bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of essential oil of Origanum onites and its major component carvacrol on the expression of toxicity pathway genes in HepG2 cells
Authors: Tomsuk Özlem , Kuete Victor , Sivas Hülya , Kürkçüoğlu Mine 
Published: July 2024

Abstract
Background
Origanum species have been used in various commercial constructions as a remedy against burns and wounds, agriculture, alcoholic drinks, fragrance, and flavoring substances of food products. The essential oil of Origanum onites L. (EOOO) and its component carvacrol (CV) possesses a wide range of biological activities including anti-cancer activity.

Purpose
The purpose of this study was to investigate the growth inhibitory activity of the essential oil and its major component CV and then hepatotoxicity pathway-related genes in HepG2 cells.

Methods
The effects of the EOOO and CV on cell growth and mRNA expressions of 84 hepatotoxicity pathway-related genes were investigated in HepG2, using trypan blue exclusion/ bromodeoxyuridine (BrdU) incorporation tests and real-time-polymerase chain reaction (RT-PCR) array, respectively.

Results
The EOOO and CV inhibited cell growth with IC50 values of 0.08 µg/mL and 45 µg/mL, respectively, after 24 h. Real-time, reverse-transcription-polymerase chain reaction (RT2-PCR) array analysis revealed that expressions of 32 genes out of 84 were changed at least 2-fold or more in the EOOO-treated cells. Among them, expression levels of 17 genes were elevated, while expression levels of 15 genes were diminished. Furthermore, after exposure of cells to 45 µg/mL of CV, the expression of 8 genes was increased while the other 8 genes were decreased. Both the EOOO and carvacrol affected the expression of 48 genes of HepG2 cells which are involved in the hepatotoxicity pathway, indicating their hepatoprotective and possible anti-hepatocarcinogenic effects.

Conclusion
The present study demonstrates that the essential oil of Origanum onites and carvacrol can be used in various applications such as anticancer or herbal drugs, since its non-hepatotoxicity.
Brief instruments for measuring nutrition literacy - the Nutrition Health Literacy Scale and the Self-Perceived Food Literacy Scale Short Form
Authors: Griebler Robert , Schütze Denise , Link Thomas , Schindler Karin 
Published: July 2024

Abstract
Background
A healthy diet is a critical factor in maintaining long-term health. In addition to a health-promoting food environment, the nutrition health literacy (NHL) and food literacy (FL) of the population are important in this context. This paper describes the development and validation of two short instruments to measure the nutrition literacy of the population, used in the Austrian Nutrition Literacy Survey 2021.

Methods
An instrument to measure NHL (Nutrition Health Literacy Scale; NHLS) has been adapted and further developed. To measure FL, the Self-perceived Food Literacy Scale by Poelman et al. has been modified and shortened (SPFL-SF). Validation of the instruments was based on data from a web survey conducted in Austria in 2021 with almost 3,000 participants aged 18 years and older. Exploratory and confirmatory factor analyses were performed to assess the factorial validity/dimensionality of the instruments. Additionally, internal consistency was assessed using Cronbach’s alpha, ordinal alpha, and McDonald’s omega.

Results
Both instruments demonstrate excellent data-model fit. The NHLS also shows excellent internal consistency (α = 0.91), while the SPFL-SF displays a sufficient internal consistency for all (α between 0.70 and 0.89) but one sub-dimension (resisting temptation α = 0.61). Furthermore, the distribution of the items indicates that the measures are understandable and suitable, as evidenced by the absence of missing values in the sample. In addition, the items of both instruments differ in their level of difficulty or agreement.

Conclusions
The NHLS and SPFL-SF are reliable and valid instruments for measuring NHL and FL in the general adult population. The brief instruments measuring the different aspects of nutrition literacy can be easily used in nutritional or evaluation studies. Further work is required to investigate other aspects of validity.
Lung cancer brain metastasis and hemorrhagic cerebral venous thrombosis: experiences and lessons
Authors: Tian Qilong , Wu Yingxi , Li Gang , Huang Xiaofeng , Cai Qing 
Published: July 2024

AbstractThe incidence of lung cancer brain metastasis combined with hemorrhagic cerebral venous sinus thrombosis (CVST) is very rare, and the understanding and treatment experience of this case is insufficient. We reported a case of lung cancer brain metastasis accompanied by venous sinus thrombosis, and describe the diagnosis and treatment plan for colleagues to learn from experience and lessons.
Health system description and assessment: a scoping review of templates for systematic analyses
Authors: Waitzberg Ruth , Pfundstein Isabel , Maresso Anna , Rechel Bernd , van Ginneken Ewout , Quentin Wilm 
Published: July 2024

Abstract
Background
Understanding and comparing health systems is key for cross-country learning and health system strengthening. Templates help to develop standardised and coherent descriptions and assessments of health systems, which then allow meaningful analyses and comparisons. Our scoping review aims to provide an overview of existing templates, their content and the way data is presented.

