bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence, Predictor, and Clinical Outcomes of Multiple Resheathing With Self‐Expanding Valves During Transcatheter Aortic Valve Replacement
Authors: Bernardi Fernando L. M. , Rodés‐Cabau Josep , Tirado‐Conte Gabriela , Amat Santos Ignacio J. , Plachtzik Claudia , Cura Fernando , Sztejfman Matias , Mangione Fernanda M. , Tumeleiro Rogério , Esteves Vinicius Borges Cardozo , Pessoa de Melo Eduardo França , Alcocer Chauvet Alejandro , Fuchs Felipe , Sarmento‐Leite Rogerio , de Campos Martins Estêvão Carvalho , Nombela‐Franco Luis , Delgado‐Arana José Raul , Bocksch Wolfgang , Lamelas Pablo , Giuliani Carlos , Campanha‐Borges Diego Carter , Mangione Jose A. , de Brito Fábio Sandoli , Abizaid Alexandre C. , Ribeiro Henrique B. 
Published: September 2021

Background
No study has evaluated the impact of the additional manipulation demanded by multiple resheathing (MR) in patients undergoing transcatheter aortic valve replacement with repositionable self‐expanding valves.

Methods and Results

This study included a real‐world, multicenter registry involving 16 centers from Canada, Germany, Latin America, and Spain. All consecutive patients who underwent transcatheter aortic valve replacement with the Evolut R, Evolut PRO, and Portico valves were included. Patients were divided according to the number of resheathing: no resheathing, single resheathing (SR), and MR. The primary end point was device success. Secondary outcomes included procedural complications, early safety events, and 1‐year mortality. In 1026 patients, the proportion who required SR and MR was 23.9% and 9.3%, respectively. MR was predicted by the use of Portico and moderate/severe aortic regurgitation at baseline (both with
P
<0.01). Patients undergoing MR had less device success (no resheathing=89.9%, SR=89.8%, and MR=80%;
P
=0.01), driven by more need for a second prosthesis and device embolization. At 30 days, there were no differences in safety events. At 1 year, more deaths occurred with MR (no resheathing=10.5%, SR=8.0%, and MR=18.8%;
P
=0.014). After adjusting for baseline differences and center experience by annual volume, MR associated with less device success (odds ratio, 0.42;
P
=0.003) and increased 1‐year mortality (hazard ratio, 2.06;
P
=0.01). When including only the Evolut R/PRO cases (N=837), MR continued to have less device success (
P
<0.001) and a trend toward increased mortality (
P
=0.05).

Conclusions
Repositioning a self‐expanding valve is used in a third of patients, being multiple in ≈10%. MR, but not SR, was associated with more device failure and higher 1‐year mortality, regardless of the type of valve implanted.
The World of the Bible—Always Strange, Forever New
Authors: Small Joseph D. 
Published: September 2021

Abstract
Although Markus Barth was a productive author and is known widely through his published written work, he was also, for many decades, a teacher of formative importance for generations of seminary and university students in both the United States and Switzerland. This essay shares personal reflections on Markus Barth’s profile as a biblical and theological educator and thereby introduces readers to something of his influential personal and theological style.
Markus Barth
Authors: Rashkover Randi 
Published: September 2021

Abstract
Like that of his father, Markus Barth’s work can be appreciated as a tireless effort to exegetically reorder Jewish-Christian relations. Even so, Barth’s writings on the Jews leave little doubt that he is vexed by a certain strain of Jewish support for Israel. More important, Barth’s writings about post-1967 Israel put his own discourse about the brotherhood of Christians and Jews into crisis. This essay will attempt to offer a working solution to this problem that can help followers of Markus Barth’s ideas continue to engage in productive and meaningful Jewish-Christian conversation.
Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
Authors: Knorz Adrian L. , Quante Arnim 
Published: September 2021

