yisha , Wen Chaoyang
Published: February 2022

Objective

To investigate the value of Vector Flow Imaging (V Flow) in the assessment of post-stenotic turbulence in the canine arterial stenosis model.

Materials and Methods

Canine femoral artery stenosis models were established using ameroid constrictors in 12 beagle dogs. 50% and then 70% femoral artery stenoses were confirmed by selective femoral artery angiography. V Flow was used to measure femoral artery flow turbulence index (Tur) preoperatively as a baseline. After establishing of a 50% and then 70% stenoses, the Tur indices were recorded in the femoral artery at 1, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mm distal to the stenosis.

Results

Baseline Tur indices of normal canine femoral arteries were <1% in 11 of 12 cases (91.7%). Distal to a 50% stenosis, the Tur index (>1%) was recorded in 83.3–100% cases between 1 and 9 mm, 41.7–58.3% between 11 and 17 mm, and 16.7% at 19 mm. For a 70% stenosis, the Tur index (>1%) occurred in 81.8–100% cases between 1 and 17 mm distal to the stenosis, and 63.6% at 19 mm. The Tur index peaked around 7 mm or 2.3 times of the initial vessel diameter (3 mm) downstream for a 50% stenosis and 11 mm or 3.7 times of vessel diameter downstream for a 70% stenosis.

Conclusion

V Flow with Tur index measurement adds quantitative information of post-stenotic turbulence when assessing an arterial stenosis with ultrasound. Tur index of 1% seems a useful threshold for assessment of flow turbulence in this small sample study. Further studies with larger sample size are needed to evaluate the value of V Flow in clinical applications.
Case Report: A Rare Case of Acute Anterior Myocardial Infarction Simultaneously Associated With Aortic Mural Thrombosis Due to Essential Thrombocytosis
Authors: Ye Sheng , Xia Wu-jie , Chen Peng
Published: February 2022

Background

Essential thrombocytosis (ET) simultaneously complicated with acute myocardial infarction and aortic thrombosis is extremely rare and associated with poor outcomes.

Case

A 54-year-old female was admitted to our emergency department with abdominal pain for 3 h. ST-segment elevation in leads V1–V3 on electrocardiography led to the diagnosis of acute anterior myocardial infarction. Coronary angiography demonstrated total occlusion of the proximal left anterior descending artery, and the patient was treated with angioplasty and placement of a drug-eluting stent. CT angiography revealed a massive mural thrombus located in the descending aorta. Bone marrow biopsy confirmed the diagnosis of ET. The patient was successfully treated with antithrombotic therapy and hydroxyurea.

Conclusion

At present, the clinical diagnosis and treatment of ET complicated with acute myocardial infarction and aortic thrombosis are mostly based on literature reports. Early target vessel revascularization, antiplatelet and anticoagulant combined with cytoreductive therapy may improve the prognosis. Clinicians should consider the risk of bleeding and thrombosis and create individualized treatment strategies for these patients.
Dynamic Interaction Between Deforestation and Rice Cultivation During the Holocene in the Lower Yangtze River, China
Authors: He Keyang , Lu Houyuan , Sun Guoping , Wang Yonglei , Zheng Yunfei , Zheng Hongbo , Lei Shao , Li Yongning , Zhang Jianping
Published: February 2022

Human activity has transformed the Earth’s landscapes pervasively for thousands of years, and the most important anthropogenic alteration was the clearing of forests and the establishment of agriculture. As a center of rice domestication and early population growth, the lower Yangtze River has been extensively transformed in the Holocene. However, the timing, extent, and process of deforestation and its relationship with the intensification of rice cultivation remain controversial. Here, four representative archaeological sites ranging from 8,100 to 4,300 cal a BP, that is, Jingtoushan, Hemudu, Yushan, and Xiawangdu sites, were selected for detailed palynological analysis, and evidence of anthropogenic deforestation and subsistence strategy were also synthesized to investigate dynamic human–forest interaction. Although natural vegetation had already been altered at the Jingtoushan site around 8,000 cal a BP, it was more likely to be the management of acorns by limiting burning to open habitats and increasing yield. As the subsistence shifted from acorn exploitation toward rice cultivation after 6,000 cal a BP, real deforestation for agriculture may occur at the Yushan and Xiawangdu sites due to conflict on labor input and land use. However, these deforestations were just confined to the archaeological sites at local scale, and no consistent vegetation change occurred at regional scales induced by human activities until the last 3,000 years.
Gender Bias Interacts With Instructor Disfluency to Negatively Affect Student Evaluations of Teaching
Authors: LaPaglia Jessica , Miller Katelyn , Protexter Samantha
Published: February 2022