Main body
Based on the WHO building blocks framework, we defined templates as having (1) an overall framework, (2) a list of indicators or topics, and (3) instructions for authors, while covering (4) the design of the health system, (5) an assessment of health system performance, and (6) should cover the entire health system. We conducted a scoping review of grey literature published between 2000 and 2023 to identify templates. The content of the identified templates was screened, analyzed and compared. We found 12 documents that met our inclusion criteria. The building block `health financing´ is covered in all 12 templates; and many templates cover ´service delivery´ and ´health workforce’. Health system performance is frequently assessed with regard to ‘access and coverage’, ‘quality and safety’, and ‘financial protection’. Most templates do not cover ‘responsiveness’ and ‘efficiency’. Seven templates combine quantitative and qualitative data, three are mostly quantitative, and two are primarily qualitative. Templates cover data and information that is mostly relevant for specific groups of countries, e.g. a particular geographical region, or for high or for low and middle-income countries (LMICs). Templates for LMICs rely more on survey-based indicators than administrative data.

Conclusions
This is the first scoping review of templates for standardized descriptions of health systems and assessments of their performance. The implications are that (1) templates can help analyze health systems across countries while accounting for context; (2) template-guided analyses of health systems could underpin national health policies, strategies, and plans; (3) organizations developing templates could learn from approaches of other templates; and (4) more research is needed on how to improve templates to better achieve their goals. Our findings provide an overview and help identify the most important aspects and topics to look at when comparing and analyzing health systems, and how data are commonly presented. The templates were created by organizations with different agendas and target audiences, and with different end products in mind. Comprehensive health systems analyses and comparisons require production of quantitative indicators and complementing them with qualitative information to build a holistic picture.
Clinical Trial Registration: Not applicable.
Spatial distribution and factors associated with high completed fertility among women aged 40–49 years in Ghana: evidence from the 2022 Ghana Demographic Health Survey
Authors: Osborne Augustus , Bangura Camilla , Aboagye Richard Gyan , Wongnaah Florence Gyembuzie , Seidu Abdul-Aziz , Ahinkorah Bright Opoku 
Published: July 2024

Abstract
Background
High completed fertility among married and cohabiting women has profound consequences, including straining resources, increasing healthcare challenges, and contributing to educational and gender inequalities. This study examined the factors associated with high completed fertility among married and cohabiting women aged 40–49 years in Ghana.

Methods
Data for the study was sourced from the 2022 Ghana Demographic and Health Survey (GDHS). A spatial map was used to present the women's geographic variations in high completed fertility. A mixed-effect multilevel binary logistic regression analysis was performed to identify the factors associated with high completed fertility. The findings were presented as adjusted odds ratios (aOR) with a 95% confidence interval (CI).

Results
The national proportion of high completed fertility among married and cohabiting women aged 40–49 years in Ghana was 52.0% [48.8, 55.2]. Women who were Ga/Dangme/Ewe by tribe [aOR = 2.32, 95% CI = 1.06, 5.08] had higher odds of high completed fertility than Akans. Women who indicated 6 + as their ideal number of children had a higher [aOR = 5.60, 95% CI = 2.90, 10.82] likelihood of high completed fertility compared to those whose ideal number of children was 0–3. Those who were using contraceptives at the time of the survey had a higher [aOR = 2.31, 95% CI = 1.17, 4.55] likelihood of high completed fertility compared to those who were not using contraceptives. Women with secondary/higher education [aOR = 0.32, 95% CI = 0.17, 0.58] had lower odds of high completed fertility than those without no formal education. Women with females as household heads [aOR = 0.56, 95% CI = 0.33, 0.95] had lower odds of high completed fertility than males. Women in Volta, Western North, Ahafo, and Bono regions had lower odds of high completed fertility compared to those living in the Northeast region, with the lowest odds among those living in the Volta region [aOR = 0.08, 95% CI = 0.02, 0.40].

