bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA011: Strategies to close the translational gap for nanoscale drug delivery systems
Authors: Straehla Joelle P. 
Published: December 2024

Abstract
Nanoscale drug delivery systems have enormous potential to leverage innovative chemistry and encapsulate a wide range of cargo. However, compared to the large number and diverse scope of nanoscale systems described in preclinical manuscripts, there are relatively few approved drug products representing a narrow range of chemistries. There are many reasons for this translational gap, ranging from manufacturing and regulatory challenges to clinical relevance and safety. This presentation outlines key strategies to address the multifaceted challenges that hinder the clinical adoption of nanoscale drug delivery systems. One of the first barriers is the difficulty of scaling up the production of nanoscale systems while maintaining quality and consistency. An illustrative case study will be shared of an approved nanotherapeutic becoming unavailable due to manufacturing concerns, and the resultant change in clinical practice. For a new investigational agent, the work required to optimize a promising nanoformulation is time-consuming and may not result in immediate, publishable findings, creating tension between essential translational work and projects more likely to yield high-profile publications and contribute to academic promotion. In the industry setting, successfully navigating this hurdle is likely to require significant capital, again without a guarantee of success. Without a stable and robust formulation that can be scaled for good manufacturing practice, the benefits of an innovative formulation cannot be fully realized. Another key principle underlying successful translation is identifying a clear clinical indication, which will guide clinical trial design and improve the likelihood of regulatory approval. Recent data suggest that national research funding trends heavily influence the focus of nanotechnology studies, resulting in a misalignment between clinical needs and the investigational agents being developed. In the future, a funding re-alignment may open additional opportunities for basket trials in patient populations lacking a standard of care, or in diseases where the current treatment options are highly toxic. Expanding the clinical indications for nanotherapeutics will likely require academic-industry partnerships to bring together a robust drug product and a strong clinical rationale. The regulatory process for nanoscale therapeutics is evolving, making early communication between investigators and regulators crucial for successfully transitioning nanoscale drug delivery systems from the lab to clinical use for cancer patients.
Citation Format: Joelle P. Straehla. Strategies to close the translational gap for nanoscale drug delivery systems [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA011.
Abstract IA013: Discovery of the dual A2A/A2B receptor antagonist MK-1088 for the treatment of solid tumors
Authors: DeMong Duane E. , Ranganath Sheila , Cumming Jared , Larsen Matthew , Zhang Yonglian , Plummer Christopher , Ali Amjad , Palmieri Anthony , Barry Evan , Daublain Pierre , Gupta Pranav , Chatterjee Manash , Presland Jeremy , Schneider Sebastian , Ciaccio Paul , Tatosian Daniel , Sather Aaron , Turnbull Ben , Silverman Steven , Chobanian Harry , Krishnamurthy Harini , Wnek Richard , Crowley Stephen , Miller Alita , Ayers Mark , Hinton Marlene , Chrencik Jill , Rottey Sylvie , O'Neil Jennifer 
Published: December 2024

Abstract
In the tumor microenvironment (TME), adenosine levels have been shown to be elevated relative to normal tissues. This increase in adenosine levels renders an immunosuppressive effect via direct effects on T cells via agonism of the A2A receptor and indirect effects via agonism of both A2A and A2B receptors on myeloid cells. With these observations as a backdrop, we sought to develop a dual A2A/A2B receptor antagonist with properties that would enable maintenance of high levels of target engagement of the A2A and A2B receptors even at trough concentration. Drawing on our organization’s significant prior experience developing A2A receptor antagonists for the potential treatment of Parkinson’s disease, we developed MK-1088, a highly potent A2A/A2B dual receptor antagonist that was purposefully designed to possess excellent selectivity over the related A1 and A3 receptors. This presentation will detail the discovery and development strategy that was employed to identify molecules that met the profile exemplified by this molecule. A single ascending dose study of MK-1088 in healthy human volunteers demonstrated our ability to achieve, at trough concentration, &gt;99% target engagement (TE) at the A2A receptor and &gt;90% TE at the A2B receptor. Details of the pharmacokinetics, safety, and tolerability from this study will be highlighted.
Citation Format: Duane E. DeMong, Sheila Ranganath, Jared Cumming, Matthew Larsen, Yonglian Zhang, Christopher Plummer, Amjad Ali, Anthony Palmieri, Evan Barry, Pierre Daublain, Pranav Gupta, Manash Chatterjee, Jeremy Presland, Sebastian Schneider, Paul Ciaccio, Daniel Tatosian, Aaron Sather, Ben Turnbull, Steven Silverman, Harry Chobanian, Harini Krishnamurthy, Richard Wnek, Stephen Crowley, Alita Miller, Mark Ayers, Marlene Hinton, Jill Chrencik, Sylvie Rottey, Jennifer O'Neil. Discovery of the dual A2A/A2B receptor antagonist MK-1088 for the treatment of solid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA013.
Abstract IA020: Discovery of brain-penetrant inhibitors for the treatment of BRAF mutant tumors
Authors: Kahn Dean 
Published: December 2024

