bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual skin toxicity associated with sustained disease response induced by nivolumab in a patient with non-small cell lung cancer
Authors: Galli Giulia , Proto Claudia , Cossa Mara , Valeri Barbara , Sdao Silvana , Signorelli Diego , Imbimbo Martina , de Braud Filippo , Garassino Marina Chiara , Lo Russo Giuseppe 
Published: August 2019

Introduction: Immunotherapy has shown efficacy in the treatment of different malignancies. Nivolumab, an immune checkpoint inhibitor directed against programmed death-1, has been approved for non-small cell lung cancer (NSCLC) in pretreated patients. Although it is generally well-tolerated, immunotherapy may be complicated by a wide range of immune-mediated adverse events. We describe the case of an uncommon skin toxicity arising as alopecia universalis induced by nivolumab in a patient with NSCLC. Case description: A 58-year-old man received nivolumab for metastatic NSCLC after progression to 3 lines of chemotherapy. The treatment was prescribed in June 2016, and induced a rapid and significant disease response. Nivolumab was well-tolerated until May 2017, when partial alopecia at hair and eyelashes appeared. In the next months, alopecia became complete and extended to the whole body surface. The dermatologic picture was compatible with alopecia areata. A topical steroid therapy was attempted, without benefit. The patient refused systemic treatments and is still undergoing nivolumab without new toxicities and with persistent disease response. Conclusions: This case suggests that alopecia areata may be a rare immune-related adverse event of immune checkpoint agents. Its late onset in our patient is uncommon and unexpected, underlining that the risk of nivolumab-induced toxicity is not limited to the beginning of treatment. Despite its rarity, alopecia areata should be considered in the range of adverse events potentially induced by immune checkpoint inhibitors even in the long term. Potential association between toxicity and efficacy of immunotherapy in NSCLC warrants further investigation.
Effects of Conditioned Medium From Osteoarthritic Cartilage Fragments on Donor-Matched Infrapatellar Fat Pad–Derived Mesenchymal Stromal Cells
Authors: Fu Zhenlan , Song Xiongbo , Guo Lin , Yang Liu , Chen Cheng 
Published: August 2019

Background: Mesenchymal stromal cell (MSC)–based therapies have emerged as a promising strategy for osteoarthritis (OA) treatment. In particular, infrapatellar fat pad (IPFP)–derived MSCs have become a good option to treat knee OA. Purpose: To investigate the influence of the local microenvironment of the knee joint, especially OA cartilage, on the bioactivities of injected/implanted IPFP MSCs. Study Design: Controlled laboratory study. Methods: Conditioned medium (CM) derived from OA cartilage fragments was collected and characterized. Donor-matched IPFP MSCs were treated with control medium (Dulbecco’s modified Eagle medium (DMEM)/F-12 or chondrogenic medium), control medium + CM, or CM alone; and a series of behaviors including the viability, migration, chondrogenic and hypertrophic differentiation, and catabolic activity of IPFP MSCs were evaluated among groups. Results: There were 14 cytokines detected in CM. CM treatment improved the viability of IPFP MSCs. CM hindered the migration of IPFP MSCs. In chondrogenic differentiation, the presence of CM increased the expression of chondrogenic markers but also enhanced the state of hypertrophy and catabolism. Conclusion: OA cartilage–secreted factors could induce chondrogenic differentiation but also resulted in negative effects including the weakened migration, increased hypertrophy, and catabolism of IPFP MSCs in vitro. Clinical Relevance: These findings provide an insight on the fate of IPFP MSCs after intra-articular injections.
The Effectiveness of a Hinged Elbow Orthosis in Medial Collateral Ligament Injuries: An In Vitro Biomechanical Study
Authors: Manocha Ranita H.K. , Johnson James A. , King Graham J.W. 
Published: August 2019

