bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centres of excellence in Latin America: how do these differ from other experiences?
Authors: Corilloclla Terbullino Pavel Gabriel 
Published: March 2023

Abstract
Centres of excellence (CoEs), as boundary-spanning structures between universities and firms, have been promoted and studied mainly in developed countries, while some Latin American countries have recently launched CoE programmes. This study explores how CoEs in Chile and Peru have been working in terms of their internal structures and interactions. It draws upon a conceptual framework that encompasses the distinction between contexts for and channels of university–industry linkages (UILs), the defining features of CoEs, their differences with other schemes and innovation intermediaries, and the patterns shown by CoEs in developed countries. Applying this framework to analyse two CoEs, we found that these fit into the concept of contexts for UILs and differ substantially from research and technology organisations. We also found that Chilean and Peruvian CoEs share certain commonalities with their counterparts in developed countries, albeit they also show sharp differences, which have both academic and policy implications.
Racial differences in upper airway collapsibility and loop gain in young adult males
Authors: Puri Shipra , Panza Gino S , Kissane Dylan , Jones Steven , Reck Kevin , Lin Ho-Sheng , Badr M Safwan , Mateika Jason H 
Published: March 2023

Abstract

Study Objectives
Previous studies reported that the apnea–hypopnea index was similar in young adult Black and White participants. However, whether this similarity reflects an analogous combination of apneas and hypopneas is unknown. Likewise, the physiological mechanisms underlying this similarity has not been explored.

Methods
60 Black and 48 White males completed the study. After matching for age and body mass index, 41 participants remained in each group. All participants completed a sleep study. Subsequently, standard sleep indices along with loop gain and the arousal threshold were determined. In addition, airway collapsibility (24 of 60 and 14 of 48 participants) and the hypoxic ventilatory response during wakefulness (30 of 60 and 25 of 48 participants) was measured.

Results
The apnea–hypopnea index was similar in Blacks and Whites (p = .140). However, the index was comprised of more apneas (p = .014) and fewer hypopneas (p = .025) in Black males. These modifications were coupled to a reduced loop gain (p = .0002) and a more collapsible airway (p = .030). These differences were independent of whether or not the groups were matched. For a given hypoxic response, loop gain was reduced in Black compared to White males (p = .023).

Conclusions
Despite a similar apnea–hypopnea index, more apneas and fewer hypopneas were evident in young adult Black compared to White males. The physiological mechanisms that contribute to these events were also different between groups. Addressing these differences may be important when considering novel therapeutic approaches to eliminate apnea in Black and White participants.
Exploring research team members’ and trial participants’ perceptions of acceptability and implementation within one videoconference-based supportive care program for individuals affected by systemic sclerosis during COVID-19: a qualitative interview study
Authors: Wurz Amanda , Ellis Kelsey , Duchek Delaney , Bansal Mannat , Carrier Marie-Eve , Tao Lydia , Dyas Laura , Kwakkenbos Linda , Levis Brooke , El-Baalbaki Ghassan , Rice Danielle B , Wu Yin , Henry Richard S , Bustamante Laura , Harb Sami , Hebblethwaite Shannon , Patten Scott B , Bartlett Susan J , Varga John , Mouthon Luc , Markham Sarah , Thombs Brett D , Culos-Reed S Nicole ,   SPIN-CHAT Patient Advisory Team,   Program Facilitators
Published: March 2023

Abstract
The SPIN-CHAT Program was designed to support mental health among individuals with systemic sclerosis (SSc; commonly known as scleroderma) and at least mild anxiety symptoms at the onset of COVID-19. The program was formally evaluated in the SPIN-CHAT Trial. Little is known about program and trial acceptability, and factors impacting implementation from the perspectives of research team members and trial participants. Thus, the propose of this follow-up study was to explore research team members’ and trial participants’ experiences with the program and trial to identify factors impacting acceptability and successful implementation. Data were collected cross-sectionally through one-on-one, videoconference-based, semi-structured interviews with 22 research team members and 30 purposefully recruited trial participants (Mage = 54.9, SD = 13.0 years). A social constructivist paradigm was adopted, and data were analyzed thematically. Data were organized into seven themes: (i) getting started: the importance of prolonged engagement and exceeding expectations; (ii) designing the program and trial: including multiple features; (iii) training: research team members are critical to positive program and trial experiences; (iv) offering the program and trial: it needs to be flexible and patient-oriented; (v) maximizing engagement: navigating and managing group dynamics; (vi) delivering a videoconference-based supportive care intervention: necessary, appreciated, and associated with some barriers; and (vii) refining the program and trial: considering modification when offered beyond the period of COVID-19 restrictions. Trial participants were satisfied with and found the SPIN-CHAT Program and Trial to be acceptable. Results offer implementation data that can guide the design, development, and refinement of other supportive care programs seeking to promote psychological health during and beyond COVID-19.
The implementation of ask-advise-connect in a federally qualified health center: a mixed methods evaluation using the re-aim framework
Authors: Shorey Fennell Bethany , Cottrell-Daniels Cherell , Hoover Diana Stewart , Spears Claire A , Nguyen Nga , Piñeiro Bárbara , McNeill Lorna H , Wetter David W , Vidrine Damon J , Vidrine Jennifer I 
Published: March 2023

