bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Metabolomic Profile Between Colistin Susceptible and Colistin Resistant Strains of A. baumanni
Authors: Atron Bydaa , Hasbek Mursit , Doğan Halef O. , ŞENOL Onur 
Published: February 2023

Abstract
Acinetobacter baumannii, has emerged as a critical nosocomial pathogen with the ability to develop resistance to all available antimicrobials, including colistin. Metabolomics tools may aid in the observation of the low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. The objective of this work was to compare the differential expression of metabolites between colistin-susceptible and resistant clinical strains of A. baumannii. The Q-TOF LC/MS method was used together with multivariate data analysis, Annotation of identified metabolites was performed along with the analysis of the metabolic pathways. Our results revealed that colistin-susceptible and colistin-resistant A. baumannii Strains have different metabolic profiles. Some of the identified metabolites were found to be involved in multiple biochemical pathways, such as cell wall biosynthesis and recycling, astaxanthin biosynthesis, and nucleotide metabolism. Cell wall recycling and nucleic acid degradation-related metabolites were up-regulated in colistin-sensitive strains. The lipid profile was down-regulated in colistin-resistant strains. On the other hand, a virulence factor that can serve as a drug target was found to be up-regulated in resistant strains. Our findings can provide a basis for further research on the elucidation of metabolites' role in resistance mechanisms and the determination of novel drug targets that would aid in the development of effective therapeutics against A. baumannii.
Numerical Assessment of Polyoxymethylene Dimethyl Ether (OME3) Injection Timing in Compression Ignition Engine
Authors: Marković Marijan , Jurić Filip , Šošić Dominik Pečaver , Schmalhorst Carsten , Hoang Anh Tuan , Vujanović Milan 
Published: February 2023

Abstract
This research encompasses the numerical analysis of trioxymethylene dimethyl ether (OME-3) e-fuel on an industrial compression ignition engine, as a viable replacement for diesel fuel. The performed simulations examined single injection and multi injection operating conditions of OME-3, varying injection rates and timing. The combustion process is modelled employing two approaches: three-dimensional Extended Coherent Flame Model (ECFM-3Z) and General Gas Phase Reactions (GGPR) with the reduced chemical kinetic mechanism. ECFM-3Z gives a faster convergence, where pretabulated autoignition and laminar flame speed databases are integrated into the model to decrease computational time. GGPR approach is validated on the experimental values for mean pressure, temperature, and rate of released heat in the same engine with diesel fuel and then again on an OME-3. Both approaches confirmed that a higher amount of OME-3 and a longer injection time is needed to achieve equivalent output power as diesel fuel since OME-3 has a lower net calorific value. It is established that multi injection case with an adapted injection timing is the optimal choice for OME-3 combustion since it achieves a 15% higher mean pressure peak compared to the diesel case. Nitrogen oxides emissions for OME-3 are also compared to the diesel case for both combustion modelling approaches.
A novel mutation of the EYA1 gene in a branchio-otic syndrome child with secretory otitis media and bilateral vestibular weakness
Authors: He Jun , Gu Yu , Jin Li , Ren Jihao , Yin Tuanfang , Fu Jinfeng , Liu Wei 
Published: February 2023

Abstract

Objective To investigate the phenotypic manifestations and molecular etiology of branchio-otic syndrome (BOS) in a Chinese family. Methods We recruited two generations of a Chinese family with BOS. Family history was obtained and detailed physical and hearing examinations were performed on all family members. Whole-exome sequencing (WES) was used to screen the candidate disease genes using phenolyzer software. Sanger sequencing was used for validation. The pathogenicity of the candidate mutations was analyzed. Results The proband had severe-to-profound sensorineural hearing loss in the left ear, and mixed hearing loss, type III cup-shaped ear, external auditory canal stenosis and cochlea hypoplasia in the right ear; Cochlear hypoplasia together with the fused lateral semicircular canal and vestibular in the left ear, with bilateral preauricular pits and branchial fistulae. Moreover, the patient had unilateral secretory otitis media(SOM) in the right ear and bilateral vestibular weakness (BVW), which has not been reported in previous studies. The patient’s hearing on the right side was restored to nearly normal after myringotomy with grommet insertion. We also identified a novel frameshift mutation in the proband (c.1697_1698delinsT[p.Lys566Ilefs*73]) in exon 17 of theEYA1gene, which was assessed as “pathogenic” according to American College of Medical Genetics and Genomics guidelines. Sanger sequencing was used to validate the novel heterozygous mutation and WES accuracy. Conclusion This is the first report of a child with BOS with SOM and BVW, further enriching the known phenotypes of this gene mutation. We also observed a novelEYA1gene mutation site in a patient with BOS, expanding the mutation map and providing a reference for genetic diagnosis.
Unintentional Pediatric Exposures to Household Cleaning Products: A Cross-Sectional Analysis of the National Poison Data System (2000-2015)
Authors: Pacini Anthony , Tsutaoka Ben , Lai Leslie , Durrani Timur S. 
Published: February 2023

