bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Exclusive Use of Very Low Nicotine Cigarettes on Compensatory Smoking: An Inpatient Crossover Clinical Trial
Authors: Smith Tracy T. , Koopmeiners Joseph S. , White Cassidy M. , Denlinger-Apte Rachel L. , Pacek Lauren R. , De Jesús Víctor R. , Wang Lanqing , Watson Clifford , Blount Benjamin C. , Hatsukami Dorothy K. , Benowitz Neal L. , Donny Eric C. , Carpenter Matthew J. 
Published: February 2020

Abstract

Background:
The FDA is considering a mandated reduction in the nicotine content of cigarettes. Clinical trials have been limited by non-study cigarette use (noncompliance), which could mask compensation. The goal of this study was to assess whether compensation occurs when smokers provided with very low nicotine cigarettes cannot access normal nicotine cigarettes.

Methods:
In a within-subjects, crossover design, current smokers (n = 16) were confined to a hotel for two 4-night hotel stays during which they were only able to access the research cigarettes provided. The hotel stays offered normal nicotine cigarettes or very low nicotine content (VLNC) cigarettes, in an unblinded design, available for “purchase” via a study bank.

Results:
In the context of complete compliance with the study cigarettes (n = 16), there was not a significant increase during the VLNC condition for cigarettes smoked per day, expired carbon monoxide, or N-acetyl-S-(cyanoethyl)-l-cysteine (cyanoethyl-MA, metabolite of acrylonitrile). There was a significant nicotine × time interaction on urine N-acetyl-S-(3-hydroxypropyl)-l-cysteine (hydroxypropyl-MA, metabolite of acrolein), driven by an increase in the VLNC condition during the first 24 hours. By the end of the VLNC condition, there was no evidence of compensation across any measure of smoking or smoke exposure.

Conclusions:
Among current smokers who exclusively used VLNC cigarettes for 4 days, there was no significant compensatory smoking behavior.

Impact:
These data, combined with the larger body of work, suggest that a mandated reduction in nicotine content is unlikely to result in an increase in smoking behavior to obtain more nicotine.
Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC
Authors: Hellmann Matthew D. , Nabet Barzin Y. , Rizvi Hira , Chaudhuri Aadel A. , Wells Daniel K. , Dunphy Mark P.S. , Chabon Jacob J. , Liu Chih Long , Hui Angela B. , Arbour Kathryn C. , Luo Jia , Preeshagul Isabel R. , Moding Everett J. , Almanza Diego , Bonilla Rene F. , Sauter Jennifer L. , Choi Hyejin , Tenet Megan , Abu-Akeel Mohsen , Plodkowski Andrew J. , Perez Johnston Rocio , Yoo Christopher H. , Ko Ryan B. , Stehr Henning , Gojenola Linda , Wakelee Heather A. , Padda Sukhmani K. , Neal Joel W. , Chaft Jamie E. , Kris Mark G. , Rudin Charles M. , Merghoub Taha , Li Bob T. , Alizadeh Ash A. , Diehn Maximilian 
Published: February 2020

Abstract

Purpose:
Treatment with PD-(L)1 blockade can produce remarkably durable responses in patients with non–small cell lung cancer (NSCLC). However, a significant fraction of long-term responders ultimately progress and predictors of late progression are unknown. We hypothesized that circulating tumor DNA (ctDNA) analysis of long-term responders to PD-(L)1 blockade may differentiate those who will achieve ongoing benefit from those at risk of eventual progression.

Experimental Design:
In patients with advanced NSCLC achieving long-term benefit from PD-(L)1 blockade (progression-free survival ≥ 12 months), plasma was collected at a surveillance timepoint late during/after treatment to interrogate ctDNA by Cancer Personalized Profiling by Deep Sequencing. Tumor tissue was available for 24 patients and was profiled by whole-exome sequencing (n = 18) or by targeted sequencing (n = 6).