AbstractAsk-Advise-Connect (AAC) efficiently links smokers in healthcare settings with evidence-based Quitline-delivered tobacco treatment through training clinic staff to systematically ask patients about smoking status, advise smokers to quit, and connect patients with state Quitlines using the electronic health record. This study utilized a mixed-methods approach, guided by the RE-AIM framework, to evaluate the implementation of AAC in a Federally Qualified Health Center (FQHC). AAC was implemented for 18 months at a FQHC serving primarily low-socioeconomic status (SES) Latinos and Latinas. Results are presented within the RE-AIM conceptual framework which includes dimensions of reach, effectiveness, adoption, implementation, and maintenance. Quantitative patient-level outcomes of reach, effectiveness, and Impact were calculated. Post-implementation, in-depth interviews were conducted with clinic leadership and staff (N = 9) to gather perceptions and inform future implementation efforts. During the implementation period, 12.0% of GNHC patients who reported current smoking both agreed to have their information sent to the Quitline and were successfully contacted by the Quitline (Reach), 94.8% of patients who spoke with the Quitline enrolled in treatment (Effectiveness), and 11.4% of all identified smokers enrolled in Quitline treatment (Impact). In post-implementation interviews assessing RE-AIM dimensions, clinic staff and leadership identified facilitators and advantages of AAC and reported that AAC was easy to learn and implement, streamlined existing procedures, and had a positive impact on patients. Staff and leadership reported enthusiasm about AAC implementation and believed AAC fit well in the clinic. Staff were interested in AAC becoming the standard of care and made suggestions for future implementation. Clinic staff at a FQHC serving primarily low-SES Latinos and Latinas viewed the ACC implementation process positively. Findings have implications for streamlining clinical smoking cessation procedures and the potential to reduce tobacco-related disparities.
Econometric evaluation of implementing a behavioral health integration intervention in primary care settings
Authors: Nagykaldi Zsolt , Littenberg Benjamin , Bonnell Levi , Breshears Ryan , Clifton Jessica , Crocker Abigail , Hitt Juvena , Kessler Rodger , Mollis Brenda , Miyamoto Robin E S , van Eeghen Constance 
Published: March 2023

AbstractIntegrated behavioral health (IBH) is an approach to patient care that brings medical and behavioral health providers (BHPs) together to address both behavioral and medical needs within primary care settings. A large, pragmatic, national study aimed to test the effectiveness and measure the implementation costs of an intervention to improve IBH integration within primary care practices (IBH-PC). Assess the time and cost to practices of implementing a comprehensive practice-level intervention designed from the perspective of clinic owners to move behavioral service integration from co-location toward full integration as part of the IBH-PC study. IBH-PC program implementation costs were estimated in a representative sample of 8 practices using standard micro-econometric evaluation of activities outlined in the implementation workbook, including program implementation tasks, remote quality improvement coaching services, educational curricula, and learning community activities, over a 24-month period. The total median cost of implementing the IBH-PC program across all stages was $20,726 (range: $12,381 - $60,427). The median cost of the Planning Stage was $10,258 (range: $4,625 - $14,840), while the median cost of the Implementation Stage was $9,208 (range: $6,017 – 49,993). There were no statistically significant differences in practice or patient characteristics between the 8 selected practices and the larger IBH-PC practice sample (N=34). This study aimed to quantify the relative costs associated with integrating behavioral health into primary care. Although the cost assessment approach did not include all costs (fixed, variable, operational, and opportunity costs), the study aimed to develop a replicable and pragmatic measurement process with flexibility to adapt to emerging developments in each practice environment, providing a reasonable ballpark estimate of costs associated with implementation to help guide future executive decisions.
“No Excuses Anymore”: Substance Use Screening and Treatment for Justice-involved Youth
Authors: Goldman Paula N. , Hull Ilana , Wilson J. Deanna 
Published: March 2023

Objective
The aim of this study was to present best practices for substance use disorder (SUD) screening and treatment in the juvenile justice setting.

