bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group plus “mini” individual pre-test genetic counselling sessions for hereditary cancer shorten provider time and improve patient satisfaction
Authors: Hynes Jaclyn , MacMillan Andrée , Fernandez Sara , Jacob Karen , Carter Shannon , Predham Sarah , Etchegary Holly , Dawson Lesa 
Published: February 2020

Abstract
Background
Genetic counselling (GC) is an integral component in the care of individuals at risk for hereditary cancer predisposition syndromes (CPS). In many jurisdictions, access to timely counselling and testing is limited by financial constraints, by the shortage of genetics professionals and by labor-intensive traditional models of individual pre and post-test counselling. There is a need for further research regarding alternate methods of GC service delivery and implementation. This quality improvement project was initiated to determine if pretest group GC followed immediately by a ‘mini’ individual session, would be acceptable to patients at risk for hereditary breast and colon cancer.

Methods
Patients on waitlists for GC at the Provincial Medical Genetics Program in St. John’s, NL, Canada (n = 112), were contacted by telephone and offered the option of a group counselling session (GGC), followed by a “mini” individual session, versus (TGC) traditional private appointments. GGC sessions consisted of a cancer genetics information session given to groups of 6–20 followed by brief 20 min “mini” individual sessions with the patient and genetic specialist. TGC individual appointments provided the same cancer genetics information and counselling to one patient at a time in the classic model. All but 2 participants selected group+mini session. A de-identified confidential 12-item, Likert scale survey was distributed at the conclusion of mini-sessions to measure perceptions of GGC and satisfaction with this counselling model.

Results
Sixty participants completed questionnaires. The majority of participants strongly agreed that they were comfortable with the group session (58/60); the explanation of cancer genetics was clear (54/59); they understood their cancer risks (50/60); and they would recommend such a session to others (56/59). 38/53 respondents disagreed or strongly disagreed that they would prefer to wait for a traditional private appointment. All 5 participating genetic counselors reported a preference for this model. At the end of the pilot project, the waitlist for counselling/testing was reduced by 12 months.

Conclusions
Group pre-test genetic counselling combined with immediate “mini” individual session is strongly supported by patients and reduces wait times. Additional formal investigation of this approach in larger numbers of patients is warranted.
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke
Authors: Otero-Ortega Laura , Laso-García Fernando , Frutos Mari Carmen Gómez-de , Diekhorst Luke , Martínez-Arroyo Arturo , Alonso-López Elisa , García-Bermejo María Laura , Rodríguez-Serrano Macarena , Arrúe-Gonzalo Mercedes , Díez-Tejedor Exuperio , Fuentes Blanca , Gutiérrez-Fernández María 
Published: February 2020

Abstract
Background
Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke.

Materials and methods
For this purpose, various doses of EVs were tested in an in vitro oxygen-glucose deprivation (OGD) model of oligodendrocytes and neuronal ischemia. At least 50 μg of EVs were necessary to induce proliferation and differentiation of oligodendrocyte and neurons in OGD conditions. For in vivo study, rats were subjected to subcortical stroke and various doses (50 μg, 100 μg, or 200 μg) of EVs were intravenously administered after 24 h.

Results
All the animals in the EV groups showed significant improvement in functional tests, with an increase in tract connectivity and brain repair-associated markers, and a decrease in cell death and in astrocyte-marker expression. Cell proliferation was increased in the groups receiving 50 μg and 100 μg doses. Only the 50-μg dose was associated with significant increases in brain-derived neurotrophic factor expression.