Abstract
Background
Household cleaning products are the second most common cause of unintentional poisoning in the United States.
Methods
This cross-sectional study analyzed all household cleaner calls classified as ages five and under made to the American Association of Poison Control Centers between the dates of 1 January 2000 and 31 December 2015.
Results
Significant clinical effects or injury was low, making up only 2.6% of cases with a known medical outcome. Alkali-based cleaning products accounted for the third highest frequency of overall exposures and the highest number of all exposure outcomes determined to have a significant clinical effect or injury.
Conclusions
Future injury prevention efforts should focus on increased awareness for parents of alkali cleaning products such as oven cleaners and drain cleaners, emphasizing purchasing products with child resistant packaging and proper storage and use practices.
Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer
Authors: Yamaki Hidekiyo , Kono Michihisa , Wakisaka Risa , Komatsuda Hiroki , Kumai Takumi , Hayashi Ryusuke , Sato Ryosuke , Nagato Toshihiro , Ohkuri Takayuki , Kosaka Akemi , Ohara Kenzo , Kishibe Kan , Takahara Miki , Hayashi Tatsuya , Kobayashi Hiroya , Katada Akihiro 
Published: February 2023

Abstract
Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T-cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.
Driving the conversion of phytosterol to steroid synthons in Mycolicibacterium neoaurum by engineering the supply and regeneration of flavin adenine dinucleotide
Authors: Lu Song , Ke Jie , Luo Zhi-Kun , Xiong Liang-Bin , Dong Yu-Guo , Wei Dong-Zhi , Wang Feng-Qing 
Published: February 2023

Abstract
Background
The conversion of phytosterols to steroid synthons by engineered Mycolicibacteria comprises one of the core steps in the commercial production of steroid hormones. This is a complex oxidative catabolic process, and taking the production of androstenones as example, it requires about 10 equivalent flavin adenine dinucleotide (FAD). As the high demand for FAD, the insufficient supply of FAD may be a common issue limiting the conversion process.
Results
We substantiated, using the production of 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) as a model, that increasing intracellular FAD supply could effectively increase the conversion of phytosterols into 9-OHAD. Overexpressing ribB and ribC, two key genes involving in FAD synthesis, could significantly enhance the amount of intracellular FAD by 167.4% and the production of 9-OHAD by 25.6%. Subsequently, styrene monooxygenase NfStyA2B from Nocardia farcinica was employed to promote the cyclic regeneration of FAD by coupling the oxidation of nicotinamide adenine dinucleotide (NADH) to NAD+, and the production of 9-OHAD was further enhanced by 9.4%. However, the viable cell numbers decreased by 20.1%, which was attributed to sharply increased levels of H2O2 because of the regeneration of FAD from FADH2. Thus, we tried to resolve the conflict between FAD regeneration and cell growth by the promotor replacement. Finally, a robust strain NF-P2 was obtained, which could produce 9.02 g/L 9-OHAD after adding 15 g/L phytosterols with productivity of 0.075 g/(L∙ h), which was 66.7% higher than that produced by the original strain.
Conclusions
This study highlighted that the cofactor engineering, including the supply and recycling of FAD and NAD+ in Mycolicibacterium, should be adopted as a parallel strategy with pathway engineering to improve the productivity of the industrial strains in the conversion of phytosterols into steroid synthons.
Molecular insight into the expression level of an immunosuppression gene, VTCN1, and its regulatory factors in breast cancer patients and non-cancerous samples with a higher level of IgE
Authors: Sichani Adel Rezvani , Dadkhah Pouya , Tabandeh Tara , Dehkordi Nafiseh Kaviani , Rezaei Mohammad , Rahimirad Samira , Azadeh Mansoureh 
Published: February 2023

