bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib
Authors: Wander Seth A , O’Brien Neil , Litchfield Lacey M , O’Dea Declan , Morato Guimaraes Claudia , Slamon Dennis J , Goel Shom 
Published: August 2022

Abstract
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and 6) are approved for the treatment of subsets of patients with hormone receptor positive (HR+) breast cancer (BC). In metastatic disease, strategies involving endocrine therapy combined with CDK4 and 6 inhibitors (CDK4 and 6i) improve clinical outcomes in HR+ BCs. CDK4 and 6i prevent retinoblastoma tumor suppressor protein phosphorylation, thereby blocking the transcription of E2F target genes, which in turn inhibits both mitogen and estrogen-mediated cell proliferation. In this review, we summarize preclinical data pertaining to the use of CDK4 and 6i in BC, with a particular focus on several of the unique chemical, pharmacologic, and mechanistic properties of abemaciclib. As research efforts elucidate the novel mechanisms underlying abemaciclib activity, potential new applications are being identified. For example, preclinical studies have demonstrated abemaciclib can exert antitumor activity against multiple tumor types and can cross the blood-brain barrier. Abemaciclib has also demonstrated distinct activity as a monotherapeutic in the treatment of BC. Accordingly, we also discuss how a greater understanding of mechanisms related to CDK4 and 6 blockade highlight abemaciclib’s unique in-class properties, and could pave new avenues for enhancing its therapeutic efficacy.
Matching in Dynamic Imbalanced Markets
Authors: Ashlagi Itai , Nikzad Afshin , Strack Philipp 
Published: August 2022

Abstract
We study dynamic matching in exchange markets with easy- and hard-to-match agents. A greedy policy, which attempts to match agents upon arrival, ignores the positive externality that waiting agents provide by facilitating future matchings. We prove that the trade-off between a “thicker” market and faster matching vanishes in large markets; the greedy policy leads to shorter waiting times and more agents matched than any other policy. We empirically confirm these findings in data from the National Kidney Registry. Greedy matching achieves as many transplants as commonly used policies (1.8$\%$ more than monthly batching) and shorter waiting times (16 days faster than monthly batching).
Fibroblast expression of CD248 may contribute to exacerbation of microvascular damage during systemic sclerosis
Authors: Cipriani Paola , Ruscitti Piero , Di Cola Ilenia , Vomero Marta , Abbruzzese Franca , Di Nino Elena , Ross Rebecca , Del Galdo Francesco , Giacomelli Roberto 
Published: August 2022

AbstractObjectivesCD248 is a glycoprotein, highly expressed on pericytes and fibroblasts (FBs), that is implicated in the fibrotic process. During angiogenesis, CD248 can promote vessel regression, binding multimerin-2 (MMRN-2). Thus, we investigated the expression of MMRN-2 in systemic sclerosis (SSc)-skin and of CD248 in isolated SSc-FBs. The anti-angiogenic property of CD248+ SSc-FBs was evaluated by co-culturing these cells with healthy control endothelial cells (HC-ECs). The apoptotic effect of CD248 on HC-ECs was evaluated. Finally, the ability of CD248 to prevent activation of VEGF receptor 2 (VEGFR2) was assessed.MethodsBy IF, MMRN-2 was investigated in SSc-skin and CD248 in SSc FBs. The anti-angiogenic property of CD248+ SSc-FBs was evaluated by HC-ECs/SSc-FBs co-cultures. Lentiviral-induced CD248 short-hairpin RNA delivery was employed for loss-of-function studies in SSc-FBs. HC-ECs were cultured in the presence of CD248 to assess apoptosis by IF and VEGFR2 phosphorylation by western blot.ResultsMMRN-2 expression was increased in skin SSc-ECs, whereas CD248 expression was increased in SSc-FBs. Functionally, CD248+-SSc-FBs suppressed angiogenesis in the organotypic model, as assessed by the reduction in total tube length of HC-ECs. This anti-angiogenetic behaviour was reversed by CD248 silencing. Furthermore, the presence of CD248 promoted the apoptosis of HC-ECs. Finally, CD248 prevented activation of VEGFR2 by reducing its phosphorylation after VEGF stimulation.ConclusionCD248 was anti-angiogenic in vitro due to a reduction in tube formation and to induction of apoptosis of ECs. Increased expression of CD248 in SSc could contribute to the microvascular rarefaction observed at the tissue level in SSc. Our results suggest a pathogenic role for CD248-MMRN-2 in SSc.
House dust mite‐induced Akt‐ERK1/2‐C/EBP beta pathway triggers CCL20‐mediated inflammation and epithelial–mesenchymal transition for airway remodeling
Authors: Park Shin‐Young , Kang Min‐Jeong , Jin Nuri , Lee So Young , Lee Yun Young , Jo Sungsin , Eom Jeong Yun , Han Heejae , Chung Sook In , Jang Kiseok , Kim Tae‐Hwan , Park Jungwon , Han Joong‐Soo 
Published: August 2022