Conclusion
In conclusion, 50 μg of EVs appears to be the minimal effective dose to enhance protection, brain repair, and recovery in subcortical ischemic stroke.
Ecological perspectives on variable retention forestry
Authors: Martínez Pastur Guillermo J. , Vanha-Majamaa Ilkka , Franklin Jerry F. 
Published: February 2020

AbstractForest management globally affects the ecosystem services, especially those related to ecosystem functioning and biodiversity conservation, by altering forest structure and composition. The degree of alteration was related to the intensity and type of harvesting; therefore, the major silvicultural challenge is to develop alternatives to mitigate climate change and maintain forest functions and biodiversity while also providing acceptable levels of timber production. Variable retention forestry (VRF) is a highly flexible concept, with continuity of forest cover, structure, function, and species composition, thereby supporting multiple economic, environmental, and cultural goals. This special issue provides an overview of the concepts and applications related to VRF implementation around the world. It shows that VRF has been applied globally for several decades, with varying levels and retention types, depending on local conditions and the economic importance of forestry. The challenges of VRF seem to differ to some extent on different continents, yet the general aims have been accepted in most of the continents. VRF has been successful in mitigating many effects of intensive harvesting, though in some forests of the world, the retention levels are too low to maintain acceptable levels of biodiversity and ecosystem functions. We conclude that an active collaboration between scientists and forest practitioners is needed to realize all of the opportunities provided by VRF in solving global forestry-related issues.
A text message intervention for quitting cigarette smoking among young adults experiencing homelessness: study protocol for a pilot randomized controlled trial
Authors: Tucker Joan S. , Pedersen Eric R. , Linnemayr Sebastian , Shadel William G. , DeYoreo Maria , Zutshi Rushil 
Published: February 2020

Abstract
Background
Cigarette smoking is much more prevalent among young people experiencing homelessness than in the general population of adolescents and young adults. Although many young homeless smokers are motivated to quit, there are no empirically-evaluated smoking cessation programs for this population. It is important that any such program address the factors known to be associated with quitting-related outcomes among homeless young people, to provide ongoing support in a way that accommodates the mobility of this population, and does not rely on scarce service provider resources for its delivery. The objective of this project is to develop and pilot test a text messaging-based intervention (TMI), as an adjunct to brief cessation counseling and provision of nicotine patches, to help homeless young people who want to quit smoking.

Methods/design
This pilot study will utilize a cluster cross-over randomized controlled design with up to 80 current smokers who desire to quit and are recruited from three drop-in centers serving young people experiencing homelessness in the Los Angeles area. All participants will be provided with a minimum standard of care: a 30-min group-based smoking cessation counseling session and free nicotine replacement. Half of these smokers will then also receive the TMI, as an adjunct to this standard care, which will provide 6 weeks of ongoing support for quitting. This support includes continued and more intensive education regarding nicotine dependence, quitting smoking, and relapse; does not require additional agency resources; can be available “on demand” to users; and includes features to personalize the quitting experience. This study will investigate whether receiving the TMI adjunct to standard smoking cessation care results in greater reductions in cigarette smoking compared to standard care alone over a 3-month period.

Discussion
This study has the potential to address an important gap in the clinical research literature on cigarette smoking cessation and provide empirical support for using a TMI to provide ongoing assistance and support for quitting among young smokers experiencing homelessness.
Trial registration ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585.
Effects of dietary valine supplementation during late gestation on the reproductive performance and mammary gland development of gilts
Authors: Che Long , Xu Mengmeng , Gao Kaiguo , Wang Li , Yang Xuefen , Wen Xiaolu , Xiao Hao , Jiang Zongyong 
Published: February 2020

Abstract
Background
Mammary gland development during late gestation in gilts is a major factor that alters the composition of colostrum and growth performance of piglets. Plasma valine is taken up and metabolized extensively by the mammary gland; however, the effects of valine on mammary gland development during late gestation are still unclear. Thirty primiparous gilts were divided into three treatment groups (n = 10) and received one of the three diets starting on day 75 of gestation until the day of farrowing. The total dietary valine to lysine ratio of the three diets was 0.63 (LV), 0.73 (MV), and 0.93 (HV), respectively.