Results:
Thirty-one patients with NSCLC with long-term benefit to PD-(L)1 blockade were identified, and ctDNA was analyzed in surveillance blood samples collected at a median of 26.7 months after initiation of therapy. Nine patients also had baseline plasma samples available, and all had detectable ctDNA prior to therapy initiation. At the surveillance timepoint, 27 patients had undetectable ctDNA and 25 (93%) have remained progression-free; in contrast, all 4 patients with detectable ctDNA eventually progressed [Fisher P &lt; 0.0001; positive predictive value = 1, 95% confidence interval (CI), 0.51–1; negative predictive value = 0.93 (95% CI, 0.80–0.99)].

Conclusions:
ctDNA analysis can noninvasively identify minimal residual disease in patients with long-term responses to PD-(L)1 blockade and predict the risk of eventual progression. If validated, ctDNA surveillance may facilitate personalization of the duration of immune checkpoint blockade and enable early intervention in patients at high risk for progression.
Space–Time Characteristics of Areal Reduction Factors and Rainfall Processes
Authors: Breinl Korbinian , Müller-Thomy Hannes , Blöschl Günter 
Published: February 2020

AbstractWe estimate areal reduction factors (ARFs; the ratio of catchment rainfall and point rainfall) varying in space and time using a fixed-area method for Austria and link them to the dominating rainfall processes in the region. We particularly focus on two subregions in the west and east of the country, where stratiform and convective rainfall processes dominate, respectively. ARFs are estimated using a rainfall dataset of 306 rain gauges with hourly resolution for five durations between 1 h and 1 day. Results indicate that the ARFs decay faster with area in regions of increased convective activity than in regions dominated by stratiform processes. Low ARF values occur where and when lightning activity (as a proxy for convective activity) is high, but some areas with reduced lightning activity exhibit also rather low ARFs as, in summer, convective rainfall can occur in any part of the country. ARFs tend to decrease with increasing return period, possibly because the contribution of convective rainfall is higher. The results of this study are consistent with similar studies in humid climates and provide new insights regarding the relationship of ARFs and dominating rainfall processes.
The importance of infiltration pathways in assessing and modelling overheating risks in multi-residential buildings
Authors: McLeod Robert S , Swainson Michael , Hopfe Christina J , Mourkos Kostas , Goodier Chris 
Published: February 2020

With the help of building diagnostics, the causes and solutions to complex problems in buildings can be determined. In central and greater London, an increasing number of cases of chronic, year-round, overheating in buildings have been reported. We present three cases of unexpected temperatures in multi-storey residential buildings. Detailed analysis and modelling of these scenarios have led to an investigation of whether the way in which infiltration is currently modelled in building performance simulation may be exerting a pronounced effect on the results of overheating studies. An EnergyPlus model, of one of the dwellings in a multi-residential building in London, was created to investigate the influence of infiltration and exfiltration pathway assumptions on the prediction of overheating. The simulation results were compared to empirical data and show that the predicted indoor temperatures are highly sensitive to how the infiltration airflow network is modelled. The findings of this study have been used to provide practical guidance for modellers and building designers on critical aspects to consider when creating building performance simulation models to ensure more reliable outcomes. Overheating in buildings is an emerging topic of critical importance to the future of the built environment. The importance of understanding infiltration pathways in assessing and modelling overheating risks in flats and multi-residential buildings has been hitherto underestimated or simply ignored. In this paper, examples are given which highlight the need for a fuller understanding of internal air movement where accurate predictions of internal temperatures are required. At present, common building simulation practices and existing technical memorandum (TM) standards are masking the problem and do not provide a basis from which typical or worst-case scenarios can be adequately considered.
Risk Factors for Pharyngocutaneous Fistula After Total Pharyngolaryngectomy
Authors: Lemaire Emilien , Schultz Philippe , Vergez Sébastien , Debry Christian , Sarini Jérome , Vairel Benjamin , de Bonnecaze Guillaume , Takeda-Raguin Catherine , Cabarrou Bastien , Dupret-Bories Agnès 
Published: February 2020

