bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T-cell Ratio and Induces Tumor Regression
Authors: Sainson Richard C.A. , Thotakura Anil K. , Kosmac Miha , Borhis Gwenoline , Parveen Nahida , Kimber Rachael , Carvalho Joana , Henderson Simon J. , Pryke Kerstin L. , Okell Tracey , O'Leary Siobhan , Ball Stuart , Van Krinks Cassie , Gamand Lauriane , Taggart Emma , Pring Eleanor J. , Ali Hanif , Craig Hannah , Wong Vivian W.Y. , Liang Qi , Rowlands Robert J. , Lecointre Morgane , Campbell Jamie , Kirby Ian , Melvin David , Germaschewski Volker , Oelmann Elisabeth , Quaratino Sonia , McCourt Matthew 
Published: September 2020

AbstractThe immunosuppressive tumor microenvironment constitutes a significant hurdle to immune checkpoint inhibitor responses. Both soluble factors and specialized immune cells, such as regulatory T cells (Treg), are key components of active intratumoral immunosuppression. Inducible costimulatory receptor (ICOS) can be highly expressed in the tumor microenvironment, especially on immunosuppressive Treg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from tumor-bearing mice and patients with cancer to demonstrate differential expression of ICOS in immune T-cell subsets in different tissues. ICOS expression was higher on intratumoral Treg than on effector CD8 T cells. In addition, by immunizing an Icos knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that bound ICOS from different species. We showed that KY1044 induced sustained depletion of ICOShigh T cells but was also associated with increased secretion of proinflammatory cytokines from ICOSlow effector T cells (Teff). In syngeneic mouse tumor models, KY1044 depleted ICOShigh Treg and increased the intratumoral TEff:Treg ratio, resulting in increased secretion of IFNγ and TNFα by TEff cells. KY1044 demonstrated monotherapy antitumor efficacy and improved anti–PD-L1 efficacy. In summary, we demonstrated that using KY1044, one can exploit the differential expression of ICOS on T-cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response.
Doença fabricada ou induzida pelos cuidadores
Authors: Miziara Carmen Silvia Molleis Galego , Serrano Virginia Aparecida Gelmeti , Ferro Emílio Zuolo , Miziara Ivan Dieb 
Published: September 2020

A doença fabricada ou induzida pelo cuidador, também conhecida como síndrome de Munchausen por procuração, é uma das formas graves de maus-tratos, na qual o cuidador, geralmente a mãe biológica da criança, exagera ou causa deliberadamente sintomas na criança, assim, o seu diagnóstico torna-se difícil de ser realizado. Diversos métodos podem ser utilizados pelo perpetrador para produzir os sinais e sintomas na criança, os quais, em grande parte, são compatíveis com as enfermidades observadas nessa época da vida, dificultando ainda mais seu reconhecimento. As consequências advindas da falha diagnóstica são inúmeras, incluindo sofrimento físico e emocional decorrentes dos meios diagnósticos aplicados e eventos adversos a medicamentos desnecessários. A utilização de insulina para desencadear crises epilépticas de origem metabólica e de medicamentos antiepilépticos para induzir reações motoras e cognitivas podem ser artifícios frequentes empregados pelo agressor. Este estudo teve como objetivo relatar o caso de um menino diagnosticado com encefalopatia epiléptica, cujos sinais e sintomas, como foi descoberto posteriormente, eram produzidos pela mãe por meio da administração de insulina, de fenobarbital e de carbamazepina. A importância dessa discussão versa sobre a necessidade de os médicos ficarem atentos a esse possível diagnóstico. Alguns critérios podem ser considerados na busca pelo diagnóstico correto.
Altered Enhancer and Promoter Usage Leads to Differential Gene Expression in the Normal and Failed Human Heart
Authors: Gacita Anthony M. , Dellefave-Castillo Lisa , Page Patrick G.T. , Barefield David Y. , Wasserstrom J. Andrew , Puckelwartz Megan J. , Nobrega Marcelo A. , McNally Elizabeth M. 
Published: September 2020

Background:
The failing heart is characterized by changes in gene expression. However, the regulatory regions of the genome that drive these gene expression changes have not been well defined in human hearts.

