bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Mound a Horse? Remembrance and Thoughts of Afterlife at Finnish Companion Animal Cemetery
Authors: Äikäs Tiina , Ikäheimo Janne , Leinonen Riitta-Marja
Published: July 2021

This article presents the results of a combined archaeological and cultural anthropological study of 170 horse burials at a pet (companion animal) cemetery in Mikonkangas, Oulu, Finland. The applied methods include archaeological documentation, interviews with the horse caretakers, and visits to the site. Contrary to socially and legislatively controlled human burial grounds with organized maintenance, companion animal cemeteries with their inherent do-it-yourself character are often displays for more spontaneous expressions of grief and longing. The evidence of remembrance varies from nearly unmarked graves to elaborate memorials with headstones, epitaphs, flowers, and personal objects. The thought of a reunion in the afterlife is evident in some of the epitaphs and could also have influenced the use of crosses and angel symbols on some of the graves.
Is It Possible to Overrule a Constitutional Precedent in the Egyptian Legal System?
Authors: Chiha Islam Ibrahim , el-Shimy Abdel Hafiz
Published: July 2021

This article examines the constitutionality of the Egyptian Supreme Constitutional Court’s (hereinafter SCC) authority to overrule its prior precedents. The authors argue, contrary to the assertions of the predominant conservative approach in Egypt, that bestowing the SCC with such an overruling power neither violates the Constitution nor undermines fundamental legal principles such as the principles of equality, legal certainty, or the justified expectations of litigants. Indeed, we make the argument that the Court’s ability to overrule its prior precedents seems to be the most conceivable and plausible way to correct the Court’s past mistakes or inaccuracies. We finally claim that endowing the court with such overruling power enhances the constitutional protection of fundamental rights and freedoms and strengthens the Court’s credibility not only via other public authorities, but also via public opinion.
The Obligation to Cooperate in the Fight against Climate Change
Authors: Rudall Jason
Published: July 2021

Cooperation has a relatively long history under international law. This duty is evident in and has been developed by a variety of international instruments as well as the jurisprudence of courts and tribunals, treaty-bodies and other international institutions. This article examines cooperation as it pertains to climate governance. It appraises the current and emerging dimensions of cooperation, the relationship with other obligations, principles and concepts in this area, as well as asking which aspects of cooperation must be ameliorated to better serve the fight against climate change.
Why Don’t You Get It?
Authors: Fox Richard
Published: July 2021

This essay explores the relationship between language and mutual (mis)understanding in Candra Aditya’s short film Dewi pulang. The film follows Dewi, a young Javanese woman, as she travels from Jakarta to her natal home in Central Java to attend her father’s funeral. The tension between Dewi’s multiple and often conflicting obligations is marked by the use of language—from the colloquial Indonesian she speaks with her friends in Jakarta to a brief exchange with her English-speaking boss on the telephone and the various forms of Javanese employed ‘at home’. Drawing on examples in both Indonesian and Javanese, it is argued that the film’s use of language may be understood as a form of social commentary, reflecting critically on the complex and at times incongruous desires, expectations, and aversions at play in the lives of a growing number of young Indonesians.
Let them Come to Me: A Youth Inclusive and Missional Perspective in Presbyterian Context
Authors: Ndereba Kevin Muriithi
Published: July 2021

The contemporary context creates complexities for the young person. These include the political and socio-economic realities of African states, the cultural renaissance of Africanism and the reality of postmodernity. From both a practical theological perspective as well as experience in higher education, the author claims that ministers in the Presbyterian Church lack a missional perspective to the contemporary African (Kenyan) youth. The author proposes that theological education in Kenya must seriously consider youth ministry education. Second, Presbyterian ecclesiology must be missional minded by moving from an inward posture to a missional posture that considers the African (Kenyan) youth. This reflection will engage practical ministry and higher education experience, as well as an inter-disciplinary literature survey, to offer a missional perspective for the church and theological education.
Research on the Effect of p35 for Secretion of Proinflammatory Factor and Apoptosis of Chondrocyte in Chondrocytopathic Articular Fluid
Authors: Yang LvLin , Zhang Bowen , Liang Yuqi , Feng Gangning , Shang Xiaoke , Guo Chongjun , Yang Xiaochun , Meng Zhiqiang , Hua Jinqun
Published: July 2021

