bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency of cysteinyl cathepsin K suppresses the development of experimental intimal hyperplasia in response to chronic stress
Authors: Meng Xiangkun , Piao Limei , Wang Hailong , Inoue Aiko , Huang Zhe , Jiang Haiying , Nakamura Kae , Sasaki Takeshi , Li Xiang , Xu Wenhu , Yu Chenglin , Hu Lina , Wu Hongxian , Murohara Toyoaki , Shi Guo-Ping , Kuzuya Masafumi , Cheng Xian Wu 
Published: March 2020

Background:
Chronic psychological stress (CPS) is linked to cardiovascular disease initiation and progression. Given that cysteinyl cathepsin K (CatK) participates in vascular remodeling and atherosclerotic plaque growth in several animal models, we investigated the role of CatK in the development of experimental neointimal hyperplasia in response to chronic stress.

Methods and results:
At first, male wild-type (CatK+/+) mice that underwent carotid ligation injury were subjected to chronic immobilization stress. On postoperative and stressed day 14, the results demonstrated that stress accelerated injury-induced neointima hyperplasia. On day 4, stressed mice showed following: increased levels of monocyte chemoattractant protein-1, gp91phox, toll-like receptor-2 (TLR2), TLR4, and CatK mRNAs or/and proteins, oxidative stress production, aorta-derived smooth muscle cell (SMC) migration, and macrophage infiltration as well as targeted intracellular proliferating-related molecules. Stressed mice showed increased matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA expressions and activities and elastin disruption in the injured carotid arteries. Second, CatK+/+ and CatK deficiency (CatK−/−) mice received ligation injury and stress to explore the role of CatK. The stress-induced harmful changes were prevented by CatK−/−. Finally, CatK+/+ mice that had undergone ligation surgery were randomly assigned to one of two groups and administered vehicle or CatK inhibitor for 14 days. Pharmacological CatK intervention produced a vascular benefit.

Conclusion:
These data indicate that CatK deletion protects against the development of experimental neointimal hyperplasia via the attenuation of inflammatory overaction, oxidative stress production, and VSMC proliferation, suggesting that CatK is a novel therapeutic target for the management of CPS-related restenosis after intravascular intervention therapies.
Fertility considerations in transgender patients
Authors: Wang Betty , Hengel Ross , Ren Runhan , Tong Steven , Bach Phil Vu 
Published: March 2020

Purpose of review
An update on the latest advances in fertility preservation for transgender women, with an emphasis on the attitudes, access, and techniques.

Recent findings
With recent warming in perception toward transgendered individuals, fertility preservation services are becoming increasingly available. Although new multidisciplinary transgender clinics are appearing in North America, a 2018 report shows a referral rate for fertility preservation of only 13.5%. Despite interest in child rearing, uptake of fertility preservation is still low as patients are transitioning at increasingly younger ages. Sperm cryopreservation, ideally prior to hormonal therapy, continues to be the mainstay of fertility preservation in transwomen. It is used in conjunction with other assisted reproductive technologies such as intrauterine insemination or in-vitro fertilization with intracytoplasmic sperm injection depending on the quantity of sperm available. Recent research reporting successful autologous grafting of cryopreserved prepubertal testis leading to sperm production and offspring in macaques show great promise in the context of fertility preservation in prepubertal patients.

Summary
Despite the increasing accessibility of fertility preservation, referral rates and usage continue to be low, suggesting that barriers are still in place for these individuals. Clinicians must continue to counsel patients regarding the process of fertility preservation and advocate for reduction of financial and infrastructural barriers.
Relationships Between Somatic Symptoms and Panic-Agoraphobic Spectrum Among Frequent Attenders of the General Practice in Italy
Authors: Carmassi Claudia , Dell'Oste Valerio , Cordone Annalisa , Pedrinelli Virginia , Cappelli Andrea , Ceresoli Diana , Massimetti Gabriele , Nisita Cristiana , Dell'Osso Liliana 
Published: March 2020

Abstract
Frequent attenders (FAs) of general practitioners (GPs) often complain of nonspecific physical symptoms that are difficult to define according to typical medical syndromes criteria but could be acknowledged as atypical manifestations of mental disorders. We investigated the possible correlation between somatic symptoms and panic-agoraphobic spectrum symptoms in a sample of 75 FAs of GPs in Italy, with particular attention to the impact on functional impairment. Assessments included the Patient Health Questionnaire, Panic-Agoraphobic Spectrum–Self-Report (PAS-SR) lifetime version, Global Assessment of Functioning, and Clinical Global Impression. The PAS-SR total and domains scores were significantly higher among low-functioning FAs, especially anxious somatizations, hypochondriasis, anxious expectation, and reassurance orientation domains, suggesting this undetected symptom may determine the selective attention to the physical symptoms, illness-phobic/hypochondriac elaboration, and GP frequent attendance, often aimed at searching for reassurance, leading to severe impact on overall functioning and often inefficacious treatments.
Estimation of Age Using Third Molar Development
Authors: Ashifa Nisha , Parakh Mayank Kumar , Ulaganambi Shriraam 
Published: March 2020

Objectives
This study was carried out to correlate chronological age of the patients with dental age using to Demirjian's method and to evaluate if orthopantamogram examination of third molar development correlates with age estimation.

