bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogenic T-Cells Targeting CD123 for Adoptive Immunotherapy of Acute Myeloid Leukemia (AML)
Authors: Galetto Roman , Lebuhotel Celine , Gouble Agnes , Schiffer-Mannioui Cecile , Smith Julianne 
Published: October 2019

Abstract
Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors (CARs) has emerged as a promising new approach to treating cancer. However, a limitation of this approach is that CAR T-cells must be generated on a bespoke basis. To overcome this limitation, we have developed an allogeneic based platform for large scale production of “off-the-shelf” CAR T-cells from unrelated 3rd party donors. This platform utilizes Transcription Activator-Like Effector Nuclease (TALENTM) gene editing technology to inactivate the TCRα constant (TRAC) gene, eliminating the potential for T-cells bearing alloreactive TCR’s to mediate Graft versus Host Disease (GvHD). We have previously demonstrated that editing of the TRAC gene can be achieved at high frequencies, obtaining up to 80% of TCRαβ negative cells. This allows us to efficiently produce TCR-deficient T-cells that have been shown to no longer mediate alloreactivity in a xeno-GvHD mouse model. Furthermore, the capacity to perform efficient multiplex genome editing using TALENTM offers the possibility of simultaneously rendering cells resistant to standard chemotherapy or to tumor evasion mechanisms.
In this work we present the adaptation of this allogeneic platform to the production of T cells targeting CD123, the transmembrane alpha chain of the interleukin-3 receptor, which is expressed in tumor cells from the majority of patients with Acute Myeloid Leukemia (AML). In a first step, we have screened human primary T-cells harboring CARs with different antigen recognition domains in the context of multiple CAR architectures in order to identify candidates displaying specific activity against cell lines expressing variable levels of the CD123 antigen. To provide proof of concept for the general applicability of the allogeneic approach we have manufactured a TCR-deficient CD123 CAR T-cell (UCART123) and demonstrated that this product maintains a potent anti-tumoral activity in vitro. Experiments in an orthotopic AML mouse model using UCART123 cells are currently ongoing, in order to establish the absence of alloreactivity and the anti-tumoral activity in vivo. The ability to carry out large scale manufacturing of allogeneic, non alloreactive CD123 specific T Cells from a single healthy donor could thus offer the possibility of an off-the-shelf treatment that would be immediately available for administration to a large number of AML patients.

Disclosures
Galetto: Cellectis SA: Employment. Lebuhotel:Cellectis SA: Employment. Gouble:Cellectis SA: Employment. Schiffer-Mannioui:Cellectis SA: Employment. Smith:Cellectis SA: Employment.
Graft Versus HIV-1 Reservoir Effect after Allogeneic Stem Cell Transplantation
Authors: Kwon Mi , Nijhuis Monique , Balsalobre Pascual , Gayoso Jorge , Anguita Javier , Buno Ismael , Martinez-Laperche Carolina , Serrano David , Berenguer Juan , Miralles Pilar , Wensing Annemarie , Diez-Martin Jose Luis 
Published: October 2019

Abstract
Background: The use of a stem cell source homozygous for the CCR5 delta32 mutation is of particular interest in HIV+ patients in need of an allogeneic hematopoietic stem cell transplantation (SCT) given the high natural resistance against HIV-1 acquisition. In the absence of such cell source, the impact of allogeneic SCT on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is unknown.
Methods: Size of HIV-1 reservoirs was investigated in 3 patients with hematological malignancies receiving cART, who underwent allogeneic SCT (Table 1). Patient 1 received a myeloablative single cord blood (wild type (WT) CCR5), supported with third party HLA-mismatched CD34+ cells (haplo-cord SCT). Patients 2 and 3 underwent reduced intensity conditioning SCT of an HLA-matched sibling (heterozygous CCR5 delta32 donor and WT CCR5 donor, respectively). In-depth analysis of the HIV-1 reservoir was performed in the post-transplant period using droplet digital PCR and hemi-nested qPCR (proviral DNA copies/million PBMC). Chimerism analysis was performed by short tandem repeat PCR (STR-PCR).
Results: Proviral DNA showed a decreasing dynamics after allogeneic SCT and became undetectable in all 3 patients at 9, 18 and 1 months, respectively (Table 1). In patient 1, negativity of proviral HIV-1 DNA coincided with achievement of complete chimerism while being free of immunosuppression. Patient 2 showed undetectable proviral DNA together with the development of skin chronic GvHD. Finally, undetectable proviral DNA and complete chimerism was achieved in patient 3 early after transplantation. All patients remained in complete hematological remission.
Conclusion: All our patients showed a small HIV-1 reservoir after allogeneic SCT. The coincidence of achievement of negative proviral HIV-1 DNA and complete chimerism and/or development of GvHD suggests a role of Ògraft versus HIV-1 reservoir effectÓ in the control of HIV infection.