To study on the effect of transcriptional regulation factor as p35 for secretion of proinflammatory factor and apoptosis of chondrocyte in chondrocytopathic articular fluid so as to improve the chondropathy. The fifty SD rats were selected for our study. It was divided into three groups
including A group (control group), B group (chondrocytopathic model group of osteoarthritis) and C group (transcriptional regulation factor as p35 intervention group. The samples were collected after intervention in sixteen weeks. The sampling position was cartilage tissue of rat leg. It was
adopted for immunohistochemical inspection and histopathology examination. At the same time the synovial fluid was collected. The concentration of TNF-α and IL-6 was detected. And the expression of mRNA in gene related with apoptosis was detected. The chondrocyte morphology of
rats in A group was normal. The chondrocyte was damaged and goblet cell was reduced in B group. The infiltrating inflammatory cells in C group were less than in B group from pathological results. And the goblet cells in C group was increased than in B group. The expression of TNF-α,
Bax, NF-κB, IL-6: B group > C group > A group. The expression of Bcl-2: A group > C group > B group. The transcriptional regulation factor as p35 related with anti-apoptosis could regulate the level of inflammatory factor as TNF-α and IL-6 in synovial
fluid and restrain the lesion and apoptosis of chondrocyte.
Effect of Yes Associated Protein on Osteogenic/Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Under Oxidative Stress
Authors: Zhou Yonghuan , Lan Guotang , Zhou Yan , Qu Tianhao , Xiong Qing
Published: July 2021

Oxidative stress affects bone marrow mesenchymal stem cells (BMSCs). YAP is an effector in Hippo signaling, but its’ role in BMSCs osteogenesis/adipogenesis under oxidative stress has not been reported. Mice BMSCs were isolated and assigned into 3 groups, normal control group;
oxidative stress group; and YAP group (transfected with YAP plasmid) followed by analysis of YAP expression by Real time PCR. After 14 days of osteogenesis or adipogenic induction, RUNX2, OPN, FABP4 and PPARγ2 mRNA level was measured along with ROS and SOD activities, ALP activity
and Wnt5 expression by western blot. Under oxidative stress, YAP expression significantly decreased, RUNX2 and OPN mRNA expression decreased, ROS expression increased, SOD activity decreased, FABP4 and PPARγ2 protein expression increased, ALP activity and Wnt5 expression decreased
(P <0.05). YAP plasmid transfection could significantly up-regulate YAP, RUNX2 and OPN mRNA level, decrease ROS, increase SOD and ALP activity, reduce FABP4 and PPARγ2 mRNA expression and increase Wnt5 expression (P <0.05). YAP level in BMSCs is decreased under
oxidative stress. Up-regulating YAP can improve the redox balance, promote BMSCs osteogenic differentiation under oxidative stress and inhibit their differentiation to adipocytes.
Effects of Epidermal Growth Factor Receptor Signal Pathway on Proliferation, Invasion and E-Cadherin/Vimentin Protein Expression in Laryngeal Carcinoma Hep-2 Cells
Authors: Wu Tingting , Zhou Xuhong , Ye Linfeng , Li Shuang , Huang Jing , Huang Shuo , Luo Huizhou
Published: July 2021

Epidermal growth factor receptor (EGFR) is one transmembrane receptor with a high expression in more than 90% of head-neck squamous carcinoma cells. This study investigated the role of EGFR signal pathway on proliferation, invasion and expression of related proteins E-cadherin/Vimentin
expression in laryngeal carcinoma cells. Laryngeal carcinoma Hep-2 cells were treated with EGFR agonist EGF or inhibitor Gefitinib followed by measuring cell cycle, proliferation index (PI) and apoptosis by flow cytometry. Transwell assay was employed for cell invasion and migration. Western
blotting was further employed to test E-cadherin and Vimentin level. Compared to blank control group, EGF-treated cells had significantly lower S percentage of cell cycle at 6 h, 12 h and 24 h, plus higher PI. With prolonged incubation time, S ratio and PI were further significantly elevated,
with more potent cell invasion and migration abilities, lower E-cadherin and Vimentin protein levels (p < 0.05). Gefitnib significantly elevated S ratio at 6 h, 12 h and 24 h cell cycle, reduced PI, invasion or migration ability, as upregulated E-cadherin and downregulated Vimentin
protein (p < 0.05). Suppressing EGFR signal pathway could inhibit proliferation of laryngeal carcinoma cells, decrease cell invasion or migration, upregulate E-cadherin and downregulate Vimentin.
Comparison Between Ultrasonography and Magnetic Resonance Imaging in Achilles Tendon
Authors: Ying Jianhua , Fekete Gusztáv
Published: July 2021

