bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behcet’s-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy
Authors: Thomas Steffi , Bae Chay , Joy-Ann Tabanor , Traverse William 
Published: October 2019

Introduction The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. Case report We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. Management and outcome Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. Discussion Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet’s disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet’s-like syndrome presentation.
Bone modifying agents for patients with bone metastases from breast cancer managed in routine practice setting: Treatment patterns and outcome
Authors: Zekri Jamal , Farag Kamel , Yousof Osama , Zabani Yazeed , Mohamed Wael , Ahmed Goma A 
Published: October 2019

Introduction Bone metastases are common in patients with breast cancer and can lead to pain and skeletal-related events. Bone modifying agents are licensed to be used for these patients. We report the treatment patterns and outcome of zoledronic acid and denosumab in routine practice. Methodology Women with bone metastases from breast cancer who have started denosumab or zoledronic acid between 2011 and 2016 were eligible. Those with history of bone modifying agent use prior to diagnosis of bone metastases or with switching treatment between zoledronic acid and denosumab were excluded. Details of patients, tumors, bone modifying agent treatment, selected bone modifying agent toxicity, time to skeletal-related event development, and overall survival were collected retrospectively. Results In total, 163 women were eligible and included in this analysis. Number of skeletal-related events prior to starting bone modifying agents was 0, 1, 2, and 3 in 91 (55.8%), 53 (32.5%), 13 (8%), and 6 (3.7%), respectively. Zoledronic acid was started for 107 (65.6%) and denosumab for 56 (34.4%) patients. The proportion of patients receiving denosumab increased from 23.1 to 54.3% in years 2011 and 2016, respectively. Dose delay, reduction, and discontinuation due to toxicity were reported more frequently in patients receiving zoledronic acid. Denosumab delayed time to first on-treatment skeletal-related event compared with zoledronic acid (hazard ratio, 0.64; 95% CI, 0.41–0.98; log rank P = 0.044). There was no significant difference in median survival (zoledronic acid: 62 and denosumab: 58 months; log rank P = 0.956). Conclusion Denosumab is superior to zoledronic acid in reducing risk of skeletal-related events and in tolerance profile. However, overall survival is similar with both treatments. Our findings mirror those reported in scrutinized environment of landmark clinical trials.
Ruxolitinib for the treatment of lymphoma-associated hemophagocytic lymphohistiocytosis: A cautionary tale
Authors: Trantham Tanner , Auten Jessica , Muluneh Benyam , Van Deventer Hendrik 
Published: October 2019

Introduction Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome characterized by fever, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and pancytopenia. Three publications reported success with ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor. This therapy interrupts the production of cytokines associated with hemophagocytic lymphohistiocytosis, namely interferon-γ and interleukins 2, 6, and 10. Case report We administered ruxolitinib to two patients with lymphoma-associated hemophagocytic lymphohistiocytosis who had failed standard treatment with dexamethasone and etoposide. Management and outcome Patient #1 was started on ruxolitinib 10 mg BID, and titrated to 15 mg BID. All but two of the hemophagocytic lymphohistiocytosis criteria resolved within two weeks, and she was able to restart therapy for lymphoma. During her ruxolitinib taper, she again presented with relapsed hemophagocytic lymphohistiocytosis. She was taking 2.5 mg a day at the time. Despite salvage treatment, she died from the disease. Patient #2 was a diffuse large B-cell lymphoma patient who presented with hemophagocytic lymphohistiocytosis and was treated with chemoimmunotherapy and achieved a complete response (CR). Hemophagocytic lymphohistiocytosis symptoms relapsed, and he was treated with ruxolitinib. He developed relapsed lymphoma and unfortunately died. Discussion While treating the underlying lymphoma is a clear priority, the cytopenias and other symptoms of hemophagocytic lymphohistiocytosis complicate the delivery of this therapy. Hence, the use of ruxolitinib as a bridge to definitive therapy was appealing. However, we are concerned about the progression of lymphoma while these patients were taking ruxolitinib. Ruxolitinib may be controlling cytokine storm associated with hemophagocytic lymphohistiocytosis, while other aspects of the condition are progressing. Therefore, we would advise caution in its use in lymphoma-associated-hemophagocytic lymphohistiocytosis until more data are available.
Phacoemulsification, visco-goniosynechialysis, and goniotomy in patients with primary angle-closure glaucoma: A comparative study
Authors: Shokoohi-Rad Saeed , Karimi Farshid , Zarei-Ghanavati Siamak , Tireh Hossein 
Published: October 2019

