bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR-16: Evaluating direct KRASQ61H inhibition in pancreatic cancer models
Authors: Long Szu-Aun , Amparo Amber M , Todd Haley , Goodhart Grace , Ahmad Syed A , Waters Andrew M 
Published: September 2024

Abstract
KRASQ61 mutations are associated with the worst prognosis among the various KRAS mutational subtypes of pancreatic ductal adenocarcinoma (PDAC). RMC-7977 is a RAS(ON) multi-selective noncovalent inhibitor with broad spectrum activity against oncogenic RAS mutants and wild-type RAS. The related investigational agent RMC-6236 is currently undergoing clinical trials. Binary complexes of CypA: RMC-7977 bind equipotently to multiple KRAS mutational subtypes however RMC-7977 is less potent at inhibiting growth in KRASQ61H-mutant cell lines. In contrast, RM-047 is a preclinical RAS(ON) Q61H-selective inhibitor tool compound. We evaluated direct KRASQ61H inhibition using both RMC-7977 and RM-047 in cell culture models. We found that in KRASQ61H-rescued RASless mouse embryonic fibroblasts (MEFs), RM-047 inhibited ERK activity and suppressed growth more potently than RMC-7977. Conversely, in a panel of KRASQ61H-mutant PDAC cell lines, RM-047 was less potent than RMC-7977 in two out of three KRASQ61H-mutant PDAC cell lines. Furthermore, we discovered that ERK activity rapidly rebounded with treatment in KRASQ61H-mutant PDAC cell lines, whereas ERK activity remained suppressed in KRASQ61H-rescued RASless MEFS lacking WT RAS alleles. Our analysis of DepMap data indicated that among the KRAS mutational subtypes frequently found in pancreatic cancer, KRASQ61H is the least dependent on KRAS for survival. This suggests that in a KRASQ61H-mutant PDAC setting, additional factors such as WT RAS expression may mediate growth. From our KRAS drug-anchored CRISPR loss-of-function screens, we found that the loss of EGFR sensitized cells to KRAS inhibition, particularly in a KRASQ61H-dependent context. Therefore, we combined erlotinib, an FDA-approved EGFR inhibitor, with either RM-047 or RMC-7977, and found that the addition of erlotinib prevented ERK rebound activity and synergized with RM-047 or RMC-7977 to reduce growth in KRASQ61H-mutant PDAC cell lines. These data provide insights into mechanisms by which KRASQ61H-mutant PDAC may be less dependent on KRAS for survival and further support the clinical evaluation of combined EGFR and RAS(ON) inhibition as a potential therapeutic strategy in the treatment of PDAC patients harboring KRASQ61H mutations.
Citation Format: Szu-Aun Long, Amber M Amparo, Haley Todd, Grace Goodhart, Syed A Ahmad, Andrew M Waters. Evaluating direct KRAS inhibition in pancreatic cancer models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-16.
Abstract PR-19: Cell polarity proteins as novel regulators of macropinocytosis
Authors: Barjau Guillem Lambies , Lee Szu-Wei , Duong-Polk Duong-Polk Karen , Dawson David , Galapate Cheska Marie , Maganti Swetha , Commisso Cosimo 
Published: September 2024

Abstract
Macropinocytosis has emerged as a nutrient-scavenging pathway that cancer cells exploit to survive the nutrient-deprived conditions of the tumor microenvironment. Cancer cells are especially reliant on glutamine for their survival, and in pancreatic ductal adenocarcinoma (PDAC) cells, glutamine deficiency can enhance the stimulation of macropinocytosis, allowing the cells to escape metabolic stress through the production of extracellular-protein-derived amino acids. Here, we identify the atypical protein kinase C (aPKC) enzymes, PKCz and PKCi, as novel regulators of macropinocytosis. In normal epithelial cells, aPKCs are known to regulate cell polarity in association with the scaffold proteins Par3 and Par6, controlling the function of several targets, including the microtubule-associated Par1 kinases. In PDAC cells, we identify that each of these cell polarity proteins are required for glutamine stress-induced macropinocytosis. Mechanistically, we find that the aPKCs are regulated by EGFR signaling or by the transcription factor CREM to promote the relocation of Par3 to microtubules, facilitating macropinocytosis in a dynein-dependent manner. Importantly, we determine that cell fitness impairment caused by aPKC depletion in glutamine stress is rescued by the restoration of macropinocytosis and that aPKCs support PDAC growth in vivo. These results identify a previously unappreciated role for the cell polarity protein network in the regulation of macropinocytosis and provide a better understanding of the mechanistic underpinnings that control macropinocytic uptake in the context of metabolic stress.
Citation Format: Guillem Lambies Barjau, Szu-Wei Lee, Karen Duong-Polk Duong-Polk, David Dawson, Cheska Marie Galapate, Swetha Maganti, Cosimo Commisso. Cell polarity proteins as novel regulators of macropinocytosis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-19.
Perceived Learning and Feedback of Students Following the Competency-based Clinical Rotation in Psychiatry: A Retrospective Review From Tertiary-care Teaching Institute in Central India
Authors: Kumar Akash , Gupta Snehil , Jain Jyotsna , Ghosh Sanjukta , Basera Devendra , Pakhre Ashish , Modak Tamonud 
Published: September 2024