Abstract
Many tumors are driven by oncogenic kinases. While a majority of the most prevalent oncogenic kinases currently have existing targeted therapies available, most of the molecules were not designed to be CNS penetrant and are therefore unable to control CNS metastatic tumors. By employing principles for the design of CNS penetrant molecules, we discovered two brain-penetrant BRAF inhibitors, which both progressed into clinical trials. The first candidate, ARRY-461, was designed to inhibit class I mutant BRAF V600E tumors. The second candidate, ARRY-440, was designed to inhibit class I, II, III, and indel mutant BRAF tumors. Additionally, ARRY-440 was designed to overcome both the paradoxical activation of BRAF as well as inhibit mBRAF:wtCRAF heterodimers, two features that most 1st generation BRAF V600E inhibitors lack. Finally, we were pleased to see that ARRY-440 led to clinical responses in a variety of different BRAF V600E tumors, including in some tumors that harbored both a BRAF V600E mutation and an oncogenic NRAS mutation.
Citation Format: Dean Kahn. Discovery of brain-penetrant inhibitors for the treatment of BRAF mutant tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA020.
Abstract PR003: Structure-guided design and optimization of small molecule CD73 inhibitors with excellent drug-like properties: discovery of quemliclustat
Authors: Jeffrey Jenna 
Published: December 2024

Abstract
In the tumor microenvironment, high concentrations of extracellular adenosine promote tumor proliferation through various immunosuppressive mechanisms. High expression of CD73—an ecto-nucleotidase that produces adenosine from adenosine monophosphate—has been associated with poorer prognosis in several tumor types. Herein, we describe the drug discovery efforts that resulted in the discovery of quemliclustat, a highly potent and selective inhibitor of CD73. As a small molecule with excellent drug-like properties, quemliclustat offers several advantages over CD73 antibodies in development, such as greater inhibition of CD73 enzymatic activity (both soluble and membrane-bound), deeper tumor penetration, and the potential for both IV and oral formulations. Quemliclustat was the first small molecule CD73 inhibitor to enter clinical development and is currently being evaluated in various Phase 1/2 studies in advanced solid tumors, including lung and pancreatic cancers. Recent data in metastatic pancreatic cancer are supportive of further study in this disease setting.
Citation Format: Jenna Jeffrey Structure-guided design and optimization of small molecule CD73 inhibitors with excellent drug-like properties: discovery of quemliclustat. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr PR003
Factors That Limit Evaluation of Velopharyngeal Closure During Nasopharyngoscopy
Authors: Snodgrass Taylor D. , Sitzman Thomas J. , Chee-Williams Jessica L. , Temkit Hamy , Perry Jamie L. 
Published: December 2024