Recent research has shown that instructor fluency can impact student judgments of learning and instructor ratings but has no real effect on actual learning. In addition, women tend to receive lower course and instructor evaluations than men. In the current study, we examined how instructor fluency and instructor gender influenced instructor evaluations and student learning. Participants watched a short lecture video. The speaker was either male or female and was either fluent (i.e., even paced in their speech) or disfluent (i.e., disorganized, made mistakes). Following the video, participants evaluated the instructor and took a quiz over the lecture. Results indicated that disfluency negatively affected quiz scores, but instructor gender did not. Participants rated the female speaker significantly lower than the male speaker, but only when the speaker was disfluent. These results are explained through the lens of attributional gender bias.
Interdisciplinary and Transferable Concepts in Bioinformatics Education: Observations and Approaches From a UK MSc Course
Authors: Johnston Iain G. , Slater Mark , Cazier Jean-Baptiste
Published: February 2022

Bioinformatics is a highly interdisciplinary subject, with substantial and growing influence in health, environmental science and society, and is utilised by scientists from many diverse academic backgrounds. Education in bioinformatics therefore necessitates effective development of skills in interdisciplinary collaboration, communication, ethics, and critical analysis of research, in addition to practical and technical skills. Insights from bioinformatics training can additionally inform developing education in the tightly aligned and emerging disciplines of data science and artificial intelligence. Here, we describe the design, implementation, and review of a module in a UK MSc-level bioinformatics programme attempting to address these goals for diverse student cohorts. Reflecting the philosophy of the field and programme, the module content was designed either as “diversity-addressing”—working toward a common foundation of knowledge—or “diversity-exploiting”—where different student viewpoints and skills were harnessed to facilitate student research projects “greater than the sum of their parts.” For a universal introduction to technical concepts, we combined a mixed lecture/immediate computational practical approach, facilitated by virtual machines, creating an efficient technical learning environment praised in student feedback for building confidence among cohorts with diverse backgrounds. Interdisciplinary group research projects where diverse students worked on real research questions were supervised in tandem with interactive contact time covering transferable skills in collaboration and communication in diverse teams, research presentation, and ethics. Multi-faceted feedback and assessment provided a constructive alignment with real peer-reviewed bioinformatics research. We believe that the inclusion of these transferable, interdisciplinary, and critical concepts in a bioinformatics course can help produce rounded, experienced graduates, ready for the real world and with many future options in science and society. In addition, we hope to provide some ideas and resources to facilitate such inclusion.
The Hepatokine FGF21 Increases the Human Spermatozoa Motility
Authors: Bourdon Guillaume , Estienne Anthony , Chevaleyre Claire , Ramé Christelle , Guérif Fabrice , Brun Jean-Sébastien , Vasseur Claudine , Fromont Gaelle , Plotton Ingrid , Dufour-Rainfray Diane , Caldas-Silveira Erika , Dupont Joëlle , Froment Pascal , Ducluzeau Pierre-Henri
Published: February 2022

Lifestyle, environment and excess body weight are not only associated with an increased risk of metabolic disorders, such as type 2 diabetes, but also to other pathological processes, such as infertility. A hormone produced mainly by the liver called fibroblast growth factor 21 (FGF21) is closely linked to the energy status and is increased in patients suffering from obesity or insulin resistance. Recently, FGF21 has been shown to be associated with female fertility disorders, but no or few data about the role of FGF21 on human male fertility has been described. In the present study, FGF21 was measured in the seminal fluid at a lower level in comparison to the blood level. Thus, in the present in vitro study, we aimed to decipher the FGF21 system in human semen. To evaluate the putative role of FGF21 on spermatozoa function, we incubated human spermatozoa with increasing concentrations of recombinant human FGF21. The FGF21 in seminal fluid is potentially produced by male reproductive tract tissues. In spermatozoa, the FGF21 signal was transduced by the two main receptors FGFR1-c and FGFR3 and the cofactor β-klotho, which are colocalized in the middle piece of spermatozoa and stimulated the PI3K/Akt and MAPK pathways. Finally, in vitro treatment by FGF21 significantly increased sperm motility and ATP levels. Concomitantly, exposure to FGF21 improved the oxidative stress, as a lower ROS level was observed. Overall, these results seem to indicate that the metabolic factor, FGF21, positively modifies the activity and quality of the parameters of human spermatozoa.
Healthcare Professionals’ Views of Factors Influencing Diabetes Self-Management and the Utility of a mHealth Application and Its Features to Support Self-Care
Authors: Yoon Sungwon , Ng Jun Hao , Kwan Yu Heng , Low Lian Leng
Published: February 2022