Methods
Semistructured qualitative interviews, informed by the Capability-Opportunity-Motivation-Behavior Model, were conducted with medical and behavioral health providers with experience caring for justice-involved youth. Interviews were analyzed using thematic and content analysis to elucidate best practices and identify facilitators and barriers affecting implementation of evidence-based substance use screening and treatment.

Results
We interviewed 14 participants from 12 unique institutions and 9 states. All participants described the populations in their facilities as predominately male and minoritized, with substance use being an exceedingly common problem. Eight main themes emerged from analysis of the barriers and facilitators discussed by participants. These included the importance of (1) ensuring substance use–specific training for all team members, (2) integrating medical and behavioral health care, (3) addressing staff reticence and stigma, (4) building an institutional culture that supports screening and treatment, (5) dedicating adequate resources with respect to time, staffing, and funding, (6) formalizing and standardizing screening and treatment protocols, (7) engaging youth using trauma-informed approaches that emphasize youth strengths and autonomy, and (8) collaborating with multidisciplinary teams and community partners to maximize linkage to follow-up care after release.

Conclusions
Our findings highlight an urgent need for improved implementation of evidence-based, developmentally appropriate substance use treatment for justice-involved youth. Although the majority of participants screen youth, they described variable implementation of behavioral health interventions and limited provision of on-site withdrawal management and treatment using medications for SUD.
Effects of Sacubitril–Valsartan in Patients With Various Types of Heart Failure: A Meta-analysis
Authors: Zhang Hongyu , Huetteman Abigail T. , Reyes Eduardo A. , Appelbaum Jonathan S. 
Published: March 2023

Abstract
We performed a meta-analysis investigating the efficacy and adverse effects of sacubitril–valsartan in various types of heart failure including more recent studies and a larger sample size. We conducted an electronic search through Cochrane, Web of Science, PubMed, and Embase. Included studies were randomized controlled trials analyzing the efficacy of sacubitril–valsartan compared with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) in patients with heart failure. Fourteen trials were included. Pooled estimates were analyzed using RevMan 5.4.1. The odds ratio (OR) of hospitalization from worsening heart failure that compared sacubitril–valsartan with control was 0.70 (95% CI, 0.51–0.97; P = 0.03) in patients with heart failure with reduced ejection fraction (HFrEF) with a relative risk reduction (RRR) of 24.3% and absolute risk reduction (ARR) of 3.4%. In patients with heart failure with midrange (HFmEF) and preserved (HFpEF) ejection fraction, the OR was 0.80 (95% CI, 0.71–0.90; P = 0.0001) with RRR of 14.5% and ARR of 3.3%. There was a significant reduction in cardiovascular deaths (OR = 0.79; 95% CI, 0.70–0.89; P = <0.0001) and all-cause mortality (OR = 0.84; 95% CI, 0.75–0.94; P = 0.002) in patients with HFrEF, with no significant differences in patients with HFmEF and HFpEF. Hospitalization rate was significantly reduced in patients taking sacubitril–valsartan across all analyzed cohorts. Sacubitril–valsartan significantly reduced the risk of all-cause mortality and cardiovascular death in patients with HFrEF but not in patients with HFmEF/HFpEF. These findings support sacubitril–valsartan use in reducing hospitalization of patients with HFmEF and HFpEF. More studies should be performed to further analyze the efficacy of sacubitril–valsartan in patients with HFmEF/HFpEF.
Humoral response to two doses of the mRNA-1273 vaccine in Taiwanese liver transplant recipients unaffected by antimetabolites: A single-institute experience
Authors: Huang Wei , Lai Chia-Yu , Liu Hsiao-Tien , Chen Yi-Ju , Tsai Hui-Chu , Liu Po-Yu , Cheng Shao-Bin 
Published: March 2023

Abstract

Background
Data on the immunogenicity of mRNA vaccines in solid transplant recipients are emerging; however, data on liver transplant recipients of Taiwanese ethnicity remain limited.

Methods
We recruited 33 Taiwanese liver transplant recipients who received two doses of the Moderna mRNA-1273 vaccine and obtained blood samples for the semiquantitative determination of antibodies to the severe acute respiratory syndrome coronavirus 2 S protein RBD (receptor-binding domain) 2 weeks after each vaccination. The participants were also required to note any adverse events 1 week after the booster vaccination.

Results
Antibody response after the priming and booster doses of the mRNA-1273 vaccine was 50% and 100%, respectively. The participants were further stratified into optimal (n = 27, >250 U/mL) and inadequate (n = 6, <250 U/mL) response groups according to the upper limit of the numeric antibody titer. A shorter time after transplantation and lower estimated glomerular filtration rate were significantly associated with an inadequate titer. The postvaccination humoral response seemed unaffected by use of antimetabolites. No severe adverse events were reported.