Objective To assess the quality of nasopharyngoscopy video recordings used for velopharyngeal insufficiency (VPI) surgical planning and identify factors that limit evaluation of velopharyngeal closure. Design Prospective observational study. Setting Metropolitan-based hospitals with craniofacial clinics in the United States and Canada. Participants One-hundred and forty-two (142) patients with VPI across 10 hospitals. Assessment(s) Nasopharyngoscopy video recordings used for VPI surgical planning . Main Outcome Measure(s) Ratability of nasopharyngoscopy video recordings, with “ratable” defined as the video (1) visualized the velum, lateral pharyngeal wall, and posterior pharyngeal walls at some point during speech production and (2) contained an oral speech sample at the phrase level or above. Results One-hundred and forty-two (142) nasopharyngoscopy video recordings were obtained from patients undergoing VPI evaluation, of which 59.9% (n=85) were ratable. A multilevel logistic regression model was used to identify factors that influenced the quality of nasopharyngoscopy video recordings. Factors associated with unratable nasopharyngoscopy videos were age ( P=.030), sex ( P=.005*), type of scope camera used ( P=.039), presence of compensatory misarticulations ( P=.008), and a limited speech sample ( P=.040). Conclusions A substantial proportion of nasopharyngoscopy video recordings obtained during VPI evaluation are not sufficient for rating velopharyngeal closure. Lack of ratability could impact the surgery selected to treat VPI. Younger patients, those with limited speech samples, or patients with extensive compensatory articulations may be more successful in completing other VPI imaging techniques, such as videofluoroscopy or magnetic resonance imaging.
β-Thalassemia minor is associated with high rates of worsening anemia in pregnancy
Authors: Langer Arielle L. , Goggins Brynn B. , Esrick Erica B. , Fell Geoffrey , Berliner Nancy , Economy Katherine E. 
Published: December 2024

Abstract
We identified 347 pregnancies in patients with β-thalassemia minor. Hemoglobin was &lt;9 g/dL in 31% during third trimester and 7.6% at delivery. Postpartum hemorrhage occurred in 8.9%. Forty-six percent of IV iron administration was to iron-replete patients.
Comparison of different treatment options in submacular haemorrhage
Authors: Hillenmayer Anna , Wertheimer Christian M. , Hillenmayer Marlene , Strehle Laura D. , Hartmann Lennart M. , Vounotrypidis Efstathios , Wolf Armin 
Published: December 2024

Abstract
Background/aims
Submacular haemorrhages (SMH) cause significant visual impairment. Until now, the comparative effectiveness of different treatment approaches remains inconclusive without clear treatment guidelines. The aim of our study was to evaluate the effectiveness of 5 surgical treatment modalities in terms of visual prognosis and success rate.

Methods
This retrospective study included 201 patients with SMH. Primary endpoint was best corrected visual acuity (BCVA), secondary endpoints included haemorrhage size and complications. Group 1 was treated with pneumatic displacement and rtPA-injection. Group 2 followed the "Manchester protocol" with rtPA-injection and—if needed—a standardised secondary procedure with pars plana vitrectomy (ppV) and subretinal rtPA. Group 3 underwent vitrectomy with subretinal rtPA, group 4 vitrectomy only and group 5 received subretinal lavage.

Results
Baseline characteristics were a mean age of 79 years and a follow-up of 4.6 months. Pre-intervention BCVA of 1.7 logMAR improved to 1.4 logMAR at follow-up. A gain of > 0.2 logMAR was achieved in 47% of patients, while 20% lost > 0.2 logMAR. Only group 2 achieved a statistically significant visual gain. While group 5 was statistically larger in haemorrhage size preoperatively (p < 0.05), all groups were statistically equal in SMH size at follow-up. Complications led to additional interventions in 20% of patients.

Conclusions
No significant change in visual prognosis could be achieved depending on the intervention. As more invasive techniques seem to lack the benefit of a better postoperative prognosis while carrying higher risks, it may be beneficial considering a less invasive option first.
Effects of Eccentric Exercise of the Extensors on Eccentric Exercise-Induced Muscle Damage of the Flexors in Limbs
Authors: Chen Trevor C. , Tseng Wei-Chin , Kang Hsing-Yu , Chan Chuan-Wei , Chen Hsin-Lian , Nosaka Kazunori 
Published: December 2024

ABSTRACT

Introduction
We tested the hypothesis that muscle damage protection effect would be induced by its antagonist muscle eccentric exercise.