Purpose: To evaluate the risk factors of pharyngocutaneous fistula after total pharyngolaryngectomy (TPL) in order to reduce their incidence and propose a perioperative rehabilitation protocol. Materials and Methods: This was a multicenter retrospective study based on 456 patients operated for squamous cell carcinoma by total laryngectomy or TPL. Sociodemographic, medical, surgical, carcinologic, and biological risk factors were studied. Reactive C protein was evaluated on post-op day 5. Patients were divided into a learning population and a validation population with patients who underwent surgery between 2006 and 2013 and between 2014 and 2016, respectively. A risk score of occurrence of salivary fistula was developed from the learning population data and then applied on the validation population (temporal validation). Objective: To use a preoperative risk score in order to modify practices and reduce the incidence of pharyngocutaneous fistula. Results: Four hundred fifty-six patients were included, 328 in the learning population and 128 in the validation population. The combination of active smoking over 20 pack-years, a history of cervical radiotherapy, mucosal closure in separate stitches instead of running sutures, and the placement of a pedicle flap instead of a free flap led to a maximum risk of post-op pharyngocutaneous fistula after TPL. The risk score was discriminant with an area under the receiver operating characteristic curve of 0.66 (95% confidence interval [CI] = 0.59-0.73) and 0.70 (95% CI = 0.60-0.81) for the learning population and the validation population, respectively. Conclusion: A preoperative risk score could be used to reduce the rate of pharyngocutaneous fistula after TPL by removing 1 or more of the 4 identified risk factors.
Neighborhood Influences on Physical Activity Among Low-Income African American Adults With Type 2 Diabetes Mellitus
Authors: Park Soim , Zachary Wayne W. , Gittelsohn Joel , Quinn Charlene C. , Surkan Pamela J. 
Published: February 2020

Purpose The purpose of the study was to explore the influences of the neighborhood environment on physical activity (PA) among people living with type 2 diabetes mellitus (T2DM) in a community with limited resources. Methods Participants were adults with T2DM and their family members or friends who help in the management of T2DM and who were living in a low-income African American (AA) community. Health care providers working in the neighborhood were also included. Using an emergent design, qualitative data were collected through 7 focus group discussions (N = 63) and 13 in-depth interviews. Verbatim transcriptions were analyzed via thematic coding to explore contextual factors that limit PA and meaning around neighborhood features that promote or discourage PA. Results Levels of PA were strongly limited by neighborhood insecurity and a lack of recreational facilities in the neighborhood. People with T2DM and physical/mobility disabilities were more affected by the neighborhood environment than those without disabilities, particularly due to perceived safety concerns and social stigma. Despite socioeconomic inequalities within neighborhoods, participants showed resilience and made efforts to overcome social-environmental barriers to PA, applied various coping strategies, and received social support. Conclusions Results suggested that in an underserved neighborhood, individual barriers to physical activity were amplified by neighborhood-level factors such as crime, especially among individuals who have T2DM and disabilities. Socioeconomic inequalities should be addressed further to improve management of T2DM and its complications.
Systematic Review of the Prevalence, Predictors, and Treatment of Insomnia in Palliative Care
Authors: Nzwalo Isa , Aboim Maria Ana , Joaquim Natércia , Marreiros Ana , Nzwalo Hipólito 
Published: February 2020

Introduction: The primary function of palliative care is to improve quality of life. The recognition and treatment of symptoms causing suffering is central to the achievement of this goal. Insomnia reduces quality of life of patients under palliative care. Knowledge about prevalence, associated factors, and treatment of insomnia in palliative care is scarce. Methodology: Literature review about the prevalence, predictors, and treatment options of insomnia in palliative care patients. Primary sources of investigation were identified and selected through Pubmed and Scopus databases. The research was complemented by reference search in identified articles and selected reviews. OpenGrey and Google Scholar were used for searching grey literature. Study quality analysis was based on the Newcastle-Ottawa Scale. Results: A total of 65 studies were included in the review. Most studies had acceptable /good quality. The prevalence of insomnia in the included studies ranged from 2.1% to 100%, with a median overall prevalence of 49.5%. Sociodemographic factors such as age; clinical characteristics such as functional status, disease stage, pain, and use of specific drugs, including opioids; psychological factors such as anxiety/depression; and spiritual factors such as feelings of well-being were identified as predictors. The treatment options identified were biological (pharmacological and nonpharmacological), psychological (visualization, relaxation), and spiritual (prayer). Conclusions: The systematic review showed that the prevalence of insomnia is high, with at least one in 3 patients affected in most studies. Insomnia’s risk factors and treatment in palliative care are both associated to physical, psychological, social, and spiritual factors, reflecting its true holistic nature.
Technique for Arthroscopic Deltoid Ligament Repair With Description of Safe Zones
Authors: Acevedo Jorge I. , Kreulen Christopher , Cedeno Andres A. , Baumfeld Daniel , Nery Caio , Mangone Peter G. 
Published: February 2020

