bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac-specific inactivation of Prdm16 effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes
Authors: Nam Jeong Min , Lim Ji Eun , Ha Tae Woong , Oh Bermseok , Kang Ji-One 
Published: February 2020

A variant in the PRDM16 locus has been correlated with QRS duration in an electrocardiogram genome-wide association study, and the deletion of PRDM16 has been implicated as a causal factor of the dilated cardiomyopathy that is linked to 1p36 deletion syndrome. We aimed to determine how a null mutation of Prdm16 affects cardiac function and study the underlying mechanism of the resulting phenotype in an appropriate mouse model. We used cardiac-specific Prdm16 conditional knockout mice to examine cardiac function by electrocardiography. QRS duration and QTc interval increased significantly in cardiac-specific Prdm16 knockout animals compared with wild-type mice. Further, we assessed cardiomyopathy-associated features by trichrome staining, densitometry, and hydroxyproline assay. Prdm16-null hearts showed greater fibrosis and cardiomyocyte hypertrophy. By quantitative real-time PCR, Prdm16-null hearts upregulated extracellular matrix-related genes ( Ctgf, Timp1) and α-smooth muscle actin ( Acta2), a myofibroblast marker. Moreover, TGF-β signaling was activated in Prdm16-null hearts, as evidenced by increased Tgfb1–3 transcript levels and phosphorylated Smad2. However, the inhibition of TGF-β receptor did not reverse the aberrations in conduction in cardiac-specific Prdm16 knockout mice. To determine the underlying mechanisms, we performed RNA-seq using mouse left ventricular tissue. By functional analysis, Prdm16-null hearts experienced dysregulated expression of ion channel genes, including Kcne1, Scn5a, Cacna1h, and Cacna2d2. Mice with Prdm16-null hearts develop abnormalities in cardiac conduction and cardiomyopathy-associated phenotypes, including fibrosis and cellular hypertrophy. Further, the RNA-seq findings suggest that impairments in ion homeostasis (Ca2+, K+, and Na+) may at least partially underlie the abnormal conduction in cardiac-specific Prdm16 knockout mice. NEW & NOTEWORTHY This is the first study that describes aberrant cardiac function and cardiomyopathy-associated phenotypes in an appropriate murine genetic model with cardiomyocyte-specific Prdm16-null mutation. It is noteworthy that the correlation of PRDM16 with QRS duration is replicated in a murine animal model and the potential underlying mechanism may be the impairment of ion homeostasis.
The compendium of matrix metalloproteinase expression in the left ventricle of mice following myocardial infarction
Authors: Kaminski Amanda R. , Moore Edwin T. , Daseke Michael J. , Valerio Fritz M. , Flynn Elizabeth R. , Lindsey Merry L. 
Published: February 2020

Matrix metalloproteinases (MMPs) are proteolytic enzymes that break down extracellular matrix (ECM) components and have shown to be highly active in the myocardial infarction (MI) landscape. In addition to breaking down ECM products, MMPs modulate cytokine signaling and mediate leukocyte cell physiology. MMP-2, -7, -8, -9, -12, -14, and -28 are well studied as effectors of cardiac remodeling after MI. Whereas 13 MMPs have been evaluated in the MI setting, 13 MMPs have not been investigated during cardiac remodeling. Here, we measure the remaining MMPs across the MI time continuum to provide the full catalog of MMP expression in the left ventricle after MI in mice. We found that MMP-10, -11, -16, -24, -25, and -27 increase after MI, whereas MMP-15, -17, -19, -21, -23b, and -26 did not change with MI. For the MMPs increased with MI, the macrophage was the predominant cell source. This work provides targets for investigation to understand the full complement of specific MMP roles in cardiac remodeling. NEW & NOTEWORTHY To date, a number of matrix metalloproteinases (MMPs) have not been evaluated in the left ventricle after myocardial infarction (MI). This article supplies the missing knowledge to provide a complete MI MMP compendium.
Mesenchymal Stem Cells Promote the Resolution of Cardiac Inflammation After Ischemia Reperfusion Via Enhancing Efferocytosis of Neutrophils
Authors: Zhang Zeyu , Tian Hongzhen , Yang Chen , Liu Jixuan , Zhang Huawei , Wang Jinda , Hu Shunying , Sun Zhijun , He Kunlun , Chen Guanghui 
Published: February 2020

Background
Neutrophils play a major role in inflammation after myocardial ischemia‐reperfusion (I/R) injury. The effects of mesenchymal stem cells (MSCs) on neutrophils in I/R are complex and not fully understood. This study was designed to investigate the effects and mechanism of MSCs on alleviating myocardial I/R injury in rats.