Methods
Sedentary young (20-28y) men were randomly assigned into six groups; three groups each for arm or leg exercise group (n = 12/group). One group performed two bouts of 30 maximal eccentric contractions (30MaxEC) of the elbow flexors (EF) or 60 maximal eccentric contractions (60MaxEC) of the knee flexors (KF) using a different arm (contra-EF-EF) or leg (contra-KF-KF) between bouts. The other two groups performed 30MaxEC of the elbow extensors (EE) or 60MaxEC of the knee extensors (KE) first followed by the 30MaxEC of EF or 60MaxEC of KF using the ipsilateral (ipsi-EE-EF, ipsi-KE-KF) or contralateral limb (contra-EE-EF, contra-KE-KF). The two exercise bouts were separated by 2 weeks for all groups. Changes in muscle damage markers before to 5 days following exercise were compared among the groups by mixed-design two-way ANOVAs.

Results
Changes in the markers following the second bout of the ipsi-EE-EF, contra-EE-EF, ipsi-KE-KF, and contra-KE-KF groups were smaller (P < 0.05) than those after the first bout of the contra-EF-EF and contra-KF-KF groups, respectively. The changes after the second bout were smaller (P < 0.05) for the ipsi-EE-EF than contra-EE-EF, and ipsi-KE-KF than contra-KE-KF group; however, those in the contra-EE-EF and contra-KE-KF groups were larger (P < 0.05) than those following the second bout of the contra-EF-EF and contra-KF-KF groups.

Conclusions
These results showed that the magnitude of muscle damage of EF or KF was reduced by the initial bout of EE or KE eccentric exercise performed by both ipsilateral and contralateral limbs, suggesting that muscle damage protective effect is conferred by the antagonist muscle in the same and opposite limbs.
Minimal hepatic encephalopathy - from cirrhosis to neurological disorders
Authors: Jarmołowicz Jakub , Boczar Agata , Dryja Patryk , Solisch Sven , Stawicka Izabela , Orzołek Izabela 
Published: December 2024

Introduction and aim
Minimal hepatic encephalopathy (MHE) is a subtle but significant brain dysfunction resulting from chronic liver damage, with symptoms that can be difficult to detect. It affects patients' quality of life by causing problems with concentration, memory, and motor coordination. Untreated MHE may progress to more severe neurological disorders, such as overt hepatic encephalopathy. The importance of this condition lies in its impact on patients' daily functioning and the increased risk of accidents, particularly in situations requiring quick responses, such as driving.Neurological symptoms caused by the disease are potentially reversible with treatment.

Materials and Methods
Available literature from the PubMed and Google Scholar databases was reviewed using the following keywords: "minimal hepatic encephalopathy," "hepatic encephalopathy," "cirrhosis," and "SIBO."

Conclusion
The significance of Minimal Hepatic Encephalopathy is crucial from the perspective of preventing further progression and the onset of overt hepatic encephalopathy, as well as improving the quality of life for our patients. Patients and their families are often unaware of the condition, and the cognitive impairments are frequently underestimated. Enhancing diagnostic methods would enable physicians to identify these patients more promptly.
Patient satisfaction with nursing care during biological therapy for inflammatory bowel disease: an observational study
Authors: Napolitano Daniele , Cocchieri Antonello , Orgiana Nicoletta , Durini Eleonora , Strazzeri Martina , Fanali Caterina , Poscia Andrea , Scaldaferri Franco 
Published: December 2024