Purpose: This study aims was to compared the effectiveness of Magnetic Resonance Imaging (MRI) and Ultrasonography (US) imaging techniques in the diagnosis of tendon pathology. Method: The databases search of PubMed, Scopus, and Embase extracted 567 articles for a title
and abstract review. After removing and evaluating, a total of 6 articles were collected. Results and conclusion: There are three views on the diagnosis of Achilles tendon (AT) by US and MRI: US has higher sensitivity and reliability than MRI; MRI is more effective than the US, and
there is a similar diagnosis result between US and MRI. It may not be necessary to distinguish between the diagnostic role of US and MRI, since US and MRI tools can be used as effective means to provide valuable information for the diagnosis and treatment of AT.
Radiographic Vertebral Fracture Assessment of Vertebral Fracture by the Three-Line Method
Authors: Hu Nan-Zhi , Huang Shu-Meng , Xu Yi-Ren , Liu Ting , Hu Bai-Wen , Yao Qi , Wang Cui , Huang Qiu-Li , Yu Jing-Bo , Xia Dong-Dong
Published: July 2021

Purpose: To evaluate the value of the three-line (TL) method in the diagnosis of vertebral fractures. Methods: 286 patients over 50 years old who received thoracolumbar X-ray examination in our hospital from 2013 to 2019 were selected and divided into three groups according
to their age. The incidence and severity of vertebral fractures were measured by the TL method and Genant semi-quantitative technique by the same observer. Eight vertebrae were measured in each patient, ranging from T10 to L5. Results: The TL method was consistent with the Genant semi-quantitative
method when evaluating whether patients had vertebral fractures (k >0.75), and the McNemar-bowker test showed no difference in the diagnosis between the two methods (P >0.05). However, Wilcoxon rank sum test found a difference between the two methods in assessing the severity
of fractured vertebrae (P < 0.05), and the TL method was more sensitive. Conclusion: The two methods can be substituted for each other in the diagnosis of vertebral fractures. However, TL method is more sensitive in the diagnosis of the severity of spinal fractures. And the
TL method is more quantitative and easier for beginners to master.
The Manukau Salivary Symptoms Score for Assessing the Impact of Sialendoscopy in Recurrent Obstructive Sialadenitis
Authors: Hardcastle Tim , Rasul Usman , de Paiva Leite Sandro , Zheng Kevin , Donaldson Gabriella , Ahmad Zahoor , Morton Randall P.
Published: July 2021

Objective

To examine the Manukau Salivary Symptom Score (MSSS) questionnaire as a validated tool to assess obstructive sialadenitis‐specific symptoms to both indicate disease severity and assess the outcome after sialendoscopic procedures.

Study Design

A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic chronic obstructive salivary gland disease (COSGD).

Setting

Department of Otolaryngology–Head and Neck Surgery at the Manukau Surgical Centre, Auckland, New Zealand, between June 2010 and September 2019.

Methods

A prospective observational study was performed from 2010 to 2019 comprising 164 patients undergoing sialendoscopy for nonneoplastic COSGD. Patients completed the MSSS preoperatively and at postoperative follow‐up. Statistical tests were used to compare pre‐ and postoperative answers. Cronbach’s α was used to measure internal consistency. Finally, construct validity was determined by comparing the 5‐question MSSS questionnaire to the preexisting 20‐question Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire.

Results

Postoperatively, patients had significant improvements in pain, eating, talking, swelling, and quality of life (P <. 001). The MSSS questionnaire was found to have high internal consistency (α = 0.938). Questions in the MSSS had a very strong positive correlation with 3 COSS questions, a strong positive correlation with 8, a moderate positive correlation with 4, and a weak positive correlation with 1. Four COSS questions were not considered relevant and were not included in the MSSS questionnaire.

Conclusion

The MSSS questionnaire is a simple, validated questionnaire that is useful for assessing the impact of sialendoscopy in patients with COSGD.
Children With Down Syndrome and Obstructive Sleep Apnea: Outcomes After Tonsillectomy
Authors: Abijay Claire A. , Tomkies Anna , Rayasam Swathi , Johnson Romaine F. , Mitchell Ron B.
Published: July 2021

Objective

To evaluate outcomes of tonsillectomy and predictors for persistent obstructive sleep apnea (OSA) in children with Down syndrome in an ethnically diverse population.

Study Design

Case series with chart review.

Setting

UT Southwestern/Children’s Medical Center Dallas.

Methods

Polysomnographic, clinical, and demographic characteristics of children with Down syndrome ages 1 to 18 years were collected, including pre‐ and postoperative polysomnography. Simple and multivariable regression models were used for predictors for persistent OSA. P≤. 05 was considered significant.