Disclosures
No relevant conflicts of interest to declare.
Survival in Adult Stage I Follicular Lymphoma Treated with and without Radiotherapy – a Population Based Study
Authors: Shah Binay K. , Ghimire Krishna B 
Published: October 2019

Abstract
Introduction:
NCCN guidelines recommend involved site radiotherapy is the preferred treatment option for Stage I follicular lymphoma. Other options include immunotherapy, immunotherapy ± chemotherapy, immunotherapy ± chemotherapy + involved site radiotherapy and observervation only. Studies have not shown overall survival benefit with one modality over other. We conducted this study to evaluate survival rate among patients who are treated with observation alone or external beam radiation.
Methods:
We selected patients with stage I follicular lymphoma diagnosed during 1992-2006 from Surveillance, Epidemiology and End Results (SEER) 18 database. We analyzed 1- and 5-years relative survival (RS) rates using SEER*stat program. We used Z test to compare relative survival rates of patients treated with (RT) or without radiotherapy (no RT) by age (>18 years, 18-60 years and >60 years) and sex.
Results:
A total of 1914 out of 5,145 adults patients with stage I follicular lymphoma diagnosed during 1992-2006 received radiotherapy. 1- and 5- year RS in patients with out vs with EBT were : 96.1 vs 100% ( Z value 6.9/ p value < 0.001) and 89.3 vs 98.7%.( Z value: 7.6/ p value < 0.001). The survival rates were significantly higher in the RT group for younger patients (1 year: 98.4 vs 100%; Z value 2.99/ p value < 0.01 and 5 year: 93.2 vs 98%; Z value 4.45/ p value < 0.001) and older patients (1 year: 94.6 vs 100%; Z value 5.8/ p value < 0.001 and 5 year: 86.5 vs 99.2%; Z value 6.21/<p value < 0.001).
Similarly 1- and 5-yr RS rates were significantly higher in the RT group compared to no RT group for all cohorts (Table 1).
Conclusion:
This study showed that relative survival rates of stage I follicular lymphoma patients receiving radiotherapy were significantly better compared to those who did not receive radiotherapy. Abstract 1317. TableSexAge in yearssurvival yearsNo External Beam RadiationExternal Beam RadiationZ value/ p valueNRelative survival ± SE %NRelative survival ± SE%Male and female≥1813,23196.10±0.401,914100.00±0.006.90/<0.001589.30±0.9098.70±0.807.61/<0.00118-6011,26398.40±0.40932100.00±0.203.00/<0.01593.20±0.9098.00±0.704.45/<0.001≥6111,96894.60 ±0.70982100.00±0.005.81/<0.001586.50±1.3099.20±1.506.21/<0.001Male≥1811,53195.50±0.70983100.00±0.006.05/<0.001587.30±1.30100.0±0.007.55/<0.001Female≥1811,70096.70±0.6093199.70±0.503.34/<0.001591.00±1.2096.20±1.302.75/<0.01Table 1: 1 year and 5 year relative survival of Follicular lymphoma stage I treated with and without external beam radiation

Disclosures
No relevant conflicts of interest to declare.
Selective occlusion of the hepatic artery and portal vein improves liver hypertrophy for staged hepatectomy
Authors: Jia Changku , Ge Ke , Xu Sunbing , Liu Ling , Weng Jie , Chen Youke 
Published: October 2019

Abstract

Background
To evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC)

Methods
From December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded.

Results
In the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively.

Conclusion
SOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.
Serum and tissue miRNAs: potential biomarkers for the diagnosis of cervical cancer
Authors: Farzanehpour Mahdieh , Mozhgani Sayed-Hamidreza , Jalilvand Somayeh , Faghihloo Ebrahim , Akhavan Setareh , Salimi Vahid , Azad Talat Mokhtari 
Published: October 2019

AbstractBackgroundFinding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects.MethodsThe expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction.ResultsThe results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192.ConclusionsGiven the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.
Online Social anxiety Cognitive therapy for Adolescents (OSCA): protocol for a randomised controlled trial
Authors: Leigh Eleanor , Clark David M. 
Published: October 2019