Importance: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear. Objective: To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy. Methods: The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020. Results: Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on Gingko biloba in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research. Conclusion: Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
Narrow Notch Width and Low Anterior Cruciate Ligament Volume Are Risk Factors for Anterior Cruciate Ligament Injury: A Magnetic Resonance Imaging-Based Study
Authors: Gupta Ravi , Jhatiwal Sanjay , Kapoor Anil , Kaur Ravinder , Soni Ashwani , Singhal Akash 
Published: September 2021

Background: The relationship between anterior cruciate ligament (ACL) injury and anatomical structures is still a topic of debate. Purpose: The aim of this study was to compare knee geometry in demographically matched ACL-injured and ACL-intact athletes. Methods: We conducted a case-control study comparing 2 groups, each consisting of 55 professional athletes (44 men and 11 women): 1 group with complete ACL tears (cases) and 1 group with intact ACLs (controls). The groups were compared using magnetic resonance imaging (MRI) in terms of intercondylar notch geometry, tibial plateau characteristics, and ACL volume. Results: Among cases and controls, we found the cases had lower notch width (20.24 ± 2.68 mm vs. 22.04 ± 2.56 mm, respectively) and notch width index (0.29 ± 0.03 vs. 0.31 ± 0.03, respectively). The mean ACL volume in the cases (1181.63 mm3 ± 326 mm3) was also lower than in controls (1352.61 mm3 ± 279.84 mm3). The parameters of tibial slope geometry were comparable between groups. In addition, women had lower ACL volume than men (1254 ± 310 mm3 vs. 890 ± 267 mm3, respectively) and higher medial posterior tibial slope (4.76 ± 2.6 vs. 6.63 ± 1.83, respectively). Among cases, women had narrower notch width than men (16.9 ± 2.42 mm vs. 21.08 ± 2.03 mm). However, notch width index was comparable between male (0.3 ± 0.02) and female (0.28 ± 0.03) cases. Conclusion: Our findings suggest that narrow notch width and low ACL volume may enhance the risk of ACL injury among athletes. There was no association found between posterior tibial slope and ACL injury between athletes with injured ACLs and controls. Further study is indicated.
Focused Assessment with Sonography for Trauma (FAST) training for first-year resident physicians at a university hospital in Japan: A longitudinal, observational study
Authors: Ota Koshi , Oba Koji , Ito Yuri , Cheng Jacky , Ota Kanna , Takasu Akira 
Published: September 2021

Background: Ultrasound training is an essential part of residency programs during emergency medicine rotations for first-year trainees (postgraduate year 1). The Focused Assessment with Sonography for Trauma examination used to assess for internal bleeding in trauma patients is one of the essential skills postgraduate year 1 residents must acquire during the emergency medicine rotation. Method: A prospective, longitudinal, observational study of postgraduate year 1 residents during a 2-month long emergency medicine rotation conducted from 1 April 2019 to 31 May 2021. The primary outcome was the mean difference between the hands-on Focused Assessment with Sonography for Trauma examination scores of the first week of the emergency medicine rotation and the same hands-on Focused Assessment with Sonography for Trauma examination scores of the last week of the emergency medicine rotation. All postgraduate year 1 residents had open access to the ultrasound machine to practice examining on other postgraduate year 1 residents or could use it on real patients under supervision of emergency medicine physicians. Result: A total of 91 postgraduate year 1 residents (65 male and 26 female) were recruited and submitted to the hands-on Focused Assessment with Sonography for Trauma test in both the first and last weeks of the rotation. The mean test score for the postgraduate year 1 residents in the first week was 7.81 (standard deviation = 2.11). The mean test score in the last week was 16.17 (standard deviation = 2.60). The primary outcome of this study was the score difference between the first and last weeks (mean = 8.35, 95% confidence interval = 7.73 to 8.94, p < 0.001, paired t-test). Conclusion: Hands-on practical Focused Assessment with Sonography for Trauma training for postgraduate year 1 residents during emergency medicine rotations significantly improved their Focused Assessment with Sonography for Trauma test scores.
Perspectives of LGBTQ Youth and Pediatricians in the Primary Care Setting: A Systematic Review
Authors: Stern Molly 
Published: September 2021