Results

Eighty‐one children were included with a mean age of 6.6 years, 44 of 81 (54%) males, and 53 of 81 (65%) Hispanic. Preoperatively, 60 of 81 (74%) patients had severe OSA. Posttonsillectomy improvements occurred for apnea‐hypopnea index (27.9 to 14.0, P <. 001), arousal index (25.2 to 18.8, P =. 004), percent time with oxygen saturations <90% (8.8% to 3.4%, P =. 003), and oxygen nadir (81.4% to 85%, P <. 001). Forty‐seven children (58%) had persistent OSA. Fifteen children (18.5%) had increased apnea‐hypopnea index postoperatively: 2 from mild to moderate, 2 from mild to severe, and 2 from moderate to severe obstructive sleep apnea. Persistent OSA predictors were asthma (odds ratio, 4.77; 95% CI, 1.61‐14.09; P =. 005) and increasing age (odds ratio, 1.25; 95% CI, 1.09‐1.43; P =. 001).

Conclusion

Children with Down syndrome are at high risk for persistent OSA after tonsillectomy with about 20% worsening after tonsillectomy. Asthma and increasing age are predictors for persistent OSA in children with Down syndrome.
Implementation of a Novel Protocol for Preventing Venous Thromboembolism in Otolaryngology Patients
Authors: Levi Lirit , Spectre Galia , Nesichi Ofir , Leader Avi , Raanani Pia , Reuven Yonatan , Schindel Hilla , Shpitzer Thomas , Reifen Ella , Bachar Gideon , Mizrachi Aviram
Published: July 2021

Objective

Venous thromboembolism (VTE) is a preventable cause of postoperative morbidity and mortality. The Caprini risk assessment model (CRAM) is a validated tool for estimating the risk for postoperative VTE. Previous studies demonstrated a low risk of VTE among otorhinolaryngology–head and neck surgery (ORL‐HNS). Hence, our objective was to modify the CRAM‐based protocol to be applicable for otolaryngology patients and assess protocol efficacy and safety.

Study Design

Observational pilot study conducted on ORL‐HNS patients undergoing surgery.

Setting

University‐affiliated tertiary care center.

Methods

We constructed a modified protocol based on the CRAM and previous reports in the ORL‐HNS literature using a reduced postoperative anticoagulation regimen. Primary end point was symptomatic VTE up to 3 months after surgery. Main secondary outcome was postoperative bleeding.

Results

A total of 508 patients were enrolled. Of them, 48% underwent head and neck surgery, 18% direct laryngoscopy and transoral robotic surgery, 15% endoscopic sinus surgery, and 11% otology surgery. Adherence to the protocol was 79%. Mean follow‐up time was 115 days (range, 30‐448 days). Only 1 patient developed deep vein thrombosis, and none developed pulmonary embolism. Two patients had major bleeding not related to the use of anticoagulation.

Conclusions

Our novel CRAM‐based protocol appears to be efficacious and safe for VTE prevention in otolaryngology. A larger‐scale study is required to validate these findings.

Level of Evidence

Level 2b.
Feasibility of an Innovative Absorbable Ventilation Tube Designed to Provide Intermediate‐Term Middle Ear Ventilation
Authors: Skovlund Sandra , Cofer Shelagh , Weinreich Heather
Published: July 2021

Myringotomy with ventilation tube placement is a common surgical procedure performed in children and adults to remove fluid buildup behind the tympanic membrane. However, retention of tubes beyond achievement of therapeutic response increases risk for complications and additional intervention. This small feasibility study was conducted to demonstrate proof of concept of a novel bioabsorbable ventilation tube that provides the necessary duration of ventilation with absorption shortly thereafter. Tubes were placed in 15 ears of 14 patients meeting indications for short or intermediate duration of middle ear ventilation. Two independent examiners documented tube patency and tube absorption status at 3, 6, and 12 weeks or until absorption was complete. Results indicate that average ventilation time was 12 weeks (range, 3 weeks to 18 months). There was no observation of blockage. These findings support the feasibility of a novel bioabsorbable ventilation tube.
Immune‐Mediated Sensorineural Hearing Loss in the Pediatric Population
Authors: Gorthey Scott , Patel Ravi , Vambutas Andrea
Published: July 2021

