bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative evaluation of oncogenic KRAS signaling and therapeutic effects of molecular-targeted drugs in living cells by single-molecule imaging.
Authors: Yokoi Ryoma , Tajima Jesse Yu , Kiyama Shigeru , Tanaka Yoshihiro , Murase Katsutoshi , Futamura Manabu , Suzuki Kenichi , Matsuhashi Nobuhisa 
Published: August 2024

76 Background: Oncogenic KRAS mutations pose challenges due to their constitutive activation and resistance to drugs in colorectal cancer. However, several aspects remain unresolved. Single-molecule imaging has revealed distinct behaviors of KRAS. Inactive KRAS wild-type (WT) molecules exhibit continuous lateral diffusion on the plasma membrane, while activated or oncogenic KRAS molecules display slower diffusion and transient trapping due to interactions with signaling molecules. These observations suggest that the overall signal intensity of KRAS within a cell is finely regulated by integrating short-term pulse signals during transient trapping. Methods: We conducted single-molecule observations of KRAS (WT, G13D, and G12D/C/V) in living colon cancer cells, both with and without molecular-targeted drugs, before and after EGF stimulation. We quantitatively analyzed their diffusional behavior to evaluate KRAS signaling and the therapeutic effects of molecular-targeted drugs. Results: The temporal fraction of trapped KRAS WT was highest at 2 minutes (6.4%) and decreased to pre-activation level (3.0%) at 5 minutes after EGF stimulation. Although the temporal fractions of trapped KRAS mutants were higher than those of KRAS WT both before stimulation (5%) and after stimulation (10%), their diffusional behaviors were mutation-specific. The temporal fraction of trapped KRAS G13D increased sharply, and those of KRAS G12D and G12C increased at a moderate rate, while that of KRAS G12V did not elevate after EGF stimulation. Cetuximab treatment significantly reduced the temporal fraction of trapped KRAS WT after stimulation, but only moderately decreased those of KRAS mutants. Notably, transient trappings of KRAS G12D and G12C were abrogated by KRAS inhibitors, and the combined therapy of KRAS inhibitors and cetuximab demonstrated additive effects. Conclusions: Our findings indicate that the mutation-specific diffusional behavior of oncogenic KRAS can be quantitatively assessed by single-molecule imaging. This method serves as a powerful tool to uncover the mechanisms underlying oncogenic KRAS signaling and evaluate the therapeutic efficacy of molecular-targeted drugs in living cells.
Racial differences of secondary metastasis in patients with colon cancer: A United States population-based cohort study.
Authors: Suenghataiphorn Thanathip , Kulthamrongsri Narathorn , Tribuddharat Narisara , Danpanichkul Pojsakorn , Lohawatcharagul Tuntanut , Saowapa Sakditad , Thongpiya Jerapas , Chaisidhivej Natapat , Osataphan Soravis Alm 
Published: August 2024

80 Background: Disparities in health outcomes exist among racial and ethnic groups in the United States, notably in patients with colon cancer. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with colon cancer is still limited. Therefore, we aim to assess the association between metastatic colon cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have colon cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 80,130 patients with primary diagnosis of colon cancer at discharge. The mean age was 67.4 years; 49.7% were female. Caucasians accounted for 69.3%, with African Americans at 13.3% and Hispanics at 8.2%. 15% of the patients had liver metastasis, whereas 22% had lung metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of lung metastasis (aOR 1.22; 95%CI (1.07, 1.40), p = 0.003), higher risk of liver metastasis (aOR 1.51; 95%CI (1.31, 1.74), p = 0.021) and longer length of stay (b = 0.95; 95%CI (0.56, 1.33), p = 0.001). Hispanics also had higher risk of lung (aOR 1.22, p < 0.05) and liver metastasis (aOR 1.24, p = 0.021). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. To establish a causal relationship between races, metastasis, and mortality in patients with colon cancer, further longitudinal research is necessary. [Table: see text]
Trends in megestrol acetate prescription among Korean patients with biliary-pancreatic cancer and their impact.
Authors: Kim Ju Won , Oh Hoon Ji 
Published: August 2024