Repair of the deltoid ligaments is suggested in patients with medial ankle instability after a ligamentous injury or lateral malleolar fracture fixation. Arthroscopy can be a definitive mode of determining whether there is medial instability and, therefore, help to determine whether there is a need to repair the deltoid ligaments. The authors describe a technique for the arthroscopic repair of the deltoid ligaments, using a suture passer and suture anchors. Cadaveric analysis was utilized to establish safe zones and indicate that there is a relatively wide safe zone between the posterior tibialis tendon and the saphenous vein when performing the technique. The authors have performed more than 87 arthroscopic deltoid repairs, with a greater than 90% satisfaction rate among patients. However, future studies with validated outcome measures are needed. Level of Evidence: Level V, expert opinion.
A systematic review: Role of systemic therapy on treatment and prevention of brain metastasis in renal cell carcinoma
Authors: Yekedüz Emre , Arzu Yaşar H. , Utkan Güngör , Ürün Yüksel 
Published: February 2020

Aim To define the inclusion/exclusion status of patients with brain metastasis in phase-III clinical trials and the effect of systemic therapies in metastatic renal cell cancer patients with brain metastasis. Methods “kidney neoplasms”[MeSH Terms] OR (“kidney”[All Fields] AND “neoplasms”[All Fields]) OR “kidney neoplasms”[All Fields] OR (“kidney”[All Fields] AND “cancer”[All Fields]) OR “kidney cancer”[All Fields] AND “brain metastasis” were used for searching “PubMed” electronic database and “clinicaltrials.gov” website. Results Five of 19 landmark phase-III clinical trials included patients with stable or asymptomatic brain metastasis and there was no data about outcomes of brain metastasis. The effect of systemic therapy on prevention of brain metastasis in renal cell cancer was evaluated in four studies. Two studies showed that the incidence of brain metastasis decreased, while the other two studies showed no effect of antiangiogenic agents on the prevention of brain metastasis in patients with renal cell cancer. There were 10 trials regarding systemic therapy of renal cell cancer brain metastasis. The overall response rate improved through a combination of targeted therapies and local treatment. The results of the trials studying the effect of tyrosine kinase inhibitors without local treatment were controversial. None of the ongoing clinical trials included patients with active brain metastasis. Conclusion In metastatic renal cell cancer patients with brain metastasis, the overall response rate improved with the combination of targeted agents and local treatment. Further trials are needed to evaluate the effect of systemic treatment on the prevention or treatment of brain metastasis in patients with renal cell cancer.
Composition of fecal microbiota in low-set rectal cancer patients treated with FOLFOX
Authors: Li Jing , Li Jingtao , Lyu Na , Ma Yue , Liu Fei , Feng Yuqing , Yao Li , Hou Zhiyong , Song Xiaofeng , Zhao Hongchuan , Li Xiaoya , Wang Yingdian , Xiao Cheng , Zhu Baoli 
Published: February 2020