Study Design
The study was designed as a radiological cross sectional study. Simple random sampling method was used to obtain study subjects.

Methods
Total of 231 patients between the age group of 10 to 25 years, visiting the Department of Oral Medicine and Radiology were selected. The digital orthopantomogram was obtained for these patients.

Results
Our data showed that, in the maxilla, the stages of tooth developments A to E were reached earlier in men than in women, whereas stages F to H were reached earlier in women than men. In mandible stages B, C, E to F were reached earlier in men than women, whereas stages A and D were reached earlier by the female counterparts. There was a statistically significant difference noted between right and left third molar teeth in all the stages of tooth development.

Conclusions
Our study showed that between the sexes in maxilla, men reached stages A to E earlier than women, whereas for stages F to H, women reached the stage earlier than men. For mandible, all stages except stage D were reached earlier by male subjects than female subjects. Our study showed that the third molar development can be affected positively by the chronological age of the patient, being developed either in maxilla or mandible, right or left side.
Impact of Loneliness on Brain Health and Quality of Life Among Adults Living With HIV in Canada
Authors: Harris Marianne , Brouillette Marie-Josée , Scott Susan C. , Smaill Fiona , Smith Graham , Thomas Réjean , Fellows Lesley K. , Mayo Nancy E. 
Published: March 2020

Background:
People aging with HIV are at risk for loneliness, with stigmatization and economic marginalization added to the health challenges arising from chronic infection. This study provides evidence for the extent, contributors, and consequences of loneliness in people living with HIV, focusing on brain health and quality of life.

Setting:
Cross-sectional data from 856 middle-aged and older adults living with HIV recruited from 5 urban specialty clinics in Canada were drawn from the inaugural visit of the Positive Brain Health Now cohort study.

Methods:
Participants completed an extensive assessment of biopsychosocial variables. The prevalence, severity, and quality of life impact of self-reported loneliness were described. Clinical and environmental factors hypothesized as contributing to loneliness, and the consequences of loneliness on health and function were identified using logistic, ordinal, and linear regression.

Results:
Eighteen percent reported being “quite often” and 46% “sometimes” lonely. Those with more loneliness were younger, less mobile, suffered more financial hardship, and were more likely to use opioids. HIV symptoms, pain, fatigue, low motivation, stigma, and unemployment were related to loneliness. Loneliness increased the odds of cognitive impairment, low mood, stress, and poor physical health. Those who were “quite often” lonely were over 4 times more likely to report poor or very poor quality of life than those who were “almost never” lonely.

Conclusion:
Loneliness is common in middle-aged and older people living with HIV in Canada. Many of the associated factors are modifiable, offering novel targets for improving brain health, general health, and quality of life in HIV.
Creation of a Rat Lower Limb Lymphedema Model
Authors: Harb Amro A. , Levi Maxwell A. , Corvi John J. , Nicolas Celine F. , Zheng YuanDian , Chaudhary Kunal R. , Akelina Yelena , Connolly Eileen P. , Ascherman Jeffrey A. 
Published: March 2020

Background
Lymphedema is a frequent complication after surgical treatments of cancer involving lymph node resection. However, research of lymphedema treatments, such as vascularized lymph node transfer, is limited by the absence of an adequate lymphedema animal model. The purpose of this study was to determine if we could create sustainable lower limb lymphedema in the rat with a combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy.

Methods
Inguinal lymphadenectomies were completed in 15 Sprague-Dawley rats. In cohort A, 5 rats received a 0.5- to 1.0-cm wide excision of proximal thigh skin and subcutaneous tissue. This step was omitted for the 10 rats in cohort B. Cohort A then received a single radiation dose of 22.7 Gy, whereas cohort B received a cumulative dose of 40.5 Gy. Bioimpedance measurements were obtained monthly to assess lymphedema progression, and lymphatic drainage at 6 months postradiation was visualized via indocyanine green (ICG) lymphangiography.

Results
Two rats in cohort A developed visually appreciable lymphedema in the lower limb, with bioimpedance ratios of 0.684 and 0.542 and ankle circumference ratios of 1.294 and 1.061, respectively, consistent with lymphedema. Furthermore, ICG lymphangiography in these cohort A rats revealed impaired lower limb lymphatic drainage. In cohort B, however, bioimpedance and circumference ratios, and ICG lymphangiography, did not reveal abnormal lymphatic drainage.

