bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Design and Practice of English Education under the Network Learning Space
Authors: Shi Jing , Zheng Junhui
Published: July 2022

With the comprehensive coverage of the Internet in China, the online learning space can basically cover the whole country, but in terms of the use of online learning space in education, it has not been fully used. The basic application mode of the school, namely, autonomous learning, flipped classroom learning, collaborative learning, exchange, and discussion learning, and personalized learning mode, based on flipped classroom learning and relying on network learning space, design the corresponding English teaching process based on network learning space, according to the teaching process, the specific design of the platform, content, organization, implementation, and evaluation. From the research results, the students in the experimental class are more active and active in class than in the control class, their work scores are generally higher than those in the control class, and their interest in English has been significantly improved. The ability has also been significantly improved. After long-term practical research, it has been shown that the performance of the experimental class students in the online learning space has also been significantly improved. Therefore, it can be shown that the English course based on the network learning space has a certain positive influence and promotion effect on the teaching effect.
[Retracted] Antioxidant and Anti‐Inflammatory Activities of Coenzyme‐Q10 and Piperine against Cyclophosphamide‐Induced Cytotoxicity in HuH‐7 Cells
Authors: AL-Johani Norah S. , Al-Zharani Mohammed , Aljarba Nada H. , Alhoshani Norah M. , Alkeraishan Nora , Alkahtani Saad
Published: July 2022

Cyclophosphamide (CP) alkylates DNA and RNA produce crosslinks that cause gene expression and protein synthesis inhibition to exert its anticancer effect. However, adverse effects of CP have restricted the CP application in cancer treatment. We investigate coenzyme‐Q10 (Q10) and piperine (P) protective role on CP oxidant and inflammatory effect. HuH‐7 cells were exposed to varying concentrations and combinations of Q10, P, and CP and evaluated intracellular ROS generation as well as inflammatory responses upon exposure. Our results showed Q10 and/or P suppressed both basal and CP‐induced ROS generation without upsetting the balance in activities of SOD, catalase, and GSH levels. Analysis of proinflammatory cytokine gene expression showed that CP treatment alone only induced expression of IL-6β. However, coexposure of the cells to both Q10 and CP caused significant suppression of basal Cox-2 and TNF-α gene expression, while coexposure of the cells to CP and P with Co‐Q10 suppressed basal IL-1β gene expression. Q10 also suppressed CP‐induced expression of Cox-1. P and CP suppressed basal expression of IL-6β and IL-12β, while P and Q10 suppressed CP‐induced IL1-α gene expression. Taken together, both Q10 and P seem to be inhibiting NFκβ pathway to suppress CP‐mediated inflammation. In conclusion, Q10 and/or P induced suppression of ROS generation mediated by CP and also suppressed CP‐induced inflammation by inhibiting expression of specific inflammatory cytokine.
Human Endothelial Cell Seeding in Partially Decellularized Kidneys
Authors: Haeublein Geraldine , Lombardi Gabriela , Caro Fiorella , Guerrieri Diego , Remolins Carla , Incardona Claudio , Casadei Domingo , Chuluyan Eduardo
Published: July 2022

The excessive demand for organ transplants has promoted the development of strategies that increase the supply of immune compatible organs, such as xenotransplantation of genetically modified pig organs and the generation of bioartificial organs. We describe a method for the partial replacement of rat endothelial cells for human endothelial cells in a rat’s kidney, obtaining as a final result a rat‐human bioartificial kidney. First, in order to maintain parenchymal epithelial cells and selectively eliminate rat endothelial cells, three methods were evaluated in which different solutions were perfused through the renal artery: 0.1% sodium dodecyl sulfate (SDS), 0.01% SDS, and hyperosmolar solutions of sucrose. Then, partially decellularized kidneys were recellularized with human endothelial cells and finally transplanted in an anesthetized rat. The solution of 0.1% SDS achieved the highest vascular decellularization but with high degree of damage in the parenchyma side. On the contrary, 0.01% SDS and hyperosmolar solutions achieved a partial degree of endothelial decellularization. TUNEL assays reveal that hyperosmolar solutions maintained a better epithelial cell viability contrasting with 0.01% SDS. Partially decellularized kidneys were then recellularized with human endothelial cells. Histological analysis showed endothelial cells attached in almost all the vascular bed. Recellularized kidney was transplanted in an anesthetized rat. After surgery, recellularized kidney achieved complete perfusion, and urine was produced for at least 90 min posttransplant. Histological analysis showed endothelial cells attached in almost all the vascular bed. Therefore, endothelial decellularization of grafts and recellularization with human endothelial cells derived from transplant recipients can be a feasible method with the aim to reduce the damage of the grafts.
Effects of Docetaxel plus Degarelix on Quality of Life and Vascular Endothelial Growth Factor in Patients with Prostate Cancer
Authors: Li Weiping , Xu Dongbo , Li Fudong , Chang Pengcheng , Zhang Bin
Published: July 2022