Results
Dietary valine supplementation during late gestation did not affect (P > 0.05) the litter size and weight at farrowing; however, the piglet weight and average daily gain at weaning were linearly increased (P < 0.05) as the dietary valine increased. The highest piglet weight at weaning was observed when the gilts were provided the HV diet. Dietary valine supplementation linearly elevated (P < 0.05) protein, fat and solids-not-fat and some free amino acids content in colostrum. The concentration of prolactin in plasma of gilts was linearly increased in response to valine supplementation at days 1 and 10 of lactation (P < 0.05). Furthermore, with increasing dietary valine allowance, a linear increase (P < 0.05) was observed in the area of the lumen of alveolus and the content of DNA, RNA, and total protein in the mammary tissues at day 1 of lactation. Moreover, the protein expression of cyclin D1, p-mTOR, p-S6, and p-4EBP1 was also linearly increased (P < 0.05) in the mammary tissue at day 1 of lactation. However, no difference (P > 0.05) was observed in the indices related to mammary development and the mTOR signaling pathway at day 21 of lactation.

Conclusion
The results revealed that increasing the total dietary valine to lysine ratio to 0.93 during late gestation significantly enhances the piglet weight and average daily gain at weaning probably due to improved development of mammary gland.
Improving collapsibility robustness of an EPS-CD by means of simulation and six sigma
Authors: Costas Muñoz Didac , Majzel Michał 
Published: February 2020

AbstractSteering columns for column assist Electric Steering are one of the main elements of the passive safety restraint system in a passenger vehicle. It is designed to collapse applying an optimized ride down force to reduce chest and head injuries of the driver during a frontal crash event, making this requirement one of the most important ones for its development. The system crash response is generated by several elements and interfaces due to the fact of many other different product requirements that a steering column must fulfill. This could lead into a complex validation process throughout the development, as it is needed to integrate the product into the vehicle in order to meet the passive safety requirements. As part of ZF lean Validation approach a new method has been developed to improve the system robustness in ZF Active safety division by means of virtual simulation and six sigma disciplines. This resultant method is also applicable for a model based development process and also contributes to improve frontloading development techniques. An analysis of variance has been done using a correlated virtual model for crash simulation, where the main parameters of the system are known (normally the case when same product generation is reused in a new vehicle). Obtaining as a result of the analysis the regression equation of the system response. This equation defines and quantifies the importance of each factor, and consequently is defining the component contribution and how to develop a column from bottom to top. Moreover, as a second step, a Monte Carlo analysis has been applied using the equation obtained generating statistical results for a number of cases (based in the design tolerances) not manageable from the hardware testing perspective neither from the finite elements methods. In that project Monte Carlo analysis has been applied for 100,000 cases generating response confident intervals instead of the classic FEM deterministic response where only the nominal case is considered.
Survival outcomes and risk group validation from SWOG S0925, a randomized phase II study of androgen deprivation (AD) +/- cixutumumab, in new metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Wong Risa Liang , Duong Mai T. , Tangen Catherine , Agarwal Neeraj , Cheng Heather H. , Vogelzang Nicholas J. , Hussain Maha H. A. , Thompson Ian Murchie , Quinn David I. , Yu Evan Y. 
Published: February 2020

106 Background: Cixutumumab, a monoclonal antibody targeting insulin-like growth factor I receptor, did not improve rate of undetectable PSA at 28 weeks when combined with AD in the randomized phase II SWOG S0925 trial for patients with new mHSPC. We now present mature radiographic progression-free survival (rPFS) and overall survival (OS) analyses, along with pre-specified secondary and exploratory endpoints. Methods: We used Kaplan-Meier curves to analyze OS, rPFS, and castration resistance-free survival by treatment arm, disease volume (as per CHAARTED), and risk (as per LATITUDE). We explored differences in survival by treatment arm via covariate-adjusted Cox proportional hazard models adjusted for disease volume and risk. Results: The trial enrolled 210 patients, 105 per treatment arm. Median follow-up was 5.3 years. No difference was seen between treatment arms in OS (HR 1.01 [0.70-1.45]; p=0.97), rPFS (HR 1.17 [0.85-1.60]; p=0.35), or castration resistance-free survival (HR 1.02 [0.75-1.41]; p=0.88). At baseline, 105/198 (53.0%) patients had high risk and 119/210 (56.7%) had high volume disease. 17.3% of high volume patients were classified as low risk and 15.9% of low volume patients were classified as high risk; together, 16.7% of patients had discordant classification of high or low category for risk and volume. Adjusting for risk or volume yielded no differences in OS between arms. Inferior survival was observed in high risk (HR 1.89 [1.29-2.80]; p=0.001) and high volume (HR 2.75 [1.84-4.10]; p<0.0001) disease. Disease volume was a better fit to survival data than risk (AIC 878.3 vs. 889.2). Compared to patients achieving undetectable PSA at 28 weeks, inferior survival was observed in patients whose PSA was >0.2 to ≤4.0 ng/mL (HR 3.72 [1.99-6.95]; p<0.0001) or >4.0 ng/mL (HR 7.13 [4.24-11.9]; p<0.0001). Conclusions: In new mHSPC, adding cixutumumab to AD did not improve survival measures. Baseline risk and disease volume carried prognostic value for this distinct trial population, though disease volume was a better predictor of survival. PSA treatment response was a strong intermediate endpoint for survival. Clinical trial information: NCT01120236.
Randomized phase II study of olaparib with or without cediranib in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Kim Joseph W. , McKay Rana R. , Taplin Mary-Ellen , Davis Nancy B. , Monk Paul , Appleman Leonard Joseph , Lara Primo , Vaishampayan Ulka N. , Zhang Jingsong , Paul Asit K. , Bubley Glenn , Van Allen Eliezer Mendel , Huang Ying , Zhang Zhenwei , Loda Massimo , Shapiro Geoffrey , LoRusso Patricia , Ivy S. Percy , Petrylak Daniel Peter 
Published: February 2020