Objective: The aim of this study was to evaluate the effects of goniotomy on patients with primary angle-closure glaucoma who underwent “phacoemulsification and visco-goniosynechialysis.” Materials and methods: This prospective randomized clinical trial was carried out on 63 eyes of 61 patients (48–85 years) with primary angle-closure glaucoma who were enrolled. The subjects were randomly assigned into two groups. In the first group (32 eyes) and the second group (31 eyes), the patients underwent “phacoemulsification + visco-goniosynechialysis + goniotomy” and “phacoemulsification + visco-goniosynechialysis,” respectively. Intraocular pressure and antiglaucoma medication were evaluated (1 week, as well as 1, 3, and 6 months after the surgery). Anterior segment optical coherence tomography parameters (Casia, Tomey, USA) and goniotomy were evaluated preoperatively and 6 months after the surgery. Results: The mean intraocular pressure lowering the effects in the “phacoemulsification + visco-goniosynechialysis + goniotomy” group was higher than that in the “phacoemulsification + visco-goniosynechialysis” group (6.93 and 4.6, respectively). Furthermore, the difference in intraocular pressure between the two groups was significant at 3 months (P = 0.014) and 6 months (P = 0.021) after the surgery. There was no difference in anterior segment optical coherence tomography findings before the intervention; however, after the intervention, the anterior segment optical coherence tomography indices were significantly different between the two groups. Moreover, the difference in “phacoemulsification + visco-goniosynechialysis + goniotomy” indices was more than the changes in the “phacoemulsification + visco-goniosynechialysis” group. Conclusion: The results of this study showed that phacoemulsification + visco-goniosynechialysis + goniotomy is a more effective surgery than phacoemulsification + visco-goniosynechialysis alone in undercounted primary angle-closure glaucoma.
Predictors of Groin Access Pseudoaneurysm Complication: A 10-Year Institutional Experience
Authors: Naddaf Abdallah , Williams Stephen , Hasanadka Ravishankar , Hood Douglas B. , Hodgson Kim J. 
Published: October 2019

Objective: In clinical practice, the incidence of femoral pseudoaneurysms requiring repair is small, but at a tertiary care center, the repair rate is higher due to referrals. We sought to specifically study patients who suffered postcatheterization pseudoaneurysms requiring thrombin injection or operative repair and compare them to our routine transfemoral endovascular patients to identify predictors of clinically significant pseudoaneurysms. The underlying goal would be to identify what makes these patients that develop pseudoaneurysms different. Methods: A search of our billing records for Current Procedural Technology (CPT) codes of these 2 procedures between January 2008 and April 2018 was combined with our institution’s Peripheral Vascular Intervention Vascular Quality Initiative database spanning from January 2013 to December 2017. A comparison was then performed between patients who had the outcome of operative intervention for a pseudoaneurysm complication and those who did not, with the goal of elucidating patient demographics and periprocedural factors that would predict pseudoaneurysm formation using univariate and multivariate analyses. Results: There were 77 patients who required thrombin injection or open repair for access-related pseudoaneurysms and 324 patients who did not. Complications occurred more often in patients who were older than 75 (40.2% vs 21.9%; P = .0009), female (57.1% vs 38.6%; P = .003), obese (59.7% vs 33.3%; P < .001), hypertensive (96.1% vs 79.3%; P = .0005), who received a sheath >6F (32.4% vs 13%; P < .0001), intraoperative and postoperative anticoagulation (77.3% vs 32.7% and 52.1% vs 24.2%, respectively; P < .0001), and periprocedural P2Y12 inhibitors (48.7% vs 28%; P = .0005). Less complications were observed in patients who had a closure device used (42.9% vs 8.45%; P < .0001) and protamine reversal (26.5% vs 13.3%; P = .0163). Conclusions: Our findings validate published reports that incriminate a larger sheath size, perioperative anticoagulation, and female gender as increasing the rate of access site complications, with the use of a closure device being protective.
Spatiotemporal Expression of 3-B-3(−) and 7-D-4 Chondroitin Sulfation, Tissue Remodeling, and Attempted Repair in an Ovine Model of Intervertebral Disc Degeneration
Authors: Farrugia Brooke , Smith Susan M. , Shu Cindy C. , Melrose James 
Published: October 2019