Background: Medial collateral ligament (MCL) injuries are common after elbow trauma and in overhead throwing athletes. A hinged elbow orthosis (HEO) is often used to protect the elbow from valgus stress early after injury and during early return to play. However, there is minimal evidence regarding the efficacy of these orthoses in controlling instability and their influence on long-term clinical outcomes. Purpose: (1) To quantify the effect of an HEO on elbow stability after simulated MCL injury. (2) To determine whether arm position, forearm rotation, and muscle activation influence the effectiveness of an HEO. Study Design: Controlled laboratory study. Methods: Seven cadaveric upper extremity specimens were tested in a custom simulator that enabled elbow motion via computer-controlled actuators and motors attached to relevant tendons. Specimens were examined in 2 arm positions (dependent, valgus) and 2 forearm positions (pronation, supination) during passive and simulated active elbow flexion while unbraced and then while braced with an HEO. Testing was performed in intact elbows and repeated after simulated MCL injury. An electromagnetic tracking device measured valgus angulation as an indicator of elbow stability. Results: When the arm was dependent, the HEO increased valgus angle with the forearm in pronation (+1.0°± 0.2°, P = .003) and supination (+1.5°± 0.0°, P = .006) during active motion. It had no significant effect on elbow stability during passive motion. In the valgus position, the HEO had no effect on elbow stability during passive or active motion in pronation and supination. With the arm in the valgus position with the HEO, muscle activation reduced instability during pronation (–10.3°± 2.5°, P = .006) but not supination ( P = .61). Conclusion: In this in vitro study, this HEO did not enhance mechanical stability when the arm was in the valgus and dependent positions after MCL injury. Clinical Relevance: After MCL injury, an HEO likely does not provide mechanical elbow stability during rehabilitative exercises or when the elbow is subjected to valgus stress such as occurs during throwing.
Early Tracheostomy for Severe Pediatric Traumatic Brain Injury is Associated with Reduced Intensive Care Unit Length of Stay and Total Ventilator Days
Authors: Sheehan Brian M. , Grigorian Areg , Gambhir Sahil , Maithel Shelley , Kuza Catherine M. , Dolich Matthew O. , Lekawa Michael E. , Nahmias Jeffry 
Published: August 2019

Objectives: To determine whether, similar to adults, early tracheostomy in pediatric patients with severe traumatic brain injury (TBI) improves inhospital outcomes including ventilator days, intensive care unit (ICU) length of stay (LOS), and total hospital LOS when compared to late tracheostomy. Design: Retrospective cohort analysis. Setting: The Pediatric Trauma Quality Improvement Program (TQIP) database Patients: One hundred twenty-seven pediatric patients <16 years old with severe (>3) abbreviated injury scale TBI who underwent early (days 1-6) or late (day ≥7) tracheostomy between 2014 and 2016. Interventions: Not applicable. Measurements and Main Results: The Pediatric TQIP database was queried for patients <16 years old with severe TBI, who underwent tracheostomy. Patient demographics and outcomes of early versus late tracheostomy were compared using Student t test, Mann-Whitney U test, and χ2 analysis. Sixteen patients underwent early tracheostomy while 111 underwent late tracheostomy. The groups had similar distributions of age, gender, mechanism of injury, and mean injury severity scores (P > .05). Early tracheostomy was associated with decreased ICU LOS (early: 17 vs late: 32 days, P < .05) and ventilator days (early: 9.7 vs late: 27.1 days, P < .05). There was no difference in total LOS (early: 26.7 vs late: 41.3 days, P = .06), the incidence of acute respiratory distress syndrome (early: 6.3% vs late: 2.7%, P = .45), pneumonia (early: 12.5% vs late: 29.7%, P = .15), or mortality (early: 0% vs late: 2%, P = .588) between the 2 groups. Conclusion: Similar to adults, early tracheostomy in pediatric patients with severe TBI is associated with decreased ICU LOS and ventilator days. Future prospective trials are needed to confirm these findings. Article Tweet: Early tracheostomy in pediatric patients with severe TBI is associated with decreased ICU LOS and ventilator days.
Consensus Building Gaming Which Promotes Creative Solutions to Wildlife Management Dilemmas
Authors: Oyamada Shin , Kitani Shinobu 
Published: August 2019