Conclusions
The combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy can successfully create lower limb lymphedema in the rat. When soft tissue excision is omitted, lymphedema does not develop.
Efficacy of Fibrin Sealants in Preventing Seroma Formation in Reduction Mammaplasty
Authors: Marquez Jocellie E. , Kapadia Kailash , Ghosh Kanad , Silvestri Brittni , Singh Gurtej , Huston Tara L. 
Published: March 2020

Background
Fibrin sealant is a controversial method for reducing seroma formation. It is comprised of human proclotting factors, fibrinogen and thrombin. Fibrin sealants have been extensively studied for their efficacy in reducing the rates of seroma by sealing the dead space; however, in most studies, the sealants are used with surgical drains. According to the U.S. Food and Drug Administration, fibrin sealant carries the risk of life-threatening thromboembolic complications, gas emboli, and transmission of infectious agents. Despite these concerns, many plastic surgeons use such products in ambulatory surgeries even though its effect on seroma formation has yet to be elucidated. The aim of our study is to determine the efficacy of fibrin sealants in seroma prevention in reduction mammoplasty with and without surgical drains.

Methods
A retrospective chart review was performed of all bilateral reduction mammaplasty by a single-surgeon from 2014 to 2018. Patients had at least 90 days postoperative follow-up. Exclusion criteria consisted of patients younger than 18 years, had prior breast surgery, or had an incidental cancer diagnosis in breast reduction tissue specimen.

Results
On analysis, 159 patients met inclusion criteria and were categorized into group 1, with fibrin sealant (n = 101) and group 2, no fibrin sealant (n = 58). There were no statistical differences in patient demographics. There was no significant difference in the incidence of seroma between group 1 and group 2 (21% vs 19%, P = 0.782). Group 1 incidence of seroma was further analyzed by sealant type: Tisseal, Floseal, and Evicel (12% vs 27% vs 23%, P = 0.436). In group 1, the use of sealant alone was more likely to result in seroma formation when compared with the combination of sealant and surgical drains (25% vs 8%, P = 0.069).

Conclusions
There is no difference in rate of seroma formation with the use of fibrin sealants in reduction mammaplasty. The use of fibrin sealants without surgical drains may increase the rate of seromas. Plastic surgeons could consider weighing the risk versus benefits in using fibrin sealants with or without drains in ambulatory surgeries.
The Incidence of Post-Electroconvulsive Therapy Headache
Authors: Mulder Laura Aleida Christina , Grootens Koen Pieter 
Published: March 2020

Abstract
Headache is a common side effect of electroconvulsive therapy (ECT), but reports on its incidence vary widely. A broad array of treatment regimens have been proposed in the literature. The pathophysiology of post-ECT headache is unclear but a vascular origin has been suggested. A systematic literature search was executed in PubMed and Embase to identify relevant articles. Articles were screened on title, abstract, and full text according to predefined inclusion and exclusion criteria. Study characteristics and results concerning the incidence of post-ECT headache were extracted, and a weighted mean incidence was calculated. Forty-seven relevant articles were found, of which 36 reported on the incidence of post-ECT headache in patients and 9 on the incidence in sessions. The incidence of post-ECT headache varied greatly in the literature. The weighted mean incidence in patients was 32.8%, as 786 of a total population of 2399 patients experienced headache. The weighted mean incidence in sessions was between 9.4% (246 of 2604 sessions) and 12.1% (236/1958 sessions). The variation in incidences of post-ECT headache found might be due to different methods of measuring headache, different study designs, and different drugs used for anesthesia. The mean-weighted incidence of post-ECT headache in patients was 32.8% and in sessions between 9.4% and 12.1%.
Novel mosaic mice with diverse applications
Authors: Chen Yuxin , Mao Shaoshuai , Liu Bo , Jing Zhengyu , Zang Ying , Xia Jing , Sun Jianlong , Chi Tian 
Published: March 2020

AbstractGene-deficient mouse models are indispensable for interrogating mammalian gene functions, but the conventional models allow the study of only one or few genes per mouse line, which has been a bottleneck in functional genomics. To confront the challenge, we have combined the CRISPR-Cas and Cre-Lox systems to develop a novel type of mosaic mice termedMARC(MosaicAnimal based on gRNA andCre) for targeting many genes per mouse but only one gene per cell. This technology employs a transgene comprising a modified U6 promoter upstream of a series of floxed gRNA genes linked together in tandem, with one gRNA expressed per cell following Cre-mediated recombination. At least 61 gRNA genes can be stably maintained in the transgene, and importantly, enables robust proof-of-principlein vivoscreens, demonstrating the potential for quickly evaluating the functions of many genes in diverse tissues in a single MARC line. In theory, MARC can also be analyzed by single-cell sequencing, and should enable cost-effective derivation of conventional single-gene-KO lines via simple breeding. Our study establishes MARC as an important addition to the mouse genetics toolbox.
Hematopoietic p53 loss cell-extrinsically defines an immune infiltrated microenvironment in leukemia and pre-leukemia
Authors: Posey Ryan R. , Lee Jonathan D. , Clohessy Sean , Mendez Lourdes M. , Pandolfi Pier Paolo 
Published: March 2020