AbstractHouse dust mite (HDM) allergens cause inflammatory responses and chronic allergic diseases such as bronchial asthma and atopic dermatitis. Here, we investigate the mechanism by which HDM induces C–C chemokine ligand 20 (CCL20) expression to promote chronic inflammation and airway remodeling in an HDM‐induced bronchial asthma mouse model. We showed that HDM increased CCL20 levels via the Akt‐ERK1/2‐C/EBPβ pathway. To investigate the role of CCL20 in chronic airway inflammation and remodeling, we made a mouse model of CCL20‐induced bronchial asthma. Treatment of anti‐CCL20Ab in this mouse model showed the reduced airway hyper‐responsiveness and inflammatory cell infiltration into peribronchial region by neutralizing CCL20. In addition, CCL20 induced the Nod‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation through NLRP3 deubiquitination and transcriptional upregulation in BEAS‐2B cells. As expected, anti‐CCL20Ab markedly suppressed NLRP3 activation induced by CCL20. Moreover, HDM‐induced CCL20 leads to epithelial–mesenchymal transition in the lung epithelium which appears to be an important regulator of airway remodeling in allergic asthma. We also found that anti‐CCL20Ab attenuates airway inflammation and remodeling in an HDM‐induced mouse model of bronchial asthma. Taken together, our results suggest that HDM‐induced CCL20 is required for chronic inflammation that contributes airway remodeling in a mouse model of asthma.
BRAF increases endothelial cell stiffness through reorganization of the actin cytoskeleton
Authors: Hollósi Anna , Pászty Katalin , Bunta Bálint Levente , Bozó Tamás , Kellermayer Miklós , Debreczeni Márta Lídia , Cervenak László , Baccarini Manuela , Varga Andrea 
Published: August 2022

AbstractThe dynamics of the actin cytoskeleton and its connection to endothelial cell–cell junctions determine the barrier function of endothelial cells. The proper regulation of barrier opening/closing is necessary for the normal function of vessels, and its dysregulation can result in chronic and acute inflammation leading to edema formation. By using atomic force microscopy, we show here that thrombin‐induced permeability of human umbilical vein endothelial cells, associated with actin stress fiber formation, stiffens the cell center. The depletion of the MEK/ERK kinase BRAF reduces thrombin‐induced permeability prevents stress fiber formation and cell stiffening. The peripheral actin ring becomes stabilized by phosphorylated myosin light chain, while cofilin is excluded from the cell periphery. All these changes can be reverted by the inhibition of ROCK, but not of the MEK/ERK module. We propose that the balance between the binding of cofilin and myosin to F‐actin in the cell periphery, which is regulated by the activity of ROCK, determines the local dynamics of actin reorganization, ultimately driving or preventing stress fiber formation.
An overview of the current state of food desensitization
Authors: Galletta Francesca , Crisafulli Giuseppe , Arasi Stefania 
Published: August 2022

Purpose of review
To highlight the current evidence on food desensitization in children with food allergy.

Recent findings
Food Allergen Specific Immunotherapy (FA-AIT) is currently recognised as a treatment option for treating children with allergy at least to the main common foods (i.e. milk, egg and peanut). The oral route of administration has been proven to be the most effective in achieving desensitisation. Efforts are devoted to overcome the current unmet needs mainly related to safety issues and long-term efficacy, as well as adherence to the treatment and improvement of health-related quality of life. In this perspective, alternative routes of administration and adjunctive treatments are under investigation.

