bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-Conjugating Enzyme OsUBC11 Affects the Development of Roots via Auxin Pathway
Authors: Han Yunfei , Zhang Chuanzhong , Sha Hanjing , Wang Xiaojing , Yu Yue , Liu Jia , Zhao Guangxin , Wang Jingying , Qiu Guankai , Xu Xingjian , Fang Jun 
Published: February 2023

AbstractRice has 48 ubiquitin-conjugating enzymes, and the functions of most of these enzymes have not been elucidated. In the present study, a T-DNA insertional mutant named R164, which exhibited a significant decrease in the length of primary and lateral roots, was used as the experimental material to explore the potential function of OsUBC11. Analysis using the SEFA-PCR method showed that the T-DNA insertion was present in the promoter region of OsUBC11 gene, which encodes ubiquitin-conjugating enzyme (E2), and activates its expression. Biochemical experiments showed that OsUBC11 is a lysine-48-linked ubiquitin chain-forming conjugase. OsUBC11 overexpression lines showed the same root phenotypes. These results demonstrated that OsUBC11 was involved in root development. Further analyses showed that the IAA content of R164 mutant and OE3 line were significantly lower compared with wild-type Zhonghua11. Application of exogenous NAA restored the length of lateral and primary roots in R164 and OsUBC11 overexpression lines. Expression of the auxin synthesis regulating gene OsYUCCA4/6/7/9, the auxin transport gene OsAUX1, auxin/indole-3-acetic acid (Aux/IAA) family gene OsIAA31, auxin response factor OsARF16 and root regulator key genes, including OsWOX11, OsCRL1, OsCRL5 was significantly down-regulated in OsUBC11 overexpressing plants. Collectively, these results indicate that OsUBC11 modulates auxin signaling, ultimately affecting root development at the rice seedling stage.
Genomic and phenotypic profiling of Staphylococcus aureus isolates from bovine mastitis for antibiotic resistance and intestinal infectivity
Authors: Majumder Satwik , Sackey Trisha , Viau Charles , Park Soyoun , Xia Jianguo , Ronholm Jennifer , George Saji 
Published: February 2023

Abstract
Background
Staphylococcus aureus is one of the prevalent etiological agents of contagious bovine mastitis, causing a significant economic burden on the global dairy industry. Given the emergence of antibiotic resistance (ABR) and possible zoonotic spillovers, S aureus from mastitic cattle pose threat to both veterinary and public health. Therefore, assessment of their ABR status and pathogenic translation in human infection models is crucial.

Results
In this study, 43 S. aureus isolates associated with bovine mastitis obtained from four different Canadian provinces (Alberta, Ontario, Quebec, and Atlantic provinces) were tested for ABR and virulence through phenotypic and genotypic profiling. All 43 isolates exhibited crucial virulence characteristics such as hemolysis, and biofilm formation, and six isolates from ST151, ST352, and ST8 categories showed ABR. Genes associated with ABR (tetK, tetM, aac6’, norA, norB, lmrS, blaR, blaZ, etc.), toxin production (hla, hlab, lukD, etc.), adherence (fmbA, fnbB, clfA, clfB, icaABCD, etc.), and host immune invasion (spa, sbi, cap, adsA, etc.) were identified by analyzing whole-genome sequences. Although none of the isolates possessed human adaptation genes, both groups of ABR and antibiotic-susceptible isolates demonstrated intracellular invasion, colonization, infection, and death of human intestinal epithelial cells (Caco-2), and Caenorhabditis elegans. Notably, the susceptibilities of S. aureus towards antibiotics such as streptomycin, kanamycin, and ampicillin were altered when the bacteria were internalized in Caco-2 cells and C. elegans. Meanwhile, tetracycline, chloramphenicol, and ceftiofur were comparatively more effective with ≤ 2.5 log10 reductions of intracellular S. aureus.

Conclusions
This study demonstrated the potential of S. aureus isolated from mastitis cows to possess virulence characteristics enabling invasion of intestinal cells thus calling for developing therapeutics capable of targeting drug-resistant intracellular pathogens for effective disease management.
Nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia in the absence of intracranial devices: a case report
Authors: Mizuno Shinsuke , Fujikawa Tomoko , Uemura Suguru , Hasegawa Daiichiro , Kosaka Yoshiyuki , Kasai Masashi 
Published: February 2023

Abstract
Background
Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices.

Case presentation
A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient’s symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72.

Conclusions
To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.
Enhanced antitumor activity of a novel, oral, helper epitope-containing WT1 protein vaccine in a model of murine leukemia
Authors: Minagawa Hikaru , Hashii Yoshiko , Nakajima Hiroko , Fujiki Fumihiro , Morimoto Soyoko , Nakata Jun , Shirakawa Toshiro , Katayama Takane , Tsuboi Akihiro , Ozono Keiichi 
Published: February 2023

Abstract
Background
A Wilms’ tumor 1 (WT1) oral vaccine, Bifidobacterium longum (B. longum) 420, in which the bacterium is used as a vector for WT1 protein, triggers immune responses through cellular immunity consisting of cytotoxic T lymphocytes (CTLs) and other immunocompetent cells (e.g., helper T cells). We developed a novel, oral, helper epitope-containing WT1 protein vaccine (B. longum 2656) to examine whether or not B. longum 420/2656 combination further accelerates the CD4+ T cell help-enhanced antitumor activity in a model of murine leukemia.