Introduction

The perspectives of healthcare professionals (HCPs) are pivotal to co-development of self-management strategies for patients with diabetes. However, literature has been largely limited to perspectives of patients within the context of a Western healthcare setting. This study aims to explore factors influencing diabetes self-management in adult patients with diabetes from the perspectives of HCPs and their views of the value of mHealth application for diabetes self-management.

Materials and Methods

We conducted focus group discussions (FGD) with purposively selected HCPs in Singapore. All FGDs were audio-recorded and transcribed verbatim. Thematic analysis was conducted using NVivo 12.

Results

A total of 56 HCPs participated in the study. Barriers to self-management included limited patient commitment to lifestyle changes, suboptimal adherence to medication and treatment, patient resistance to insulin initiation and insufficient rapport between patients and HCPs. Patients’ perceived susceptibility to complications, social support from family and community, multidisciplinary team care and patient’s understanding of the benefits of self-care were viewed as facilitating self-management. HCPs saw mHealth apps as a vital opportunity to engage patients in the self-management of conditions and empower them to foster behavior changes. Yet, there were concerns regarding patient’s limited digital literacy, lack of integration into routine electronic system and reluctance.

Discussion

We identified a set of factors influencing self-management in adult patients with diabetes and useful app features that can empower patients to manage their conditions. Findings will inform the development of a mHealth application, and its features designed to improve self-care.
Hashimoto’s Thyroiditis: A “Double-Edged Sword” in Thyroid Carcinoma
Authors: Xu Jiangyue , Ding Ke , Mu Lan , Huang Jiangsheng , Ye Fei , Peng Yu , Guo Can , Ren Chutong
Published: February 2022

Background

The prevalence of thyroid carcinoma (TC) and Hashimoto’s thyroiditis (HT) has been increasing dramatically over the past decades. We investigated the relationship between HT and TC.

Methods

We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for carrying out and reporting this meta-analysis. The literature from January 1, 2010 to December 31, 2020, regardless of region and publication type, was searched comprehensively in PubMed, Embase, Web of Science, and Cochrane Library databases. After careful selection and data extraction, the pooled odds ratio of various clinical characteristics in 39 studies were calculated. Publication bias was analyzed using funnel plots.

Results

Meta-analysis of 39 original research articles showed HT to be a risk factor of TC (pooled odds ratio = 1.71; 95% confidence interval, 1.57–1.80; p < 0.00001) and papillary thyroid carcinoma (1.67, 1.51–1.85, <0.00001). Patients with papillary thyroid carcinoma (PTC) combined with HT were more likely to have multifocal carcinomas. The prevalence of an extrathyroidal extension, metastasis, BRAFV600E mutation, and recurrence was significantly lower in patients with PTC combined with HT.

Conclusions

HT is a “double-edged sword” in TC patients. HT increases the risk of TC and PTC but is a protective factor against PTC progression.
Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Zhang Yuyuan , Liu Xiaobo , Zhang Huazhu , Wang Xuechang
Published: February 2022

Objective

Clinical trials have recently shown a connection between nonalcoholic fatty liver disease (NAFLD) and empagliflozin. This paper aimed at comprehensively assessing the effectiveness and security of empagliflozin in NAFLD patients.

Methods

PubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wan-Fang digital database, VIP, and WHO ICTRP were searched for randomized controlled trials (RCTs) on the role of empagliflozin in NAFLD from inception to November 2, 2021. For continuous dating, we used values of mean differences (MD) to present.

Results

A total of four articles involving 244 NAFLD patients were included. Compared with the control group, empagliflozin could significantly reduce the body mass index (BMI) (MD: −0.98 [95% CI: −1.87, −0.10], p = 0.03), liver stiffness measurement (LSM) (MD: 0.49 [95% CI: −0.93, −0.06], p = 0.03), aspartate aminotransferase (AST) (MD: −3.10 [95% CI: −6.18, −0.02], p = 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (MD: −0.45 [95% CI: −0.90, 0.00], p = 0.05) of the treatment group.