Conclusion
High completed fertility is prevalent in Ghana, with more than half of married and cohabiting women having at least five or more children. The government and policymakers in Ghana should promote education for women, increase culturally sensitive family planning programs, increase access to family planning resources, address ideal family size preferences, and improve understanding of contraceptive use.
Isolation methods and characterization of primary rat neurovascular cells
Authors: Floryanzia Sydney , Lee Seoyoung , Nance Elizabeth 
Published: July 2024

Abstract
Background
There is significant interest in isolating cells of the blood-brain barrier (BBB) for use in in vitro screening of therapeutics and analyzing cell specific roles in neurovascular pathology. Primary brain cells play an advantageous role in BBB models; however, isolation procedures often do not produce cells at high enough yields for experiments. In addition, although numerous reports provide primary cell isolation methods, the field is lacking in documentation and detail of expected morphological changes that occur throughout culturing and there are minimal troubleshooting resources. Here, we present simplified, robust, and reproducible methodology for isolating astrocytes, pericytes, and endothelial cells, and demonstrate several morphological benchmarks for each cell type throughout the process and culture timeframe. We also analyze common considerations for developing neurovascular cell isolation procedures and recommend solutions for troubleshooting.

Results
The presented methodology isolated astrocytes, pericytes, and endothelial cells and enabled cell attachment, maturation, and cell viability. We characterized milestones in cell maturation over 12 days in culture, a common timeline for applications of these cell types in BBB models. Phase contrast microscopy was used to show initial cell plating, attachment, and daily growth of isolated cells. Confocal microscopy images were analyzed to determine the identity of cell types and changes to cell morphology. Nuclear staining was also used to show the viability and proliferation of glial cells at four time points. Astrocyte branches became numerous and complex with increased culture time. Microglia, oligodendrocytes, and neurons were present in mixed glial cultures for 12 days, though the percentage of microglia and neurons expectedly decreased after passaging, with microglia demonstrating a less branched morphology.

Conclusions
Neurovascular cells can be isolated through our optimized protocols that minimize cell loss and encourage the adhesion and proliferation of isolated cells. By identifying timepoints of viable glia and neurons within an astrocyte-dominant mixed culture, these cells can be used to evaluate drug targeting, uptake studies, and response to pathological stimulus in the neurovascular unit.
Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer
Authors: Bajpai Prachi , Agarwal Sumit , Afaq Farrukh , Al Diffalha Sameer , Chandrashekar Darshan S. , Kim Hyung-Gyoon , Shelton Abigail , Miller C. Ryan , Singh Santosh K. , Singh Rajesh , Varambally Sooryanarayana , Nagaraju Ganji Purnachandra , Manne Ashish , Paluri Ravi , Khushman Moh’d , Manne Upender 
Published: July 2024

Abstract
Background
Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models.

Methods
The cytotoxicity of JAK/HDACi, regorafenib, and their combination were tested with normal colonic and CRC cells exhibiting various genetic backgrounds. Kinomic, ATAC-seq, RNA-seq, cell cycle, and apoptosis analyses were performed to evaluate the cellular functions/molecular alterations affected by the combination. Efficacy of the combination was assessed using patient-derived xenograft (PDX) and experimental metastasis models of CRC. To evaluate the interplay between tumor, its microenvironment, and modulation of immune response, MC38 syngeneic mice were utilized.

Results
The combination therapy decreased cell viability; phosphorylation of JAKs, STAT3, EGFR, and other key kinases; and inhibited deacetylation of histone H3K9, H4K8, and alpha tubulin proteins. It induced cell cycle arrest at G0-G1 phase and apoptosis of CRC cells. Whole transcriptomic analysis showed that combination treatment modulated molecules involved in apoptosis, extracellular matrix-receptor interaction, and focal adhesion pathways. It synergistically reduces PDX tumor growth and experimental metastasis, and, in a syngeneic mouse model, the treatment enhances the antitumor immune response as evidenced by higher infiltration of CD45 and cytotoxic cells. Pharmacokinetic studies showed that combination increased the bioavailability of regorafenib.

Conclusions
The combination treatment was more effective than with regorafenib or JAK/HDACi alone, and had minimal toxicity. A clinical trial to evaluate this combination for treatment of mCRCs is warranted.
Human Babesia odocoilei and Bartonella spp. co-infections in the Americas
Authors: Maggi Ricardo G. , Calchi Ana Cláudia , Moore Charlotte O. , Kingston Emily , Breitschwerdt Edward B. 
Published: July 2024

Abstract
Background
In recent years, Babesia and Bartonella species co-infections in patients with chronic, nonspecific illnesses have continued to challenge and change the collective medical understanding of “individual pathogen” vector-borne infectious disease dynamics, pathogenesis and epidemiology. The objective of this case series is to provide additional molecular documentation of Babesia odocoilei infection in humans in the Americas and to emphasize the potential for co-infection with a Bartonella species.

Methods
The development of improved and more sensitive molecular diagnostic techniques, as confirmatory methods to assess active infection, has provided increasing clarity to the healthcare community.

Results
Using a combination of different molecular diagnostic approaches, infection with Babesia odocoilei was confirmed in seven people suffering chronic non-specific symptoms, of whom six were co-infected with one or more Bartonella species.

Conclusions
We conclude that infection with Babesia odocoilei is more frequent than previously documented and can occur in association with co-infection with Bartonella spp.

Graphical Abstract
Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report
Authors: Ishida Naoko , Nagata Kenji , Fukuda Jyunki , Oguma Yasuo , Hirashima Tomonori , Minami Kenichi , Nishimura Yasumasa , Matsuo Yukinori 
Published: July 2024

Abstract
Background
Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer.

Case presentation
We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings.

Conclusion
A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.
Clinical outcomes and efficacy of HER2-targeted therapy in breast cancer with uncommon in situ hybridization (ISH) patterns or discordant immunohistochemistry (IHC).
Authors: Zhang Qianchen , Freeman Jincong Q. , Zhao Fangyuan , Chen Nan , Nanda Rita , Huo Dezheng , Howard Frederick Matthew 
Published: July 2024

604 Background: HER2-targeted therapy (Tx) improves outcomes in HER2+ breast cancer, but efficacy in patients (pts) with discordant IHC/ISH results, or with ASCO/CAP Group 2–4 ISH results (representing mono/polysomy and borderline positivity), remains uncertain. We sought to characterize the epidemiology and response to HER2-directed Tx in these subgroups. Methods: This retrospective cohort study included pts from the National Cancer Database diagnosed in 2013 - 2020. Cases were classified as HER2+, HER2–, discordant ISH/IHC, or HER2+ with ISH Group 2 (HER2/CEP17 ratio ≥ 2, HER2 copy number [CN] < 4), 3 (ratio < 2, CN > 6), or 4 (ratio < 2, CN ≥ 4 and < 6) per the 2023 ASCO/CAP guidelines. In pts receiving neoadjuvant chemotherapy (NAC) with HER2-targeted Tx, odds ratio (OR) for pathologic complete response (pCR) was calculated adjusting for age, comorbidity, stage, and hormone receptor expression, for HER2+ subgroups relative to HER2– cases; pCR rate was also compared between pts who did vs. did not receive HER2-targeted Tx. Adjusted hazard ratio (HR) for overall survival (OS) in Stage IV pts was calculated relative to HER2– cases, and as a function of receipt of HER2-targeted Tx. Results: We identified 1,105,890 cases for inclusion (mean age, 62 years; median follow-up, 43 months). Of HER2 IHC 3+ cases with dual probe ISH testing (n=6808), 9.4%, 4.2%, 2.7%, and 8.2% had ISH results classified as ASCO/CAP Group 5 (i.e. discordant negative), 4, 3, and 2, respectively. Of HER2 IHC 0 or 1+ cases with dual probe ISH (n=47,817), 2.4% had discordant positive Group 1 ISH results. Among 148,099 pts receiving NAC, HER2+ and Group 2 IHC 3+ treated with HER2-targeted Tx had higher pCR rates than HER2– cases (Table), with no pCR improvement seen in Group 3/4 ISH or discordant ISH/IHC cases. Few pts in HER2+ subgroups did not receive HER2-directed Tx, but improved pCR with HER2-targeted Tx was seen in HER2+ cases with a trend toward improvement in Group 2 ISH cases. Similarly, OS was superior in Stage IV HER2+ (HR 0.49, 95% confidence interval [CI] 0.45 - 0.53) and Group 2/IHC 3+ cases (HR 0.29, 95% CI 0.10 – 0.77) receiving HER2-targeted Tx relative to HER2– cases. Conclusions: HER2+ cases with ASCO/CAP Group 3/4 ISH results, as well as pts with discordant ISH/IHC have inferior outcomes with HER2-targeted Tx, and alternative treatment strategies for these pts incorporating agents approved for HER2– disease should be considered. [Table: see text]