Methods:
To define genome-wide enhancer and promoter use in heart failure, cap analysis of gene expression sequencing was applied to 3 healthy and 4 failed human hearts to identify promoter and enhancer regions used in left ventricles. Healthy hearts were derived from donors unused for transplantation and failed hearts were obtained as discarded tissue after transplantation.

Results:
Cap analysis of gene expression sequencing identified a combined potential for ≈23 000 promoters and ≈5000 enhancers active in human left ventricles. Of these, 17 000 promoters and 1800 enhancers had additional support for their regulatory function. Comparing promoter usage between healthy and failed hearts highlighted promoter shifts which altered aminoterminal protein sequences. Enhancer usage between healthy and failed hearts identified a majority of differentially used heart failure enhancers were intronic and primarily localized within the first intron, revealing this position as a common feature associated with tissue-specific gene expression changes in the heart.

Conclusions:
This data set defines the dynamic genomic regulatory landscape underlying heart failure and serves as an important resource for understanding genetic contributions to cardiac dysfunction. Additionally, regulatory changes contributing to heart failure are attractive therapeutic targets for controlling ventricular remodeling and clinical progression.
Recounting the Orbs
Authors: Raposo Pedro M.P. 
Published: September 2020

Abstract
This paper explores how the idea of discovery in astronomy gained a footing in the production and use of planetary models. It focuses on the period 1780–1850, during which the number of known bodies in the solar system increased concomitantly with a growing market for didactic instruments and toys. Specific examples of tridimensional models are discussed, in order to illustrate two main themes: the orrery as a changeable planetary model open to the choices of consumers and users, and the development of the armillary sphere from its original Ptolemaic configuration to a Copernican design suitable to incorporate newly found orbs. It is argued that the idea of discovery as applied to the realm of educational planetary models entailed marketing advantages, but also raised issues of credibility and posed challenges concerning the exactness, functionality, and actuality of models.
Dichotomy in Fasciotomy: Practice Patterns Among Trauma/Acute Care Surgeons With Performing Fasciotomy With Peripheral Arterial Repair
Authors: Romagnoli Anna N. , Morrison Jonathan J. , DuBose Joseph J. , Feliciano David V. 
Published: September 2020

Introduction Failure to perform adequate fasciotomy for a presumed or diagnosed compartment syndrome after revascularization of an acutely ischemic limb is a potential cause of preventable limb loss. When required, outcomes are best when fasciotomy is conducted with the initial vascular repair. Despite over 100 years of experience with fasciotomy, the actual indications for its performance among acute care and trauma surgeons performing vascular repairs are unclear. The hypothesis of this study was that there are many principles of fasciotomy that are uniformly accepted by surgeons and that consensus guidelines could be developed. Methods A 20-question survey on fasciotomy practice patterns was distributed to trauma and acute care surgeons of a major surgical society which had approved distribution. Results The response to the survey was 160/1066 (15 %). 92.5% of respondents were fellowship trained in trauma and acute care surgery, and 74.9% had been in practice for fewer than 10 years. Most respondents (71.9%) stated that they would be influenced to perform a preliminary fasciotomy (fasciotomy conducted prior to planned exploration and arterial repair) based upon specific signs and symptoms consistent with compartment syndrome—including massive swelling (55.6%), elevated compartment pressures (52.5%), delay in transfer >6 hours (47.5%), or obvious distal ischemia (33.1%). 20.6% responded that they would conduct exploration and repair first, regardless of these considerations. Prophylactic fasciotomies (fasciotomy without overt signs of compartment syndrome) would be performed by respondents in the setting of the tense compartment (87.5%), ischemic time >6 hours (88.1%), measurement of elevated compartment pressures (66.9%), and in the setting of large volume resuscitation requirements (31.3%). 69.4% of respondents selectively measure compartment pressures, with nearly three-fourths utilizing a Stryker needle device (72.5%). The most common sequence of repairs following superficial femoral artery injury with a >6-hour limb ischemia was cited as the initial insertion of a shunt, followed by fasciotomy, then vein harvest, and finally interposition repair. Conclusions While there is some general consensus on indications for fasciotomy, there is marked heterogeneity in surgeons’ opinions on the precise indications in selected scenarios. This is particularly surprising in light of the long history with fasciotomy in association with major arterial repairs and strongly suggests the need for a consensus conference and/or meta-analysis to guide further care.
Quality Improvement for Surgical Resection of Pancreatic Head Adenocarcinoma
Authors: Nuckles Brandon W. , Lam Kenneth , Young Katelyn A. , Dove James T. , Shabahang Mohsen M. , Blansfield Joseph A. 
Published: September 2020