Background. Wildlife management is becoming a more challenging problem throughout the world. One of the main difficulties it encounters is that residents tend to have ambivalent attitudes regarding whether wildlife should be eliminated or conserved. Aim. We made a consensus building gaming scenario for promoting creative solutions to wildlife management dilemmas. In this article, we aim to show the prerequisites for high performance of this gaming. Method. The gaming consists of three phases: a game playing phase, a presenting dilemma phase, and a game remodeling phase. The game playing phase consists of playing the game which is based on the actual wildlife management problem in Japan. Players can learn the difficulties of real wildlife management from the perspective of farmers. In presenting the dilemma phase, they are presented with the dilemma structure of wildlife problems and motivated to solve the dilemma. In the game remodeling phase, the players remodel the played game to design a new society wherein the residents can coexist successfully with wildlife. The remodeling phase is a kind of well-constructed debriefing process. With this game remodeling process, players can use their creativity for consensus building. Results. The gaming society functioned well especially for players with high pragmatic attitudes or those good at generating ideas especially through talking with others. Conclusion. The prerequisites for high performance of this gaming were verified. But further research is necessary for producing creative consensus building theory and objectively evaluating the quality of players’ ideas.
Partnership or insanity: why do health partnerships do the same thing over and over again and expect a different result?
Authors: Perkins Neil , Hunter David J , Visram Shelina , Finn Rachael , Gosling Jennifer , Adams Lee , Forrest Amanda 
Published: August 2019

Objectives The paper reports on an empirical study of Health and Wellbeing Boards (HWBs) in England. Established by the Health and Social Care Act 2012, HWBs act as place-based hubs for leaders in health, social care, local government and other sectors to come together to address health improvement and the wider determinants of health. Methods We conducted a three-year study of HWBs (2015–2017) in five localities across England. This involved collecting qualitative data from semi-structured interviews with key actors in the HWBs at strategic and operational levels, and focus group sessions with voluntary-sector participants at each HWB. Results HWBs have largely followed the path of previous partnerships in terms of a lack of clear aims and objectives, lack of ownership and accountability by partners, and an absence of any significant impact on health outcomes. Conclusions Many of the features of unsuccessful partnership working were largely displayed by HWBs. Boards require more executive power and ownership from the bottom up if they are to have any real impact.
Prospects of siRNA cocktails as tools for modifying multiple gene targets in the injured spinal cord
Authors: Michael Felicia Mary , Chandran Preeja , Chandramohan Khaviyaa , Iyer Krithika , Jayaraj Kevin , Sundaramoorthy Revathidevi , Venkatachalam Sankar 
Published: August 2019

Gene silencing through RNA interference (RNAi) has been touted as a boon for identifying potential therapies for difficult-to-treat pathologies. In this regard, siRNA-mediated gene silencing for tackling the multifaceted pathophysiology of spinal cord injury seemed promising. The genes caspase 3 and sarm1 were targeted in the present study, using siRNAs in a rodent model of spinal cord injury, as the feasibility of concomitant silencing of more than one gene had not been previously attempted. The results indicated meager benefits in terms of functional recovery and tissue preservation. Interestingly, differential transfection efficiencies due to the heterogeneous nature of cells in the spinal cord along with variability in efficacy based on time of intervention affected the reproducibility of this approach. Complex gene interactions and inadequacies in molecular evaluation strategies further complicated the interpretation of the outcome. If these glitches are resolved through further research, gene therapy in general and RNAi, in particular, may become a mainstay approach for treating contusion spinal cord injury.Impact statementGene therapy has reached the level of clinical trials. However, safety and efficacy are yet to be confirmed. The present study tested the prospects of gene silencing using siRNAs in a rat model of spinal cord injury. Some noteworthy observations include the effective and long-lasting silencing effects of siRNAs, inhibition of one gene's expression resulting in silencing of multiple genes in associated pathways, possibility of targeting more than one gene through siRNA cocktails, and differential gene silencing effects based on temporal changes in their expression patterns. It is argued that differential uptake of siRNAs by cells as observed and limitations in the analysis methods available can skew interpretations. Thus, this study may serve as a cautionary tale indicating that gene silencing using siRNAs for spinal cord injury can be a potential therapy, but practical issues are to be addressed in order to ensure consistency and safety.
Cholangioscopy-guided steroid injection for refractory post liver transplant anastomotic strictures: a rescue case series
Authors: Franzini Tomazo , Sagae Vitor M.T. , Guedes Hugo G. , Sakai Paulo , Waisberg Daniel R. , Andraus Wellington , D’Albuquerque Luiz A.C. , Sethi Amrita , de Moura Eduardo G.H. 
Published: August 2019