A case series with chart review of pediatric patients with immune‐mediated sensorineural hearing loss, including sudden sensorineural hearing loss and autoimmune‐mediated hearing loss, was performed. Ninety‐eight patients with sensorineural hearing loss were reviewed, and 41 patients met the inclusion criteria, which included corticosteroid therapy for a decline in sensorineural hearing. The primary outcome was the corticosteroid response rate: 61% of patients responded. The secondary outcome was a sustained response following multiple courses of corticosteroids for additional hearing loss, which correlated with timely corticosteroid treatment: 57% showed sustained response with multiple treatments, but as anticipated, patients were more likely to respond when treated promptly. Sustained responses fell over time with multiple treatments. These data demonstrate pediatric immune‐mediated sensorineural hearing loss is corticosteroid responsive in at a rate similar to their adult counterparts and should be considered for similar treatment approaches.
Recent acoustic energy harvesting methods and mechanisms: A review
Authors: Patil Avadhut T , Mandale Maruti B
Published: July 2021

This review article summarises the mechanism of the acoustic energy harvester or converter which includes the compact structure of the piezoelectric element, electromagnetic transducer and Helmholtz resonator; different shapes of Helmholtz resonators, piezoelectric cantilever, acoustic metamaterial-based approach, electrostatic transduction method, auxetic structure of material and other techniques. The recently established methods of acoustic energy harvesting and converting mechanisms; devices are carefully reviewed, and their results are compared and listed in the table. The technique of energy conversion by using acoustic metamaterial will tend to be more efficacious due to its complexity and the structure. Even in the few noise attenuation applications, more metamaterial is used, where, with the help of the conversion mechanism, the noise or sound energy can be converted into electrical energy for small electronic applications. It is demonstrated that the acoustic energy-conversion technique will become an essential part of the environmental energy harvesting research field.
“I’m Going to Love and Tolerate the Shit Out of You”: Hybrid Masculinities in the Brony Community
Authors: Palmer Zachary D.
Published: July 2021

Based on interviews with 30 men who are fans of My Little Pony and ethnographic observations at four My little Pony conventions, this article examines men’s engagement with feminized media as a form of hybrid masculinities. I identify two major subgroups of fans. The first utilized the brony community as a space that expanded the norms for men around emotional expression without challenging systemic inequality and distanced themselves from privilege by aligning themselves with a “gender defying” fandom. The second and dominant group expressed an aggrieved masculinity and engaged with the community as an explicitly antifeminist project, reinterpreting the show to assert hegemonic masculinity. This article contributes to understanding how men may articulate power through their engagement with feminized media and, more generally, expands the concept of hybrid masculinities.
Real-World Clinical Experience on the Usage of High-Dose Metformin (1500-2500 mg/day) in Type 2 Diabetes Management
Authors: Das Ashok Kumar , Shah Sanjiv , Singh Santosh Kumar , Juneja Archana , Mishra Niroj Kumar , Dasgupta Arundhati , Deka Nilakshi , Abhyankar Mahesh , Revankar Santosh
Published: July 2021

Background:

To evaluate the clinical characteristics, treatment patterns, and clinical effectiveness and safety of high doses of metformin (1500-2500 mg/day) in Indian adults with type 2 diabetes mellitus (T2DM).

Materials and methods:

A retrospective, multicentric (n = 241), real-world study included patients with T2DM (aged >18 years) receiving high doses of metformin. Details were retrieved from patient’s medical records.

Results:

Out of 5695 patients, 62.7% were men with median age was 50.0 years. Hypertension (67.5%) and dyslipidemia (48.7%) were the prevalent comorbidities. Doses of 2000 mg (57.4%) and 1500 mg (29.1%) were the most commonly used doses of metformin and median duration of high-dose metformin therapy was 24.0 months. Metformin twice daily was the most frequently used dosage pattern (94.2%). Up-titration of doses was done in 96.8% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.08%; P < .001). The target glycemic control was achieved in 91.2% patients. A total of 83.0% had decreased weight. Adverse events were reported in 156 patients. Physician global evaluation of efficacy and tolerability showed majority of patients on a good to excellent scale (98.2% and 97.7%).

Conclusion:

Clinical effectiveness and safety of a high-dose metformin was demonstrated through significant improvement in HbA1c levels and weight reduction.
Islet Function in the Pathogenesis of Cystic Fibrosis-Related Diabetes Mellitus
Authors: Westholm Efraim , Wendt Anna , Eliasson Lena
Published: July 2021