Objectives: Conduct a systematic review designed to determine needs and experiences of LGBTQ adolescents in the pediatric primary care setting and to the ability of primary care practitioners to provide the most inclusive care to LGBTQ adolescents. Methods: PubMed, CINAHL, and Embase searches using the following keywords: LGBTQ, Adolescents, Pediatrics, Sexual-Minority, Gender-Identity, and primary care, to identify peer-reviewed publications from 1998 to 2017 that focused on stigma in the healthcare setting related to LGBTQ youth and the knowledge of healthcare providers on enhancing care for their sexual and gender minority patients. Article inclusion criteria include: primary research studies conducted in a pediatric primary care describing LGBTQ patients, pediatric patients as described by the American Academy of Pediatrics (AAP), and written in the English language. Articles were excluded if they used inaccurate definitions for LGBTQ identity, inappropriate patient ages outside of those defined by the AAP, and studies not in a pediatric primary care setting. Results: Four articles were identified for the review. Of the included articles, the majority of LGBTQ adolescents experience stigma in the healthcare setting. A limited number of physicians providing care to LGBTQ adolescents felt equipped to care for their sexual-minority patients due to lack of education and resources. Conclusions: The education of physicians should include a more detailed approach to providing care to the LGBTQ population, particularly to those training to become pediatricians. A standard guide to treating LGBTQ adolescents could eliminate stigma in the healthcare setting.
When Internal Migration Fails: A Case Study of Central American Youth Who Relocate Internally Before Leaving Their Countries
Authors: Escamilla García Angel Alfonso 
Published: September 2021

Executive Summary This paper examines the experiences of Central American youth who have attempted internal relocation before migrating internationally. Based on interviews and participant observation with Guatemalan, Honduran, and Salvadoran youth migrating through Mexico, this paper shows how youth from the Northern Countries of Central America turn to their domestic networks to escape labor exploitation and gang violence before undertaking international journeys. The paper further demonstrates how those domestic networks lead youth into contexts of poverty and violence similar to those they seek to escape, making their internal relocation a disappointment. The failure of their internal relocation attempts makes them turn to international migrant networks as their next option. This paper sheds light on the underexplored issue of internal migration among Central American youth and that migration's synergy with Central American youths’ migration to the United States. The paper finds that internal relocation is unsuccessful when the internal destination fails to resolve the issues from which youth are attempting to escape. This failure ultimately triggers their departure from their home country.
Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma
Authors: Neelapu Sattva S. , Locke Frederick L. , Bartlett Nancy L. , Lekakis Lazaros J. , Reagan Patrick M. , Miklos David B. , Jacobson Caron A. , Braunschweig Ira , Oluwole Olalekan O. , Siddiqi Tanya , Lin Yi , Crump Michael , Kuruvilla John , Van Den Neste Eric , Farooq Umar , Navale Lynn , DePuy Venita , Kim Jenny J. , Gisselbrecht Christian 
Published: September 2021

Abstract
The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2-year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than were SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate (ORR) and complete response rate were 83% and 54% in ZUMA-1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit vs non–CAR T-cell salvage regimens for patients with refractory LBCL.
Enhanced self-renewal of human long-term hematopoietic stem cells by a sulfamoyl benzoate derivative targeting p18INK4C
Authors: Li Yinghui , Zhang Wenshan , Zhang Yu , Ding Yahui , Yang Ming , He Mei , Liu Xiaolei , Gu Jiali , Xu Shiqi , Feng Zhiwei , Li Yafang , Yin Jingjing , Gao Huier , Song Henan , Xu Hui , Wang Chaoqun , Ji Qing , Ma Shihui , Yang Wanzhu , Yuan Weiping , Xie Xiang-Qun , Cheng Tao , Gao Yingdai 
Published: September 2021