111 Background: Cediranib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly (ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in men with DNA repair deficient, mCRPC. We therefore performed a randomized phase 2 trial comparing olaparib with or without cediranib in men with mCRPC. Methods: Men with a minimum of one prior line of systemic therapy for mCRPC were randomized 1:1 to receive cediranib 30mg po daily plus olaparib 200mg po BID (Arm A) or olaparib 300mg BID alone (Arm B). At radiographic progression, patients (pts) in Arm B could crossover to Arm A. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were objective response rate (ORR) and PSA50 decline rate (PSA50). Tumor biopsy specimens were obtained for biomarker analyses pre- and on-treatment. Results: Baseline characteristics of the 90 pts enrolled are summarized below. The median rPFS was 11.1 versus 4.0 months in Arm A and Arm B, respectively (Hazard Ratio 0.54, 95% CI 0.317, 0.928, p=0.026). Trends toward a higher ORR (19% and 12%), Disease Control Rate (Stable Disease + Partial Response) (77% and 64%,) and PSA50 (29% and 17%) were observed in Arm A compared to Arm B, respectively. Thirteen pts in Arm B crossed over to Arm A. One pt had a PR after crossover. Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 77% and 58% of Arm A and Arm B pts, respectively. G3/4 AEs occurring in >10% of pts were hypertension (32%), fatigue (23%) and diarrhea (11%) in Arm A, and anemia (16%) and lymphopenia (11%) in Arm B. Conclusions: The cediranib/olaparib combination significantly improves rPFS in unselected, mCRPC pts. AEs were manageable. Analyses of mutation status in homologous recombination DNA repair genes are pending and will be key in interpreting the data. Clinical trial information: NCT02893917. [Table: see text]
A pilot study of docetaxel and carboplatin for treatment of patients with mCRPC containing biallelic inactivation of genes in the BRCA1/2 pathway.
Authors: Cheng Heather H. , DeJong Makayla , Yu Evan Y. , Gulati Roman , Rettig Matthew , Higano Celestia S. , Nelson Peter , Pritchard Colin C. , Montgomery Robert B. 
Published: February 2020