Summary
The future of food allergy management is a personalised approach based on a shared decision-making that takes into account the needs of patients and families. Health professionals will be able to offer multiple treatment options, including FA-AIT with adjunctive or alternative therapies. Thus, patients should be correctly identified, using validated predictive factors, in order to select appropriate candidates for these therapies.
Outcomes of Reamed Intramedullary Nailing for Lower Extremity Diaphyseal Fractures in COVID-Positive Patients: A Multi-institutional Observational Study
Authors: Pectol Richard W. , Kavolus Matthew W. , Sneed Chandler R. , Albano Ashley Y. , Landy David C. , Aneja Arun ,   and the “COVID-ORTHO” research group
Published: August 2022

Objective:
To determine if reamed intramedullary nailing (IMN) of tibial and femoral shaft fractures exacerbated the hypercoagulable state of COVID infection, resulting in increased thromboembolic and pulmonary complications.

Design:
Retrospective chart review.

Setting:
Eleven Level I trauma centers.

Patients:
From January 1, 2020, to December 1, 2022, 163 patients with orthopaedic trauma and COVID positivity and 36 patients with tibial and femoral shaft fractures were included.

Intervention:
Reamed IMN.

Main Outcome Measures:
Incidence of postoperative thromboembolic and respiratory complications.

Results:
Thirty-six patients with a median age of 52 years (range, 18–92 years; interquartile range, 29–72 years) met criteria. There were 21 and 15 patients with femoral and tibial shaft fractures. There were 15 patients sustaining polytrauma; of which, 10 had a new injury severity score of >17. All patients underwent reamed IMN in a median of 1 day (range, 0–12 days; interquartile range = 1–2 days) after injury. Two patients developed acute respiratory distress syndrome (ARDS) and 3 pneumonia. No patients had pulmonary embolism, deep vein thrombosis, or died within 30 days.

Conclusion:
In this multi-institutional review of COVID-positive patients undergoing reamed IMN, there were no thromboembolic events. All patients developing pulmonary complications (ARDS or pneumonia) had baseline chronic obstructive pulmonary disease, were immune compromised, or sustained polytraumatic injuries with new injury severity score of >20. Given this, it seems reasonable to continue using reamed IMN for tibial and femoral shaft fractures after evaluation for COVID severity, comorbidities, and other injuries.

Levels of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Stress Hyperphenylalaninemia Is Associated With Mortality in Cardiac ICU: Clinical Factors, Genetic Variants, and Pteridines*
Authors: Wang Chao-Hung , Chen Wei-Siang , Liu Min-Hui , Lee Chi-Ying , Wang Mei-Ying , Liang Chung-Yu , Chu Chien-Ming , Wu Huang-Ping , Chen Wen-Hsin 
Published: August 2022

OBJECTIVES:
Hyperphenylalaninemia predicts poor outcomes in patients with cardiovascular disease. However, the prognostic value and factors associated with stress hyperphenylalaninemia (SHP) were unknown in critical patients in the cardiac ICU.

DESIGN:
Prospective observational study.

SETTING:
Single-center, cardiac ICU in Taiwan.

PATIENTS:
Patients over 20 years old with Acute Physiology And Chronic Health Evaluation II scores greater than or equal to 15 and/or ventilatory support in the cardiac ICU.

INTERVENTIONS:
We measured plasma phenylalanine levels serially during patients’ stays in the ICU to investigate their prognostic value for 90-day mortality. Gene array was performed to identify genetic polymorphisms associated with SHP (phenylalanine level ≥ 11.2 μmol/dL) and to develop a Genetic Risk Score (GRS). We analyzed the associations between SHP and clinical factors and genetic variants and identified the correlation between pteridines and genetic variants.

MEASUREMENTS AND MAIN RESULTS:
The study enrolled 497 patients. Increased phenylalanine concentration was independently associated with increased mortality risk. Patients with SHP had a higher mortality risk compared with those without SHP (log rank = 41.13; p < 0.001). SHP was associated with hepatic and renal dysfunction and with genetic polymorphisms on the pathway of tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2). Higher GRSs were associated with lower BH4 bioavailability in response to stress (p < 0.05). In patients without SHP at baseline, those with GRSs gretaer than or equal to 2 had a higher frequency of developing SHP during the ICU stay (31.5% vs 16.1%; p = 0.001) and a higher mortality risk (p = 0.004) compared with those with GRSs less than 2. In patients with SHP at baseline, genetic variants did not provide additional prognostic value.

