bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral toxicological study of titanium dioxide nanoparticles with a crystallite diameter of 6 nm in rats
Authors: Akagi Jun-ichi , Mizuta Yasuko , Akane Hirotoshi , Toyoda Takeshi , Ogawa Kumiko 
Published: June 2023

Abstract
Background
Though titanium dioxide (TiO2) is generally considered to have a low impact in the human body, the safety of TiO2 containing nanosized particles (NPs) has attracted attention. We found that the toxicity of silver NPs markedly varied depending on their particle size, as silver NPs with a diameter of 10 nm exhibited fatal toxicity in female BALB/c mice, unlike those with diameters of 60 and 100 nm. Therefore, the toxicological effects of the smallest available TiO2 NPs with a crystallite size of 6 nm were examined in male and female F344/DuCrlCrlj rats by repeated oral administration of 10, 100, and 1000 mg/kg bw/day (5/sex/group) for 28 days and of 100, 300, and 1000 mg/kg bw/day (10/sex/group) for 90 days.

Results
In both 28- and 90-day studies, no mortality was observed in any group, and no treatment-related adverse effects were observed in body weight, urinalysis, hematology, serum biochemistry, or organ weight. Histopathological examination revealed TiO2 particles as depositions of yellowish-brown material. The particles observed in the gastrointestinal lumen were also found in the nasal cavity, epithelium, and stromal tissue in the 28-day study. In addition, they were observed in Peyer's patches in the ileum, cervical lymph nodes, mediastinal lymph nodes, bronchus-associated lymphoid tissue, and trachea in the 90-day study. Notably, no adverse biological responses, such as inflammation or tissue injury, were observed around the deposits. Titanium concentration analysis in the liver, kidneys, and spleen revealed that TiO2 NPs were barely absorbed and accumulated in these tissues. Immunohistochemical analysis of colonic crypts showed no extension of the proliferative cell zone or preneoplastic cytoplasmic/nuclear translocation of β-catenin either in the male or female 1000 mg/kg bw/day group. Regarding genotoxicity, no significant increase in micronucleated or γ-H2AX positive hepatocytes was observed. Additionally, the induction of γ-H2AX was not observed at the deposition sites of yellowish-brown materials.

Conclusions
No effects were observed after repeated oral administration of TiO2 with a crystallite size of 6 nm at up to 1000 mg/kg bw/day regarding general toxicity, accumulation of titanium in the liver, kidneys, and spleen, abnormality of colonic crypts, and induction of DNA strand breaks and chromosomal aberrations.
Comparative effectiveness of financing models in development assistance for health and the role of results-based funding approaches: a scoping review
Authors: Mushasha Rand , El Bcheraoui Charbel 
Published: June 2023

AbstractOver the past three decades, there has been an unprecedented growth in development assistance for health through different financing models, ranging from donations to results-based approaches, to improve health in low- and middle-income countries. Since then, the global burden of disease has started to shift. However, it is still not entirely clear what the comparative effect of the different financing models is. To assess the effect of these financing models on various healthcare targets, we systematically reviewed the peer-reviewed and gray literature. We identified 19 studies and found that results-based financing approaches have an overall positive impact on institutional delivery rates and numbers of healthcare facility visits, though this impact varies greatly by context.Donors might be better served by providing a results-based financing scheme combining demand and supply side health-related schemes. It is essential to include rigorous monitoring and evaluation strategies when designing financing models.
Non-hyalinizing trabecular thyroid adenoma: a novel thyroid tumor with diagnostic pitfalls of hyalinizing trabecular adenoma and medullary thyroid carcinoma
Authors: Hirokawa Mitsuyoshi , Matsuse Michiko , Mitsutake Norisato , Suzuki Ayana , Higuchi Miyoko , Hayashi Toshitetsu , Kamma Hiroshi , Miyauchi Akira , Akamizu Takashi 
Published: June 2023

Abstract
Background
Only one thyroid follicular cell-derived tumor with a purely trabecular growth pattern has previously been described. This report aims to describe the histological, immunohistochemical, and molecular findings of our second case, propose a novel thyroid tumor, and discuss its diagnostic pitfalls.