85 Background: Chemotherapy-induced anorexia poses a significant challenge for cancer patients, particularly in biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC), known for their poor response to treatment. Megestrol acetate (MA), a commonly prescribed appetite stimulant, is associated with concerns regarding thrombosis and polypharmacy. Understanding the trends in MA prescription and its cascade effects is essential for optimizing cancer care. Methods: We conducted a retrospective cohort study using data from the Health Insurance and Review Assessment Service (HIRA) database in South Korea. The study included patients diagnosed with BTC and PDAC between 2008 and 2017. Prescription trends for MA, thrombosis events, anticoagulant prescriptions, and total parenteral nutrition (TPN) were analyzed. Statistical analysis included Chi-square tests and Kaplan-Meier estimates. Results: In our analysis of 41,670 patients with BTC and PDAC between 2008 and 2017, MA prescriptions increased notably, with PDAC patients rising from 7.85% to 51.84%. TPN prescriptions remained consistently high, especially among patients prescribed MA. For instance, in 2008, 94.71% of BTC patients prescribed MA received TPN, compared to 70.34% without MA. Similarly, in 2017, 87.56% of those prescribed MA received TPN, compared to 61.63% without MA. Among BTC patients with long-term MA prescriptions, 16.34% received anticoagulants, compared to 4.92% without MA (p<0.001). Among PDAC patients, 18.3% with long-term MA prescriptions received anticoagulants, compared to 7.12% without MA (p<0.001). Conclusions: The study highlights the escalating trend in MA prescriptions among BTC and PDAC patients, along with increased thrombosis diagnoses and anticoagulant prescriptions. These findings underscore the importance of understanding and managing the cascade effects of MA use and associated polypharmacy in optimizing cancer care and improving patient outcomes.
Exploratory phase I study of HF1K16 for the treatment of patients with refractory/recurrent advanced glioma.
Authors: Huang Ruofan , Zheng Anjie , Xu Yuhong , Zhang Xiaochen , Wu Jinsong 
Published: August 2024

TPS32 Background: Glioblastoma (GBM) is the most common primary and aggressive malignant brain tumor in adults. Almost all patients with glioblastoma eventually have disease relapse and the median overall survival (OS) remains at only 30 weeks for those recurrent GBM patients. However, very few therapies had been approved over the past two decades, emphasizing the need for novel treatments. It is now wildly acknowledged that the immune microenvironment in brain offers adequate opportunities to implement immunotherapy for the treatment. Since most recurrent tumors had previously been exposed to the genotoxic stress of irradiation and/or chemotherapy, it is predicted to resulted in a higher mutational load and more immunogenic. However, The limited success of T cell immunomodulatory approach for advanced glioma has prompted a deeper understanding of the brain tumor and the immune microenvironment. GBM tumors are well-appreciated to be a immunosuppressive and a hallmark of GBM immunosuppression is the appearance of circulating myeloid-derived suppressor cells (MDSCs) at higher levels. Our preliminary data suggests that HF1K16, a liposome ATRA (all trans retinoic acid) suspension, is capable of relieving immune suppression induced by MDSCs. Further, we recently completed a phase I dose escalation study which showed that HF1K16 is safe, well-tolerated with preliminary efficacy in brain tumor. Thus, we hypothesized that HF1K16 may reverse GBM-associated immune suppression and leading to an increase in TILs and improved survival. Methods: This is an advanced glioma-specific expansion arm for adult patients with prior confirmed brain tumor and failed standard treatment. We plan to enroll 20~30 evaluable patients. Key eligibility criteria include candidates age ≥ 18 years, Karnofsky performance status ≥ 60 with and at least one measurable lesion. The primary endpoint is determination of overall response rate (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) according to RANO criteria. Secondary endpoints include longitudinal assessment of the peripheral immune response by changes in MDSC and T cell subsets and numbers. HF1K16 infusions were administered in 21-day cycles (q.o.d days 1-14). Prior to and during treatment, peripheral blood mononuclear cells were collected and analyzed with flow cytometry to monitor the changes in myeloid cell phenotype and T cell composition. The recruitment of patients is anticipated completed in 2024. Clinical trial information: NCT05388487 .
Predictors of Hydrocephalus Risk After Stereotactic Radiosurgery for Vestibular Schwannomas: Utility of the Evans Index
Authors: Santhumayor Brandon A. , Mashiach Elad , Meng Ying , Rotman Lauren , Golub Danielle , Bernstein Kenneth , Vasconcellos Fernando De Nigris , Silverman Joshua S. , Harter David H. , Golfinos John G. , Kondziolka Douglas 
Published: August 2024

BACKGROUND AND OBJECTIVES:
Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined.

METHODS:
A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)—maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull—were measured on axial postcontrast T1-weighted magnetic resonance imaging.

RESULTS:
A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001).

CONCLUSION:
Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.
Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis
Authors: Sam Jessica , Torregroza Ingrid , Evans Todd 
Published: August 2024

ABSTRACT
Mutations in GATA6 are associated with congenital heart disease, most notably conotruncal structural defects. However, how GATA6 regulates cardiac morphology during embryogenesis is undefined. We used knockout and conditional mutant zebrafish alleles to investigate the spatiotemporal role of gata6 during cardiogenesis. Loss of gata6 specifically impacts atrioventricular valve formation and recruitment of epicardium, with a prominent loss of arterial pole cardiac cells, including those of the ventricle and outflow tract. However, there are no obvious defects in cardiac progenitor cell specification, proliferation or death. Conditional loss of gata6 starting at 24 h is sufficient to disrupt the addition of late differentiating cardiomyocytes at the arterial pole, with decreased expression levels of anterior secondary heart field (SHF) markers spry4 and mef2cb. Conditional loss of gata6 in the endoderm is sufficient to phenocopy the straight knockout, resulting in a significant loss of ventricular and outflow tract tissue. Exposure to a Dusp6 inhibitor largely rescues the loss of ventricular cells in gata6−/− larvae. Thus, gata6 functions in endoderm are mediated by FGF signaling to regulate the addition of anterior SHF progenitor derivatives during heart formation.
Regulation of ROP GTPase cycling between active and inactive states is essential for vegetative organogenesis in Marchantia polymorpha
Authors: Sakai Yuuki , Ueno Aki , Yonetsuka Hiroki , Goh Tatsuaki , Kato Hirotaka , Kondo Yuki , Fukaki Hidehiro , Ishizaki Kimitsune 
Published: August 2024

ABSTRACT
Rho/Rac of plant (ROP) GTPases are plant-specific proteins that function as molecular switches, activated by guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). The bryophyte Marchantia polymorpha contains single copies of ROP (MpROP), GEFs [ROPGEF and SPIKE (SPK)] and GAPs [ROPGAP and ROP ENHANCER (REN)]. MpROP regulates the development of various tissues and organs, such as rhizoids, gemmae and air chambers. The ROPGEF KARAPPO (MpKAR) is essential for gemma initiation, but the functions of other ROP regulatory factors are less understood. This study focused on two GAPs: MpROPGAP and MpREN. Mpren single mutants showed defects in thallus growth, rhizoid tip growth, gemma development, and air-chamber formation, whereas Mpropgap mutants showed no visible abnormalities. However, Mpropgap Mpren double mutants had more severe phenotypes than the Mpren single mutants, suggesting backup roles of MpROPGAP in processes involving MpREN. Overexpression of MpROPGAP and MpREN resulted in similar gametophyte defects, highlighting the importance of MpROP activation/inactivation cycling (or balancing). Thus, MpREN predominantly, and MpROPGAP as a backup, regulate gametophyte development, likely by controlling MpROP activation in M. polymorpha.
An overview of the distribution and natural history of Anthaxia olympica Kiesenwetter, 1880 and A. astoreth Obenberger, 1934 (Coleoptera: Buprestidae), with a new synonymy and lectotype designation
Authors: TROJAN ILJA 
Published: August 2024

The distribution of Anthaxia olympica Kiesenwetter, 1880 and A. astoreth Obenberger, 1934 is critically reviewed throughout their range. Anthaxia olympica has been recorded from 1026 localities in 21 countries of Europe and Western Asia, while A. astoreth has been recorded from 135 localities in seven Western Asian countries. For the first species, the first detailed distributional record from the Republic of Moldova is presented, while the latter species is for the first time recorded for Iraq. In addition, detailed occurrence data of A. olympica from Azerbaijan with details are provided here for the first time. Similarly, although A. astoreth has already been listed for Israel, Jordan and Lebanon detailed occurence data from these countries are presented for the first time. Records from literature from all countries are presented here in details, in many cases supplemented by data of the author. A grid map with the distribution of A. olympica in the Czech Republic and Slovakia is presented, as well as a map of the general distribution of both species. Remarks on biology of both species as well as graphs of seasonal dynamics are also provided. The collected data show that A. olympica is monophagous on dog rose (Rosa canina), with only four documented developments in different plant species; on the other hand, A. astoreth has been documented as a polyphagous species. A lectotype for A. olympica is designated here. Based on the study of type materials, Anthaxia denesi Svoboda, 2000 is proposed as junior subjective synonym of A. astoreth.
Quality of Life Analysis of Primary Glaucoma Patients Based on Glaucoma Quality of Life-15 Score at Dr. Moewardi Hospital Surakarta
Authors: Changifer Stephen , Indrakila Senyum , Widiati Retno 
Published: August 2024

<p class="Default"><strong>Introduction: </strong>Visual acuity is vital for human's daily life. Glaucoma is a disease that affects visual acuity. In Indonesia, the number of glaucoma cases is quite high and its therapy focuses on eye health indicators. Whereas, Many studies have demonstrated that the quality of life of glaucoma patients diminishes. This research aimed to determine the quality of life of primary glaucoma patients in Dr. Moewardi hospital.</p><p class="Default"><strong>Method: </strong>This research was conducted using observational analytic method with cross sectional approach. Sampling process uses probability sampling with purposive sampling method. The subjects of this study were primary glaucoma patients in Dr. Moewardi hospital from July to November 2022. The sample size obtained from the formula was 38 people. Data were analyzed with independent t-test and one-way ANOVA. </p><p class="Default"><strong>Result: </strong>From the data analysis of GQL-15<strong> </strong>questionnaire's answer, it was found that there was a decrease in quality of life marked by higher GQL-15 questionnaire score in older patients, longer duration of diagnosis, partially or totally blind and no history of surgery. There was no increase in GQL-15 questionnaire result on patients with higher level of education. GQL-15 score in patients with longer duration of diagnosis (p-value = 0.011) and lower visual acuity (p-value = 0,000) was statistically significant.</p><p class="Default"><strong>Conclusion: </strong>Older patient groups, patients with longer duration of diagnosis, blind patients (unilateral or bilateral), and those who had not undergone glaucoma surgery has a worse quality of life. Patients’ visual acuity and duration of diagnosis are significantly correlated with their quality of life.</p>
Laser enrichment of the 62Ni isotope for betavoltaic devices
Authors: Suryanarayana M. V. , Sankari M. 
Published: August 2024

We have studied the laser isotope separation of the 62Ni isotope using a three-step ladder type photoionization scheme. Using density matrix formalism, optimum conditions for the efficient separation of the 62Ni isotope have been derived. The optimum bandwidth of the excitation lasers has been found to be 200 MHz, 1200 MHz, and 1200 MHz for the enrichment of the 62Ni isotope. It has also been shown that it is possible to produce 75 mg/day of 90% enriched 62Ni using the optimized experimental operating parameters derived in this work. Upon irradiation of this enriched 62Ni isotopic mixture, it is possible to produce ∼19mg/day of the 63Ni isotope, which is sufficient to manufacture a 100 µW betavoltaic device each day.
Pain medication tapering for patients with Persistent Spinal Pain Syndrome Type II, treated with Spinal Cord Stimulation: A RCT–study protocol of the PIANISSIMO study
Authors: Moens Maarten , Crunelle Cleo Lina , Putman Koen , Wuyts Elke , Bultinck Frenn , Van Puyenbroeck Hubert ,   PIANISSIMO consortium, Goudman Lisa 
Published: August 2024

Background
Spinal Cord Stimulation (SCS) may provide pain relief in patients with therapy-refractory Persistent Spinal Pain Syndrome Type II (PSPS-T2). Despite the evidence that SCS can reduce disability and reduce pain medication usage, only 25% of the patients is able to completely omit pain medication usage after 12 months of SCS. To tackle the high burden of patients who consume a lot of pain medication, tapering programs could be initiated before starting a trajectory with SCS. The current objective is to examine whether a pain medication tapering program before SCS alters disability in PSPS-T2 patients compared to no tapering program.

Methods and design
A three-arm, parallel-group multicenter randomized controlled trial will be conducted including 195 patients who will be randomized (1:1:1) to either (a) a standardized pain medication tapering program, (b) a personalized pain medication tapering program, or (c) no tapering program before SCS implantation, all with a follow-up period until 12 months after implantation. The primary outcome is disability. The secondary outcomes are pain intensity, health-related quality of life, participation, domains affected by substance use, anxiety and depression, medication usage, psychological constructs, sleep, symptoms of central sensitization, and healthcare expenditure.

Discussion
Within the PIANISSIMO project we propose a way to reduce the risks of adverse events, medication-induced hyperalgesia, tolerance, and dependence by providing pain medication tapering before SCS. Due to the lack of a commonly accepted in-hospital tapering approach, two different tapering programs will be evaluated in this study. If pain medication tapering programs are deemed to be more effective than no tapering on disability, this would add to the evidence towards an improved patient-centered care model in this patient group and set a clear path to advocate for pain medication tapering before SCS as the new standard treatment guideline for these patients.

Trial registration
ClinicalTrials.gov NCT05861609. Registered on May 17, 2023.