Background: FOLFOX treatment is a method used widely to reduce tumor size in low-set rectal cancer, with variable clinical results. FOLFOX agents comprise a mixture of oxaliplatin and 5-fluorouracil, the efficacy of which might be modulated by the gut microbiome in humans. This study aimed to determine whether the bowel microbiota is a factor that influences FOLFOX treatment. Methods: To investigate the role of gut microbiota during FOLFOX treatment, we carried out comprehensive metagenomic and metabolomic analyses on 62 fecal samples collected from 37 low-set rectal cancer patients. A set of 31 samples was collected before the patients underwent treatment; another 31 samples were obtained after the treatment was completed. Among these samples, 50 were paired samples collected before and after FOLFOX treatment. The patients were divided into responder and nonresponder groups according to the treatment outcome. Metagenomic sequencing was performed on these fecal samples. Diverse bacterial taxa were identified by MetaGeneMark, Soapaligner, and DIAMOND; microbiotal data analyses were carried out in the R environment. Differences in microbial taxa and metagenomic linkage groups were observed in multiple comparative analyses. Results: The gut microbiota was altered after treatment. Compared with before treatment, the changes in bacterial diversity and microbiotal composition after treatment were more apparent in the responder group than in the nonresponder group. Bacterial species analysis revealed a group of gut bacteria in multiple comparisons, with a group of eight specific species being associated with the outcome of FOLFOX treatment. Responders and nonresponders before treatment were clearly separated based on this bacterial subset. Finally, the metagenomic linkage group network and metabolomic analyses based on the genomic data confirmed a more significant change in the gut microbiota during FOLFOX treatment in the responder group than in the nonresponder group. Conclusions: Overall, our results describe a dynamic process of gut microbiotal changes from the start to the end of FOLFOX treatment, and verified a close relationship between microbiota and treatment outcome. Recognition of the significance of microbiotal intervention before FOLFOX treatment for low-set rectal cancer may improve the effects of these agents.
Complications of Bioabsorbable Tibial Interference Screws After Anterior Cruciate Ligament Reconstruction in Pediatric and Adolescent Athletes
Authors: Kramer Dennis E. , Kalish Leslie A. , Kocher Mininder S. , Yen Yi-Meng , Micheli Lyle J. , Heyworth Benton E. 
Published: February 2020

Background: Interference screw fixation using bioabsorbable implants has become the most common form of tibial-sided graft fixation in anterior cruciate ligament reconstruction (ACLR). Complications related to implant use in the pediatric and adolescent population have not been well studied. Purpose/Hypothesis: The purpose of this study was to retrospectively analyze the complications associated with tibial bioabsorbable interference screw use in adolescents after ACLR. We hypothesized that complication rates would be low (<5%) and that different screw types would have similar complication rates and clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: Included in this study were patients aged ≤18 years who underwent ACLR with a bioabsorbable tibial interference screw between 2000 and 2011 at a single institution. The subpopulation with screw-related symptoms or complications were identified through chart review. The following 2 outcomes were considered: screw-related symptoms and secondary surgery related to the screw. Multivariable logistic regression was used for adjusted analysis of any screw-related problem. Results: There were 925 ACLR procedures in 858 patients (mean age, 15.7 years; range, 10-18 years) who met inclusion criteria. The median follow-up period was 32.0 months. Of the 925 knees, 89 (9.6%) developed a screw-related problem. In 44 (4.8%) cases, no surgery was required; in 45 (4.9%) cases, surgery for a screw-related problem occurred at a median of 24 months postoperatively. The most common surgical indication was pain at the tibial screw site (42/45, 93%), followed by intra-articular screw issues (3/45, 7%). In adjusted analysis, ACLR procedure performed by a “low-volume” ACL surgeon was the only significant predictor identified. After screw removal surgery, 25 of 27 (93%) patients with at least 12 months of follow-up had complete resolution of screw site symptoms, 18 of 23 (78%) evaluable patients returned to sports, while 8 of 27 (30%) patients underwent additional surgeries, 7 of which were unrelated to the screw procedure. Conclusion: The rate of clinical sequelae from bioabsorbable tibial interference screws was surprisingly high, with symptoms arising after approximately 1 of 10 ACLRs in adolescents. Reoperation for these symptoms was performed in approximately 5% of the knees in the study, at a median 2 years postoperatively. Most patients were able to return to sports after screw removal surgery.