127 Background: Despite new treatments, metastatic castration resistant prostate cancer (mCRPC) remains ultimately lethal. Upwards of 25% of mCRPC tumors have alterations in homologous recombination DNA repair (HRD) genes, most frequently BRCA2. Retrospective data suggest addition of the DNA damaging agent carboplatin to standard docetaxel for patients with mCRPC whose tumors have biallelic inactivation of BRCA2 may be effective. Methods: In this prospective, pilot single-arm phase 2 study, we assess response to the combination of docetaxel 60mg/m2 and carboplatin AUC 5 IV q21 days in patients with mCRPC whose tumors have evidence of biallelic inactivation of BRCA1, BRCA2 or ATM and have progressed after any prior treatment, including prior docetaxel and/or PARP inhibitor (PARPi). The primary endpoint is rate of ≥50% PSA decline from baseline (PSA50). With H0 of PSA50 of 26%, 14 patients will provide 80% power to conclude H1 of PSA50 of 60% based on Simon's 2-stage design with 1-sided α = 5%. Secondary endpoints include PSA30, response duration, time to progression and correlative studies. Biallelic inactivation of other HRD-related genes were included at investigators’ discretion. Results: The study opened in Jan 2016 and has enrolled 8/14 (57%) of patients plus 5 patients with other HRD-related genes. 6/13 (46%) treated pts had grade 3 expected AEs, and no grade 4-5 AEs were observed. To date, 7/8 (88%) of pts with biallelic inactivation of BRCA1, BRCA2 and ATM (Table) and 10/13 (77%) of all pts achieved a PSA50 (other HRD-related genes include CDK12, CHD1, MRE11A and PALB2). Updated results will be reported at final presentation. Conclusions: Addition of carboplatin to docetaxel appears to be well-tolerated and effective for patients with mCRPC whose tumors have biallelic inactivation in selected HRD genes such as BRCA2, including those with prior treatment with PARP inhibitor. Clinical trial information: NCT02598895. [Table: see text]
Assessing different sequencing regimens of atezolizumab (atezo) and sipuleucel-T (sipT) in patients who have asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer.
Authors: Dorff Tanya B. , Acoba Jared David , Pal Sumanta K. , Scholz Mark C. , Tamura David Jon , Huang Jeffrey , Rosser Charles Joel 
Published: February 2020

141 Background: Combining an immune checkpoint inhibitor with a vaccine may leverage complementary mechanisms of action for treatment of mCRPC. We present a randomized study evaluating atezo (anti PD-L1) + sipT in patients (pts) with mCRPC. Methods: Pts who met standard criteria for sipT were randomized to receive (Arm1): atezo 1200 mg IV every 3 weeks for 2 doses then SipT every 2 weeks for a total of 3 infusions (induction) followed by maintenance atezo every 3 weeks until toxicity or loss of clinical benefit or (Arm2) sipT every 2 weeks for a total of 3 infusions followed by atezo 1200 mg IV every 3 weeks for 2 doses (induction) followed by maintenance atezo every 3 weeks until same. The primary endpoint was safety (CTCAE v4.0); secondary endpoints were PFS by PCWG2, objective response (modified RECIST1.1) and systemic immune responses after induction. Results: 37 pts, median age 75 [range 53–86] enrolled; median prior treatments was 4 [range 1-8] and 76% had ECOG PS = 0. Three patients did not complete induction (1 withdrew consent, 1 due to toxicity, and 1 progressed). There were no delays in induction dosing for Arm1 but 9 delays (1 week) for Arm2 (collection failure=6, holiday=2 and other=1). There were no grade 5 toxicities attributed to study drugs. 1 grade 4 toxicity was noted in each arm (Arm 1 bronchitis, Arm 2 hypotension). Eight grade 3 toxicities were noted in arm 1 (hyponatremia, pulmonary embolus x3, bone pain, hypophosphatemia, shock, fall with tooth fracture), while 4 grade 3 toxicities were noted in arm 2 (anemia, hypertension x 2, pneumonia). None of the grade 3 or 4 AEs were immune related. AEs led to discontinuation in 5 patients in Arm1 and 1 patient in Arm2. In Arm1 11 patients were RECIST evaluable at 6 months, with 1 PR (5.8%), 4 SD (23.5%) and 6 PD. In Arm2 13 patients were evaluable, with 1 PR (5.8%), 6 SD (32%) and 6 PD. 10/24 evaluable patients (41.7%) had stable disease at 6 months. Conclusions: The combination of atezo with sipT was safe, AEs consistent with the agents as monotherapy, with no immune related AEs. 2 pts had RECIST PR and 10 had stable disease at 6 months, more than expected with monotherapy. Clinical trial information: 03024216.