Background The mainstay of treatment for pancreatic cancer is surgical resection; however, positive surgical margins remain commonplace. We identified hospitals with higher than predicted rates of positive margins and isolated factors that caused this discordance. Methods This is a retrospective review of patients with head of the pancreas adenocarcinoma in the National Cancer Database between 2004 and 2015. A nomogram was used to calculate the observed to expected positive margin rates (O/E) for facilities. If the O/E differed significantly ( P < .05), it was considered an outlier. Results Among a total of 19 968 patients, 24.3% had positive margins. Among hospitals with lower than expected positive margin rates, 73.6% were academic or research programs, 17% were comprehensive community cancer programs, and none were community cancer programs ( P = .0002). Within the group with higher than expected positive margin rates, 47% were comprehensive community cancer programs and 38.6% were academic or research programs ( P = .0002). The mean hospital volume was higher in the low positive margin group (110.4 vs 48.8, P < .0001). Conclusions Facility type and hospital volume can predict improvement in the O/E ratio for margin positivity in pancreatic adenocarcinoma resection. Surgeons should consider referral to academic or research facilities with higher case volumes for improved surgical resection.
Blunt Cerebrovascular Injury Screening Criteria Should Include Motor Vehicle Crash Characteristics
Authors: Farhat-Sabet Ashley , Lauerman Margaret , Chavez Alicia , Lloyd Joe , Scalea Thomas , Stein Deborah 
Published: September 2020

Background Current screening criteria miss 30% of blunt cerebrovascular injuries (BCVIs). Motor vehicle collisions (MVCs) are the leading BCVI mechanism, and delineating MVC characteristics associated with BCVI formation may augment current screening criteria. Methods We retrospectively identified BCVI Denver injury screening criteria as able from the Crash Injury Research and Engineering Network (CIREN) database. Severe MVC markers were considered: mean change in velocity (delta-v) greater than 40 km/hour, steering wheel airbag deployment, ejection, or rollover. Results 93 BCVIs were included. Injury screening criteria were not present in 37/93 (39.8%) BCVIs. Vertebral BCVI more often had injury screening criteria than internal carotid BCVIs (73.2% vs 26.8%, P = .001). There was a significant difference in delta-v (30.78 km/hour vs 51.00 km/hour, P < .001) between BCVI with and without injury screening criteria. BCVI without injury screening criteria more often had safety device use through seatbelt position snug across the hips (94.6% vs 74.5%, P = .01) and pretensioner deployment (92.6% vs 70.2%, P = .04). Examining only drivers, BCVI without injury screening criteria more often had steering wheel airbag deployment (89.7% vs 68.9%, P = .05). Markers of severe MVC were seen in 36/37 (97.3%) BCVIs without injury screening criteria. Discussion BCVI without injury screening criteria occurred during higher deceleration MVCs with more frequent/appropriate safety device use, suggesting crash deceleration as a mechanism of BCVI formation. Expanding BCVI screening criteria to encompass severe MVCs may lessen the number of BCVI missed.
Nurses’ Communication With the Families of Patients at the End-of-Life
Authors: Norouzadeh Reza , Anoosheh Monireh , Ahmadi Fazlollah 
Published: September 2020