Methods and Results
MSCs induced M2 macrophages polarization in vitro and enhanced macrophage efferocytosis of apoptotic neutrophils, measured by fluorescence‐activated cell sorting analysis and immunofluorescence staining. Rats myocardial I/R were induced by transient ligation of left anterior descending coronary. Adipose‐derived MSCs or vehicle were infused at initiation (immediate after reperfusion) or peak of inflammation (24 hours after I/R). Hematoxylin and eosin, 2,3,5‐triphenyltetrazolium chloride/Evans Blue staining and immunofluorescence staining were applied within 72 hours after cell infusion. Cardiac function was assessed by echocardiography and left cardiac catheterization analysis at 28 days post‐operation. MSCs infused immediately and 24 hours later both markedly ameliorated myocardial I/R injury, and immediate infusion had more significant outcome. These improvements were associated with neutrophils infiltration, measured by fluorescence‐activated cell sorting analysis and immunofluorescence staining. When infused immediately, MSCs did not significantly change neutrophil number at 24 hours but CD11b expression was significantly higher. When infused at 24 hours, MSCs markedly decreased neutrophil number by enhanced M2 macrophage infiltration and macrophage efferocytosis of neutrophils within 72 hours.

Conclusions
Efferocytosis is pivotal to relieve neutrophil‐mediated I/R injury and initial the immune response for healing. MSCs infusion improves cardiac function in rats after myocardial I/R via the possible mechanism of enhancing M2 macrophages‐induced efferocytosis of apoptotic neutrophils.
Follow-Up Adherence Is Associated with Outcomes After Endoscopic Sinus Surgery
Authors: Shen Sarek A. , Jafari Aria , Qualliotine Jesse R. , DeConde Adam S. 
Published: February 2020

Background: Clinical follow-up after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) allows for assessment of the sinonasal cavity, debridement, and tailoring of medical therapies. Frequency and timing of postoperative clinical visits is debated, but the impact of adherence on disease-specific outcomes is not well understood. In this longitudinal study, we assessed the association between follow-up adherence and quality of life (QOL) outcomes in the 12 months after ESS. Methods: A retrospective review of patients undergoing ambulatory ESS for CRS between 11/2016 and 1/2018 was performed. We assessed sociodemographic characteristics, radiographic severity, and QOL utilizing the 22-item sinonasal outcome test (SNOT-22). Patients were categorized as “non-adherent,” “moderately-adherent,” and “fully-adherent” to a 1-, 3- and 5-week postoperative visit schedule. Results: A total of 166 patients met the inclusion criteria. Of these, 55 (33.1%) were fully-adherent, 105 (63.2%) were moderately-adherent, and 6 (3.6%) were non-adherent within the 6 weeks following ESS. In the immediate postoperative period, fully-adherent patients demonstrated worse QOL (SNOT-22: 31.2 ± 23.1 vs 27.5 ± 17.6, P = .047). This cohort also had greater psychological dysfunction at baseline and 12-months ( P < .05) after ESS. Extra-nasal symptom scores increased at a lower rate in the fully-adherent cohort (0.12 vs 1.29 points per 6 months, P = .038), as did ear/facial symptoms (1.17 vs 3.05 points per 6 months, P = .044). Conclusion: Despite worse symptom severity in the immediate postoperative period, patients who are more adherent to the follow-up schedule demonstrated slower return of symptoms in the extra-rhinological and ear-facial domains. These findings suggest that clinical adherence and management may impact the long-term evolution of ESS outcomes.
Infrapopliteal Arterial Pseudoaneurysm Development Secondary to Blunt Trauma: Case Series and Literature Review
Authors: Chrencik Matthew T. , Caraballo Brian , Yokemick John , Pappas Peter J. , Lal Brajesh K. , Nagarsheth Khanjan 
Published: February 2020

Objectives: Infrapopliteal arterial pseudoaneurysms (IAP) following blunt trauma with associated orthopedic injuries are uncommon, often present in a delayed fashion, and encompass a diagnostic and therapeutic dilemma. Herein, we present a series of IAPs that were diagnosed following blunt trauma and their management. Methods: Case series consisting of 3 patients and a review of the international literature. Results: Our case series included 3 patients presenting with IAPs following blunt trauma with associated orthopedic injuries. They were all identified in a delayed manner (>3 weeks) after the orthopedic injuries were treated. All patients presented with pain and a pulsatile mass while one concurrently had neurologic deficits. The pseudoaneurysms were diagnosed by duplex ultrasound and confirmed by angiography to be originating from the tibioperoneal trunk, anterior tibial, and posterior tibial arteries respectively. Two patients were treated with surgical excision. Of these, one required an arterial bypass procedure while the other underwent direct ligation only. The third patient was treated by endovascular coiling. A literature review from 1950 to the present found 51 reported cases of IAP resulting from blunt trauma. Ninety percent of trauma-related infrapopliteal injuries occurred in men with a mean delay in diagnosis of 5.6 months (median 1.8 months) after injury. Since 1950, management has shifted from primarily ligation to incorporating minimally invasive endovascular techniques when appropriate. Conclusions: Infrapopliteal artery pseudoaneurysms are rare following blunt skeletal trauma. A delay in diagnosis often occurs and can result in major morbidity and extensive surgical intervention. We recommend a high index of suspicion and a thorough vascular examination in patients with lower extremity skeletal trauma to help identify and treat these injuries early and effectively.
Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis
Authors: Orellana Cristóbal , Calvet Joan , Berenguer-Llergo Antoni , Albiñana Néstor , García Manrique María , Galisteo Lencastre Carlos , Arévalo Marta , Llop María , Caixàs Assumpta , Gratacós Jordi 
Published: February 2020