Background: Competency-based medical education (CBME) offers avenues for effective psychiatry teaching to medical students. However, data concerning the feasibility, effectiveness, and students’ perspectives on CBME-based clinical rotation, including psychiatry, needs to be explored in India. Therefore, this research aims to evaluate the student’s learning effectiveness and feedback on the CBME-informed psychiatry posting. Methods: This cross-sectional retrospective research evaluated the 7th-semester MBBS students (n = 101, 39 [38.6%] females and 62 [71.4%] males), from a tertiary-care teaching hospital in central India, perceived change in Knowledge, Attitude, and Skill and feedback on the CBME-based clinical rotation (July-December 2023) using a mixed-method approach through an online feedback form. Results: A “considerable or marked perceived change,” ranging from 70% to 97%, in the knowledge, attitude, ethical aspects, psychomotor skills, and soft skills were noted. 84%–91% of students were “satisfied/quite satisfied (or rated it good to very good)” with the pattern and content of the program, including the assessment. 37% expressed their desire to take psychiatry as an elective. Descriptive responses showed that participants felt improvement in their communication skills, knowledge about non-pharmacological interventions, opportunity to observe and present cases in the Outpatient Department, and satisfaction with the teaching and assessment methods. The need for minor changes regarding case-based formative assessment and the opportunity for more case workups were also cited. Conclusion: The CBME-informed psychiatry clinical rotation can be instrumental in improving psychiatry training and promoting mental health among students. Research involving a comparison arm, longitudinal design, and validated assessment tools can bring greater insights into the subject.
Using a Smart Phone Based Application for Learning Physiology for 1st Professional Medical Students: Merits, Demerits and Challenges
Authors: Anjusha I.B.  , Nayak Vineetha K. Ramdas , Y.C. Nalini , Basavarajegowda Abhishekh 
Published: September 2024

Background and Aims: The aim of this study was to conduct a survey on usefulness of medical education-based software applications in learning physiology as an aid to regular academics among first-year medical and dental students in India. Methodology: This is a survey-based cross-sectional study which included 282 students from medical and dental health sciences. Results: Out of 282 medical students, 267 (95%) students found the app simple to follow, 257 (91%) students said that app was easy to understand and 243 (86%) found it as a learning aid to didactic learning. Conclusion: Our study reports that students widely use medical education-based apps for academic benefits and as an aid to didactic learning.
“You just can’t do that in dementia care”: Barriers to partnership working within dementia services for people from south Asian communities
Authors: Cheston R , Dodd E , Smith P , Woodstoke NS , Jutlla K , Fry G , Truswell D , Butt J , Parveen S 
Published: September 2024

Background: People from South Asian communities are under-represented at all levels of dementia services. Consequently, there is pressure for the statutory sector to deliver services in partnership with Voluntary, Community, Faith and Social Enterprises (VCFSEs). This study set out to explore the constraints to effective partnership working which prevent dementia care from being delivered in an equitable way. Methods: Data collection consisted of two phases. First, we interviewed seven people with experience of partnership working and developed three fictional vignettes that were representative of the challenges they faced. We then used these vignettes to stimulate discussion in focus groups and interviews with 13 VCFSE and 16 statutory sector participants. Data was analysed using deductive thematic analysis. Findings: Three themes were developed during the analysis. First, White British-centric services focused on the challenges for statutory services in meeting the needs of South Asians, developing flexible, responsive services and making inclusive partnership working truly meaningful. Second, VCFSE participants (but not statutory service participants) associated a failure to deliver effective partnership working with unconscious bias operating within systems, leading to the devaluing of their expertise and to their views being ignored. Finally, participants emphasised the need to prioritise relationships if they were to meet the challenges of developing partnership working. Conclusion: We identified three constraints acting to prevent effective partnership working. First, the different meanings that statutory and VCFSE participants attach to challenges threatens their ability to develop a shared understanding of the needs of communities. Second, a reluctance to explicitly address service deficiencies can mean that stereotypes remain unaddressed. Finally, while both parties lacked power to change the fundamentals of service delivery, power and resources were also unbalanced with VCSFE services being more reliant on the statutory sector.
Is less more? Intravenous immunoglobulin for pediatric immune thrombocytopenia
Authors: Elron Eyal , Yacobovich Joanne , Efros Orly , Tanous Osama , Levy-Mendelovich Sarina , Shamba Esti , Steinberg-Shemer Orna , Goldberg Tracie , Izraeli Shai , Gilad Oded 
Published: September 2024