Conclusions
The postvaccination immunogenicity of Taiwanese liver transplant recipients was satisfactory, whereas the reactogenicity to the novel vaccine was minimal.
Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers
Authors: Yoo Changhoon , Javle Milind M. , Verdaguer Mata Helena , de Braud Filippo , Trojan Jörg , Raoul Jean-Luc , Kim Jin Won , Ueno Makoto , Lee Choong-kun , Hijioka Susumu , Cubillo Antonio , Furuse Junji , Azad Nilofer , Sato Masashi , Vugmeyster Yulia , Machl Andreas , Bajars Marcis , Bridgewater John , Oh Do-Youn , Borad Mitesh J. 
Published: March 2023

Background and Aims:
Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers.

Approach and Results:
This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. The primary endpoint was confirmed objective response according to Response Evaluation Criteria in Solid Tumors 1.1 assessed by IRC. Secondary endpoints included duration of response, durable response rate, safety, progression-free survival, and overall survival.
Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0–19.3) months; 17 patients (10.7%; 95% CI: 6.4%–16.6%) achieved an objective response. Median duration of response was 10.0 (range, 1.9–15.7) months; 10 patients (6.3%; 95% CI: 3.1%–11.3%) had a durable response (≥6 mo). Median progression-free survival was 1.8 months (95% CI: 1.7–1.8 mo); median overall survival was 7.6 months (95% CI: 5.8–9.7 mo). Overall survival rates were 57.9% (6 mo) and 38.8% (12 mo). Grade ≥3 adverse events occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%).

Conclusions:
Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.
Epigenetic regulation of HBV-specific tumor-infiltrating T cells in HBV-related HCC
Authors: You Maojun , Gao Yanan , Fu Junliang , Xie Runze , Zhu Zhenyu , Hong Zhixian , Meng Lingzhan , Du Shunda , Liu Junliang , Wang Fu-Sheng , Yang Pengyuan , Chen Liang 
Published: March 2023

Background and Aims:
HBV shapes the T-cell immune responses in HBV-related HCC. T cells can be recruited to the nidus, but limited T cells participate specifically in response to the HBV-related tumor microenvironment and HBV antigens. How epigenomic programs regulate T-cell compartments in virus-specific immune processes is unclear.

Approach and Results:
We developed Ti-ATAC-seq. 2 to map the T-cell receptor repertoire, epigenomic, and transcriptomic landscape of αβ T cells at both the bulk-cell and single-cell levels in 54 patients with HCC. We deeply investigated HBV-specific T cells and HBV-related T-cell subsets that specifically responded to HBV antigens and the HBV + tumor microenvironment, respectively, characterizing their T-cell receptor clonality and specificity and performing epigenomic profiling. A shared program comprising NFKB1/2-, Proto-Oncogene, NF-KB Sub unit, NFATC2-, and NR4A1-associated unique T-cell receptor-downstream core epigenomic and transcriptomic regulome commonly regulated the differentiation of HBV-specific regulatory T-cell (Treg) cells and CD8 + exhausted T cells; this program was also selectively enriched in the HBV-related Treg-CTLA4 and CD8-exhausted T cell-thymocyte selection associated high mobility subsets and drove greater clonal expansion in HBV-related Treg-CTLA4 subset. Overall, 54% of the effector and memory HBV-specific T cells are governed by transcription factor motifs of activator protein 1, NFE2, and BACH1/2, which have been reported to be associated with prolonged patient relapse-free survival. Moreover, HBV-related tumor-infiltrating Tregs correlated with both increased viral titer and poor prognosis in patients.

Conclusions:
This study provides insight into the cellular and molecular basis of the epigenomic programs that regulate the differentiation and generation of HBV-related T cells from viral infection and HBV + HCC unique immune exhaustion.
Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection
Authors: Jackson Carl-Christian A. , Newland Jason , Dementieva Nataliia , Lonchar Julia , Su Feng-Hsiu , Huntington Jennifer A. , Bensaci Mekki , Popejoy Myra W. , Johnson Matthew G. , De Anda Carisa , Rhee Elizabeth G. , Bruno Christopher J. 
Published: March 2023

Background:
Ceftolozane/tazobactam, a cephalosporin–β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

Methods:
This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

Results:
The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: −14.3; 95% confidence interval: −26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: −19.1; 95% confidence interval: −30.18 to −2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol.

Conclusion:
Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.