AbstractTP53is the most frequently mutated gene in human cancers. In Acute Myeloid Leukemia (AML) and Clonal Hematopoiesis of Indeterminate Potential (CHIP), it is one of several recurrent genetic alterations. Despite multiple recent therapeutic advances for AML,TP53mutated AML is associated with resistance to currently approved therapies and thus, a very poor prognosis. Emerging evidence suggests that mutations inTP53may be a predictor of positive response to immunotherapy. To model cell - extrinsic consequences of hematopoietic p53 loss, we generated bone marrow chimeric mice bearingp53-/-and congenic wild type cells. Following reconstitution, we observed increased levels of wild type CD8+ and CD4+ T cells in mice transplanted withp53-/-hematopoietic cells compared to controls. In addition, we observed a change in the frequency of T cell subsets inp53-/-chimeras including an increase in Tregs. To determine if these alterations were mirrored in the leukemic setting, we next generatedp53-/-;nRasG12Dleukemia. While the bone marrow ofp53-/-;nRasG12Dleukemia showed the presence of both T and B lymphocytes, MLL-AF9 showed a near complete absence of lymphocytes, akin to ‘immune-infiltrated’ and ‘immune-desert’ phenotypes seen in solid tumors. These data clearly demonstrate a causal cell-extrinsic effect of hematopoietic p53 loss on the immune system, both in the context of leukemia and preleukemic states. Modeling AML genetics in murine models serves as a powerful tool to define the association between genetic drivers and immune subtypes of AML towards precise patient stratification critical for the application of emerging targeted and immune therapies.Statement of SignificanceTP53mutations are frequent in both AML and CHIP, and are associated with both resistance to therapy as well as very poor prognosis. We provide evidence to investigate the immunotherapy as a treatment option for this subgroup of AML.
Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying essential circRNAs
Authors: Zhang Yang , Nguyen Tuan M. , Zhang Xiao-Ou , Phan Tin , Clohessy John G. , Pandolfi Pier Paolo 
Published: March 2020

AbstractCircular RNAs (circRNAs) are widely expressed, but their functions remain largely unknown. To study circRNAs in a high-throughput manner, short hairpin RNA (shRNA) screens1have recently been used to deplete circRNAs by targeting their unique back-splicing junction (BSJ) sites. Here, we report frequent discrepancies between shRNA-mediated circRNA knockdown efficiency and the corresponding biological effect, raising pressing concerns about the robustness of shRNA screening for functional circRNAs. To address this issue, we leveraged the CRISPR/Cas13d system2for circRNAs functional screenings. We optimized a strategy for designing single guide RNAs to deplete circRNAs. We then performed shRNA and CRISPR/Cas13d parallel screenings and demonstrated that shRNA-mediated circRNAs screening yielded a high rate of false positives phenotypes, while optimized CRISPR/Cas13d led to the identification ofbona-fidefunctional circRNAs. Collectively, we developed a specific and reliable approach to functionalize circRNAs in a high-throughput manner.
Organizational pride as an antecedent of employee creativity in the petrochemical industry
Authors: Durrah Omar , Allil Kamaal , Gharib Moaz , Hannawi Souzan 
Published: March 2020

PurposeThis empirical study aims to explore the impact of two facets of organizational pride (namely, emotional and attitudinal) on employee creativity in petrochemical companies in the Sultanate of Oman.Design/methodology/approachUsing a simple random sample technique, data were collected using a questionnaire from 278 respondents working in five major petrochemical organizations operating in Oman. Data were examined using structural equation modeling.FindingsThe findings revealed that attitudinal organizational pride is the only dimension of organizational pride that has a direct significant positive effect on creativity, while emotional pride does not affect creativity.Research limitations/implicationsThe current study is considered among the pioneering studies in its contextual field. However, despite its importance, it has several limitations. First, this study is limited to the petrochemical sector. Second, the study is limited to two variables: organizational pride and creativity. Last, this study examined creativity as one variable.Practical implicationsAttitudinal organizational pride directly affects employee creativity. Petrochemical managers should consider and enhance attitudinal organizational pride.Originality/valueThis study contributes to the literature investigating the attitudinal and emotional aspects as facets of organizational pride in relation to employee creativity, and it is the first to do so in the context of the Sultanate of Oman.