Background and aims: Post liver transplant biliary anastomotic strictures have traditionally been treated with balloon dilation and multiple plastic stents. Fully covered self-expandable metallic stents may be used as an initial alternative or after multiple plastic stents failure. Refractory strictures can occur in 10–22% and require revisional surgery. Alternatively, cholangioscopy allows direct visualization and therapeutic approaches. We aimed to assess the feasibility, safety, and efficacy of balloon dilation combined with cholangioscopy-guided steroid injection for the treatment of refractory anastomotic biliary strictures. Methods: Three post-orthotopic liver transplant patients who failed standard treatment of their biliary anastomotic strictures underwent endoscopic retrograde cholangiopancreatography with balloon dilation followed by cholangioscopy-guided steroid injection at a tertiary care center. Patients had follow-up with images and laboratorial tests to evaluate for residual stricture. Results: Technical success of balloon dilation + cholangioscopy-guided steroid injection was achieved in all patients. Cholangioscopy permitted accurate evaluation of bile ducts and precise localization for steroid injection. No adverse events occurred. Mean follow-up was 26 months. Two patients are stent free and remain well in follow-up, with no signs of biliary obstruction. No further therapeutic endoscopic procedures or revisional surgery were required. One patient did not respond to balloon dilation + cholangioscopy-guided steroid injection after 11 months of follow-up and required repeat balloon dilation of new strictures above the anastomosis. Conclusion: Cholangioscopy-guided steroid injection combined with balloon dilation in the treatment of refractory post liver transplant strictures is feasible and safe. This method may be used as a rescue alternative before surgical approach. Randomized controlled trials comparing balloon dilation + cholangioscopy-guided steroid injection to fully covered self-expandable metallic stents are needed to determine the role of this treatment for anastomotic biliary strictures.
Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration
Authors: Tobin Joshua W.D. , Keane Colm , Gunawardana Jay , Mollee Peter , Birch Simone , Hoang Thanh , Lee Justina , Li Li , Huang Li , Murigneux Valentine , Fink J. Lynn , Matigian Nicholas , Vari Frank , Francis Santiyagu , Kridel Robert , Weigert Oliver , Haebe Sarah , Jurinovic Vindi , Klapper Wolfram , Steidl Christian , Sehn Laurie H. , Law Soi-Cheng , Wykes Michelle N. , Gandhi Maher K. 
Published: August 2019

PURPOSE Understanding the immunobiology of the 15% to 30% of patients with follicular lymphoma (FL) who experience progression of disease within 24 months (POD24) remains a priority. Solid tumors with low levels of intratumoral immune infiltration have inferior outcomes. It is unknown whether a similar relationship exists between POD24 in FL. PATIENTS AND METHODS Digital gene expression using a custom code set—five immune effector, six immune checkpoint, one macrophage molecules—was applied to a discovery cohort of patients with early- and advanced-stage FL (n = 132). T-cell receptor repertoire analysis, flow cytometry, multispectral immunofluorescence, and next-generation sequencing were performed. The immune infiltration profile was validated in two independent cohorts of patients with advanced-stage FL requiring systemic treatment (n = 138, rituximab plus cyclophosphamide, vincristine, prednisone; n = 45, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), with the latter selected to permit comparison of patients experiencing a POD24 event with those having no progression at 5 years or more. RESULTS Immune molecules showed distinct clustering, characterized by either high or low expression regardless of categorization as an immune effector, immune checkpoint, or macrophage molecule. Low programmed death-ligand 2 (PD-L2) was the most sensitive/specific marker to segregate patients with adverse outcomes; therefore, PD-L2 expression was chosen to distinguish immune infiltrationHI (ie, high PD-L2) FL biopsies from immune infiltrationLO (ie, low PD-L2) tumors. Immune infiltrationHI tissues were highly infiltrated with macrophages and expanded populations of T-cell clones. Of note, the immune infiltrationLO subset of patients with FL was enriched for POD24 events (odds ratio [OR], 4.32; c-statistic, 0.81; P = .001), validated in the independent cohorts (rituximab plus cyclophosphamide, vincristine, prednisone: OR, 2.95; c-statistic, 0.75; P = .011; and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: OR, 7.09; c-statistic, 0.88; P = .011). Mutations were equally proportioned across tissues, which indicated that degree of immune infiltration is capturing aspects of FL biology distinct from its mutational profile. CONCLUSION Assessment of immune-infiltration by PD-L2 expression is a promising tool with which to help identify patients who are at risk for POD24.
Existence of standing waves for quasi-linear Schrödinger equations on T
n
Authors: Zhao Xin , Yan Weiping 
Published: August 2019

Abstract
This paper is devoted to the study of the existence of standing waves for a class of quasi-linear Schrödinger equations on T

n
with dimension n ≥ 3. By construction of a suitable Nash-Moser-type iteration scheme, we overcome the clusters of “small divisor” problem, then the existence of standing waves for quasi-linear Schrödinger equations is established.
Solar photodegradation of carbamazepine from aqueous solutions using a compound parabolic concentrator equipped with a sun tracking system
Authors: Yazdanbakhsh Ahmadreza , Nemati Reza , Massoudinejad Mohamadreza , Jafari Mohamadjavad , Dashtdar Masoomeh 
Published: August 2019

AbstractThe primary purpose of this study was to investigate the efficiency of a Compound Parabolic Concentrator (CPC) equipped with a sun tracking system in the photolysis of carbamazepine as a refractory organic compound. The natural sunlight experiments were accomplished during the period May–July 2017 in Tehran, Iran. The intermediate by-products of the process of solar photodegradation of carbamazepine (CBZ) were characterized using LC–MS. The results showed that increasing the reactor temperature did not significantly change CBZ degradation efficiency. However, the solution pH played a comparatively important role in CBZ solar photo degradation: removal efficiency increased considerably with pH from about 49% at pH 7 to almost 61% at pH 9. According to our findings, using a CPC reactor equipped with a sun tracker system promotes the solar photo-transformation rate of CBZ by 2-3 fold. In addition, LC/MS analysis showed that eight main intermediates were formed in the treated solution after solar photodegradation of CBZ. Therefore, complete mineralization of CBZ was not accomplished.
Impact of storage temperature and time on Moldavian dragonhead oil – spectroscopic and chemometric analysis
Authors: Oniszczuk Tomasz , Matwijczuk Arkadiusz , Matwijczuk Alicja , Kocira Sławomir , Niemczynowicz Agnieszka , Combrzyński Maciej , Wójtowicz Agnieszka , Kuboń Maciej , Kusz Andrzej , Oniszczuk Anna 
Published: August 2019

AbstractMoldavian dragonhead (Dracocephalum moldavica L.) is a plant endemic to Asia where it has been used for centuries for the production of essential oils. With the constantly growing demand for vegetable fats it is necessary to find new methods of ensuring their high quality from the moment of production until their eventual purchase by the consumer. Correct assessment of the quality of oleaginous products is therefore one of the intensively explored scientific problems that stimulates the development of innovative methods of analysing such substances. One of the newer and, most importantly, faster alternatives in the context of analysing the quality of oil and the changes it undergoes during storage is offered by FTIR spectroscopy (Fourier-Transform Infrared spectroscopy). By measuring the relevant FTIR spectra, we were able to observe clear discrepancies in the intensity of bands characteristic of the aging processes taking place in the oleaginous samples due to the oxidation of their fat fractions. The chemometric analysis of FTIR spectra confirmed the high quality of the analysed oils. It is noteworthy that the analysed samples of Moldavian dragonhead oil did not show particularly extensive changes in terms of their FTIR spectra during long-term storage. It confirms their high durability and usability in food production as an excellent product. This is valuable information in order to make progress in the use of Moldavian dragonhead oil in food products.
Crouzeix–Raviart Finite Element Approximation for the Parabolic Obstacle Problem
Authors: Gudi Thirupathi , Majumder Papri 
Published: August 2019

Abstract
We introduce and study a fully discrete nonconforming finite element approximation for a parabolic variational inequality associated with a general obstacle problem.
The method comprises of the Crouzeix–Raviart finite element method for space discretization and implicit backward Euler scheme for time discretization.
We derive an error estimate of optimal order

𝒪
⁢

(

h
+

Δ
⁢
t

)

{\mathcal{O}(h+\Delta t)}

in a certain energy norm defined precisely in the article. We only assume the realistic regularity

u
t

∈

L
2

⁢

(
0
,
T
;

L
2

⁢

(
Ω
)

)

{u_{t}\in L^{2}(0,T;L^{2}(\Omega))}

and moreover the analysis is performed without any assumptions on the speed of propagation of the free boundary. We present a numerical experiment to illustrate the theoretical order of convergence derived in the article.