Objective. To investigate the effects of docetaxel plus degarelix on quality of life and vascular endothelial growth factor in patients with prostate cancer. Methods. Between 2018 and 2020, 38 patients with castration-resistant prostate cancer (CRPC) treated in our institution were assessed for eligibility and recruited. They were assigned at a ratio of 1 : 1 to receive either docetaxel plus degarelix (observation group) or degarelix (control group). Outcome measures included treatment efficacy, inflammatory factors level, vascular endothelial growth factor (VEGF) level, and quality of life of patients. Results. Docetaxel plus degarelix was associated with a significantly higher treatment efficacy (94.74%, including 9 (47.37%) cases of complete response (CR), 6 (31.58%) cases of partial response (PR), 4 (21.05%) cases of stable disease (SD), and 1 (5.36%) case of progressive disease (PD)) versus degarelix alone (63.16%, including 4 (21.05%) cases of CR, 5 (26.32%) cases of PR, 3 (15.79%) cases of SD, and 7 (36.84%) cases of PD) (

P
<
0.05

). Before treatment, the two groups showed comparable levels of C-reaction protein (CRP), interleukin- (IL-) 6, and IL-10 (

P
>
0.05

). Docetaxel plus degarelix resulted in significantly reduced levels of CRP and IL-6 and a significantly higher IL-10 level (

28.84
±
5.42

,

25.31
±
5.74

, and

53.32
±
11.02

) versus degarelix alone (

35.17
±
6.31

,

31.54
±
8.17

, and

42.76
±
11.25

) (

P
<
0.05

). There were no significant differences in the urinary function, intestinal function, and hormone function scores between the two groups before treatment (

P
>
0.05

). The patients receiving docetaxel plus degarelix had higher urinary function, intestinal function, and hormone function scores (

38.87
±
4.46

,

86.51
±
8.14

, and

76.65
±
7.15

) versus monotherapy of degarelix (

29.84
±
3.58

,

78.51
±
7.31

, and

66.78
±
6.56

) (

P
<
0.05

). The two groups had similar pretreatment VEGF levels (

P
>
0.05

). Docetaxel plus degarelix resulted in significantly lower VEGF levels (

119.17
±
21.38

) versus degarelix (

124.36
±
23.14

) at 6 months after treatment (

P
<
0.05

). Conclusion. Docetaxel plus degarelix can enhance the therapeutic efficacy of patients with prostate cancer, mitigate inflammatory response, inhibit the VEGF expression of cancer cells, and improve the patients’ quality of life. Further clinical trials are, however, required prior to general use in clinical practice.
The Relationship between Machine Translation and Human Translation under the Influence of Artificial Intelligence Machine Translation
Authors: Lihua Zhao
Published: July 2022

Machine translation based on artificial intelligence has many commercial applications, such as Google translation, Baidu translation, and Youdao translation. More artificial intelligence and its translation are still used in all aspects of life. Therefore, we should reexamine its impact on the relationship between human translation and machine translation. Therefore, based on this background, this paper discusses the impact of the development of artificial intelligence machine translation on the relationship between human translation and machine translation. Although the translation accuracy and overall situation of machine translation based on artificial intelligence are similar to that of human translation, the basic algorithm of machine translation is still a program that judges right and wrong through computer code. It cannot simulate the “faithfulness, expressiveness, and elegance” of human translation in combination with social background and human culture. However, for some mechanical operations, such as business translation, scenes with low requirements, such as common vocabulary in daily tourism, can still meet the needs. Therefore, under the influence of artificial intelligence machine translation, the relationship between the two is that machine translation can replace human translation in some aspects, but it cannot replace human translation.
Application Research of Image Processing Technology for Fire Detection and Fire Alarm Based on Blockchain
Authors: Zhao Fan
Published: July 2022

Aiming at the problems of leakage alarms and false alarms in fire detection systems, this paper explores the commonality and characteristics of its development process through in-depth analysis of typical fire detection and fire alarm modes at home and abroad and effectively summarizes the process of building fire alarms. In the case of fully grasping the principles of fire alarm and related policy protection, find out the appropriate development mode of fire alarm. At the same time, it can also study the perspectives of the government, the market, and the public, according to the needs of the market, it can be driven by industry and technological innovation can be used as a strong support for the development of fire alarm. Finally, the results of example analysis show that: using blockchain, this paper can effectively obtain high-precision fire detection and fire alarm target analysis results, and meet the needs of real-time analysis of fire detection and fire alarm analysis. Experiments show that the system can detect fires correctly and quickly, and identify interference sources such as fluorescent lamps and alcohol lamps. It has strong interference and good economic benefits.
Resource Allocation Strategy Using Deep Reinforcement Learning in Cloud-Edge Collaborative Computing Environment
Authors: Cen Junjie , Li Yongbo
Published: July 2022

With the development of technologies such as IoT and 5G, the exponential explosion in the amount of new data has put more stringent requirements on ultrareliable and low-delay communication of services. To better meet these requirements, a resource allocation strategy using deep reinforcement learning in a cloud-edge collaborative computing environment is proposed. First, a collaborative mobile edge computing (MEC) system model, which combines the core cloud center with MEC to improve the network interaction ability, is constructed. The communication model and computation model of the system are considered at the same time. Then, the goal of minimizing system delay is modeled as a Markov decision process, and it is solved by using the deep Q network (DQN) which is improved by hindsight experience replay (HER), so as to realize the resource allocation with the minimum system delay. Finally, the proposed method is analyzed based on the simulation platform. The results show that when the number of user terminals is 80, the maximum user delay is 1150 ms, which is better than other comparison strategies and can effectively reduce the system delay in complex environment.
Improvement of English Classroom Teaching Effect Based on Real-Time Supervision of Student Status
Authors: Yin Ping
Published: July 2022

For English courses, the interaction between teachers and students in the classroom teaching process has a crucial impact on the improvement of classroom teaching effects, and through real-time supervision of students’ classroom learning status, students’ learning dynamics and learning effects can be grasped in time. For this reason, this paper proposes a learning state semisupervised learning method and real-time state monitoring system based on a clustering algorithm and a self-training SVM classification algorithm. At the same time, combined with the reform of English classroom teaching, the teaching effect can be improved to the greatest extent through the supervision of students’ learning state. The experimental results show that monitoring the primary school English classroom teaching quality subject and providing skill training can help the primary school English classroom teaching quality subject predict the possible situation in the monitoring and prepare in advance in terms of thinking and skill teaching. Schools can urge primary school English classroom teaching quality monitoring subjects to have basic monitoring knowledge literacy, monitoring ability literacy, and monitoring moral literacy through primary school English classroom teaching quality monitoring knowledge training, skill training, and moral training. On the basis, the main body of primary school English classroom teaching quality monitoring can give full play to the role of the main body of monitoring when it organizes and implements monitoring. It is proved that real-time supervision of students’ status can effectively improve the effect of English classroom teaching.
Preparation and Synergistic Anti-Tumor Effect of Iridium Oxide Nanocomposites under Microscope
Authors: He Xudong , Xiang Feng , Xu Zhangyi
Published: July 2022

In order to solve the great difficulties in cancer prevention, diagnosis, and treatment, a preparation method of iridium oxide nanocomposites under the microscope was proposed in this paper. Through a retrospective analysis of an experiment, IrOx nanoparticles were prepared by direct hydrothermal hydrolysis and loaded with chemotherapy drug adriamycin to construct nanodrug-loaded complex IrOx@DOX. At the same time, IrOx, as a sound-sensitive agent, can produce ROS under US irradiation, amplify intracellular oxidative stress, accelerate tumor cell death, and finally achieve the effect of SDT chemotherapy synergistic therapy. The experimental results show that IrOx@DOX has the dual response of pH and US, and the inhibition rates are 27%, 57%, and 76%, respectively. At the same time, ultrasound not only can enhance the uptake of nanoparticles by cells but also can promote the release of DOX in cells, which provides a basis for subsequent SDT chemotherapy synergistic therapy. Conclusion. Iridium oxide nanocomposite DOX combined with SDT can obtain a good therapeutic effect, which has positive feedback on the efficacy of chemotherapy and the therapeutic effect of cancer surgery.
Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?
Authors: Zaki Marco Y.W. , Alhasan Sari F. , Shukla Ruchi , McCain Misti , Laszczewska Maja , Geh Daniel , Patman Gillian L. , Televantou Despina , Whitehead Anna , Maurício João P. , Barksby Ben , Gee Lucy M. , Paish Hannah L. , Leslie Jack , Younes Ramy , Burt Alastair D. , Borthwick Lee A. , Thomas Huw , Beale Gary S. , Govaere Olivier , Sia Daniela , Anstee Quentin M. , Tiniakos Dina , Oakley Fiona , Reeves Helen L.
Published: July 2022

Introduction: Heparin sulphate proteoglycans in the liver tumour microenvironment (TME) are key regulators of cell signalling, modulated by sulfatase-2 (SULF2). SULF2 overexpression occurs in hepatocellular carcinoma (HCC). Our aims were to define the nature and impact of SULF2 in the HCC TME. Methods: In liver biopsies from 60 patients with HCC, expression and localization of SULF2 were analysed associated with clinical parameters and outcome. Functional and mechanistic impacts were assessed with immunohistochemistry (IHC), in silico using The Cancer Genome Atlas (TGCA), in primary isolated cancer activated fibroblasts, in monocultures, in 3D spheroids, and in an independent cohort of 20 patients referred for sorafenib. IHC targets included αSMA, glypican-3, β-catenin, RelA-P-ser536, CD4, CD8, CD66b, CD45, CD68, and CD163. SULF2 impact of peripheral blood mononuclear cells was assessed by migration assays, with characterization of immune cell phenotype using fluorescent activated cell sorting. Results: We report that while SULF2 was expressed in tumour cells in 15% (9/60) of cases, associated with advanced tumour stage and type 2 diabetes, SULF2 was more commonly expressed in cancer-associated fibroblasts (CAFs) (52%) and independently associated with shorter survival (7.2 vs. 29.2 months, p = 0.003). Stromal SULF2 modulated glypican-3/β-catenin signalling in vitro, although in vivo associations suggested additional mechanisms underlying the CAF-SULF2 impact on prognosis. Stromal SULF2 was released by CAFS isolated from human HCC. It was induced by TGFβ1, promoted HCC proliferation and sorafenib resistance, with CAF-SULF2 linked to TGFβ1 and immune exhaustion in TGCA HCC patients. Autocrine activation of PDGFRβ/STAT3 signalling was evident in stromal cells, with the release of the potent monocyte/macrophage chemoattractant CCL2 in vitro. In human PBMCs, SULF2 preferentially induced the migration of macrophage precursors (monocytes), inducing a phenotypic change consistent with immune exhaustion. In human HCC tissues, CAF-SULF2 was associated with increased macrophage recruitment, with tumouroid studies showing stromal-derived SULF2-induced paracrine activation of the IKKβ/NF-κB pathway, tumour cell proliferation, invasion, and sorafenib resistance. Conclusion: SULF2 derived from CAFs modulates glypican-3/β-catenin signalling but also the HCC immune TME, associated with tumour progression and therapy resistance via activation of the TAK1/IKKβ/NF-κB pathway. It is an attractive target for combination therapies for patients with HCC.
Facing the Challenge of Drug-Induced Acute Interstitial Nephritis
Authors: Sanchez-Alamo Beatriz , Cases-Corona Clara , Fernandez-Juarez Gema
Published: July 2022

Background: Acute interstitial nephritis (AIN) is one of the chief causes of acute kidney injury (AKI). AIN might be produced by drugs, infections, autoimmune diseases, or can be idiopathic. Among these etiologies, drug-induced AIN (DI-AIN) is the dominant one in many countries. Even when DI-AIN is suspected, identification of the putative drug is challenging. Summary: DI-AIN is an increasingly common cause of AKI. Diagnosis continues to pose a challenge for physicians due to nonspecific clinical symptoms, and the fact that it can be triggered by a wide variety of medications. Furthermore, the gold standard for the diagnosis is kidney biopsy. All these aspects render the diagnosis more difficult. The withdrawal of the causative drug of DI-AIN is the centerpiece of the treatment, and if early restoration of original kidney function is not obtained, several studies support the treatment with steroids especially when they are started quickly. Key Messages: Almost all drugs have the potential to produce drug-induced acute interstitial nephritis (DI-AIN); however, antibiotics, nonsteroidal anti-inflammatory agents, and proton pump inhibitors account for the majority of the reported cases. DI-AIN is produced by an idiosyncratic delayed type IV hypersensitivity reaction, but the precise pathophysiological mechanism remains to be elucidated. DI-AIN symptoms are nonspecific, and most of the patients will present mild symptoms including malaise, nausea, and vomiting. The classical triad, associating fever, rash, and eosinophilia, is seldom present. Nonoliguric acute kidney injury is the main renal manifestation of DI-AIN. Tubular nonnephrotic range proteinuria is usually present. Diagnosis of DI-AIN relies on maintaining a high index of suspicion in those patients at greater risk, but kidney biopsy is required to confirm diagnosis. Histologically, AIN is characterized by the presence of an extensive interstitial infiltrate, mainly composed of lymphocytes and monocytes, but eosinophils, plasma cells, histiocytes, and polymorphonuclear cells can also be found. The withdrawal of the presumed causative drug of DI-AIN is the mainstay of the treatment. When there is no evidence of kidney function recovery after an interval of 5–7 days since interrupting the treatment with the suspected drug, several studies support the treatment with steroids, especially when they are promptly started. Early corticosteroids would decrease the inflammatory infiltrates of the kidney interstitium, thus preventing the risk of subsequent fibrosis.
A Longitudinal Course of ICD-11 Adjustment Disorder Symptom Profiles: A 12-Month Follow-Up Study
Authors: Kazlauskas Evaldas , Elklit Ask , Truskauskaite Inga
Published: July 2022

Introduction: Adjustment disorder is frequently diagnosed in clinical practice; however, the course of adjustment disorder over time has not yet been studied extensively. Methods: This longitudinal study was one of the first that aimed to analyze trajectories of adjustment disorder symptoms in a 12-month follow-up among a high-risk community sample (n = 205) exposed to various stressors. Adjustment disorder symptoms were measured at baseline and 12-month follow-up with the Brief Adjustment Disorder New Module based on the definition of adjustment disorder provided in the 11th Edition of International Classification of Diseases (ICD-11) released in 2018 by the World Health Organization (WHO). Results: A latent transition analysis of adjustment symptoms identified four distinct trajectories: “high symptom,” “recovery,” “onset,” and “low symptom.” We found 46% of ICD-11 adjustment disorder at baseline, and 29% of the sample was classified as having a high-symptom adjustment symptom profile. The high-symptom profile was predicted by ongoing stressors, female gender, and higher education. Conclusion: Study findings indicate that adjustment disorder among high-risk samples, in particular, those exposed to ongoing stressors, could have a high-symptom course over 12 months.
Impact of Social Isolation on the Physical and Mental Health of Older Adults: A Follow-Up Study at the Apex of the COVID-19 Pandemic in Brazil
Authors: Vidal Bravalhieri Anna Alice , Oliveira Rodrigues Nathália , Batiston Adriane Pires , de Souza Pegorare Ana Beatriz Gomes , Christofoletti Gustavo
Published: July 2022

Introduction: The COVID-19 pandemic has affected people’s lives and caused changes in habits. The World Health Organization recommends social isolation as a way of minimizing the risk of contagion of the disease. Objective: The aim of the study was to assess the impact of social isolation due to COVID-19 pandemic on the physical and mental health of older adults and to investigate how anthropometric, functional, and clinical aspects are associated with this process. Methods: Fifty healthy older adults were followed-up during 5 months. The subjects had their physical and mental health assessed during social isolation (pre-vaccine situation) and after the opening of stores and activities in the municipality (post-vaccine situation). Physical evaluation was performed using the 30-s sit and stand test. Participants’ mental health was assessed with the Geriatric Depression Scale and the Loneliness Index. In this methodological design, muscle strength, depressive symptoms, and loneliness index were subject to pre-post analyses. In addition, these variables were included as outcomes in linear regression models. Participants’ anthropometric, functional, and clinical factors were included as predictors of the statistical model. Results: Participants’ scores at baseline were consistent with mild depressive symptoms and low loneliness. The muscle strength of the subjects was appropriate to their ages. After 5 months of social isolation, all variables declined, but with statistical significance only for depressive symptoms (p = 0.017, effect size of 0.11). Anthropometric, functional, and clinical factors explained 42.8% of depressive symptoms, 22.3% of loneliness, and 30.2% of muscle strength in the elderly. Discussion/Conclusion: Older adults presented baseline scores consistent with mild depressive symptoms and low loneliness. The muscular strength of the subjects was appropriate for their ages. After 5 months of social isolation, all variables declined. Anthropometric, functional, and clinical factors explained a substantial part of the depressive symptoms, loneliness, and muscular strength in the elderly. Health care professionals should be aware of performing a wide assessment in subjects’ lives to ensure better health status.
Atezolizumab plus Bevacizumab versus Sorafenib for Unresectable Hepatocellular Carcinoma: Results from Older Adults Enrolled in the IMbrave150 Randomized Clinical Trial
Authors: Li Daneng , Toh Han Chong , Merle Philippe , Tsuchiya Kaoru , Hernandez Sairy , Verret Wendy , Nicholas Alan , Kudo Masatoshi
Published: July 2022

Introduction: The efficacy of systemic first-line treatments in older adults with unresectable hepatocellular carcinoma (HCC) has not been well-studied. We compared the safety and efficacy of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment in younger versus older patients with unresectable HCC. Methods: This global, phase 3, open-label, randomized clinical trial (IMbrave150) recruited patients aged ≥18 years with locally advanced metastatic or unresectable HCC, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and Child-Pugh class A liver function who had not previously received systemic therapy for liver cancer. Patients received either 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily until loss of clinical benefit or unacceptable toxicity. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the incidence of adverse events and time to deterioration of patient-reported outcomes (PROs). This subgroup analysis evaluated safety and efficacy endpoints in patients <65 years, ≥65 to <75 years, and ≥75 years. Results: Of 501 patients, 165 patients were randomized to sorafenib and 336 were randomized to atezolizumab plus bevacizumab (175 patients <65 years; 106 patients ≥65 to <75 years; 55 patients ≥75 years). Across all age groups, patients receiving atezolizumab plus bevacizumab had longer median OS (<65: 18.0 vs. 12.2 months [HR, 0.57; 95% CI: 0.40–0.82]; ≥65 to <75: 19.4 vs. 14.9 months [HR, 0.80; 95% CI: 0.52–1.23]; ≥75: 24.0 vs. 18.0 months [HR, 0.72, 95% CI: 0.37–1.41]) and PFS than those receiving sorafenib. Time to deterioration for multiple PROs was delayed for patients receiving atezolizumab plus bevacizumab, including older adults. There were no clinically meaningful differences in toxicity between age groups. Conclusion: Atezolizumab plus bevacizumab is safe and effective in adults <65, ≥65 to <75, and ≥75. Treatment was well-tolerated even in elderly patients.
Retained Pesticide Bottle in the Rectum
Authors: Ho Chia-Chieh , Su Yu-Jang
Published: July 2022

Case Report: A 51-year-old male patient visited the emergency department (ED) for abdominal pain with bloody stool passage after inserting a pesticide bottle into his anus by himself. No fever or shock sign was presented. Plain film revealed a 23 cm × 8 cm cylindrical foreign body in the lower abdomen. A proctologist was consulted for foreign-body removal. Under general anesthesia, an anal retractor was put into the anus, and a large aluminum pesticide bottle was then removed successfully. Discussion: Many kinds of rectal foreign-body (RFBs) insertion into the rectum were reported, such as bottles, cans, vegetables like cucumber or carrots, wood sticks, and sexual devices. RFBs are more common in men than in women, with average cases presenting in middle age. Patients may be presented to ED with lower abdominal or anorectal pain, with failure to remove foreign bodies after several attempts. Delay of ED visit may lead to mucosal edema or mucosal break with bleeding. In more high-lying or nonradiolucent foreign bodies, a computed tomography provides clearer relative location to the adjacent organs. A transanal approach should be the first attempt if there are no signs of peritonitis and the foreign body is within 10 cm from the anal orifice. For foreign bodies with a deeper location, endoscopy may aid the retrieval work. If transanal approaches fail or the patient has signs of bowel perforation, an abdominal approach with laparoscopy or laparotomy should be considered.
Puberty Timing and Sex-Specific Trajectories of Systolic Blood Pressure: a Prospective Cohort Study
Authors: O’Neill Kate N. , Bell Joshua A. , Davey Smith George , Tilling Kate , Kearney Patricia M. , O’Keeffe Linda M.
Published: July 2022

Background:

Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP preceding and following puberty and examined the impact of puberty timing on SBP trajectories in females and males.

Methods:

Trajectories of SBP before and after puberty and by timing of puberty in females and males in a contemporary birth cohort study were analyzed. Repeated measures of height from age 5 to 20 years were used to identify puberty timing (age at peak height velocity). SBP was measured on ten occasions from 3 to 24 years (N participants, 4062; repeated SBP measures, 29 172). Analyses were performed using linear spline multilevel models based on time before and after puberty and were adjusted for parental factors and early childhood factors.

Results:

Mean age at peak height velocity was 11.7 years (SD, 0.8) for females and 13.6 years (SD, 0.9) for males. Males had faster rates of increase in SBP before puberty leading to 10.19 mm Hg (95% CI, 6.80–13.57) higher mean SBP at puberty which remained similar at 24 years (mean difference, 11.43 mm Hg [95% CI, 7.22–15.63]). Puberty timing was associated with small transient differences in SBP trajectories postpuberty in both sexes and small differences at 24 years in females only.

Conclusions:

A large proportion of the higher SBP observed in males compared with females in early adulthood is accrued before puberty. Interventions targeting puberty timing are unlikely to influence SBP in early adulthood.
IsoLGs (Isolevuglandins) Drive Neutrophil Migration in Hypertension and Are Essential for the Formation of Neutrophil Extracellular Traps
Authors: Krishnan Jaya , de la Visitación Néstor , Hennen Elizabeth M. , Amarnath Venkataraman , Harrison David G. , Patrick David M.
Published: July 2022

Background:

IsoLGs (isolevuglandins) are electrophilic products of lipid peroxidation formed in the presence of reactive oxygen species. IsoLGs contribute to hypertension by an unknown mechanism. Studies have shown that reactive oxygen species production drives the formation of neutrophil extracellular traps (NETs) and that NETs accumulate within the aorta and kidneys of patients with hypertension. The purpose of this study was to determine the role of isoLGs in neutrophil migration and NET formation (NETosis) in hypertension.

Methods:

Mice were treated with Ang II (angiotensin II) and the specific isoLG scavenger 2-hydroxybenzylamine and examined for tissue neutrophil and NET accumulation by single-cell sequencing and flow cytometry. Isolated human neutrophils were studied to determine the role of isoLGs in NETosis and neutrophil chromatin expansion by immunofluorescence and live cell confocal microscopy.

Results:

Single-cell sequencing performed on sham, Ang II, and Ang II+2-hydroxybenzylamine treated mice revealed neutrophils as a primary target of 2-hydroxybenzylamine. Peripheral neutrophil migration, aortic NET accumulation, and renal NET accumulation is blocked with 2-hydroxybenzylamine treatment. In isolated human neutrophils, isoLGs accumulate during NETosis and scavenging of isoLGs prevents NETosis. IsoLGs drive neutrophil chromatin expansion during NETosis and disrupt nucleosome structure.

Conclusions:

These observations identified a critical role of isoLGs in neutrophil migration and NETosis in hypertension and provide a potential therapy for NET-associated diseases including hypertension and associated end organ damage.
Association Between the Gut Microbiome and Their Metabolites With Human Blood Pressure Variability
Authors: Dinakis Evany , Nakai Michael , Gill Paul , Ribeiro Rosilene , Yiallourou Stephanie , Sata Yusuke , Muir Jane , Carrington Melinda , Head Geoffrey A. , Kaye David M. , Marques Francine Z.
Published: July 2022

Background:

Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability.

Methods:

Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean±SD, 59.8±7.26 years; body mass index, 25.2±2.83 kg/m
2
). These data were used to determine nighttime dipping, morning BP surge (MBPS) and BP variability as SD. The gut microbiome was determined by 16S ribosomal RNA (rRNA) sequencing and metabolite levels by gas chromatography.

Results:

We identified specific taxa associated with systolic BP variability, nighttime dipping, and MBPS. Notably,
Alistipesfinegoldii
and
Lactobacillus
spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while
Prevotella
spp. and
Clostridium
spp., were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial α-diversity (r=−0.244,
P
=0.046). MBPS was also negatively associated with plasma levels of microbial metabolites called short-chain fatty acids (r=−0.305,
P
=0.020), particularly acetate (r=−0.311,
P
=0.017).

Conclusions:

Gut microbiome diversity, levels of microbial metabolites, and the bacteria
Alistipesfinegoldii
and
Lactobacillus
were associated with lower BP variability and
Clostridium
and
Prevotella
with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.
Effects of a Liquefied Petroleum Gas Stove Intervention on Gestational Blood Pressure: Intention-to-Treat and Exposure-Response Findings From the HAPIN Trial
Authors: Ye Wenlu , Steenland Kyle , Quinn Ashlinn , Liao Jiawen , Balakrishnan Kalpana , Rosa Ghislaine , Ndagijimana Florien , Ntivuguruzwa Jean de Dieu , Thompson Lisa M. , McCracken John P. , Díaz-Artiga Anaité , Rosenthal Joshua P. , Papageorghiou Aris , Davila-Roman Victor G. , Pillarisetti Ajay , Johnson Michael , Wang Jiantong , Nicolaou Laura , Checkley William , Peel Jennifer L. , Clasen Thomas F. ,   for the Household Air Pollution Intervention Network (HAPIN) trial Investigators
Published: July 2022

Background:

Approximately 3 to 4 billion people worldwide are exposed to household air pollution, which has been associated with increased blood pressure (BP) in pregnant women in some studies.

Methods:

We recruited 3195 pregnant women in Guatemala, India, Peru, and Rwanda and randomly assigned them to intervention or control groups. The intervention group received a gas stove and fuel during pregnancy, while the controls continued cooking with solid fuels. We measured BP and personal exposure to PM
2.5
, black carbon and carbon monoxide 3× during gestation. We conducted an intention-to-treat and exposure-response analysis to determine if household air pollution exposure was associated with increased gestational BP.

Results:

Median 24-hour PM
2.5
dropped from 84 to 24 μg/m
3
after the intervention; black carbon and carbon monoxide decreased similarly. Intention-to-treat analyses showed an increase in systolic BP and diastolic BP in both arms during gestation, as expected, but the increase was greater in intervention group for both systolic BP (0.69 mm Hg [0.03–1.35];
P
=0.04) and diastolic BP (0.62 mm Hg [0.05–1.19];
P
=0.03). The exposure-response analyses suggested that higher exposures to household air pollution were associated with moderately higher systolic BP and diastolic BP; however, none of these associations reached conventional statistical significance.

Conclusions:

In intention-to-treat, we found higher gestational BP in the intervention group compared with controls, contrary to expected. In exposure-response analyses, we found a slight increase in BP with higher exposure, but it was not statistically significant. Overall, an intervention with gas stoves did not markedly affect gestational BP.
Performance of Confirmatory Tests for Diagnosing Primary Aldosteronism: a Systematic Review and Meta-Analysis
Authors: Leung Alexander A. , Symonds Christopher J. , Hundemer Gregory L. , Ronksley Paul E. , Lorenzetti Diane L. , Pasieka Janice L. , Harvey Adrian , Kline Gregory A.
Published: July 2022

Background:

Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear.

Methods:

We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models.

Results:

Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46–21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48–17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low.

Conclusions:

Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.
Sex-Related Signaling of Aldosterone/Mineralocorticoid Receptor Pathway in Calcific Aortic Stenosis
Authors: Matilla Lara , Jover Eva , Garaikoetxea Mattie , Martín-Nuñez Ernesto , Arrieta Vanessa , García-Peña Amaia , Navarro Adela , Fernández-Celis Amaya , Gainza Alicia , Álvarez Virginia , Álvarez de la Rosa Diego , Sádaba Rafael , Jaisser Frederic , López-Andrés Natalia
Published: July 2022

Background:

There are sex differences in the pathophysiology of aortic valve (AV) calcification in patients with aortic stenosis, although the molecular and cellular mechanisms have not been elucidated. Aldosterone (Aldo) promotes proteoglycan synthesis in valve interstitial cells (VICs) from mitral valves via the mineralocorticoid receptor (MR). We investigated the influence of sex in the role of Aldo/MR pathway in AV alterations in patients with aortic stenosis.

METHODS AND RESULTS:

MR was expressed by primary aortic VICs and in AVs from patients with aortic stenosis. MR expression positively correlated with VIC activation markers in AVs from both sexes. However, MR expression was positively associated with molecules involved in AV calcification only in AV from men. Aldo enhanced VIC activation markers in cells from men and women. Interestingly, Aldo increased the expression of calcification markers only in VICs isolated from men. In female VICs, Aldo enhanced fibrotic molecules. MR antagonism (spironolactone) blocked all the above effects. Cytokine arrays showed ICAM (intercellular adhesion molecule)-1 and osteopontin to be specifically increased by Aldo in male VICs. In AVs from men, MR expression positively associated with both ICAM-1 (intercellular adhesion molecule-1) and osteopontin. Only in female VICs, estradiol treatment blocked Aldo-induced VICs activation, inflammation, and fibrosis.

Conclusions:

These findings demonstrate that the Aldo/MR pathway could play a role in early stages of aortic stenosis by promoting VICs activation, fibrosis, and ulterior calcification. Importantly, Aldo/MR pathway is involved in fibrosis in women and in early AV calcification only in men. Accordingly, MR antagonism emerges as a new sex-specific pharmacological treatment to prevent AV alterations.
Characteristics Associated With Growth Differentiation Factor 15 in Heart Failure With Preserved Ejection Fraction and the Impact of Pirfenidone
Authors: Lewis Gavin A. , Rosala‐Hallas Anna , Dodd Susanna , Schelbert Erik B. , Williams Simon G. , Cunnington Colin , McDonagh Theresa , Miller Christopher A.
Published: July 2022

Background

Growth differentiation factor 15 (GDF‐15) is elevated in heart failure with preserved ejection fraction and is associated with adverse outcome, but its relationship with myocardial fibrosis and other characteristics remains unclear. We sought to evaluate the effect of pirfenidone, a novel antifibrotic agent, on GDF‐15 in heart failure with preserved ejection fraction and identify characteristics that associate with GDF‐15 and with change in GDF‐15 over 1 year.

Methods and Results

Among patients enrolled (n=107) in the PIROUETTE (Pirfenidone in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, GDF‐15 was measured at baseline and at prespecified time points in patients randomized (n=94) to pirfenidone or placebo. The response of GDF‐15 to pirfenidone and the association with baseline patient characteristics were evaluated. Pirfenidone had no impact on circulating GDF‐15 at any time point during the 52‐week trial period. In multivariable analysis, male sex, diabetes, higher circulating levels of N‐terminal pro‐B‐type natriuretic peptide, lower renal function, and shorter 6‐minute walk test distance at baseline were associated with baseline log–GDF‐15. Impaired global longitudinal strain at baseline was the strongest predictor of increased GDF‐15 over 52 weeks.

Conclusions

In patients with heart failure with preserved ejection fraction, circulating levels of GDF‐15 were unaffected by treatment with pirfenidone and do not appear to be determined by myocardial fibrosis. Circulating GDF‐15 was associated with a spectrum of important heart failure characteristics and it may represent a marker of overall physiological disruption.

Registration

URL:
https://clinicaltrials.gov/ct2/show/NCT02932566
; Unique identifier: NCT02932566.
Renin‐Angiotensin and Endothelin Systems in Patients Post‐Takotsubo Cardiomyopathy
Authors: Khan Hilal , Rudd Amelia , Gamble David T. , Mezincescu Alice M. , Cheyne Lesley , Horgan Graham , Dhaun Neeraj , Newby David E. , Dawson Dana K
Published: July 2022

Background

We investigate if renin‐angiotensin and endothelin‐1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo cardiomyopathy.

Methods and Results

Ninety patients with takotsubo cardiomyopathy (n=30 in each of “acute,” “convalescent” [3–5 months] and “recovered” [>1 year] groups) who were on minimal or no medication and were free of any significant cardiac/metabolic comorbidities, and 30 controls were studied. Serum concentrations of renin, angiotensin‐converting enzyme, angiotensin II, big endothelin‐1, endothelin‐1 were measured using commercially available ELISA, and B‐type natriuretic peptide was measured using an immunoassay. Mean left ventricular ejection fraction was <40% during the acute phase in all groups, but recovered to 63% in convalescent and 64% in the recovered groups, respectively. Serum renin concentrations remain persistently elevated after a episode of takotsubo cardiomyopathy (
P
=0.03 versus controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared with convalescent (
P
=0.004), recovered takotsubo cardiomyopathy (
P
=0.02) or controls (
P
=0.03). Angiotensin II is increased in patients with takotsubo cardiomyopathy (
P
<0.001 versus controls) remaining persistently elevated in the chronically recovered group alone (
P
=0.03 versus controls). Big endothelin‐1 levels are unchanged, but endothelin‐1 is significantly lower after takotsubo cardiomyopathy compared with controls (
P
=0.03).

Conclusions

Despite “normalization” of the left ventricular ejection fraction, there is long‐term maladaptive activation of renin‐angiotensin system in patients with takotsubo cardiomyopathy.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT02897739, NCT02989454.
The Poetry of Jeremiah Horrocks’s Venus in sole visa (1662): Astronomy, Authority, and the ‘New Science’
Authors: Barton William M.
Published: July 2022

As one of the least common, yet predictable astronomical occurrences, the transits of Venus were to become among the most keenly anticipated events for early modern cosmologists. Basing himself on Johannes Kepler’s Tabulae Rudolphinae (1627), former Cambridge student Jeremiah Horrocks (1616–1641) made the first recorded observation of a transit from Much Hoole, Lancashire in 1639. Alongside the description of his observations, Horrocks’ Venus in sole visa contains four poems alongside the work’s prose descriptions, figures, and tables. His verses call on the long tradition of Latin scientific poetry employed for the predictable purposes of eulogy and homage, but they also serve to justify and clarify the author’s position on scientific issues of his time. Despite the long-recognized importance of Horrocks’ observations, his hexameter compositions have been largely ignored in later scholarship. In the latest translation of the Venus in sole visa (2012), one poem—the longest and arguably the best—is omitted altogether. This paper offers a study of Horrocks’ Latin poetry, his models and engagement with its subject matter. It reveals Horrocks’ efforts to promote his predecessors’ achievements, his position on questions central to the debates of his time, and the claims for authority he made for the work of others, as well as for his own. The present article also includes a new, modern translation of Horrocks’ longest, and recently forgotten poem as an appendix.
Galileo and the Epistemology of Anatomy
Authors: Sgarbi Marco
Published: July 2022

Starting from the examination of a passage of the Dialogo sopra i massimi sistemi del mondo that has been largely ignored by the scholarship, in this paper I want to reveal the true nature of Galileo’s epistemology in terms of its epistemic ideal, that is that theory is capable of providing true and certain knowledge about natural phenomena coming from sensation. The investigation examines all the occurrences of the expression sensate esperienze in its singular and plural forms, both in the Latin and in the vernacular. The research proceeds diachronically through an analysis of Galileo’s writings taken in order to show the progressive development of his epistemology. The paper will demonstrate how in thinking about sensate experiences Galileo had in mind as epistemic paradigm that of the epistemology of anatomy.