Abstract
The use of umbilical cord blood transplant has been substantially limited by the finite number of hematopoietic stem and progenitor cells in a single umbilical cord blood unit. Small molecules that not only quantitatively but also qualitatively stimulate enhancement of hematopoietic stem cell (HSC) self-renewal ex vivo should facilitate the clinical use of HSC transplantation and gene therapy. Recent evidence has suggested that the cyclin-dependent kinase inhibitor, p18INK4C (p18), is a critical regulator of mice HSC self-renewal. The role of p18 in human HSCs and the effect of p18 inhibitor on human HSC expansion ex vivo need further studies. Here we report that knockdown of p18 allowed for an increase in long-term colony-forming cells in vitro. We then identified an optimized small molecule inhibitor of p18, 005A, to induce ex vivo expansion of HSCs that was capable of reconstituting human hematopoiesis for at least 4 months in immunocompromised mice, and hence, similarly reconstituted secondary recipients for at least 4 more months, indicating that cells exposed to 005A were still competent in secondary recipients. Mechanistic studies showed that 005A might delay cell division and activate both the Notch signaling pathway and expression of transcription factor HoxB4, leading to enhancement of the self-renewal of long-term engrafting HSCs and the pool of progenitor cells. Taken together, these observations support a role for p18 in human HSC maintenance and that the p18 inhibitor 005A can enhance the self-renewal of long-term HSCs.
IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial
Authors: Mitchell Rachel J. , Kirkwood Amy A. , Barretta Emilio , Clifton-Hadley Laura , Lawrie Emma , Lee SooWah , Leongamornlert Daniel , Marks David I. , McMillan Andrew K. , Menne Tobias F. , Papaemmanuil Elli , Patel Bela , Patrick Pip , Rowntree Clare J. , Zareian Nahid , Alapi Krisztina Zuborne , Moorman Anthony V. , Fielding Adele K. 
Published: September 2021

Abstract
IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1− B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1− ΔIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1 and outcome is the older age of participants in our population. The impact of ΔIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617.
Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial
Authors: Herrera Alex F. , Burton Catherine , Radford John , Miall Fiona , Townsend William , Santoro Armando , Zinzani Pier Luigi , Lewis David , Fowst Camilla , Brar Satjit , Huang Bo , Thall Aron , Collins Graham P. 
Published: September 2021

Abstract
The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti–PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of &gt;90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post–allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.
Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition
Authors: Lew Thomas E. , Lin Victor S. , Cliff Edward R. , Blombery Piers , Thompson Ella R. , Handunnetti Sasanka M. , Westerman David A. , Kuss Bryone J. , Tam Constantine S. , Huang David C. S. , Seymour John F. , Roberts Andrew W. , Anderson Mary Ann 
Published: September 2021

Abstract
Covalent Bruton tyrosine kinase inhibitors (BTKi’s) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. However, relapses are expected with second-line TA therapy, and the clinical challenge of double class-resistant disease is now emerging with increasing frequency. To define the characteristics and outcomes of patients with double class-resistant disease, we retrospectively analyzed 17 patients who developed progressive disease (PD) on both TA classes for CLL (venetoclax, then BTKi, n=12; BTKi, then venetoclax, n = 5). The cohort was heavily pretreated (median lines of prior therapy, 4) and enriched for adverse disease genetics (complex karyotype, 12 of 12 tested [100%]; del(17p)/TP53 mutations, 15 of 17 [88%]). The median time to progression on prior venetoclax was 24 months (range, 6-94 months) and was 25 months (range, 1-55 months) on prior BTKi. Progression on second-line TA was manifest as progressive CLL in 11 patients and as Richter transformation in 6. The median overall survival after progression on second-line TA was 3.6 months (95% confidence interval, 2-11 months). Patients with double class-resistant CLL have a dismal prognosis, representing a group of high unmet need.