bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boot camp approach to surgical residency preparation: feedback from a French university hospital
Authors: Buscail Etienne , Muscari Fabrice , Hostalrich Aurélien , Bolzinger Manon , Malavaud Sandra , Minville Vincent , Martin Charlotte , Delhoste Magali , Houze-Cerfon Charles Henri , Buscail Simon , Bastiani Bruno , Roumiguié Mathieu , Weyl Ariane , Carrère Nicolas , Abbo Olivier 
Published: September 2022

Abstract
Introduction
The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture.

Material and method
We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions).

Results
The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching.

Conclusion
We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.
B-mode and color Doppler ultrasonography of normal external jugular vein in donkeys (Equus asinus)
Authors: Hussein Hussein Awad , Ibrahim Ahmed 
Published: September 2022

AbstractBackgroundAlthough the jugular vein is a major important blood vessel in equine, the literature lacks this vessel's normal B-mode and Doppler ultrasonographic examinations in donkeys. Therefore, this study aimed to determine the reference ranges of B-mode and Doppler ultrasonographic indices of jugular veins in healthy adult donkeys (Equus asinus) and the possible effect of examination side (left and right), gender, and body condition on the ultrasonographic measurements of this vessel. B-mode and Doppler ultrasound imaging of the external jugular vein was conducted on 20 adult healthy donkeys of both sexes.ResultsIn all donkeys, the jugular vein was 4.01 to 8.1 mm from the body surface. The longitudinal and transverse venous diameters ranged from 3.94 to 10.5 mm and from 0.88 to 1.9 cm, respectively. Moreover, the vein areas varied from 0.61 to 2.83 cm2. The reference values of superficial and deep wall thickness (SWT and DWT) were 0.56 ± 0.2 and 0.6 ± 0.13 mm, respectively. The blood velocity, blood follow rate, and congestion index of the external jugular vein can be expected in adult healthy donkeys as a range value from 8.4 to 13.5 cm/sec, from 0.33 to 1.78 ml/min, and from 0.06 to 0.27 cm.sec, respectively. Generally, the vein showed laminar monophasic waveforms. The examination side and gender have no significant effect on the ultrasound measurements of the vein (P > 0.05). Donkeys with a body condition score (BCS) ≥ 3 revealed increases in the depth of the vein (P < 0.05).ConclusionsThe results of this study can be used as reference values and provide a basis for comparison when evaluating donkeys with diseases that affect blood flow in the external jugular vein.
Adagrasib, a KRAS G12C inhibitor, reverses the multidrug resistance mediated by ABCB1 in vitro and in vivo
Authors: Zhang Yuchen , Li Cheukfai , Xia Chenglai , Wah To Keneth Kin , Guo Zhixing , Ren Chongyang , Wen Lingzhu , Wang Fang , Fu Liwu , Liao Ning 
Published: September 2022

Abstract
Background
Multidrug resistance (MDR) is a complex phenomenon that frequently leads to chemotherapy failure during cancer treatment. The overexpression of ATP-binding cassette (ABC) transporters represents the major mechanism contributing to MDR. To date, no effective MDR modulator has been applied in clinic. Adagrasib (MRTX849), a specific inhibitor targeting KRAS G12C mutant, is currently under investigation in clinical trials for the treatment of non-small cell lung cancer (NSCLC). This study focused on investigating the circumvention of MDR by MRTX849.

Methods
The cytotoxicity and MDR reversal effect of MRTX849 were assessed by MTT assay. Drug accumulation and drug efflux were evaluated by flow cytometry. The MDR reversal by MRTX849 in vivo was investigated in two ABCB1-overexpressing tumor xenograft models in nude mice. The interaction between MRTX849 and ABCB1 substrate binding sites was studied by the [125I]-IAAP-photoaffinity labeling assay. The vanadate-sensitive ATPase assay was performed to identify whether MRTX849 would change ABCB1 ATPase activity. The effect of MRTX849 on expression of ABCB1 and PI3K/AKT signaling molecules was examined by flow cytometry, Western blot and Quantitative Real-time PCR analyses.

Results
MRTX849 was shown to enhance the anticancer efficacy of ABCB1 substrate drugs in the transporter-overexpressing cells both in vitro and in vivo. The MDR reversal effect was specific against ABCB1 because no similar effect was observed in the parental sensitive cells or in ABCG2-mediated MDR cells. Mechanistically, MRTX849 increased the cellular accumulation of ABCB1 substrates including doxorubicin (Dox) and rhodamine 123 (Rho123) in ABCB1-overexpressing MDR cells by suppressing ABCB1 efflux activity. Additionally, MRTX849 stimulated ABCB1 ATPase activity and competed with [125I]-IAAP for photolabeling of ABCB1 in a concentration-dependent manner. However, MRTX849 did not alter ABCB1 expression or phosphorylation of AKT/ERK at the effective MDR reversal drug concentrations.