ObjectiveExamination of intervertebral disc (IVD) regeneration in an ovine annular lesion model.HypothesisSulfation motifs are important functional determinants in glycosaminoglycans (GAGs). Previous studies have correlated 3-B-3(−) and 7-D-4 chondroitin sulfate (CS) motifs in tissues undergoing morphogenetic transition in development. We hypothesize that these motifs may also be expressed in degenerate IVDs and may represent a reparative response.DesignInduction of disc degeneration by 5 mm or 6 × 20 mm lesions in the annulus fibrosus (AF) over 6 or 3 to 6 months postoperation (PO). Tissue sections were stained with toluidine blue–fast green, 3-B-3(−) and 7-D-4 CS-sulfation motifs were immunolocalized in 3-month PO 6 × 20 mm lesion IVDs. Sulfated glycosaminoglycan (GAG), 3-B-3(−), and 7-D-4 epitopes were quantitated by ELISIA (enzyme-linked immunosorbent inhibition assay) in extracts of AF (lesion site and contralateral half) and nucleus pulposus (NP) 0, 3, and 6 months PO.ResultsCollagenous overgrowth of lesions occurred in the outer AF. Chondroid metaplasia in ~20% of the 6 × 20 mm affected discs resulted in integration of an outgrowth of NP tissue with the inner AF lamellae preventing propagation of the lesion. 3-B-3(−) and 7-D-4 CS sulfation motifs were immunolocalized in this chondroid tissue. ELISIA quantified CS sulfation motifs demonstrating an increase 3 to 6 months PO in the AF lesion and a reduction in sulfated GAG not evident in the contralateral AF.Conclusions(1) Outer annular lesions underwent spontaneous repair. (2) Chondroid metaplasia of the inner 6 × 20 mm defect prevented its propagation suggesting an apparent reparative response.
Sustainable Human Resource Management: A Literature-based Introduction
Authors: Randev Kadumbri Kriti , Jha Jatinder Kumar 
Published: October 2019

The concept of sustainability has deeply penetrated in all functions of management such as supply chain, organisational behaviour, human resource, strategic management and so on. But recently, sustainable human resource management (S-HRM) has garnered a significant amount of attention from industry practitioners and academicians due to the escalation of adverse impact of existing HRM approaches on employees, society and the environment ( Mariappanadar, 2003 , International Journal of Social Economics, 30(8), 906–923; 2014a, Human Resource Management Review, 24(4), 313–329; 2014b, Sustainability and Human Resource Management, Springer). Human resource sustainability is being desired by all because of its notable implications for both the employees and the organisations. Previous literature establishes that human resource management (HRM) practices play a vital role in determining organisational success and survival. Furthermore, the harmful impact of high performance work systems and their existing HRM practices on the well-being of employees and their families has made it even more pertinent for industry practitioners to identify mechanisms to reduce employee harm and increase human resource sustainability for organisational growth and well-being. A research report by the Society for Human Resource Management in 2010 and a few other scholars claim that S-HRM can help HRM practitioners to reduce the negative impact of business practices on employees, society and the environment ( Cohen & Taylor, 2012 , HR’s role in corporate social responsibility and sustainability; Daily & Huang, 2001 , International Journal of Operations & Production Management, 21(12), 1539–1552; Dumitrana, 2009 , Human resources role in sustainable development). However, S-HRM has been studied sporadically, and there is a lack of convergence in its understanding. It has been broadly defined with the help of various perspectives borrowed from literature on strategic HRM, corporate social responsibility, Green HRM and sustainable work systems. This article aims to explore the existing literature of S-HRM to develop a deeper understanding of the concept. Through a comprehensive literature review, this article also highlights the evolution of S-HRM along with its implications for employees, HR managers and the organisations that have been studied in the previous literature.
Nitrogen application and different water regimes at booting stage improved yield and 2-acetyl-1-pyrroline (2AP) formation in fragrant rice
Authors: Mo Zhaowen , Li Yanhong , Nie Jun , He Longxin , Pan Shenggang , Duan Meiyang , Tian Hua , Xiao Lizhong , Zhong Keyou , Tang Xiangru 
Published: October 2019

Abstract

Background
Water (W) and nitrogen (N) management generally cause regulations in the 2-acetyl-1-pyrroline (2AP) accumulation in fragrant rice; nevertheless, the feasibility of such management strategies at booting stage in improving 2AP accumulation has not been examined in details.

Methods
Field experiments were conducted in the early season (March–July) and repeated in the late season (July–November) in 2013. The treatments were applied urea (90 kg ha− 1), calcium super phosphate (90 kg ha− 1) and potassium chloride (195 kg ha− 1) as basal fertilizer, and urea (65 kg ha− 1) at tillering stage. Three N levels i.e., 0 kg N ha− 1 (N1), 30 kg N ha− 1 (N2), and 60 kg N ha− 1 (N3) and three water levels i.e., W1 treatment (well-watered treatment with water layer of 2–4 cm), W2 treatment (soil water potential was − 15 ± 5 kPa), and W3 treatment (soil water potential was − 25 ± 5 kPa) at booting stage was set up for three rice varieties i.e., Nongxiang 18, Yungengyou 14 and Basmati. The grain yield, head milled rice yield, 2AP contents and the biochemical parameters related to 2AP formation were investigated.