Abstract
IgE levels increase in some cancer types due to treatment methods also autoimmune diseases can emerge and lead to worsening of the cancer. Finding a factor based on the reduction in IgE levels found in cancer can act as a determinant in providing the early diagnosis of the disease in individuals with high IgE levels in their blood. Accordingly, in the present study, the effort was made to select a gene associated with breast cancer and high IgE levels through available databases to evaluate the gene expression and the associated lncRNA and polymorphism at the binding site of a miRNA with a gene. In this study, the expression of the VTCN1 gene and the associated lncRNA called NORAD (Non-Coding RNA Activated by DNA Damage), selected through bioinformatics methods and relevant databases were assessed in breast cancer tissue samples along with the blood samples of individuals with high IgE levels, employing the real-time PCR method. Lastly, NORAD’s protein interactions and the relevant signaling pathways were further investigated via bioinformatics tools. The results indicated that the expression of VTCN1 genes increased significantly (P < 0.05), whereas NORAD increased insignificantly (P > 0.05) in both breast cancer and high IgE level samples. The prevalence of GG genotype in polymorphism rs10754339 was similarly high in both categories of samples. Bioinformatic analyses also demonstrated NORAD's association with proteins involved in immunity pathways. This study suggests the VTCN1 and NORAD genes as convenient markers for monitoring breast cancer in people with high IgE levels, as well as employing them in the research regarding the autoimmune diseases in individuals with a breast cancer diagnosis.
PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating Epithelial-Mesenchymal Transition
Authors: Zhou Xin , Li Yanshi , Pan Min , Lu Tao , Liu Chuan , Wang Zhihai , Tang Fengxiang , Hu Guohua 
Published: February 2023

AbstractObjective Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis (LM). This research aimed to determine the PKM2 role in LM in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Kaplan-Meier and COX's regression analysis were employed to determine PKM2's prognostic value, while western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasisin vitroandin vivo. After that, Transwell assay, Wound Healing assay, Flow cytometry, EdU, and anin vivoPopliteal lymphatic metastasis mice model were employed to show the role of PKM2 in FaDu cell lines.In vitroandin vivo studies also confirmed lymphatic metastasis's mechanism. Results Prominent PKM2 overexpression was seen in patients with LM of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis.In vitroresearch showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition (EMT), but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and LM. Conclusions Our findings suggest that PKM2 may be a tumor's promoter gene of LM, which may promote LM of HPC by regulating EMT. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.
Medial to lateral VS lateral to medial in laparoscopic right hemicolectomy-are both techniques the same?
Authors: Hazan Danny , Ishakov Arkadi , Levi Sammy , shimonov mordechai , dayan katia 
Published: February 2023

Abstract
Purpose
we compare MtL to LtM surgical approach for laparoscopic right hemicolectomy, with regards to number of lymph node harvested, operation duration, and length of hospitalization (LOH).
Methods
A retrospective analysis of patients who underwent laparoscopic right hemicolectomy resections for malignant neoplasms, curative-intent, between 2013 to 2020 at Edith Wolfson Medical Center. Surgical techniques were defined as Medial to lateral if the first stage included blood vessel ligation. Lateral to Medial was defined if the first step included mobilization of the lateral attachments.
Results
133 patients who were diagnosed with colon cancer (mean age 72 ± 5.8 years, 46% males) were selected for laparoscopic right hemicolectomy. 54 were treated with the MtL approach, and 79 were treated with the LtM approach. Lymph nodes harvested were similar between the 2 groups (mean of 17, SD +-11). LOH and time of first flatulence were similar between the groups (11.78 ± 1.8 for the LtM group vs. 10.56 ± 1.4 for the MtL group for LOH, and 3.75 ± 0.8 days for the LtM group vs. 4 ± 0.9 days for the MtL group for time of first flatulence, p = 0.30 and p = 0.69 respectively). No difference in patient's survival rate within 30 days. Patients after LtM approach had a shorter operation time (2.18H).
Conclusion
The laparoscopic approach performing right hemicolectomy resection can be performed safely with the same results using the two methods compared. It showed no oncological benefits, and no significant differences in the LOH or short term survival. The LtM approach was associated with a shorter surgery time.
Exploring navigation of gender in a sample of clinically referred young people attending the Gender Identity Development Service
Authors: Haywood Daisy , De Andrés María , Masic Una , Carmichael Polly 
Published: February 2023