Case presentation
A 68-year-old female presented with an encapsulated thyroid tumor composed of thin and long trabeculae. No papillary, follicular, solid, or insular patterns are observed. The tumor cells were elongated or fusiform and arranged perpendicular to the trabecular axis. No nuclear findings of papillary thyroid carcinoma and increased basement membrane material were found. Immunohistochemically, the tumor cells were positive for paired-box gene 8, thyroid transcription factor-1, and negative for thyroglobulin, calcitonin, and chromogranin A. Inter- and intra-trabecular accumulation of type IV collagen-positive materials was not demonstrated. None of PAX8/GLIS1 and PAX8/GLIS3 and mutations in BRAF, HRAS, KRAS, NRAS, TERT promoter, CTNNB1, PTEN, and RET were detected.

Conclusions
We report our case as a novel disease entity called non-hyalinizing trabecular thyroid adenoma, which has the diagnostic pitfalls of hyalinizing trabecular tumor and medullary thyroid carcinoma.
Prevalence of MMTV-like sequences in breast cancer samples in Romanian patients-there is a geographic difference compared to the Western world
Authors: Fekete Zsolt , Tertan Bristena Octavia , Raduly Lajos , Eniu Dan Tudor , Buiga Rares , Galatar Mihaela , Berindan-Neagoe Ioana 
Published: June 2023

Abstract
Background
Breast cancer, although the most frequently diagnosed malignant tumor in humans, has a less clear etiology compared to other frequent cancer types. Mouse-mammary tumor virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the etiology of some breast cancers in humans, since an MMTV-like sequence was identified in 20–40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world. The purpose of our study was to identify MMTV-like DNA sequences in breast tissue samples from breast cancer patients who underwent curative surgery in our regional academic center in Romania, EU.

Methods
We selected 75 patients with non-metastatic breast cancer treated surgically with curative intent, who did not undergo any neoadjuvant treatment. Out of these patients, 50 underwent radical lumpectomy and 25 modified radical mastectomy. Based on previous reports in the literature we searched using PCR the MMTV-like DNA env sequence in the breast cancer tissue and normal breast tissue obtained from the same patients.

Results
None of the examined samples was positive for MMTV-like target sequences on PCR.

Conclusions
We could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to those from publications of other geographically related research groups.
The impact of decentralisation on health systems in fragile and post-conflict countries: a narrative synthesis of six case studies in the Indo-Pacific
Authors: Brennan Elliot , Abimbola Seye 
Published: June 2023

AbstractA health system has three key stakeholders, the State—at national and subnational levels—the health service providers and the citizens. In most settings and especially in peacetime, these stakeholders are typically well-defined. In contrast, during conflict and crisis as well as during ceasefire and post-conflict peacebuilding, stakeholders in the health system are often more diverse and contested. Health systems in such settings tend to be more decentralised, de facto—often in addition to de jure decentralisation. Despite much debate on the potential benefits of decentralisation, assessing its impact on health system performance remains difficult and its effect is open to dispute in the literature. This narrative synthesis aims to support efforts to assess and make sense of how decentralisation impacts health system performance in fragile and post-conflict countries—by synthesising evidence on the impact of decentralisation on health system performance from six country case studies: Papua New Guinea, the Philippines, Indonesia, Pakistan, Myanmar and Nepal. The impact of decentralisation on health system performance is optimised when combining centralisation (e.g., the benefits of central coordination in improving efficiency) with decentralisation (e.g., the benefits of local decision making in improving equity and resilience). The findings may inform efforts to think through what to centralise or decentralise, the impacts of those choices, and how the impact may change over time as countries go through and emerge from conflict—and as they go through and recover from the Covid-19 pandemic and prepare for future pandemics.
Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study
Authors: Werner Marie , Bergis Benjamin , Leblanc Pierre-Etienne , Wildenberg Lucille , Duranteau Jacques , Vigué Bernard , Harrois Anatole 
Published: June 2023

Abstract
Background
Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma.

Methods
We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve.

Results
59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure.

Conclusion
In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.
Identification of annotation artifacts concerning the chalcone synthase (CHS)
Authors: Bartas Martin , Volna Adriana , Cerven Jiri , Pucker Boas 
Published: June 2023

Abstract
Objective
Chalcone synthase (CHS) catalyzes the initial step of the flavonoid biosynthesis. The CHS encoding gene is well studied in numerous plant species. Rapidly growing sequence databases contain hundreds of CHS entries that are the result of automatic annotation. In this study, we evaluated apparent multiplication of CHS domains in CHS gene models of four plant species.