Cystic fibrosis-related diabetes mellitus (CFRD) is the most common non-pulmonary co-morbidity in cystic fibrosis (CF). CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which leads to aberrant luminal fluid secretions in organs such as the lungs and pancreas. How dysfunctional CFTR leads to CFRD is still under debate. Both intrinsic effects of dysfunctional CFTR in hormone secreting cells of the islets and effects of exocrine damage have been proposed. In the current review, we discuss these non-mutually exclusive hypotheses with a special focus on how dysfunctional CFTR in endocrine cells may contribute to an altered glucose homeostasis. We outline the proposed role of CFTR in the molecular pathways of β-cell insulin secretion and α-cell glucagon secretion, and touch upon the importance of the exocrine pancreas and intra-pancreatic crosstalk for proper islet function.
A virtual island journey: place and place writing in lockdown
Authors: Moran Joe
Published: July 2021

The Covid lockdowns of 2020 and 2021 led many people to reassess their relationship to places. This article attempts, during this time of restricted movement, to imaginatively deep-map an island in the mouth of the Shannon in west Clare where my grandmother was born and raised. My deep-mapping of the island is by necessity virtual, assembled piecemeal from memories, daydreams, family recollections, historical fragments and that powerful, semi-enchanted sense of co-presence that can be found online. Unable to make a physical journey, I rely on the accretive and associative techniques of contemporary place writing. The article uses montage, juxtaposition, thick description, dense detail, imaginative reconstruction and the essayistic blending of undisciplined bits of knowledge, all of which do some of the work of conventional linear argument. As in place writing, the micro-study of a small, special place becomes a way of thinking more widely about our relationship to the earth in a time of environmental and public health emergency. The article is both my own experiment in place writing and an argument for the fresh perspectives that place writing can bring to cultural geography.
The Role of Doppler Ultrasound, CT Angiography, and Conventional Angiography in Detection of Peripheral Arterial Disease
Authors: Sarkar Sayan , Mohan Shyam , Parvathy Shakthi
Published: July 2021

The purpose of this study is to analyze how accurate duplex ultrasonography using color Doppler and computed tomography (CT) angiography are in detection of peripheral arterial disease (PAD) in comparison with the Gold Standard of digital subtraction angiography (DSA). This is a single-center prospective, analytical study done on patients with symptoms of PAD referred to the Department of Radiodiagnosis of Medical Trust Hospital (n = 53). All patients were imaged with color Doppler, CT angiography, and DSA. The peak systolic velocity (PSV) ratio was calculated by Doppler ultrasound, and the percentage stenosis for the same vascular segments was calculated using CT angiography and DSA. To test the statistical significance between the results, chi-square test was used. A P value <.05 indicates statistical significance. The PSV ratio for each grade—normal (<1.5), mild (1.5-2.8), moderate (2.9-4.9), and severe (≥5)—and the percentage of stenosis for each grade observed on CT angiography—normal (<20% stenosis), mild (20%-49% stenosis), moderate (50%-74% stenosis), severe (75%-99% stenosis), and total occlusion (100% stenosis)—were found to be highly sensitive and specific with good positive predictive value, negative predictive value, and accuracy level when compared with DSA with narrow confidence intervals for each range. The P value was <.001 for both color Doppler and CT angiography. Computed tomography angiography can be an effective tool as an alternative to DSA for gradation of stenosis if the artifacts resulting from vascular calcification can be avoided. Duplex ultrasonography can be utilized for gradation of stenosis by using the value of PSV ratio and spectral pattern together. However, it can only act as an adjunct to CT angiography because it is incapable of imaging the full length of the arterial segments in one frame.
The Big Problem With Little Interruptions to Classroom Learning
Authors: Kraft Matthew A. , Monti-Nussbaum Manuel
Published: July 2021

Narrative accounts of classroom instruction suggest that external interruptions, such as intercom announcements and visits from staff, are a regular occurrence in U.S. public schools. We study the frequency, nature, duration, and consequences of external interruptions in the Providence Public School District (PPSD) using original data from a district-wide survey and classroom observations. We estimate that a typical classroom in the PPSD is interrupted more than 2,000 times per year and that these interruptions and the disruptions they cause result in the loss of between 10 and 20 days of instructional time. Several findings suggest that there exists substantial scope for reducing interruptions. Administrators appear to systematically underestimate the frequency and negative consequences of interruptions. Furthermore, interruptions vary widely across schools and are largely caused by school staff. Schools might reduce disruptions to the learning environment by creating a culture that prioritizes instructional time, instituting better communication protocols, and addressing the challenges posed by student tardiness.
Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study
Authors: Ashina Messoud , Cohen Joshua M. , Galic Maja , Campos Verena Ramirez , Barash Steve , Ning Xiaoping , Kessler Yoel , Janka Lindsay , Diener Hans-Christoph
Published: July 2021

Background

Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab.

Methods

Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated.

Results

Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%).

Conclusion

Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes.