Abstract
Background: Gender-diverse young people navigate a cisnormative world and are subject to unique minority stressors, which have been found to contribute to adverse mental health. This research aimed to understand the experiences of clinically referred gender-diverse young people prior to commencing clinical support in gender services.
Methods: The baseline measure of a newly developed questionnaire, the GIDS Gender Questionnaire (GIDS-GQ), was sent to all young people (or caregivers for those aged under 12) attending the Gender Identity Development Service (GIDS). Eighty-four young people and caregivers completed the questionnaire, with eighty-one included in the final sample (M = 15.77 years, SD = 1.83, range = 9-17; assigned female at birth = 72, assigned male at birth = 9). Questionnaires were emailed to participants via an online survey between one and three appointments with the Service. Data were collected between April 2021 and February 2022.
Results: All young people had initiated a social transition, with 75.3% categorised as fully socially transitioned. More young people reported experiencing transphobic bullying (64.2%) and a lack of acceptance of their gender identity (85.1%) in the past than in the time just prior to attending the service (transphobic bullying: 12.3%; non-acceptance: 49.4%). 94.5% of the sample reported disliked body parts, most commonly breasts (80.8%), genitals (37%), and hips (31.5%). Participants most commonly reported a decrease in their mood (61.25%) and most areas of social connectedness.
Conclusions: The majority of this sample had socially transitioned, were supported in their identification, and had experienced less transphobic bullying and non-acceptance prior to commencing services. However, young people continued to dislike their bodies, and experience low mood and social connectedness. Prospective research is required to understand the role of clinical support in distress management.
Immunogenicity and safety of quadrivalent influenza vaccine among adults in Tianjin, China, with a focus on age as a risk factor
Authors: Xiao Tongling , Wei Miaomiao , Guo Xiaokun , Zhang Yu , Wang Zhongyan , Xia Xiaoshuang , Wang Lin , Li Xin , Leng Sean X. 
Published: February 2023

Abstract
Background
Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of elderly people to the influenza vaccine are usually poorer than those of young people. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) and the influence of age among adults in Tianjin. A total of 167 healthy adults in Tianjin were recruited and administered a single dose of IIV4 from October 2021 to March 2022. Blood samples were collected to assay hemagglutination inhibition (HAI) antibody titers before and 21 to 28 days after vaccination. Safety information was collected for 28 days and 6 months after vaccination. Differences in immunogenicity and safety were compared among different age cohorts, and multivariate logistic regression was used to estimate the effect of age and other factors on seroconversion and seroprotection.
Results
Overall, the geometric mean titers (GMTs) for all strains in the ≥ 65 age group were lower than those in the < 65 age group, whereas the seroconversion rates (SCRs) were similar. Multivariate logistic regression analysis showed that age, influenza vaccination history, and baseline HAI antibody titer were the main independent factors affecting seroconversion and seroprotection. Higher age was an unfavorable factor for seroconversion for H1N1 (OR, 0.971; 95% CI: 0.944–0.999; P = 0.042) and B/Victoria (OR, 0.964; 95% CI: 0.937–0.992; P = 0.011). All adverse events (AEs) were grade 1 or grade 2, occurred within 28 days after vaccination, and no serious adverse events occurred.
Conclusions
IIV4 was well-tolerated and immunogenic in healthy adults in Tianjin. Our findings also confirmed that age is an independent factor associated with a lower immune response to IIV4.
Recombinant FOXN1 fusion protein increases T cell generation in aged mice
Authors: Zhao Jin , Zhang Zhenzhen , Lai Kuan Chen , Lai Laijun 
Published: February 2023

Abstract
Background: Although the thymus continues to export T cells throughout life, it undergoes a profound involution/atrophy with age, resulting in decreased numbers of T cells in the older adult, which has direct etiological linkages with many diseases. T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produce a rFOXN1 fusion protein containing the N-terminal of CCR9, FOXN1 and a protein transduction domain.
Results: We show here that, when injected intravenously into aged mice, the rFOXN1 fusion protein migrates into the thymus and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ.
Conclusions: Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in the older adult.
Challenges in small cetacean telemetry: an attempt at developing a remotely deployed attachment device for single-pin dorsal fin satellite transmitters
Authors: Balmer Brian C. , Westgate Andrew J. , McFee Wayne E. 
Published: February 2023

Abstract
Movement pattern and habitat use data are essential parameters for developing effective management strategies and successful conservation efforts for marine mammals across the world. Satellite telemetry is critical for collecting fine-scale, temporal and spatial data on individual animals that has broad-scale applicability at population and species levels. There have been significant advances in the remote deployment of satellite telemetry devices on large cetacean species. However, the development of comparable remote attachment methodologies for small cetaceans is still limited. Currently, satellite tag attachment for small cetaceans requires manual capture that increases the risk to the target animal, can be logistically challenging, and cost prohibitive. The goal of this project was to develop a novel tool to remotely attach single-pin satellite telemetry devices to the dorsal fin of individual small cetaceans. Three different spring-loaded designs and one pneumatic version of the remote attachment device were built in an iterative process to identify a successful deployment methodology. Ultimately, as a result of logistical challenges associated with a Category 5 hurricane, the COVID-19 pandemic, and engineering complexities related to dorsal fin morphology and small cetacean behavior, the objective of this project was not met. However, lessons learned from these attempts to develop this new sampling tool have applicability for future researchers in the successful completion of a safe and effective methodology for remote attachment of satellite tags to small cetacean dorsal fins.