AbstractBackgroundAdolescent social anxiety disorder (SAD) is common, impairing and persistent. There is a need to intervene early to avert its long-term consequences. Cognitive Therapy for SAD is the leading treatment for adults and shows promise for adolescents. However, given the scale of the problem of adolescent SAD and the limited availability of psychological therapists in child and adolescent mental health services, there is a substantial gap in service provision. Delivering therapy via the Internet may provide part of the solution to this problem. An Internet version of adult Cognitive Therapy for SAD has been developed, with outcomes similar to face-to-face therapy. We have recently adapted this treatment for use with adolescents with SAD. Here, we describe a randomised controlled trial designed to test the efficacy of Internet Cognitive Therapy for adolescent SAD compared to waitlist.Methods/designForty adolescents aged 14–18 years with a diagnosis of SAD will be recruited via schools. Participants will be randomly allocated to Internet Cognitive Therapy or to waitlist. All participants will be assessed three times during the study—at baseline (pretreatment/wait), midtreatment/wait (week 8) and posttreatment/wait (week 15). Participants in the experimental arm will also complete weekly measures as part of the online program and they will be assessed at 3 and 6 months. Postwait, participants in the waitlist arm will be offered Internet Cognitive Therapy, and weekly and posttreatment data will also be collected for them. The trial aims to test whether Internet Cognitive Therapy is superior to waitlist in reducing social anxiety symptoms and in reducing the proportion of adolescents meeting criteria for SAD. Other outcomes of interest include depression and general anxiety symptoms. Acceptability of the online treatment will also be evaluated.DiscussionThis randomised controlled trial will provide preliminary evidence on whether this intervention, requiring relatively low levels of therapist input, is safe and clinically effective. If this is shown to be the case, Internet Cognitive Therapy for adolescents has the potential to provide a service to the large population of adolescents with untreated SAD.Trial registrationISRCTN Registry,ISRCTN15079139. Version 1 registered on 06/02/2019.
An electronic family health history tool to identify and manage patients at increased risk for colorectal cancer: protocol for a randomized controlled trial
Authors: Goldstein Karen M. , Fisher Deborah A. , Wu R. Ryanne , Orlando Lori A. , Coffman Cynthia J. , Grubber Janet M. , Rakhra-Burris Tejinder , Wang Virginia , Scheuner Maren T. , Sperber Nina , Datta Santanu K. , Nelson Richard E. , Strawbridge Elizabeth , Provenzale Dawn , Hauser Elizabeth R. , Voils Corrine I. 
Published: October 2019

Abstract

Background
Colorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3–10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, < 50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices.

Methods
In this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers’ experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective.

Discussion
This trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs.

Trial registration
ClinicalTrials.gov, NCT02247336. Registered on 25 September 2014.
Combinations of Alchornea cordifolia, Cassytha filiformis and Pterocarpus santalinoides in diarrhoegenic bacterial infections
Authors: Oli Angus Nnamdi , Obaji Monday , Enweani Ifeoma Bessie 
Published: October 2019

Abstract

Objectives
This study examines the rationale, if any, behind combining the extracts from the fruits of Alchornea cordifolia and Pterocarpus santalinoides and aerial parts of Cassytha filiformis in the traditional treatment of diarrhoegenic bacterial infections.

Results
Four diarrhoegenic bacterial isolates: Salmonella typhi, Shigellae dysenteriae, Escherichia coli and Staphylococcus aureus were used and their antibiotic susceptibility screening showed that they were multi-antibiotic resistant. The extracts exhibited activity against all the test isolates with minimum inhibitory concentration values ranging from 3.125 to 12.5 mg/mL. From the checkerboard assay, the fractional inhibitory concentration indices showed that C. filiformis has antagonistic and indifference activities in combination with either P. santalinoides or A. cordifolia. This showed that the combination of extracts from the fruits of A. cordifolia and P. santalinoides and aerial parts of C. filiformis is counterproductive and invalidates any claim for positive results in the management of diarrhoegenic bacterial infections.
Epigenetic synthetic lethality approaches in cancer therapy
Authors: Yang Haoshen , Cui Wei , Wang Lihui 
Published: October 2019

AbstractThe onset and development of malignant tumors are closely related to epigenetic modifications, and this has become a research hotspot. In recent years, a variety of epigenetic regulators have been discovered, and corresponding small molecule inhibitors have been developed, but their efficacy in solid tumors is generally poor. With the introduction of the first synthetic lethal drug (the PARP inhibitor olaparib in ovarian cancer withBRCA1mutation), research into synthetic lethality has also become a hotspot. High-throughput screening with CRISPR-Cas9 and shRNA technology has revealed a large number of synthetic lethal pairs involving epigenetic-related synthetic lethal genes, such as those encoding SWI/SNF complex subunits, PRC2 complex subunits, SETD2, KMT2C, and MLL fusion proteins. In this review, we focus on epigenetic-related synthetic lethal mechanisms, including synthetic lethality between epigenetic mutations and epigenetic inhibitors, epigenetic mutations and non-epigenetic inhibitors, and oncogene mutations and epigenetic inhibitors.
Physiological effects of high-flow oxygen in tracheostomized patients
Authors: Natalini Daniele , Grieco Domenico L. , Santantonio Maria Teresa , Mincione Lucrezia , Toni Flavia , Anzellotti Gian Marco , Eleuteri Davide , Di Giannatale Pierluigi , Antonelli Massimo , Maggiore Salvatore Maurizio 
Published: October 2019