Conclusions

Empagliflozin can improve body composition, insulin resistance, and liver fibrosis and decrease the hepatic enzymes in patients with NAFLD. Empagliflozin emerges as a new option for treating patients with NAFLD. However, further research shall determine the efficacy and safety of empagliflozin in NAFLD.
What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?
Authors: Wang Jia-Ming , Li Zhen-Fang , Yang Wan-Xi
Published: February 2022

Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.
Predicting Elevated TSH Levels in the Physical Examination Population With a Machine Learning Model
Authors: Cheng Xinqi , Li Shicheng , Deng Lizong , Luo Wei , Wang Dancheng , Cheng Jin , Ma Chaochao , Chen Luming , Jiang Taijiao , Qiu Ling , Zhang Guojun
Published: February 2022

Objective

The purpose of this study was to predict elevated TSH levels by developing an effective machine learning model based on large-scale physical examination results.

Methods

Subjects who underwent general physical examinations from January 2015 to December 2019 were enrolled in this study. A total of 21 clinical parameters were analyzed, including six demographic parameters (sex, age, etc.) and 15 laboratory parameters (thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TG-Ab), etc.). The risk factors for elevated TSH levels in the univariate and multivariate Logistic analyses were used to construct machine learning models. Four machine learning models were trained to predict the outcome of elevated TSH levels one year/two years after patient enrollment, including decision tree (DT), linear regression (LR), eXtreme Gradient boosting (XGBoost), and support vector machine (SVM). Feature importance was calculated in the machine learning models to show which parameter plays a vital role in predicting elevated TSH levels.

Results

A total of 12,735 individuals were enrolled in this study. Univariate and multivariate Logistic regression analyses showed that elevated TSH levels were significantly correlated with gender, FT3/FT4, total cholesterol (TC), TPO-Ab, Tg-Ab, creatinine (Cr), and triglycerides (TG). Among the four machine learning models, XGBoost performed best in the one-year task of predicting elevated TSH levels (AUC (0.87(+/- 0.03))). The most critical feature in this model was FT3/FT4, followed by TPO-Ab and other clinical parameters. In the two-year task of predicting TSH levels, none of the four models performed well.

Conclusions

In this study, we trained an effective XGBoost model for predicting elevated TSH levels one year after patient enrollment. The measurement of FT3 and FT4 could provide an early warning of elevated TSH levels to prevent relative thyroid diseases.
Diabetes Epidemiology Among Adults in Port-au-Prince, Haiti: A Cross-Sectional Study
Authors: Sufra Rodney , Lookens Pierre Jean , Dade Eliezer , Rouzier Vanessa , Apollon Alexandra , St Preux Stephano , Préval Fabiola , Inddy Joseph , Metz Miranda , Tymejczyk Olga , Nash Denis , Malebranche Rodolphe , Deschamps Marie , Pape Jean W. , Goncalves Marcus D. , McNairy Margaret L. , Yan Lily D.
Published: February 2022

Introduction

Diabetes mellitus is a chronic noncommunicable disease associated with death and major disability, with increasing prevalence in low- and middle-income countries. There is limited population-based data about diabetes in Haiti. The objective of this study was to assess the prevalence of diabetes and associated factors among adults in Port-au-Prince, Haiti using a population-based cohort.

Methods

This study analyzes cross-sectional enrollment data from the population-based Haiti Cardiovascular Disease Cohort Study, conducted using multistage sampling with global positioning system waypoints in census blocks in the metropolitan area of Port-au-Prince, Haiti. A total of 3,005 adults ≥18 years old were enrolled from March 2019 to August 2021. We collected socio-demographic data, health-related behaviors, and clinical data using standardized questionnaires. Diabetes was defined as any of the following criteria: enrollment fasting glucose value ≥ 126 mg/dL or non-fasting glucose ≥ 200 mg/dL, patient self-report of taking diabetes medications, or study physician diagnosis of diabetes based on clinical evaluation.

Results

Among 2985 (99.3%) with complete diabetes data, median age was 40 years, 58.1% were female, and 17.2% were obese. The prevalence of diabetes was 5.4% crude, and 5.2% age standardized. In unadjusted analysis, older age, higher body mass index (BMI), low physical activity, low education were associated with a higher odds of diabetes. After multivariable logistic regression, older age [60+ vs 18-29, Odds Ratio (OR)17.7, 95% CI 6.6 to 47.9] and higher BMI (obese vs normal/underweight, OR 2.7, 95% CI 1.7 to 4.4) remained statistically significantly associated with higher odds of diabetes.