Main findings
CHS genes with an apparent triplication of the CHS domain encoding part were discovered through database searches. Such genes were found in Macadamia integrifolia, Musa balbisiana, Musa troglodytarum, and Nymphaea colorata. A manual inspection of the CHS gene models in these four species with massive RNA-seq data suggests that these gene models are the result of artificial fusions in the annotation process. While there are hundreds of seemingly correct CHS records in the databases, it is not clear why these annotation artifacts appeared.
Selection of oleaginous yeasts isolated from sugarcane bagasse as the potential producers of single cell oils and other metabolites
Authors: Legodi Lesetja M. , Moganedi Kgabo L. M. 
Published: June 2023

Abstract
Purpose
The microorganisms that possess diverse and improved traits for biotechnological applications provide an opportunity to address some of the current industrial challenges such as the sustainability of fuel energy and food. The aim of this study was to isolate and select the potential yeast isolates from sugarcane bagasse for single oil production.

Methods
The oleaginocity of the yeasts was confirmed through a gravimetric analysis of lipids, Nile red, sulfo-phosphovanillin (SPV) and a gas chromatography method for fatty acid methyl esters (FAME). The identification of the selected yeasts was carried out through a 5.8S of the ribosomal internal transcribed spacer (ITS) and 26S ribosomal DNA (rDNA) sequences. The carbohydrate and protein contents were estimated using phenol-sulfuric acid and hot trichloroacetic acid method, respectively.

Results
The yeast isolates accumulated lipids of between 28% and 67% of the dry cell weight, and 22–33% based on the SPV assay, qualifying them as oleaginous yeasts. The selected yeasts were identified as Candida ethanolica and Pichia manshuriica. The lipids contained high levels of fatty acids in the following order: oleic acid, palmitic acid, stearic acid, and linoleic acid, which made up 82% of the total lipids.

Conclusion
All the six selected yeast strains have the potential to produce single cell oils and other metabolites. The fatty acids composition of the selected yeast species was found to be suitable for the applications in biofuel, nutraceutical, and food industry. The yeast strains require evaluation in lignocellulosic hydrolysate for the production of single cell oils to be cost effective.
Hypertriglyceridemic pancreatitis managed with heparin and insulin: a case report
Authors: Anbessie Zablon Mesfin , Gebremeskel Yohannes Birhanu 
Published: June 2023

Abstract
Background
Alcohol and gall stones are common causes of pancreatitis. Other causes of pancreatitis include hypertriglyceridemia, trauma, congenital anomalies, and medications. Hypertriglyceridemic pancreatitis is distinguished, as it is more severe and complicated. The management of hypertriglyceridemic pancreatitis, other than the basic care given to other pancreatitis patients, is to decrease the serum triglyceride level to less than 500 mg/dl as soon as possible. Plasmapheresis, hemofiltration, and other modalities have been proven effective therapies, but, are expensive and not easily accessible. Insulin and heparin which are cheaper alternatives for treatment, have been reported in case reports along with one randomized controlled trial. The number of patients in these reports was small, so, the therapy is not well established. For most African countries like ours, the only option for management is heparin and insulin. Despite this fact, there has not been any publication regarding this issue on our continent.

Case report
We report the case of a 24 years old Ethiopian male who presented with severe central abdominal pain, easy fatiguability, and vomiting of one-day duration. He was tachycardic and tachypneic with diffuse abdominal tenderness, and had tendon xanthomas. His plasma was lactescent with a serum triglyceride level of 4775 mg/dl. His abdominal CT scan showed diffuse pancreatic swelling with a peripancreatic fluid collection, and his serum lipase was elevated. With a diagnosis of hypertriglyceridemic pancreatitis, he was managed with intravenous insulin infusion along with subcutaneous heparin. His random blood sugar was checked hourly with three episodes of hypoglycemia during therapy. His serum triglyceride level dropped to less than 500 mg/dl in three days, and he was discharged with no complications.