Objective Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. Design Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. Results Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. Conclusions Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.
Anterior Versus Posterior Decompression for Degenerative Thoracic Spine Diseases: A Comparison of Complications
Authors: Abedi Aidin , Formanek Blake , Hah Raymond , Buser Zorica , Wang Jeffrey C. 
Published: February 2020

Study Design: Retrospective database. Objectives: Although posterior decompression is the most common approach for surgical treatment of degenerative thoracic spine disease, anterior approach is gaining interest due to its advantage in disc visualization. The objective of this study was to compare the intra- and postoperative medical complication rates between anterior and posterior decompression for degenerative thoracic spine pathologies. Methods: A national US insurance database was queried for patients with degenerative diagnoses who had undergone anterior or posterior thoracic decompression. Incidence of intra- and postoperative complications were evaluated on the day of surgery and within 1 and 3 months. Two subgroups were matched based on age, gender, and comorbidity. The association of decompression approach and complications was assessed using logistic regression. Results: A total of 1459 patients were included, consisting of 1004 patients in posterior and 455 patients in anterior group. Respiratory complications were the most common complications on the day of surgery (8.57%) and within 30 days (17.75%). Matched analysis showed that anterior approach was associated with organ failure, gastrointestinal, and device-/implant-/graft-related complications in all follow-up periods; and with cardiovascular, deep venous thrombosis/pulmonary embolism, and respiratory complications in at least 1 follow-up period. Among respiratory complications, anterior decompression was significantly associated with noninfectious etiologies on the day of surgery (odds ratio [OR] = 1.72), within 30 days (OR = 2.05), and within 90 days (OR = 1.92). Conclusions: Anterior approach was associated with increased rates of several complications. High rates of respiratory complications necessitate comprehensive preoperative risk stratification to identify those who may benefit more from posterior approach.
Germline variants in predisposition genes in children with Down syndrome and acute lymphoblastic leukemia
Authors: Winer Peleg , Muskens Ivo S. , Walsh Kyle M. , Vora Ajay , Moorman Anthony V. , Wiemels Joseph L. , Roberts Irene , Roy Anindita , de Smith Adam J. 
Published: February 2020

Key Points
Rare and pathogenic germline variants, including in IKZF1, contribute to acute lymphoblastic leukemia in children with Down syndrome.
The kinetic profile and clinical implication of SCC-Ag in squamous cervical cancer patients undergoing radical hysterectomy using the Simoa assay: a prospective observational study
Authors: Ye Shuang , Sun Xiaohua , Kang Bin , Wu Fei , Zheng Zhong , Xiang Libing , Lesénéchal Mylène , Heskia Fabienne , Liang Ji , Yang Huijuan 
Published: February 2020

Abstract
Background
To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay.

Methods
Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2–4, months 2–4 and months 5–7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied.

Results
Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay’s levels (Pearson’s correlation coefficient = 0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept − 0.009 (− 0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71 ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6 months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment.

Conclusions
The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.
Paediatric orbital alveolar soft part sarcoma recurrence during long-term follow-up: a report of 3 cases and a review of the literature
Authors: Wang Yujiao , Du Baixue , Yang Mei , He Weimin 
Published: February 2020

Abstract
Background
Alveolar soft part sarcoma (ASPS) is a clinically and morphologically distinct malignant soft tissue tumour. It occurs mostly in the lower extremities in adults. The purpose of our study was to describe the related clinicopathologic factors, treatment and prognosis of recurrent orbital ASPS in children.

Case presentation
Three children aged from 1 to 12 years presented with unilateral proptosis, restricted ocular motility and impaired visual acuity of the affected eye. Periodic acid Schiff (PAS) -positive diastase-resistant crystalline granules were found in all cases. Immunostaining of TFE-3, INL1 and Ki67 was positive in the tumour cells of two patients. The time until local recurrence of primary tumor in patient 2 and patient 3, who only underwent tumour resection, was shorter than that of patient 1, who underwent tumour excision and postoperative radiotherapy. The recurrent masses were successfully treated with complete tumour excision followed by adjuvant radiotherapy. Patient 1 presented metastasis at 11 years after radiotherapy.