Background Effective communication is important in providing quality care to families at the end-of-life. In the end-of-life situations, the nurses’ views on how to communicate with the family are not well understood. Aim This study was conducted to explore the nurses' experiences of their communication with families of patients at the end-of-life situations. Methods The authors used standards for reporting qualitative research. The data were analyzed by conventional content analysis. Semi-structured interviews were conducted with 24 Iranian nurses who had the experiences of dealing with patients’ families at the end-of-life. Results Nurses’ perceptions of communication with families emerged base on the main theme: “Disrupted communication” consisting of two categories: “restricted communication” and “abortive communication.” Conclusion The results of this study highlight the need to increase the professional and ethical sensitivity of nurses in dealing with patients' families at the end-of-life.
Lessons Learned from Psychological Autopsies in Armed Forces
Authors: Sinha Alok , Gupta Sriniwas , Ray Madhubrata , Kumar Sanjay , Gupta Anindya Kumar 
Published: September 2020

Background: Suicide in armed forces is a matter of concern despite adequate prophylactic measures that have been adopted to reduce it. Military psychiatrists routinely conduct psychological autopsies. It may reveal various biopsychosocial factors leading to suicide and may be helpful in suicide prevention too. A few studies have been done in Indian Armed Forces but all of them involve cases of attempted suicide. Our study is different as it uses the methodology of psychological autopsy to find out various psychosocial factors of suicide in armed forces. Methods: The present study was carried out in a large service hospital and included all suicide cases occurring in a particular strategic location from February 2014 to July 2017. A total of 16 suicide cases were investigated, and information was collected through visiting the scene, detailed semistructured interviews, the perusal of mobile call records, social website activities, notes in a social diary, bank statements, service record, and health records. Results: The majority (nine of sixteen) of suicide victims were less than 30 years of age. The most common method of suicide (ten of sixteen) was use of firearms. Family history of mental illness/suicide was seen in three of them. Three had a past history of mental illness. Two were abusing substance in the recent past. Behavioral change was noticed in three, and suicide notes were available in three cases. Five had expressed their intent to die. Conclusions: Strain of serving in frontiers is not a common stressor associated with suicide as commonly perceived.
Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer
Authors: Chen Baomin , Zheng Donghua , Yu Weiguang , Huang Cuiping , Ye Junxing , Han Guowei , Zhuang Jintao 
Published: September 2020

Objective To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). Results A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5–38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4–24.4) and 17.7 months (95% CI 11.3–19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15–0.46); median OS was 26.0 months (95% CI 23.4–28.7) and 22.7 months (95% CI 21.2–24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11–0.37). Conclusions CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.
Serum miR-29a/b expression in gestational diabetes mellitus and its influence on prognosis evaluation
Authors: Deng Li , Huang Yan , Li Ling , Chen Hongfei , Su Junyou 
Published: September 2020

Objective To evaluate serum microRNA (miR)-29a/b expression in gestational diabetes mellitus (GDM) and its influence on neonatal prognosis. Methods This was a retrospective study including 68 pregnant women with GDM (GDM group) and 55 healthy pregnant women of similar age range and gestation period (healthy group). Results The area under the curve was 0.829 for the diagnosis of GDM using serum miR-29a expression, 0.857 for diagnosis using serum miR-29b expression, and 0.944 for combined diagnosis (using both miR-29a and miR-29b). The fasting insulin (FINS) level of the GDM group was significantly lower than that of the healthy group; levels of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and glycated hemoglobin (HbA1c) were significantly higher in the GDM group than in the healthy group. Both miR-29a and miR-29b were positively correlated with FINS levels and negatively correlated with FPG, 2hPG, and HbA1c levels. Serum miR-29a/b expression in pregnant women with GDM was not correlated with neonatal weight, premature delivery, or asphyxia but was correlated with pathologic jaundice. Conclusions Serum miR-29a/b expression was downregulated in pregnant women with GDM and correlated with neonatal pathologic jaundice, showing good individual (miR-29a or miR-29b) diagnostic value and excellent combined (miR-29a and miR-29b) diagnostic value.
Expanding Student Knowledge and Confidence on Dietary Supplements Through Mock Patient Consultations
Authors: Walsh Kendra , Cohen Lisa , Hume Anne L. 
Published: September 2020