Methods
C1498-murine WT1—a genetically-engineered, murine leukemia cell line to express murine WT1—was used as tumor cell. Female C57BL/6 J mice were allocated to the B. longum 420, 2656, and 420/2656 combination groups. The day of subcutaneous inoculation of tumor cells was considered as day 0, and successful engraftment was verified on day 7. The oral administration of the vaccine by gavage was initiated on day 8. Tumor volume, the frequency and phenotypes of WT1-specific CTLs in CD8+ T cells in peripheral blood (PB) and tumor-infiltrating lymphocytes (TILs), as well as the proportion of interferon-gamma (INF-γ)-producing CD3+CD4+ T cells pulsed with WT135–52 peptide in splenocytes and TILs were determined.

Results
Tumor volume was significantly smaller (p < 0.01) in the B. longum 420/2656 combination group than in the B. longum 420 group on day 24. WT1-specific CTL frequency in CD8+ T cells in PB was significantly greater in the B. longum 420/2656 combination group than in the B. longum 420 group at weeks 4 (p < 0.05) and 6 (p < 0.01). The proportion of WT1-specific, effector memory CTLs in PB increased significantly in the B. longum 420/2656 combination group than in the B. longum 420 group at weeks 4 and 6 (p < 0.05 each). WT1-specific CTL frequency in intratumoral CD8+ T cells and the proportion of IFN-γ-producing CD3+CD4+ T cells in intratumoral CD4+ T cells increased significantly (p < 0.05 each) in the B. longum 420/2656 combination group than in the 420 group.

Conclusions
B. longum 420/2656 combination further accelerated antitumor activity that relies on WT1-specific CTLs in the tumor compared with B. longum 420.
Fibroblast growth factor receptor type 4 as a potential therapeutic target in clear cell renal cell carcinoma
Authors: Narisawa Takafumi , Naito Sei , Ito Hiromi , Ichiyanagi Osamu , Sakurai Toshihiko , Kato Tomoyuki , Tsuchiya Norihiko 
Published: February 2023

Abstract
Background
Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of FGFR4 CN amplification in ccRCC.

Methods
The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931.

Results
60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model.

Conclusion
FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.
A clinical study of topical treatment for thyroid-associated ophthalmopathy with dry eye syndrome
Authors: Sun Rou , Yang Muyue , Lin Chenyi , Wu Yu , Sun Jing , Zhou Huifang 
Published: February 2023

Abstract
Introduction
Clinically, thyroid-associated ophthalmopathy (TAO) patients were suffered from dry eye syndrome. Only a few relevant studies were about this topic. Our study was determined to provide high-level evidence for the treatment of TAO with dry eye syndrome.

Purpose
To compare the clinical effects of vitamin A palmitate eye gel and sodium hyaluronate eye drop forTAO patients with dry eye syndrome.

Methods
The study was conducted in the Ophthalmology Department of the Ninth People’s Hospital Affiliated with the Medical College of Shanghai Jiao Tong University from May to October 2020. A total of 80 mild or moderate-to-severe TAO patients with dry eye syndrome were randomly divided into two groups. The disease stages of all subjects were inactive. Patients in group A were treated with vitamin A palmitate eye gel three times/day for one month and sodium hyaluronate eye drop in group B. The index including break-up time (BUT) and Schirmer I test (ST), corneal fluorescence staining (FL), ocular surface disease index (OSDI), and adverse reactions were recorded by the same clinician at baseline and 1 month after treatment. The data were analyzed by SPSS 24.0.

Results
Finally, 65 subjects completed the treatment. The average age of the patients in Group A was 38.1 ± 11.4 years, and that in Group B was 37.26 ± 10.67 years. 82% of the subjects in group A were female and 74% in group B. There was no significant difference between the two groups at baseline, including the value of ST, BUT, OSDI, and FL grade. After the treatment, the effective rate was 91.2% in group A, of which the value of BUT and FL grade was significantly improved (P < 0.001). The effective rate in group B was 67.7%, of which the value of OSDI score and FL grade was significantly improved (P = 0.002). In addition, the BUT value of group A was significantly longer than that of group B (P = 0.009).

Conclusion
InTAO patients with dry eye syndrome, vitamin A palmitate gel and sodium hyaluronate eye drop improved the dry eye and promoted corneal epithelial repair. Vitamin A palmitate gel improves the stability of tear film, while sodium hyaluronate eye drop improves patients’ subjective discomfort.
Diagnosis-specific sickness absence among injured working-aged pedestrians: a sequence analysis
Authors: Kjeldgård Linnea , Stigson Helena , Bergsten Eva L. , Farrants Kristin , Friberg Emilie 
Published: February 2023

Abstract
Background
The knowledge about the long-term consequences in terms of sickness absence (SA) among pedestrians injured in a traffic-related accident, including falls, is scarce. Therefore, the aim was to explore diagnosis-specific patterns of SA during a four-year period and their association with different sociodemographic and occupational factors among all individuals of working ages who were injured as a pedestrian.