Results
Result indicated that W and N dynamics regulated the grain yield, head milled rice yield, and 2AP contents in brown rice across three varieties. The N2 and N3 treatment significantly increased the 2AP contents in brown rice by 9.54% and 11.95%, and 8.88% and 32.54% in the early and the late season, respectively; improved grain yield and head milled rice yield. The W3 treatment improved grain yield, head milled rice yield and 2AP content. Significant W and N interaction effect on 2AP content in brown rice was detected, where the W3 N3 treatment showed the strongest interaction regarding improvement of 2AP contents in brown rice. The 2AP accumulation and its related biochemical parameters and their relationships in different plant tissues at different growth stages under W and N treatments had also been assessed. The 2AP content, P5C content and DAO activity during grain filling periods was highly related to the 2AP content in brown rice.

Conclusion
This study revealed that the 60 kg N ha− 1 coupled with − 25 ± 5 kPa treatment showed the best positive effects on yield and aroma in fragrant rice, suggested that water and nitrogen management at booting stage can improve grain yield and fragrance in fragrant rice. However, further study to evaluate the metabolic and molecular basis of 2AP accumulation in fragrant rice is needed.
Leucine-rich repeat and sterile alpha motif containing 1 promotes the oncogenic growth of human hepatocellular carcinoma cells
Authors: Pian Lili , Huang Xiaofeng , Zhao Min , Zhang Yaolin , Qin Cheng , Zhang Jiyan , Zhang Jun , Wang Qingyang 
Published: October 2019

Abstract

Background
Hepatocellular carcinoma (HCC), the most common primary cancer of the liver, is one of the most common malignancies and the leading cause of cancer-related death worldwide. Leucine-rich repeat and sterile alpha motif containing 1 (LRSAM1) is an E3 ubiquitin ligase involved in diverse cellular activities, including the regulation of cargo sorting, cell adhesion and antibacterial autophagy. The role of LRSAM1 in HCC remains unknown.

Methods
In this study, we reviewed the TCGA database and then performed gain-of-function and loss-of-function analyses of LRSAM1 in HCC cell lines.

Results
We found that the mRNA expression level of LRSAM1 was significantly increased in clinical HCC tissues in the TCGA database. Transient LRSAM1 knockdown in several human HCC cell lines led to reduced growth in conventional culture conditions. Stable LRSAM1 knockdown in HepG2 cells led to impaired anchorage-independent growth whereas its stable ectopic overexpression yielded the opposite effects. LRSAM1 overexpression in HepG2 cells enhanced in vivo tumorigenicity, whereas LRSAM1 knockdown in this cell line significantly impaired tumor growth.

Conclusions
Our data suggest that LRSAM1 promotes the oncogenic growth of human HCC cells, although the underlying mechanisms remain to be explored.
Triple artemisinin-containing combination anti-malarial treatments should be implemented now to delay the emergence of resistance: the case against
Authors: Krishna Sanjeev 
Published: October 2019

Abstract
Managing multidrug resistant malaria can be problematic if currently available artemisinin-containing anti-malarial combination treatments are not used appropriately. Here, I debate that the best way to manage multidrug resistant malaria is to make best use of existing treatments and to develop new classes of anti-malarial drugs and not to make ‘triple combination therapies’ when there is already resistance to one or more proposed components.
A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States
Authors: Lucas Aaron , Sinha Anushua , Fowler Karen B. , Mladsi Deirdre , Barnett Christine , Samant Salome , Gibson Laura 
Published: October 2019

AbstractBackgroundIn the United States (US), congenital cytomegalovirus infection (cCMVi) is a major cause of permanent disabilities and the most common etiology of non-genetic sensorineural hearing loss. Evaluations of prevention strategies will require estimates of the economic implications of cCMVi. We aimed to develop a conceptual framework to characterize the lifetime economic burden of cCMVi in the US and to use that framework to identify data gaps.MethodsDirect health care, direct non-health care, indirect, and intangible costs associated with cCMVi were considered. An initial framework was constructed based on a targeted literature review, then validated and refined after consultation with experts. Published costs were identified and used to populate the framework. Data gaps were identified.ResultsThe framework was constructed as a chance tree, categorizing clinical event occurrence to form patient profiles associated with distinct economic trajectories. The distribution and magnitude of costs varied by patient life stage, cCMVi diagnosis, severity of impairment, and developmental delays/disabilities. Published studies could not fully populate the framework. The literature best characterized direct health care costs associated with the birth period. Gaps existed for direct non-health care, indirect, and intangible costs, as well as health care costs associated with adult patients and those severely impaired.ConclusionsData gaps exist concerning the lifetime economic burden of cCMVi in the US. The conceptual framework provides the basis for a research agenda to address these gaps. Understanding the full lifetime economic burden of cCMVi would inform clinicians, researchers, and policymakers, when assessing the value of cCMVi interventions.