Conclusion

The prevalence of diabetes was relatively low among adults in Port-au-Prince, but much higher among certain groups (participants who were older and obese). The Haitian health system should be strengthened to prevent, diagnose, and treat diabetes among high-risk groups.
Accurate Location of Catheter Tip With the Free-to-Total Metanephrine Ratio During Adrenal Vein Sampling
Authors: Christou Foteini , Pivin Edward , Denys Alban , Abid Karim A. , Zingg Tobias , Matter Maurice , Pechère-Bertschi Antoinette , Maillard Marc , Grouzmann Eric , Wuerzner Gregoire
Published: February 2022

Background

The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We aimed to determine the cutoff values of the SIs based on cortisol, free metanephrine, and the free-to-total metanephrine ratio (FTMR) using an adapted AVS protocol in combination with CT.

Methods

Adults with PA and referred for AVS were recruited in two hypertension centers. The cortisol and free metanephrine-derived SIs were calculated as the concentration of the analyte in adrenal veins divided by the concentration of the analyte in the distal vena cava. The FTMR-derived SI was calculated as the concentration of free metanephrine in the adrenal vein divided by that of total metanephrine in the ipsilateral adrenal vein. The AVS was classified as an unequivocal radiological success (uAVS) if the tip of the catheter was seen in the adrenal vein. The SI cutoffs of each index marker were established using receiver operating characteristic curve analysis.

Results

Out of 125 enrolled patients, 65 patients had an uAVS. The SI cutoffs were 2.6 for cortisol, 10.0 for free metanephrine, 0.31 for the FTMR on the left side, and 2.5, 9.9, and 0.25 on the right side. Compared to free metanephrine and the FTMR, cortisol misclassified AVS as unsuccessful in 36.6% and 39.0% of the cases, respectively.

Conclusion

This study is the first to calculate the SIs of cortisol, free metanephrine, and the FTMR indices for the AVS procedure. It confirms that free metanephrine-based SIs are better than those based on cortisol.
Compression Fractures and Partial Phenotype Rescue With a Low Phosphorus Diet in the Chihuahua Zebrafish Osteogenesis Imperfecta Model
Authors: Cotti Silvia , Huysseune Ann , Larionova Daria , Koppe Wolfgang , Forlino Antonella , Witten Paul Eckhard
Published: February 2022

Osteogenesis imperfecta (OI) is a group of heritable disorders affecting bone and other connective tissues. Dominant OI forms are mainly caused by mutations in collagen type I. Patients suffer from skeletal deformities, fractures of long bones and vertebral compression fractures from early childhood onward. Altered collagen structure and excess mineralisation are the main causes for the bone phenotype. The Chihuahua (Chi/+) zebrafish has become an important model for OI. Given that reduced dietary phosphorus (P) intake reduces the bone mineral content and promotes bone matrix formation in teleosts, including zebrafish, we tested whether a low dietary P (LP) intake mitigates the OI phenotype in the Chi/+ model. To answer this question, we characterised the Chi/+ vertebral column phenotype at a morphological, cellular and subcellular level. We present the first description of vertebral compression fractures in Chi/+ and assess the effects of LP diet on the Chi/+ phenotype (Chi/+LP). Compared to untreated Chi/+, two months of LP dietary treatment decreases vertebral deformities in the abdominal region and reduces shape variation of caudal vertebral bodies to a condition more similar to wild type (WT). At the histological level, the osteoid layer, covering the bone at the vertebral body endplates in WT zebrafish, is absent in Chi/+, but it is partially restored with the LP diet. Whole mount-stained specimens and histological sections show various stages of vertebral compression fractures in Chi/+ and Chi/+LP animals. Both Chi/+ and Chi/+LP show abundant osteoclast activity compared to WT. Finally, the ultrastructure analysis of WT, Chi/+ and Chi/+LP shows Chi/+ and Chi/+LP osteoblasts with enlarged endoplasmic reticulum cisternae and a high protein content, consistent with intracellular retention of mutated collagen. Nevertheless, the secreted collagen in Chi/+LP appears better organised concerning fibre periodicity compared to Chi/+. Our findings suggest that a reduced mineral content of Chi/+ bone could explain the lower frequency of vertebral column deformities and the restored shape of the vertebral bodies in Chi/+LP animals. This, together with the improved quality of the bone extracellular matrix, suggests that two months of reduced dietary P intake can alleviate the severe bone phenotype in Chi/+ zebrafish.