Background: Patient satisfaction is related to patients’ expectation of health services, which they use to satisfy their needs for maintaining health and curing disease. The management of inflammatory bowel disease (IBD) involves complex diagnostic and therapeutic approaches, in which nurses play a decisive role. The present study evaluated patients’ overall perception of the quality of nursing care received during biological therapy. Methods: The researchers recruited patients who underwent outpatient biological therapy for IBD at a health institution between October and December 2021. They evaluated patient satisfaction of nursing care using three sections of the Newcastle Satisfaction Nursing Scale (NSNS). Participants were categorised according to time of follow-up: long (>12 months), short (≤12 months). Results: The researchers administered 234 questionnaires and enrolled 200 participants (response rate: 86.2%). The overall levels of satisfaction relating to scales A and B of the NSNS were 88.4 and 90.7, respectively. Patient loyalty was found to have a significant positive affect on satisfaction for scales A (90.5 versus 82.9, long versus short follow-up) and B (92.5 versus 86.0, long versus short follow-up) (p<0.05). Conclusions: The level of patient satisfaction at the centre was excellent, indicating that the overall perception of nursing care was very high.
The Influence of Body Fat Percentage on Body Type Cognitive Bias Among Young Chinese Hospital Staff Members: A Cross-Sectional Study
Authors: Wang Lu , Wen Jing , Xu Zhen , Guan Ke , Chen Yongchun 
Published: December 2024

Aims/Background This study expanded the existing literature on obesity and distortion of body image by examining subjective and objective body type among young medical workers, specifically investigating whether fat percentage independently influences body type cognitive bias. Methods We recruited 264 participants (41.29% male, mean age 26.2 ± 3.1 years, mean body mass index (BMI) 21.7 ± 3.1 kg/m2) at a comprehensive hospital in central China. The questionnaire responses of the enrolled participants concerning basic information and body type self-assessment were extracted. Their weights and body compositions were evaluated by the bioelectrical impedance analysis technique (BIA). Objective indicators included measured weight, BMI, fat percentage, waist circumference (WC) and waist-to-hip ratio (WHR). Results Based on this sample, the prevalence rate of body type cognitive bias was 28.79%. For women, the univariate regression analysis showed that fat percentage was significantly correlated with body type cognitive bias (odds ratio [OR] 1.107, 95% confidence interval [CI] 1.033–1.185, p = 0.004). BMI (OR 1.303, 95% CI 1.098–1.546, p = 0.002) and WC (OR 1.109, 95% CI 1.043–1.180, p = 0.001) might also be positively associated with body type cognitive bias. After adjusting for age, BMI, WHR, and job position, the risk of body type cognitive bias decreased with fat percentage up to the first inflection point (26.8%) (OR 0.78, 95% CI 0.62–0.98, p = 0.036), and then it increased up to the second inflection point (33.0%). When fat percentage exceeded 33.0%, the relationship lost statistical significance. No significant relationships were found for men. Conclusion Fat percentage is an independent, nonlinear factor influencing women's body type cognitive bias. Gender and fat percentage should be considered when establishing weight management intervention strategies to prevent obesity from becoming a public health problem.
The Impact of Child and Adolescent Inpatient Psychiatric Admissions Out-of-Area or to Adult Wards: A Systematic Review
Authors: Holland Josephine , Lewis Leonie , Wreford Alice , Singh-Lalli Hardeep , Roe James , Sayal Kapil 
Published: December 2024

Aims/Background Child and adolescent psychiatric inpatient admissions out-of-area or to adult wards are frequently discussed in the national media. No previous systematic reviews have investigated the impact of such admissions. Methods Systematic searches of MEDLINE, Embase, CINAHL, PsycINFO, PsycArticles, King’s Fund, Google Scholar, The Health Foundation, Social Care Online, Cochrane Library, Royal College of Psychiatrists, Web of Science and Econ light databases were conducted alongside grey literature searches. All eligible studies investigating the impact of acute psychiatric inpatient admission out-of-area or to adult wards in children and adolescents were included. Risk of bias was assessed using an adapted version of the Hawker critical appraisal tool. Results 18 studies were included (4 reported on out-of-area admissions, 13 on adult ward admissions, 1 study reported on both). Study quality was variable. Out-of-area admission impacts included longer emergency department waits, higher travel costs for families, and were described as ‘time-inefficient’. For studies of admissions of under-18s to adult psychiatric wards the most commonly reported impact was on length of stay. Opinions from staff and young people of these types of admissions were mostly negative. Conclusion Further studies looking at the full range of impacts of these admissions over the long term are needed.