Conclusions
In summary, MRTX849 was found to overcome ABCB1-mediated MDR both in vitro and in vivo by specifically attenuating ABCB1 efflux activity in drug-resistant cancer cells. Further studies are warranted to translate the combination of MRTX849 and conventional chemotherapy to clinical application for circumvention of MDR.
Captopril alleviates epilepsy and cognitive impairment by attenuation of C3-mediated inflammation and synaptic phagocytosis
Authors: Dong Xinyan , Fan Jianchen , Lin Donghui , Wang Xuehui , Kuang Haoyu , Gong Lifen , Chen Chen , Jiang Jie , Xia Ningxiao , He Dahong , Shen Weida , Jiang Peifang , Kuang Rong , Zeng Linghui , Xie Yicheng 
Published: September 2022

AbstractEvidence from experimental and clinical studies implicates immuno-inflammatory responses as playing an important role in epilepsy-induced brain injury. Captopril, an angiotensin-converting enzyme inhibitor (ACEi), has previously been shown to suppress immuno-inflammatory responses in a variety of neurological diseases. However, the therapeutic potential of captopril on epilepsy remains unclear. In the present study, Sprague Dawley (SD) rats were intraperitoneally subjected to kainic acid (KA) to establish a status epilepticus. Captopril (50 mg/kg, i.p.) was administered daily following the KA administration from day 3 to 49. We found that captopril efficiently suppressed the KA-induced epilepsy, as measured by electroencephalography. Moreover, captopril ameliorated the epilepsy-induced cognitive deficits, with improved performance in the Morris water maze, Y-maze and novel objective test. RNA sequencing (RNA-seq) analysis indicated that captopril reversed a wide range of epilepsy-related biological processes, particularly the glial activation, complement system-mediated phagocytosis and the production of inflammatory factors. Interestingly, captopril suppressed the epilepsy-induced activation and abnormal contact between astrocytes and microglia. Immunohistochemical experiments demonstrated that captopril attenuated microglia-dependent synaptic remodeling presumably through C3–C3ar-mediated phagocytosis in the hippocampus. Finally, the above effects of captopril were partially blocked by an intranasal application of recombinant C3a (1.3 μg/kg/day). Our findings demonstrated that captopril reduced the occurrence of epilepsy and cognitive impairment by attenuation of inflammation and C3-mediated synaptic phagocytosis. This approach can easily be adapted to long-term efficacy and safety in clinical practice.
Graphical Abstract
Pulmonary dust foci as rat pneumoconiosis lesion induced by titanium dioxide nanoparticles in 13-week inhalation study
Authors: Yamano Shotaro , Goto Yuko , Takeda Tomoki , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Kasai Tatsuya , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Umeda Yumi 
Published: September 2022

Abstract
Background
Most toxicological studies on titanium dioxide (TiO2) particles to date have concentrated on carcinogenicity and acute toxicity, with few studies focusing of pneumoconiosis, which is a variety of airspace and interstitial lung diseases caused by particle-laden macrophages. The present study examined rat pulmonary lesions associated with pneumoconiosis after inhalation exposure to TiO2 nanoparticles (NPs).

Methods
Male and female F344 rats were exposed to 6.3, 12.5, 25, or 50 mg/m3 anatase type TiO2 NPs for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. After the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses.

Results
Numerous milky white spots were present in the lungs after exposure to 25 and 50 mg/m3 TiO2 NPs. Histopathological analysis revealed that the spots were alveolar lesions, characterized predominantly by the agglomeration of particle-laden macrophages and the presence of reactive alveolar epithelial type 2 cell (AEC2) hyperplasia. We defined this characteristic lesion as pulmonary dust foci (PDF). The PDF is an inflammatory niche, with decreased vascular endothelial cells in the interstitium, and proliferating AEC2 transformed into alveolar epithelial progenitor cells. In the present study, the AEC2 in the PDF had acquired DNA damage. Based on PDF induction, the lowest observed adverse effect concentration for pulmonary disorders in male and female rats was 12.5 mg/m3 and 6.3 mg/m3, respectively. The no observed adverse effect concentration for male rats was 6.3 mg/m3. There was a sex difference in lung lesion development, with females showing more pronounced lesion parameters than males.