Introduction: As dietary supplements are widely used in the United States, student pharmacists should be prepared to assess their appropriateness for self-care. The purpose of this project was to assess the impact of mock patient consults regarding common dietary supplements on second-year (P2) Doctor of Pharmacy (PharmD) students. Methods: This activity was part of a required course, Self-Care I. Twenty-four groups of 4 to 5 students were created, with each assigned a unique patient vignette. Students had 10 minutes to speak on the phone with their “patient” to obtain needed information in order to make an appropriate recommendation in the form of a 2 to 3-minute recorded oral response. Anonymous, voluntary pre- and post-project surveys assessing perceived dietary supplement knowledge, patient counseling skills, and attitudes about the activity were conducted during class through Google Forms. The Wilcoxon Signed-Rank Test was used to determine differences in mean 10-point Likert scale score between pre- and post-test for each survey question, with significance if p < 0.05. Results: Significant differences were found between pre- and post-survey Likert scale means. Reported confidence in using the QuEST/SCHOLAR-MAC approaches to self-care counseling increased by 45% from baseline. Perceived student knowledge on dietary supplements increased by 44%. Self-rated counseling abilities of students increased by 87% for glucosamine/chondroitin, 28% for melatonin, 39% for red yeast rice, 38% for fish oil, and 42% for cranberry regarding their use in particular cases. Conclusions: The activity provided students with realistic exposure to questions about dietary supplements that patients ask community pharmacists.
Examining a Child Welfare Parenting Intervention for Parents With Intellectual Disabilities
Authors: Augsberger Astraea , Zeitlin Wendy , Rao Trupti , Weisberg Danielle , Toraif Noor 
Published: September 2020

Purpose: There is scant child welfare research on parenting interventions for parents with intellectual and developmental disabilities (I/DD). This mixed-methods research examined client participation in an in-home parenting intervention, including client characteristics, which clients benefit most from participation, and key aspects of program participation. Method: The sample included participant program records, client satisfaction surveys, stakeholder interviews, and a staff focus group. The quantitative data were analyzed using growth curves and binary logistic regression. The qualitative data were analyzed using thematic analysis. Results: Time spent in Project Improving Parenting Achievements Together was predictive of improvement in parenting skills and the home environment and reduction in the odds of out-of-home placement for children of parents with I/DD. The intensity of services, tailored education, community engagement, and client–worker relationship were the key aspects of program participation. Discussion: With proper supports, parents with I/DD can learn parenting skills, improve the home environment, and keep their family intact.
Building Social Work Research Capacity in a Busy Metropolitan Hospital
Authors: Donley Euan , Moon Felicity 
Published: September 2020

Purpose: Recently, public health networks in Australia have introduced clinical research specialists to drive research in the allied health professions by helping clinical social workers engage in research. This study examines the benefits of a flexible research program for busy social work novice and experienced clinicians. Methods: Thirty hospital-based social workers were allocated a total of 12 research projects. Participants were given a mixed-methods survey both pre and post an education program with 17 responses for the presurvey and 12 responses postsurvey. The responses were coded via thematic analysis. Results: Despite initial clinician apprehension, the majority of participants found it beneficial. In the busy hospital context, support that was valued included simplified information and regular mentorship and training. Discussion: The role of a research lead with management support is pivotal in promoting a positive research culture and active research. However, clinical demand still reduces capacity to engage in research.