Conclusions
Orbital ASPS in children is easily misdiagnosed due to its rare occurrence and atypical clinical findings. Early diagnosis with multidisciplinary, complete surgical resection combined with adjuvant radiotherapy is essential for achieving long-term disease-free survival in orbital ASPS patients.
Strengthening community-clinical linkages to reduce cardiovascular disease risk in rural NC: feasibility phase of the CHANGE study
Authors: Samuel-Hodge Carmen D. , Gizlice Ziya , Allgood Sallie D. , Bunton Audrina J. , Erskine Amber , Leeman Jennifer , Cykert Samuel 
Published: February 2020

Abstract
Background
Community Health Workers (CHW) are recommended for delivery of interventions to prevent cardiovascular disease, but there is insufficient evidence to guide implementation of CHW interventions in rural, medically underserved areas.

Methods
Using a hybrid implementation-effectiveness design, we evaluated the implementation and effectiveness of an adapted, evidence-based cardiovascular disease risk reduction intervention among rural high-risk adults. CHWs at a community health center and local health department recruited, enrolled and counseled participants during 4 monthly home visits and 3 brief phone contacts. Participant data collection included pre- and post-intervention measurements of blood pressure, weight, and dietary and physical activity behaviors. We evaluated implementation with measures of intervention reach and delivery fidelity. Statistical analyses included descriptive statistics and paired t-tests.

Results
Study participants (n = 105) had a mean age of 62 years and included 88% Non-Hispanic Blacks and 82% females. Recruitment strategies resulted in the enrollment of 38% of interested and eligible participants who received 80% of the planned intervention visits and phone contacts. Mean differences in pre−/post-intervention measures showed significant mean reductions in blood pressure (− 5.4 mmHg systolic, p = .006; − 2.3 mmHg diastolic, p = .04) and body weight (− 3.8 lb., p = .02). Self-reported dietary and physical activity behaviors also improved significantly.

Conclusion
This feasibility study demonstrated preliminary implementation and program effectiveness of a CHW-delivered intervention to reduce cardiovascular disease risk factors. Additionally, it identified areas for future refinements to strategies that strengthen community-clinical linkages with an integrated role of CHWs in rural health care delivery. If results from this feasibility study can be enhanced in a larger sample, there would be significant potential to positively impact the excess burden of chronic diseases that adversely impact rural, low-income, and medically underserved populations.

Trial registration
ClinicalTrials.gov: NCT03582696.
Provider perspectives on contraceptive service delivery: findings from a qualitative study in Johannesburg, South Africa
Authors: Lince-Deroche Naomi , Hendrickson Cheryl , Moolla Aneesa , Kgowedi Sharon , Mulongo Masangu 
Published: February 2020

Abstract
Background
Healthcare providers’ skills and attitudes are both barriers and facilitators of contraceptive uptake. In South Africa, migration of healthcare workers and the demands of the HIV epidemic have also contributed to inequitable access to sexual and reproductive health (SRH) care. Yet, the country has committed to achieving universal access to SRH services. We explored healthcare provider’s opinions and attitudes on provision of contraceptive services in public facilities, their personal use of methods, and their thoughts on the recent integration of new contraceptive methods in their facilities.

Methods
We conducted a phenomenological, qualitative study in 2017 at an outpatient, public HIV treatment clinic and two primary healthcare clinics (PHCs) in Johannesburg, South Africa. We purposively selected providers who had worked at the facilities for at least six months and were seeing patients for HIV or SRH services. Trained study staff conducted semi-structured interviews. We conducted descriptive analyses for quantitative data, and used an iterative, thematic analysis approach for open-ended responses.

Results
We interviewed 14 healthcare providers (HIV clinic - 5; PHCs - 9). One respondent was a man; all were nurses. All respondents reported having ever personally used a contraceptive method; half (7/14) were currently using a method. Responses on service provision were conflicting. Respondents felt that their clinics currently met the contraceptive needs of their female patients through on-site services or referrals. However, they noted that staff shortages, lack of training, and a limited contraceptive offering meant that women did not always get the counselling or method they wanted. Respondents noted that the ‘best’ contraceptive methods for women were those that fit with a woman’s lifestyle and medical needs; however, providers also felt strongly that injectables were best for all women. Recent introduction of the implant at one PHC and injectable contraceptives at the HIV clinic was not overly challenging, though there were concerns about staffing and demand creation for the new methods.

Conclusions
Respondents’ conflicting responses revealed challenges with current service delivery, particularly contraceptive counselling. Addressing staff workloads and providing refresher training on contraception would contribute to increased contraceptive service capacity and quality in this setting.