Conclusions
Inhalation exposure to TiO2 NPs caused PDF, an air-space lesion which is an alveolar inflammatory niche containing particle-laden macrophages and proliferating AEC2. These PDFs histopathologically resemble some pneumoconiosis lesions (pulmonary siderosis and hard metal pneumoconiosis) in workers and lung disease in smokers, suggesting that PDFs caused by exposure to TiO2 NPs in rats are an early pneumoconiosis lesion and may be a common alveolar reaction in mammals.

Graphical Abstract
Integrating pharmacokinetics and network analysis to investigate the mechanism of Moutan Cortex in blood-heat and blood stasis syndrome
Authors: Ye Qiuli , Zhang Ying , Yan Donghui , Sun Yue , Li Ming , Cao Hui , Wang Shumei , Meng Jiang 
Published: September 2022

Abstract
Background
Raw Moutan Cortex (RMC) has been used in China and other Asian countries for thousands of years. Its medical application is the treatment of cooling blood and promoting blood circulation. However, its therapeutic mechanism is still undefined.

Methods
In this study, the pharmacokinetics strategy that integrated network analysis was employed to explore the mechanism of RMC in blood-heat and blood stasis syndrome (BHS) model rats. Firstly, Ultra-High performance Liquid Chromatography coupled with Diode Array Detector (UHPLC-DAD) method was developed to determine nine absorbed compounds in rat serum in BHS and normal rats after oral administration of RMC extract respectively. Then the pharmacology network was established based on the relationship between nine compounds absorbed into the blood and BHS targets. Finally, the predicted hub targets were validated experimentally in human umbilical vein endothelial cells (HUVECs).

Results
Pharmacokinetic study showed that the pharmacokinetic parameters of nine absorbed compounds had significant differences between BHS and normal groups (p < 0.05). Network analysis showed that 8 target genes, namely, F2, F10, F7, PLAU, MAPK14, MAPK10, AKT1, and NOS3 may be the primary targets regulated by RMC for the treatment of BHS. Among them, targets (F2, F10, F7 and MAPK14, MAPK10, AKT) and 4 active ingredients (paeonol, paeoniflorin, quercetin and oxypaeoniflorin) were selected for evaluating the reliability in vitro experiments, which revealed that the mechanism of RMC against BHS syndrome may inhibit inflammatory pathways and regulate coagulation cascades pathway for cooling and promoting blood circulation.

Conclusion
The proposed pharmacokinetics study integrated network analysis strategy provides a combination method to explore the therapeutic mechanism of RMC on BHS.

Graphical Abstract
Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial]
Authors: Adigweme Ikechukwu , Akpalu Edem , Yisa Mohammed , Donkor Simon , Jarju Lamin B. , Danso Baba , Mendy Anthony , Jeffries David , Njie Abdoulie , Bruce Andrew , Royals Michael , Goodson James L. , Prausnitz Mark R. , McAllister Devin , Rota Paul A. , Henry Sebastien , Clarke Ed 
Published: September 2022

Abstract
Background
New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants.

Methods
This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18–40 years] followed by 120 toddlers [15–18 months] and 120 infants [9–10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee.

Discussion
This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination.

Trial registration
Pan-African Clinical Trials Registry 202008836432905. ClinicalTrials.govNCT04394689
Cognitive-motor telerehabilitation in multiple sclerosis (CoMoTeMS): study protocol for a randomised controlled trial
Authors: Van Laethem Delphine , Van de Steen Frederik , Kos Daphne , Naeyaert Maarten , Van Schuerbeek Peter , D’Haeseleer Miguel , D’Hooghe Marie B. , Van Schependom Jeroen , Nagels Guy 
Published: September 2022

Abstract
Background
The management of cognitive impairment is an important goal in the treatment of multiple sclerosis (MS). While cognitive rehabilitation has been proven to be effective in improving cognitive performance in MS, research in the elderly indicates a higher effectiveness of combined cognitive-motor rehabilitation. Here, we present the protocol of a randomised controlled clinical trial to assess whether a combined cognitive-motor telerehabilitation programme is more effective in improving working memory than only cognitive or motor training.

Methods/design
The CoMoTeMS-trial is a two-centre, randomised, controlled and blinded clinical trial. A total of 90 patients with MS will receive 12 weeks of either a combined cognitive-motor telerehabilitation programme or only cognitive or motor training. The primary outcome is a change in the digit span backwards. Secondary outcomes are other cognitive changes (Brief International Cognitive Assessment for Multiple Sclerosis and Backward Corsi), Expanded Disability Status Scale (EDSS), 6-Min Walk Test, 25-Foot Walk Test, 9-Hole Peg Test, anxiety and depression, fatigue, quality of life, cognitive and physical activity level, electroencephalography and magnetic resonance imaging of the brain.