Conclusion
Since our findings are consistent with a prior randomized controlled trial and compilation of case reports, it would strengthen the evidence for safety and efficacy of insulin and heparin therapy. This therapy, which is the only available therapy in most countries of our continent, would decrease most of the complications of hypertriglyceridemic pancreatitis that we face. We believe, our report would be a wake-up call for researchers and clinicians in our continent to change their practice and strengthen the evidence for the treatment.
Gene editing with ‘pencil’ rather than ‘scissors’ in human pluripotent stem cells
Authors: Park Ju-Chan , Park Mihn Jeong , Lee Seung-Yeon , Kim Dayeon , Kim Keun-Tae , Jang Hyeon-Ki , Cha Hyuk-Jin 
Published: June 2023

AbstractOwing to the advances in genome editing technologies, research on human pluripotent stem cells (hPSCs) have recently undergone breakthroughs that enable precise alteration of desired nucleotide bases in hPSCs for the creation of isogenic disease models or for autologous ex vivo cell therapy. As pathogenic variants largely consist of point mutations, precise substitution of mutated bases in hPSCs allows researchers study disease mechanisms with “disease-in-a-dish” and provide functionally repaired cells to patients for cell therapy. To this end, in addition to utilizing the conventional homologous directed repair system in the knock-in strategy based on endonuclease activity of Cas9 (i.e., ‘scissors’ like gene editing), diverse toolkits for editing the desirable bases (i.e., ‘pencils’ like gene editing) that avoid the accidental insertion and deletion (indel) mutations as well as large harmful deletions have been developed. In this review, we summarize the recent progress in genome editing methodologies and employment of hPSCs for future translational applications.
Comparison of the therapeutic effects between stem cells and exosomes in primary ovarian insufficiency: as promising as cells but different persistency and dosage
Authors: Park Hang-soo , Chugh Rishi Man , Seok Jin , Cetin Esra , Mohammed Hanaa , Siblini Hiba , Liakath Ali Farzana , Ghasroldasht Mohammad Mousaei , Alkelani Hiba , Elsharoud Amro , Ulin Mara , Esfandyari Sahar , Al-Hendy Ayman 
Published: June 2023

Abstract
Background
Primary ovarian insufficiency (POI) refers to the loss of ovarian function under the age of 40 and results in amenorrhea and infertility. Our previous studies have shown that transplantation of mesenchymal stem cells (MSCs) and MSC-derived exosomes in chemotherapy-induced POI mouse ovaries can reverse the POI and eventually achieve pregnancy. Based on our recent studies, MSC-derived exosomes have almost equal therapeutic potentials as transplanted MSCs. However, it is still unclear whether exosomes can completely replace MSCs in POI treatment. For the reliable application of cell-free treatment for POI patients using exosomes, there is a need to understand whether there is any outcome and effectiveness difference between MSC and MSC-derived exosome treatment.

Methods
Comparing the therapeutic effect of intravenous injection using MSCs and equal amounts of exosomes in a POI mouse model will reveal the difference between the two therapeutic resources. In this study, we induced POI in C57/BL6 mice by chemotherapy (CXT) using a standard protocol. We then injected four different doses of MSCs or equal amounts of commercialized MSC-derived exosomes by retro-orbital injection post-CXT.

Result
After MSC/exosome treatment, tissue and serum samples were harvested to analyze molecular changes after treatment, while other mice in parallel experiments underwent breeding experiments to compare the restoration of fertility. Both the MSC- and exosome-treated groups had a restored estrous cycle and serum hormone levels compared to untreated POI mice. The pregnancy rate in the MSC-treated group was 60–100% after treatment, while the pregnancy rate in the exosome-treated group was 30–50% after treatment. Interestingly, in terms of long-term effects, MSC-treated mice still showed a 60–80% pregnancy rate in the second round of breeding, while the exosome-treated group became infertile again in the second round of breeding.

Conclusions
Although there were some differences in the efficacy between MSC treatment and exosome treatment, both treatments were able to achieve pregnancy in the POI mouse model. In conclusion, we report that MSC-derived exosomes are a promising therapeutic option to restore ovarian function in POI conditions similar to treatment with MSCs.
The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable
Authors: Gühne Falk , Ndum Ferdinand , Seifert Philipp , Winkens Thomas , Drescher Robert , Freesmeyer Martin 
Published: June 2023

Abstract
Background
Butylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation.

Results
458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently.

Conclusions
Butylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually.