bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic inactivation of the Carnitine/Acetyl-Carnitine mitochondrial carrier of Yarrowia lipolytica leads to enhanced odd-chain fatty acid production
Authors: Messina Eugenia , de Souza Camilla Pires , Cappella Claudia , Barile Simona Nicole , Scarcia Pasquale , Pisano Isabella , Palmieri Luigi , Nicaud Jean-Marc , Agrimi Gennaro 
Published: July 2023

Abstract
Background
Mitochondrial carriers (MCs) can deeply affect the intracellular flux distribution of metabolic pathways. The manipulation of their expression level, to redirect the flux toward the production of a molecule of interest, is an attractive target for the metabolic engineering of eukaryotic microorganisms. The non-conventional yeast Yarrowia lipolytica is able to use a wide range of substrates. As oleaginous yeast, it directs most of the acetyl-CoA therefrom generated towards the synthesis of lipids, which occurs in the cytoplasm. Among them, the odd-chain fatty acids (OCFAs) are promising microbial-based compounds with several applications in the medical, cosmetic, chemical and agricultural industries.

Results
In this study, we have identified the MC involved in the Carnitine/Acetyl-Carnitine shuttle in Y. lipolytica, YlCrc1. The Y. lipolytica Ylcrc1 knock-out strain failed to grow on ethanol, acetate and oleic acid, demonstrating the fundamental role of this MC in the transport of acetyl-CoA from peroxisomes and cytoplasm into mitochondria. A metabolic engineering strategy involving the deletion of YlCRC1, and the recombinant expression of propionyl-CoA transferase from Ralstonia eutropha (RePCT), improved propionate utilization and its conversion into OCFAs. These genetic modifications and a lipogenic medium supplemented with glucose and propionate as the sole carbon sources, led to enhanced accumulation of OCFAs in Y. lipolytica.

Conclusions
The Carnitine/Acetyl-Carnitine shuttle of Y. lipolytica involving YlCrc1, is the sole pathway for transporting peroxisomal or cytosolic acetyl-CoA to mitochondria. Manipulation of this carrier can be a promising target for metabolic engineering approaches involving cytosolic acetyl-CoA, as demonstrated by the effect of YlCRC1 deletion on OCFAs synthesis.
The mediating role of HbA1c in the association between elevated low-density lipoprotein cholesterol levels and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus
Authors: Zhang Hui , Chen Yang , Zhu Wenwen , Niu Tong , Song Bing , Wang Hongxiao , Wang Wei , Zhang Haoqiang 
Published: July 2023

AbstractBackgroundIncreased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM).MethodsHere, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator.ResultsCompared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM.ConclusionsThe impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels.
The role of onsite Implanon insertion training for HEWs for sustainable FP programs in Ethiopia: a mixed-method study
Authors: Tilahun Yewondwossen , Belayihun Bekele , Teshome Luwam , Zerihun Habtamu , Asnake Mengistu 
Published: July 2023

Abstract
Background
Training health extension workers on Implanon insertion offsite, or away from the workplace, can be cost-intensive, can depend on the human and financial resources of partners, and can compromise routine health services by taking health workers off the job. To address these limitations, the USAID Transform Primary Health Care Activity in Ethiopia designed an onsite Implanon insertion training at the primary health care level. This study compared and documented the implementation experience of onsite vs offsite Implanon insertion training for health extension workers.

Methods
In a mixed-method study conducted in March 2020, the team collected training data from 468 participants—half trained onsite and half offsite—and conducted key informant interviews with 20 purposively sampled individuals. The team analyzed this data, summarizing the data in tables and figures and performing a t test with p value < 0.05 using SPSS v.20. Qualitative data were analyzed manually in Excel and summarized in Word based on emerging themes.

Results
Health extension workers trained onsite were away from routine work an average of 3 days compared to 8 days for those trained offsite (P < 0.001). The difference in average per-trainee cost of onsite (2707 Birr = 87.3 USD) and offsite (6006 Birr = 193.7USD) training was significant (P < 0.001). There was no significant difference in mean scores of onsite and offsite trainees on the knowledge pre-test (P < 0.947) and post-test (P < 0.220) or in simulated practice on an arm model (p < 0.202). Onsite trainees, assigned to their own health post for clinical practice, performed Implanon insertions on an average of 10 clients: offsite trainees on an average of 5 clients. Most interview participants reported that the onsite Implanon training was better organized, conducted, followed up, and monitored by health centers to ensure community-level access to Implanon services, with quality and continuity.

Conclusions
Onsite training is a promising approach and minimizes service interruption. It is a likely strategy for on-demand training of health extension workers and immediate assignment of skilled providers to ensure access to and continuity of quality community-level Implanon care.
Trial registration N/A.
A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice
Authors: Evariste Lauris , Lamas Bruno , Ellero-Simatos Sandrine , Khoury Laure , Cartier Christel , Gaultier Eric , Chassaing Benoit , Feltin Nicolas , Devoille Laurent , Favre Georges , Audebert Marc , Houdeau Eric 
Published: July 2023

Abstract
Background
Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact of mineral particles used as food additives on human health are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold.

Results
E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1β was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1β, IL-17 and TGFβ levels were found in the male colon.

Conclusions
These results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the observed gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.
Associations of in-hospital postpartum feeding experiences with exclusive breastfeeding practices among infants in rural Sichuan, China
Authors: Weber Ann M. , Guo Yian , Zhang Evelyn , Gruber Susan , Medina Alexis , Zhou Huan , Darmstadt Gary L. 
Published: July 2023

Abstract
Background
In rural China, exclusive breastfeeding (EBF) prevalence is low and hospitals often fail to attain baby-friendly feeding objectives, such as ≥ 75% of newborns exclusively breastfed from birth to discharge. Empirical evidence for the impact of increased hospital compliance with recommended feeding guidelines on continued EBF in rural China is lacking. We sought to measure and model the association of newborns’ in-hospital feeding experiences with EBF practice in infancy to inform policies for EBF promotion.

Methods
Data were cross-sectional from 785 caregivers of infants < 6 months of age, collected from November to December 2019 in four underdeveloped counties/districts in Sichuan Province. In-hospital feeding practices were determined, and prevalence of current infant feeding practices was calculated from 24-h recall and categorized according to WHO/UNICEF Infant and Young Child Feeding categories as EBF, breastfed with non-milk liquids, mixed feeding, breastfed with solids, and not breastfed. Relative risk ratios were estimated using adjusted multinomial logistic regression to examine risk factors for non-EBF practices compared to EBF, including in-hospital feeding experiences. The regression model was used to investigate change in EBF prevalence under alternative in-hospital experiences.

Results
Only 38.1% of under-six-month-old infants were being exclusively breastfed when data were collected; 61.8% and 77.6% had been fed water and infant formula, respectively, in the hospital. Infants who were fed water or formula before discharge were estimated as 2–3 times as likely to be non-EBF than EBF up to age six months. According to our model, EBF prevalence would have increased to 53.7% (95% confidence interval (CI) 46.1, 61.2) had ≥ 75% of infants been exclusively breastfed and water-based feeds eliminated in-hospital.

Conclusions
Given the importance of infants’ first feeding experiences in the establishment and continuation of EBF, it is imperative that rural Chinese hospitals actively seek to limit infant formula feeds to medically indicated situations and eliminate water-based feeds.
Pulmonary interleukin 1 beta/serum amyloid A3 axis promotes lung metastasis of hepatocellular carcinoma by facilitating the pre-metastatic niche formation
Authors: Zhang Chong , Li Qing , Xu Qi , Dong Wei , Li Chunmei , Deng Bin , Gong Jiao , Zhang Li-Zhen , Jin Junfei 
Published: July 2023

Abstract
Background
Increasing evidence suggests a vital role of the pre-metastatic niche in the formation of distant metastasis of many cancers. However, how the pre-metastatic niche is formed and promotes pulmonary metastasis of hepatocellular carcinoma (HCC) remains unknown.

Methods
Orthotopic liver tumor models and RNA-Seq were used to identify dysregulated genes in the pre-metastatic lung. Il1b knockout (Il1b−/−) mice and lentivirus-mediated gene knockdown/overexpression were utilized to demonstrate the role of interleukin 1 beta (IL-1β)/serum amyloid A3 (SAA3) in the pre-metastatic niche formation and pulmonary metastasis. The potential molecular mechanisms were investigated by RNA-Seq, real-time quantitative PCR (qPCR), western blotting, immunohistochemistry (IHC), flow cytometry, luciferase reporter assay, double immunofluorescent staining and H&E staining.

Results
Accumulation of myeloid cells and upregulation of IL-1β were observed in the pre-metastatic lung of orthotopic liver tumor models. Myeloid cells accumulation and pulmonary metastasis were suppressed in Il1b−/− mice and Il1r1-silencing mice. Mechanistically, SAA3 and matrix metallopeptidase 9 (MMP9) were identified as potential downstream targets of IL-1β. Overexpression of SAA3 in the lungs of Il1b−/− mice restored myeloid cells accumulation and pulmonary metastasis of the orthotopic HCC xenografts. Moreover, alveolar macrophages-derived IL-1β dramatically enhanced SAA3 expression in alveolar epithelial cells in an NF-κB dependent manner and increased MMP9 levels in an autocrine manner. Furthermore, SAA3 recruited myeloid cells to the lung without affecting the expression of MMP9 in myeloid cells.

Conclusions
Our study suggests a key role of pulmonary IL-1β and SAA3 in creating a permissive lung pre-metastatic niche by enhancing MMP9 expression and recruiting myeloid cells, respectively, thus promoting pulmonary metastasis of HCC.
Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial
Authors: Nam Karam , Nam Jae-Sik , Kim Hye-Bin , Chung Jaeyeon , Hwang In Eob , Ju Jae-Woo , Bae Jinyoung , Lee Seohee , Cho Youn Joung , Shim Jae-Kwang , Kwak Young-Lan , Chin Ji-Hyun , Choi In-Cheol ,   for the CARdiac suRgery and Oxygen Therapy (CARROT) Investigators, Lee Eun-Ho , Jeon Yunseok 
Published: July 2023

Abstract
Background
To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB).

Methods
This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared.

Results
A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83–1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18–3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002).

Conclusions
In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB.
Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).
Clinical utility of a novel test for assessing cardiovascular disease risk in type 2 diabetes: a randomized controlled trial
Authors: Peabody John W. , Paculdo David , de Belen Enrico , Ganesan Divya , Cooney Isabella , Trujillo Nelson 
Published: July 2023

Abstract
Background
The risk for and treatment of cardiovascular disease (CVD) in type 2 diabetes (T2DM) is often incorrect and delayed. We wished to determine if a novel test improved physicians’ ability to risk stratify, diagnose, and treat patients with T2DM.

Methods
In a 2-phase randomized controlled trial comparing the clinical workup, diagnosis, and management of online, simulated patients with T2DM in a nationwide sample of cardiologists and primary care physicians, participants were randomly assigned to control or one of two intervention groups. Intervention participants had access to standard of care diagnostic tools plus a novel diagnostic CVD risk stratification test.

Results
In control, there was no change in CV risk stratification of simulated patients between baseline and round 2 (37.1 to 38.3%, p = 0.778). Pre-post analysis showed significant improvements in risk stratification in both Intervention 1 (38.7 to 65.3%) and Intervention 2 (41.9 to 65.8%) (p < 0.01) compared to controls. Both intervention groups significantly increased prescribing SGLT2 inhibitors/GLP1 receptor agonists versus control, + 18.9% for Intervention 1 (p = 0.020) and 1 + 9.4% for Intervention 2 (p = 0.014). Non-pharmacologic treatment improved significantly compared to control (+ 30.0% in Intervention 1 (p < 0.001) and + 22.8% in Intervention 2 (p = 0.001). Finally, monitoring HgbA1C, blood pressure, and follow-up visit frequency improved by + 20.3% (p = 0.004) in Intervention 1 and + 29.8% (p < 0.001) in Intervention 2 compared with control.

Conclusion
Use of the novel test significantly improved CV risk stratification among T2DM patients. Statistically significant increases treatments were demonstrated, specifically SGLT2 inhibitors and GLP1 receptor antagonists and recommendations of evidence-based non-pharmacologic treatments.
Trial registration ClinicalTrials.gov, NCT05237271
Successful treatment with doxycycline monotherapy for human infection with Babesia venatorum (Babesiidae, Sporozoa) in China: a case report and proposal for a clinical regimen
Authors: Huang Lei , Sun Yi , Huo Dan-Dan , Xu Ming , Xia Luo-Yuan , Yang Ning , Hong Wei , Huang Lin , Nie Wei-Min , Liao Ru-He , Zhang Ming-Zhu , Zhu Dai-Yun , Li Yan , Ma He-Cheng , Zhang Xin , Li Yong-Gang , Huang Xin-An , Wang Jing-Yuan , Cao Wu-Chun , Wang Fu-Sheng , Jiang Jia-Fu 
Published: July 2023

Abstract
Background
Human babesiosis is a worldwide disease caused by intraerythrocytic protozoa of the genus Babesia. It is transmitted by bites from ixodid ticks, and mechanically transmitted by blood transfusion. It is primarily treated with quinine and/or atovaquone, which are not readily available in China. In this study, we developed a novel treatment regimen involving doxycycline monotherapy in a patient with severe Babesia venatorum infection as an alternative therapeutic medication. The aim of our study is to provide a guidance for clinical practice treatment of human babesiosis.

Case presentation
A 73-year-old man who had undergone splenectomy and blood transfusion 8 years prior, presented with an unexplained fever, headache, and thrombocytopenia, and was admitted to the Fifth Medical Center of the PLA General Hospital. He was diagnosed with B. venatorum infection by morphological review of thin peripheral blood smears, which was confirmed by multi-gene polymerase chain reaction (PCR), and sequencing of the entire 18s rRNA and partial β-tubulin encoding genes, as well as isolation by animal inoculation. The doxycycline monotherapy regimen (peros, 0.1 g bisindie) was administered following pharmacological guidance and an effective outcome was observed. The patient recovered rapidly following the doxycycline monotherapy. The protozoan load in peripheral blood samples decreased by 88% in hematocrit counts after 8 days, and negative PCR results were obtained after 90 days of follow-up at the hospital. The treatment lasted for 3 months without any side effects or sequelae. The nine-month follow-up survey of the patient did not reveal any signs of recrudescence or anti-babesial tolerance.

Conclusions
We have reported a clinical case of successful doxycycline monotherapy for human babesiosis caused by B. venatorum, which provides an optional medical intervention for human babesiosis.

Graphical Abstract
A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS
Authors: Buiteman-Kruizinga Laura A. , van Meenen David M. P. , Bos Lieuwe D. J. , van der Heiden Pim L. J. , Paulus Frederique , Schultz Marcus J. 
Published: July 2023

Abstract
Introduction
The driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.

Aim
To compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.

Methods
Single-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.

Results
Thirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0–10.0] vs. 10.0 [8.0–11.0] cmH2O, mean difference − 2.5 [95% CI − 2.6 to − 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.

Conclusions
In this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation.
Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1.