Abstract

Background
High-flow oxygen therapy via nasal cannula (HFOTNASAL) increases airway pressure, ameliorates oxygenation and reduces work of breathing. High-flow oxygen can be delivered through tracheostomy (HFOTTRACHEAL), but its physiological effects have not been systematically described. We conducted a cross-over study to elucidate the effects of increasing flow rates of HFOTTRACHEAL on gas exchange, respiratory rate and endotracheal pressure and to compare lower airway pressure produced by HFOTNASAL and HFOTTRACHEAL.

Methods
Twenty-six tracheostomized patients underwent standard oxygen therapy through a conventional heat and moisture exchanger, and then HFOTTRACHEAL through a heated humidifier, with gas flow set at 10, 30 and 50 L/min. Each step lasted 30 min; gas flow sequence during HFOTTRACHEAL was randomized. In five patients, measurements were repeated during HFOTTRACHEAL before tracheostomy decannulation and immediately after during HFOTNASAL. In each step, arterial blood gases, respiratory rate, and tracheal pressure were measured.

Results
During HFOTTRACHEAL, PaO2/FiO2 ratio and tracheal expiratory pressure slightly increased proportionally to gas flow. The mean [95% confidence interval] expiratory pressure raise induced by 10-L/min increase in flow was 0.2 [0.1–0.2] cmH2O (ρ = 0.77, p < 0.001). Compared to standard oxygen, HFOTTRACHEAL limited the negative inspiratory swing in tracheal pressure; at 50 L/min, but not with other settings, HFOTTRACHEAL increased mean tracheal expiratory pressure by (mean difference [95% CI]) 0.4 [0.3–0.6] cmH2O, peak tracheal expiratory pressure by 0.4 [0.2–0.6] cmH2O, improved PaO2/FiO2 ratio by 40 [8–71] mmHg, and reduced respiratory rate by 1.9 [0.3–3.6] breaths/min without PaCO2 changes. As compared to HFOTTRACHEAL, HFOTNASAL produced higher tracheal mean and peak expiratory pressure (at 50 L/min, mean difference [95% CI]: 3 [1–5] cmH2O and 4 [1–7] cmH2O, respectively).

Conclusions
As compared to standard oxygen, 50 L/min of HFOTTRACHEAL are needed to improve oxygenation, reduce respiratory rate and provide small degree of positive airway expiratory pressure, which, however, is significantly lower than the one produced by HFOTNASAL.
Strong singularities of attractive and repulsive type to 2n-order neutral differential equation
Authors: Xin Yun , Yao Shaowen , Wang Ruichen 
Published: October 2019

AbstractThis paper is devoted to the existence of a positive periodic solution for a kind of 2n-order neutral differential equation with a singularity, where nonlinear term$g(t,x)$g(t,x)has strong singularities of attractive and repulsive type at the origin. Our proof is based on coincidence degree theory.
New parameterized quantum integral inequalities via η-quasiconvexity
Authors: Nwaeze Eze R. , Tameru Ana M. 
Published: October 2019

Abstract
We establish new quantum Hermite–Hadamard and midpoint types inequalities via a parameter $\mu \in [0,1]$
μ
∈
[
0
,
1
]
for a function F whose $|{}_{\alpha }D_{q}F|^{u}$

|

α

D
q

F
|

u

is η-quasiconvex on $[\alpha ,\beta ]$
[
α
,
β
]
with $u\geq 1$
u
≥
1
. Results obtained in this paper generalize, sharpen, and extend some results in the literature. For example, see (Noor et al. in Appl. Math. Comput. 251:675–679, 2015; Alp et al. in J. King Saud Univ., Sci. 30:193–203, 2018) and (Kunt et al. in Rev. R. Acad. Cienc. Exactas Fís. Nat., Ser. A Mat. 112:969–992, 2018). By choosing different values of μ, loads of novel estimates can be deduced. We also present some illustrative examples to show how some consequences of our results may be applied to derive more quantum inequalities.