Discussion
We hypothesise that the improvement in digit span backwards after 12 weeks of treatment will be significantly higher in the group treated with the combined cognitive-motor telerehabilitation programme, compared to the groups receiving only cognitive and only motor training.

Trial registration
ClinicalTrials.gov NCT05355389. Registered on 2 May 2022.
Both levoglucosan kinase activity and transport capacity limit the utilization of levoglucosan in Saccharomyces cerevisiae
Authors: Yang Mengdan , Wei Tiandi , Wang Kai , Jiang Liqun , Zeng Dihao , Sun Xinhua , Liu Weifeng , Shen Yu 
Published: September 2022

AbstractManufacturing fuels and chemicals from cellulose materials is a promising strategy to achieve carbon neutralization goals. In addition to the commonly used enzymatic hydrolysis by cellulase, rapid pyrolysis is another way to degrade cellulose. The sugar obtained by fast pyrolysis is not glucose, but rather its isomer, levoglucosan (LG). Here, we revealed that both levoglucosan kinase activity and the transportation of levoglucosan are bottlenecks for LG utilization in Saccharomyces cerevisiae, a widely used cell factory. We revealed that among six heterologous proteins that had levoglucosan kinase activity, the 1,6-anhydro-N-acetylmuramic acid kinase from Rhodotorula toruloides was the best choice to construct levoglucosan-utilizing S. cerevisiae strain. Furthermore, we revealed that the amino acid residue Q341 and W455, which were located in the middle of the transport channel closer to the exit, are the sterically hindered barrier to levoglucosan transportation in Gal2p, a hexose transporter. The engineered yeast strain expressing the genes encoding the 1,6-anhydro-N-acetylmuramic acid kinase from R. toruloides and transporter mutant Gal2pQ341A or Gal2pW455A consumed ~ 4.2 g L−1 LG in 48 h, which is the fastest LG-utilizing S. cerevisiae strain to date.
Simultaneous external and internal marking of Triatoma sordida nymphs: trace element efficacy and microgeographic dispersal in a peridomestic Brazilian Cerrado rural household
Authors: Dantas Edson Santos , Gurgel-Gonçalves Rodrigo , Maciel-de-Freitas Rafael , Monteiro Fernando Araújo 
Published: September 2022

Abstract
Background
Chagas disease (American trypanosomiasis) is an important neglected tropical illness, which has the flagellate protozoan Trypanosoma cruzi as etiological agent and blood-feeding insects of the Triatominae subfamily as vectors. Despite its importance for disease epidemiology, field studies targeting microgeographic dispersal of triatomines in endemic areas are rare. The ability wingless nymphs have to move (crawl) within peridomestic settings is a key component regarding the design and development of rational control strategies.

Methods
We double-marked Triatoma sordida fourth-instar nymphs (N4) with a reliable fluorescent dye and a trace element. This new methodology allowed us to simultaneously evaluate (i) nymph dispersal and (ii) the effectiveness of copper (Cu), chromium (Cr), and cadmium (Cd) trace elements as potential new markers. In the mark-release-recapture (MRR) experiment, 390 T. sordida N4 were released in the peridomicile of a single rural household, 130 individuals at each of three release points, at distances of 2, 5, and 10 m from the chicken coop (CC) and 27, 32, and 35 m away from the horse corral (HC). All specimens were double marked (Cu/blue, Cr/orange, Cd/green). Recaptures occurred in two intervals: 1–3 days and 15–17 days after release.

Results
Specimens were successfully recaptured at all distances up to 10 m. A total of 19, 23, and 10 specimens were able to disperse 2, 5, and 10 m, respectively, to reach the CC. No insects were recaptured at the HC. Of the three analyte/paint combinations tested, Cr/orange gave the most promising results; Cu/blue marker and Cd/green marker performed very poorly with only 4/19 and 0/10 analyte/paint ratios, respectively.

Conclusions
Triatoma sordida N4 could cover a distance of 10 m in 17 days. This indicates that nymphs seem to have a reduced dispersal capability compared to adults. Ninety-one percent of the 22 recaptured orange-marked nymphs were still Cr positive after the 17-day period evaluated. This makes this analyte a good candidate for future investigations that will apply this marking method in MRR studies.

Graphical Abstract