Trial registration

ClinicalTrials.govNCT03308968(FOCUS).
Benchmark of 16S rRNA gene amplicon sequencing using Japanese gut microbiome data from the V1–V2 and V3–V4 primer sets
Authors: Kameoka Shoichiro , Motooka Daisuke , Watanabe Satoshi , Kubo Ryuichi , Jung Nicolas , Midorikawa Yuki , Shinozaki Natsuko O. , Sawai Yu , Takeda Aya K. , Nakamura Shota
Published: July 2021

Background

16S rRNA gene amplicon sequencing (16S analysis) is widely used to analyze microbiota with next-generation sequencing technologies. Here, we compared fecal 16S analysis data from 192 Japanese volunteers using the modified V1–V2 (V12) and the standard V3–V4 primer (V34) sets to optimize the gut microbiota analysis protocol.

Results

QIIME1 and QIIME2 analysis revealed a higher number of unclassified representative sequences in the V34 data than in the V12 data. The comparison of bacterial composition demonstrated that at the phylum level, Actinobacteria and Verrucomicrobia were detected at higher levels with V34 than with V12. Among these phyla, we observed higher relative compositions of Bifidobacterium and Akkermansia with V34. To estimate the actual abundance, we performed quantitative real-time polymerase chain reaction (qPCR) assays for Akkermansia and Bifidobacterium. We found that the abundance of Akkermansia as detected by qPCR was close to that in V12 data, but was markedly lower than that in V34 data. The abundance of Bifidobacterium detected by qPCR was higher than that in V12 and V34 data.

Conclusions

These results indicate that the bacterial composition derived from the V34 region might differ from the actual abundance for specific gut bacteria. We conclude that the use of the modified V12 primer set is more desirable in the 16S analysis of the Japanese gut microbiota.
Investigating the genetic architecture of disease resilience in pigs by genome-wide association studies of complete blood count traits collected from a natural disease challenge model
Authors: Bai Xuechun , Yang Tianfu , Putz Austin M. , Wang Zhiquan , Li Changxi , Fortin Frédéric , Harding John C. S. , Dyck Michael K. ,   PigGen Canada, Dekkers Jack C. M. , Field Catherine J. , Plastow Graham S.
Published: July 2021

Background

Genetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal’s disease response. The aim was to identify the genetic control of disease resilience.

Results

Univariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located onSus scrofachromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation.

Conclusions

This study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience.
Transcriptome and metabolome analyses of cold and darkness-induced pellicle cysts of Scrippsiella trochoidea
Authors: Guo Xin , Wang Zhaohui , Liu Lei , Li Yang
Published: July 2021

Background

Dinoflagellates are a group of unicellular organisms that are a major component of aquatic eukaryotes and important contributors to marine primary production. Nevertheless, many dinoflagellates are considered harmful algal bloom (HAB) species due to their detrimental environmental and human health impacts. Cyst formation is widely perceived as an adaptive strategy of cyst-forming dinoflagellates in response to adverse environmental conditions. Dinoflagellate cysts play critical roles in bloom dynamics. However, our insight into the underlying molecular basis of encystment is still limited. To investigate the molecular processes regulating encystment in dinoflagellates, transcriptome and metabolome investigations were performed on cold and darkness-induced pellicle cysts of Scrippsiella trochoidea.

Results

No significant transcriptional response was observed at 2 h; however, massive transcriptome and metabolome reprogramming occurred at 5 h and in pellicle cysts. The gene-to-metabolite network demonstrated that the initial transformation from vegetative cells into pellicle cysts was highly energy demanding through the activation of catabolism, including glycolysis, β-oxidation, TCA cycle and oxidative phosphorylation, to cope with cold-darkness-induced stress. However, after transformation into pellicle cysts, the metabolism was greatly reduced, and various sugars, polyunsaturated fatty acids and amino acids accumulated to prolong survival. The identification of 56 differentially expressed genes (DEGs) related to signal transduction indicated that S. trochoidea received a cold-darkness signal that activated multiple signal transduction pathways, leading to encystment. The elevated expression of genes encoding enzymes involved in ROS stress suggested that pellicle cysts respond to increased oxidative stress. Several cell cycle-related genes were repressed. Intriguingly, 11 DEGs associated with sexual reproduction suggested that pellicle cysts (or some portion thereof) may be a product of sexual reproduction.