CONCLUSIONS:
SHP in patients admitted to the ICU was associated with a worse prognosis. In patients without SHP, genetic polymorphisms associated with SHP measured using a GRS of greater than or equal to 2 was associated with the subsequent SHP and higher mortality risk.
#Menopause: the menopause ontology project
Authors: Trieu Elissa , Davenport Abigail P. , Kingsberg Sheryl A. , Iglesia Cheryl B. 
Published: August 2022

Abstract

Objective
To create a hashtag ontology specific to menopause.

Methods
This study analyzed tweets including the hashtag #menopause between November 2019 and November 2021. Tweets performed by international or national societies as well as expert social media influencers were included in the analysis. To analyze hashtag utilization amongst all Twitter users, hashtags from the “Top” tweets Twitter search function from October 2021 were also analyzed. Co-occurring hashtags were recorded as well as the type of user who performed the tweet during the “Top” tweets analysis. Social media influencers and experts reviewed and edited the hashtag list. The hashtags were then grouped by subject.

Results
We analyzed 382 tweets with #menopause. Of the users included in the “Top” tweets, 40% were patient advocates or advocacy groups; 38% were medical professionals, academics, societies, or journals; and 22% were general users. In total, 123 unique hashtags were identified. After social media influencer and expert review, 32 hashtags were included in the final ontology. The ontology was then grouped into the following categories based on subject matter: general, premature menopause, hormones, sexual function, and genital disorders.

Conclusions
Social media is an important tool for medical professionals and patients. Our study is the first to develop a hashtag ontology specific to menopause. Adoption of a hashtag ontology with standardized terminology by medical professionals may facilitate easier communication with peers and patients.
Gonadotropin-releasing hormone agonists for ovarian protection during breast cancer chemotherapy: a systematic review and meta-analysis
Authors: Li Zhen-Yu , Dong Ying-Li , Cao Xiao-Zhong , Ren Sha-Sha , Zhang Zhen 
Published: August 2022

Abstract

Importance
The increasing trend of delaying childbirth means that more women are being diagnosed with breast cancer before having given birth to their desired number of children. Although chemotherapy can significantly improve the prognosis of this population, it also causes ovarian damage, including premature ovarian insufficiency and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have shown promising fertility protective activity in premenopausal women, but their clinical usage remains controversial.

Objective
Here, we conducted a meta-analysis to assess the efficacy of GnRHa when administered concurrently with chemotherapy that included cyclophosphamide in the prevention of chemotherapy-induced ovarian damage in premenopausal women.

Evidence Review
An extensive literature search was performed using the PubMed, Embase, and Cochrane databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were determined.

Findings
Eleven randomized controlled trials with a total of 1,219 participants were included in the analyses. A significantly higher number of women treated with GnRHa experienced the resumption of ovarian function after chemotherapy than those who did not receive this treatment (OR, 3.04; 95% CI, 1.87‐4.94; P < 0.001). Regarding spontaneous pregnancy, a statistically significant difference was observed only in hormone receptor-negative participants (OR, 2.06; 95% CI, 1.03‐4.11; P = 0.04).

Conclusions and Relevance
When treating premenopausal women with breast cancer, the administration of GnRHa concurrently with chemotherapy appeared to improve the resumption rate of ovarian function; however, the spontaneous pregnancy rate only improved in hormone receptor-negative patients. Thus, the use of GnRHa during chemotherapy may represent a feasible strategy for preserving ovarian function in women with breast cancer.
Private equity ownership of ophthalmology practices: how does it impact clinical research?
Authors: Chang Margaret A. , Pearlman Joel A. 
Published: August 2022

Purpose of review
To explore the impact of private equity ownership of ophthalmology practices on the success of their clinical research programs.