Objectives: Treatment of pediatric immune thrombocytopenia (ITP) is guided by the risk of bleeding. Intravenous immunoglobulin (IVIg) is one of the first-line therapy options for new-onset pediatric ITP. However, the exact optimal dose of IVIg has not been determined. Methods: This retrospective cohort study included all hospitalized children with newly diagnosed ITP receiving IVIg as first-line therapy during 2010–2020. We compared the safety and efficacy of two common IVIg dose regimens, 1 and 2 g/kg. Outcomes were short and long-term treatment responses and adverse events to the different doses. Results: A total of 168 children were included in our cohort. Eighty-two children were treated with 1 g/kg of IVIg and 86 with 2 g/kg. There was no difference in sustained response (platelet count > 20 × 109, > 14 days) between the groups (74.3% vs 76.7%, respectively, p = 0.72) and maximal platelet counts following treatment ( p = 0.44). No difference was found regarding the percentage of chronic ITP between the two groups (24.4% in the 1 g/kg group as compared to 17.4% in the 2 g/kg group; p = 0.34). Logistic regression analysis demonstrated there was no effect of the IVIg dose on treatment failure and development of chronic ITP. As anticipated, 47.7% of adverse events were in the 2 g/kg group and 32.9% in the 1 g/kg group, with borderline statistical significance ( p = 0.06). Conclusion: The initial treatment of newly diagnosed pediatric ITP using a 1 g/kg IVIg regimen may give comparable results to the double dose of 2 g/kg in attaining a prolonged safe hemostatic threshold, without impacting the incidence of chronic disease.
Erythropoietin regulates osteoclast formation via up-regulating PPARγ expression
Authors: Liu Xiao , Zhou Mengxue , Wu Yifan , Gao Xiang , Zhai Lei , Liu Liang , Geng Huan 
Published: September 2024

AbstractErythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPARγ expression through activating the Jak2/ERK signaling pathway. Consistently, PPARγ antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPARγ agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPARγ signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient’s recovery and quality of life.
Late Pleistocene polar bear genomes reveal the timing of allele fixation in key genes associated with Arctic adaptation
Authors: Sun Yulin , Lorenzen Eline D. , Westbury Michael V. 
Published: September 2024

AbstractThe polar bear (Ursus maritimus) occupies a relatively narrow ecological niche, with many traits adapted for cold temperatures, movement across snow, ice and open water, and for consuming highly lipid-dense prey species. The divergence of polar bears from brown bears (Ursus arctos) and their adaptation to their Arctic lifestyle is a well-known example of rapid evolution. Previous research investigating whole genomes uncovered twelve key genes that are highly differentiated between polar and brown bears, show signatures of selection in the polar bear lineage, and are associated with polar bear adaptation to the Arctic environment. Further research suggested fixed derived alleles in these genes arose from selection on both standing variation and de novo mutations in the evolution of polar bears. Here, we reevaluate these findings based on a larger and geographically more representative dataset of 119 polar bears and 135 brown bears, and assess the timing of derived allele fixation in polar bears by incorporating the genomes of two Late Pleistocene individuals (aged 130–100,000 years old and 100–70,000 years old). In contrast with previous results, we found no evidence of derived alleles fixed in present-day polar bears within the key genes arising from de novo mutation. Most derived alleles fixed in present-day polar bears were also fixed in the Late Pleistocene polar bears, suggesting selection occurred prior to 70,000 years ago. However, some derived alleles fixed in present-day polar bears were not fixed in the two Late Pleistocene polar bears, including at sites within APOB, LYST, and TTN. These three genes are associated with cardiovascular function, metabolism, and pigmentation, suggesting selection may have acted on different loci at different times.
Risk factors and prognostic factors associated with retinal detachment and visual outcomes in acute retinal necrosis
Authors: Li Yuxin , Chen Li , Li Pengcheng , Kang Hao , Tao Yong 
Published: September 2024

Abstract
Objective
To investigate the risk factors and prognostic factors that affect the long-term clinical outcomes of acute retinal necrosis (ARN).

Methods
A retrospective study of patients with ARN who underwent treatment and completed follow-up in our ophthalmology department from 2011 to 2021 was conducted. The incidence and risk factors of retinal detachment (RD) and prognostic factors affecting long-term clinical outcomes, such as late-onset RD and final vision loss (< 20/200), were analyzed.