Conclusions

This study provides the first transcriptome and metabolome analyses conducted during the encystment of S. trochoidea, an event that requires complex regulatory mechanisms and impacts on population dynamics. The results reveal comprehensive molecular regulatory processes underlying life cycle regulation in dinoflagellates involving signal transduction, gene expression and metabolite profile, which will improve our ability to understand and monitor dinoflagellate blooms.
Linking genotype to phenotype in multi-omics data of small sample
Authors: Guo Xinpeng , Song Yafei , Liu Shuhui , Gao Meihong , Qi Yang , Shang Xuequn
Published: July 2021

Background

Genome-wide association studies (GWAS) that link genotype to phenotype represent an effective means to associate an individual genetic background with a disease or trait. However, single-omics data only provide limited information on biological mechanisms, and it is necessary to improve the accuracy for predicting the biological association between genotype and phenotype by integrating multi-omics data. Typically, gene expression data are integrated to analyze the effect of single nucleotide polymorphisms (SNPs) on phenotype. Such multi-omics data integration mainly follows two approaches: multi-staged analysis and meta-dimensional analysis, which respectively ignore intra-omics and inter-omics associations. Moreover, both approaches require omics data from a single sample set, and the large feature set of SNPs necessitates a large sample size for model establishment, but it is difficult to obtain multi-omics data from a single, large sample set.

Results

To address this problem, we propose a method of genotype-phenotype association based on multi-omics data from small samples. The workflow of this method includes clustering genes using a protein-protein interaction network and gene expression data, screening gene clusters with group lasso, obtaining SNP clusters corresponding to the selected gene clusters through expression quantitative trait locus data, integrating SNP clusters and corresponding gene clusters and phenotypes into three-layer network blocks, analyzing and predicting based on each block, and obtaining the final prediction by taking the average.

Conclusions

We compare this method to others using two datasets and find that our method shows better results in both cases. Our method can effectively solve the prediction problem in multi-omics data of small sample, and provide valuable resources for further studies on the fusion of more omics data.
Postoperative pain treatment with transmuscular quadratus lumborum block and fascia iliaca compartment block in patients undergoing total hip arthroplasty: a randomized controlled trial
Authors: Xia Qin , Ding Wenping , Lin Chao , Xia Jiayi , Xu Yahui , Jia Mengxing
Published: July 2021

Background

Patients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty.

Methods

Fifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications.

Results

Fifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6–12 and 12–18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment:P < 0.001). Compared with group Q, group QF had higher quality of recovery and joint range of movement. The time to the first analgesic requirement was longer in group QF than in group Q (log-rank,P < 0.001). There was no statistically significant difference in complications postoperatively between the two groups.

Conclusions

Our study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose.

Trial registration

The study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry:ChiCTR2000038686.
Individualized mobile health interventions for cardiovascular event prevention in patients with coronary heart disease: study protocol for the iCARE randomized controlled trial
Authors: Chen Yuling , Ji Meihua , Wu Ying , Deng Ying , Wu Fangqin , Lu Yating
Published: July 2021

Background

Mobile health-based individualized interventions have shown potential effects in managing cardiovascular risk factors. This study aims to assess whether or not mHealth based individualized interventions delivered by an Individualized Cardiovascular Application system for Risk Elimination (iCARE) could reduce the incidence of major cardiovascular events in individuals with coronary heart disease.

Methods

This study is a large-scale, multi-center, parallel-group, open-label, randomized controlled clinical trial. This study will be conducted from September 2019 to December 2025. A total of 2820 patients with coronary heart disease will be recruited from two clinical sites and equally randomized into three groups: the intervention group and two control groups. All participants will be informed of six-time points (at 1, 3, 6, 12, 24, and 36 months after discharge) for follow-up visits. Over a course of 36 months, patients who are randomized to the intervention arm will receive individualized interventions delivered by a fully functional iCARE that using various visualization methods such as comics, videos, pictures, text to provide individualized interventions in addition to standard care. Patients randomized to control group 1 will receive interventions delivered by a modified iCARE that only presented in text in addition to routine care. Control group 2 will only receive routine care. The primary outcome is the incidence of major cardiovascular events within 3 years of discharge. Main secondary outcomes include changes in health behaviors, medication adherence, and cardiovascular health score.

Discussion

If the iCARE trial indeed demonstrates positive effects on patients with coronary heart disease, it will provide empirical evidence for supporting secondary preventive care in this population. Results will inform the design of future research focused on mHealth-based, theory-driven, intelligent, and individualized interventions for cardiovascular risk management.

Trial registration

Trial registered 24th December 2016 with the Chinese Clinical Trial Registry (ChiCTR-INR-16010242). URL: http://www.chictr.org.cn/showproj.aspx?proj=17398.