Recent findings
Private equity partnership in the clinical research space has been steadily occurring over the past decades. In addition to contract research organizations, private equity groups have also consolidated multiple independent clinical research networks. By investing in an increasing number of retina practices, one private equity group is attempting to create a synergistic relationship between clinical practice and clinical research with the goal of supporting a larger, more robust clinical research network.

Summary
Although there are physician concerns about the potential deleterious effects of private equity ownership on clinical research capabilities, private equity support has the potential to be an important stimulus for clinical research growth.

Video abstract

http://links.lww.com/COOP/A48.
Transitioning from a standalone practice to a private equity-partnered practice and impact on clinical operations
Authors: Donnenfeld Eric 
Published: August 2022

Purpose of review
Private equity has made significant inroads into the specialty of ophthalmology. The purpose of this review is to evaluate the effect of private equity on clinical operations in an ophthalmic practice.

Recent findings
Private equity had become an important source of capital and management expertise that has resulted in the consolidation of many ophthalmic practices as an alternative to working for a hospital system, insurance carrier, or independent private practice.

Summary
The recent growth of private equity presence in ophthalmology has resulted in significant changes in clinical operations. These changes in clinical operations include the increased importance of data management and data analytics, economies of scale, synergies, and introduction of patient-shared billing opportunities. Although physician input into clinical operations is decreased, provisional care decision-making can be maintained.
Current Practices Supporting Rigid Bronchoscopy—An International Survey
Authors: Matus Ismael , Wilton Shannon , Ho Elliot , Raja Haroon , Feng Lei , Murgu Septimiu , Sarkiss Mona 
Published: August 2022

Background:
There are no guidelines for anesthesia or staff support needed during rigid bronchoscopy (RB). Identifying current practice patterns for RB pertinent to anesthesia, multidisciplinary teams, and algorithms of intra and post-procedural care may inform best practice recommendations.

Methods:
Thirty-three-question survey created obtaining practice patterns for RB, disseminated via email to the members of the American Association of Bronchology and Interventional Pulmonology and the American College of Chest Physicians Interventional Chest Diagnostic Procedures Network.

Results:
One hundred seventy-five clinicians participated. Presence of a dedicated interventional pulmonology (IP) suite correlated with having a dedicated multidisciplinary RB team (P=0.0001) and predicted higher likelihood of implementing team-based algorithms for managing complications (39.4% vs. 23.5%, P=0.024). A dedicated anesthesiology team was associated with the increased use of high-frequency jet ventilation (P=0.0033), higher likelihood of laryngeal mask airway use post-RB extubation (P=0.0249), and perceived lower rates of postprocedural anesthesia adverse effects (P=0.0170). Although total intravenous anesthesia was the most used technique during RB (94.29%), significant variability in the modes of ventilation and administration of muscle relaxants was reported. Higher comfort levels in performing RB are reported for both anesthesiologists (P=0.0074) and interventional pulmonologists (P=0.05) with the presence of dedicated anesthesia and RB supportive teams, respectively.

Conclusion:
Interventional bronchoscopists value dedicated services supporting RB. Multidisciplinary dedicated RB teams are more likely to implement protocols guiding management of intraprocedural complications. There are no preferred modes of ventilation during RB. These findings may guide future research on RB practices.
Iron status of blood donors
Authors: Spencer Bryan R. , Mast Alan E. 
Published: August 2022

Purpose of review
This review examines recent research on the prevalence and importance of iron deficiency in blood donors, and on efforts to mitigate it.

Recent findings
Premenopausal females, teenagers, and high-frequency donors are at the highest risk for donation-induced iron deficiency, in both high-resource and low-resource settings. The physiology relating iron stores to hemoglobin levels and low hemoglobin deferral is well elucidated in blood donor populations, yet the clinical effects attributable to iron loss in the absence of anemia are challenging to identify. Expanded adoption of ferritin testing is improving donor management but may cause decreases in the blood supply from temporary donor loss. The potential for personalized donor management is emerging with development of computational models that predict individual interdonation intervals that aim to optimize blood collected from each donor while minimizing low hemoglobin deferrals.

Summary
Measures to reduce iron deficiency are available that can be deployed on a standardized or, increasingly, personalized basis. Blood centers, regulators, and donors should continue to evaluate different tactics for addressing this problem, to obtain a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health.