Results
Totally 59 ARN patients (65 eyes) with an average follow-up of 48.9 months were enrolled. During the follow-up period, RD occurred in 34 eyes (52.3%). The risk factors for RD included quadrants of involved retinal necrosis (odds ratio [OR], 4.181; 95% confidence interval [CI], 1.950–10.834) and initial intraocular viral load (OR, 1.721; 95% CI, 1.071–3.083). Early intravitreal antiviral treatment (OR, 1.204; 95% CI, 1.040–1.480) was independently associated with a decreased risk of late-onset RD. The factors independently associated with an increased risk of final vision loss were worse initial visual acuity (OR, 3.895; 95% CI, 1.551–13.662) and late-onset RD (OR, 8.043; 95% CI, 1.380–67.216). In addition, we utilized the fluctuating magnitude of viral load to quantify the extent of its reduction in comparison to its original value following the initial intravitreal antiviral injection (IAI). This ratio was strongly related to initial intraocular IL-8 concentration (Spearman correlation coefficient=-0.741, P = 0.000) and moderately related to the initial degree of aqueous flare (Spearman correlation coefficient=-0.508, P = 0.010).

Conclusion
RD is a common and severe complication of ARN with multiple risk factors, such as initial retinitis involvement area and initial intraocular viral load. Active local antiviral therapy may reduce the risk of late-onset RD. The antiviral medication should be adjusted according to the inflammatory state. Therefore, timely detection of causative viruses and intensive systemic and local antiviral therapy is crucial for preserving visual function in ARN patients.
Synthesis and evaluation of nanosized aluminum MOF encapsulating Umbelliferon: assessing antioxidant, anti-inflammatory, and wound healing potential in an earthworm model
Authors: Thabit Rabab M. , El-Aziz Fatma El-Zahraa A. Abd , El-Fadl A. Abu , Abu-Sehly A. A. , Sayed Ahmed M. 
Published: September 2024

AbstractNanoporous aluminum metal–organic framework (Al-MOF) was synthesized via solvothermal methods and employed as a carrier matrix for in vitro drug delivery of Umbelliferon (Um). The encapsulated Um was gradually released over seven days at 37 °C, using simulated body fluid phosphate-buffered saline (PBS) at pH 7.4 as the release medium. The drug release profile suggests the potential of Al-MOF nanoparticles as effective drug delivery carriers. Structural and chemical analyses of Um-loaded Al-MOF nanoparticles (Um-Al MOF) were conducted using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), and ultraviolet–visible (UV–Vis) spectroscopy. Thermal gravimetric analysis (TGA) was employed to investigate the thermal stability of the Al-MOF nanoparticles, while Transmission Electron Microscopy (TEM) was utilized to assess their morphological features. Um-Al MOF nanoparticles demonstrated notable antioxidant and anti-inflammatory properties compared to Um and Al-MOF nanoparticles individually. Moreover, they exhibited significant enhancement in wound healing in an earthworm model. These findings underscore the potential of Al-MOF nanoparticles as a promising drug delivery system, necessitating further investigations to explore their clinical applicability.
Factors associated with acculturative stress among international medical students in an Egyptian university
Authors: Ali Yomna Ayman , Hussein Rasha Saad , Mostafa Nayera Samy , Manzour Ayat Farouk 
Published: September 2024

Abstract
Background
International students frequently face difficulties that are specific to the typical college experience, in addition to facing other factors of acculturative stress, including cultural differences, language barriers, and comfortability in accommodation.

Aim
The study aims to measure the prevalence of acculturative stress among first-year international students enrolled at Faculty of Medicine in an Egyptian University and aims to reveal the factors that are associated with acculturative stress in these students.

Methodology
A cross-sectional study was conducted on 422 international students in the academic year 2021–2022, using the Acculturative Stress Scale for International Students (ASSIS). The factors associated with acculturative stress were examined using the following criteria: comfort in accommodation, student adjustment to college, language proficiency, and academic pressure.

Results
This study showed that 28.7% of the international students were “above the warning sign” of acculturative stress (above 109). The major stressors of acculturative stress among international students were the non-specific concerns, homesickness, and perceived discrimination, while the least reported stressors were fear and guilt. International students who scored in the “above the warning sign” in the (ASSIS) were mostly females (35.3%) and non-Arab students (37.8%). Having a friend or a family member living in Egypt significantly reduced the level of acculturative stress. Moreover, the ASSIS total score showed a negative correlation with the scores for overall language proficiency, comfort in accommodation, academic adjustment, and student adjustment to college.

Conclusion
Acculturative stress among the studied groups is influenced by several factors, including nationality, English and Arabic language proficiency, academic adjustment, and comfort of living. That being said, the most significant stressor is the country of origin, which is defined in terms of nationality or language proficiency. Consequently, resources that ensure the sustainability and growth of international students throughout their educational process must be made available to a multicultural environment in order to support and retain those students.

Clinical trial number
Not applicable.