Methods
A nationwide register-based study, including all individuals aged 20–59 and living in Sweden, who in 2014–2016 had in- or specialized outpatient healthcare after a new traffic-related accident as a pedestrian. Diagnosis-specific SA (> 14 days) was assessed weekly from one year before the accident up until three years after the accident. Sequence analysis was used to identify patterns (sequences) of SA, and cluster analysis to form clusters of individuals with similar sequences. Odds ratios (ORs) with 95% confidence intervals (CIs) for association of the different factors and cluster memberships were estimated by multinomial logistic regression.

Results
In total, 11,432 pedestrians received healthcare due to a traffic-related accident. Eight clusters of SA patterns were identified. The largest cluster was characterized by no SA, three clusters had different SA patterns due to injury diagnoses (immediate, episodic, and later). One cluster had SA both due to injury and other diagnoses. Two clusters had SA due to other diagnoses (short-term and long-term) and one cluster mainly consisted of individuals with disability pension (DP). Compared to the cluster “No SA”, all other clusters were associated with older age, no university education, having been hospitalized, and working in health and social care. The clusters “Immediate SA”, “Episodic SA” and “Both SA due to injury and other diagnoses” were also associated with higher odds of pedestrians who sustained a fracture.

Conclusions
This nationwide study of the working-aged pedestrians observed diverging patterns of SA after their accident. The largest cluster of pedestrians had no SA, and the other seven clusters had different patterns of SA in terms of diagnosis (injury and other diagnoses) and timing of SA. Differences were found between all clusters regarding sociodemographic and occupational factors. This information can contribute to the understanding of long-term consequences of road traffic accidents.
Telehealth utilization in U.S. Medicare beneficiaries aged 65 years and older during the COVID-19 pandemic
Authors: Lu Min , Liao Xinyi 
Published: February 2023

Abstract
Background
The COVID-19 pandemic has become a serious public health concern for older adults and amplified the value of deploying telehealth solutions. The purpose of this study was to investigate telehealth offered by providers among U.S. Medicare beneficiaries aged 65 years and older during the COVID-19 pandemic.

Methods
This cross-sectional study analyzed Medicare beneficiaries aged 65 years and older using data from the Medicare Current Beneficiary Survey, Winter 2021 COVID-19 Supplement ($$n=9,185$$

n
=
9
,
185

). We identified variables that were associated with telehealth offered by primary care physicians and beneficiaries’ access to the Internet through a multivariate classification analysis utilizing Random Forest machine learning techniques.

Findings
For study participants interviewed by telephone, 81.06% of primary care providers provided telehealth services, and 84.62% of the Medicare beneficiaries had access to the Internet. The survey response rates for each outcome were 74.86% and 99.55% respectively. The two outcomes were positively correlated ($$\chi ^2=268.58,\,p<.001$$

χ
2

=
268.58
,

p
<
.
001

). The Our machine learning model predicted the outcomes accurately utilizing 44 variables. Residing area and race/ethnicity were most informative for predicting telehealth coverage, and Medicare-Medicaid dual eligibility and income were most informative for predicting Internet access. Other strong correlates included age, ability to access basic needs and certain mental and physical health conditions. Interactions were found among statuses of residing area, age, Medicare Advantage and heart conditions that intensified the disparity of outcomes.

Conclusions
We found that telehealth offered by providers likely increased during the COVID-19 pandemic for older beneficiaries, providing important access to care for certain subgroups. Policymakers must continue to identify effective means of delivering telehealth services, modernize the framework of regulatory, accreditation and reimbursement, and address disparities in access to telehealth with a particular focus on underserved communities.
Dental caries experience among qat chewers in dental college clinics, Jazan, Saudi Arabia
Authors: Halboub Esam , Alamri Abdulwahab Ahmed , Kamili Ghazi , Alqahtani Ahmed Shaher 
Published: February 2023

Abstract
Aims
There is a considerable debate on the impact of qat chewing on dental and oral health. Thereby, this study aimed at assessing the dental caries among qat chewers (QC) and non-qat chewers (NQC) who attend outpatient dental clinics, College of Dentistry, Jazan, Saudi Arabia.

Materials and methods
A sample of 100 QC and 100 NQC were recruited amongst those attended dental clinics, college of dentistry, Jazan University during the 2018–2019 academic year. Their dental health was assessed by three pre-calibrated male interns using DMFT index. The Care Index, Restorative Index and Treatment Index were calculated. Comparisons between both subgroups were done using independent t test. Multiple linear regression analyses were further conducted to stand on the independent determinants of the oral health among this population.

Results
QC were unintentionally older (36.55 ± 8.74 years) than NQC (32.96 ± 8.49 years; P = 0.004). Fifty-six percent of QC reported brushing their teeth compared to only 35% (P = 0.001). NQC with university and postgraduate educational levels were more than QC. The mean Decayed [5.91 (5.16)] and DMFT [9.15 (5.87)] were higher among QC compared to NQC [3.73 (3.62) and 6.7 (4.58); P = 0.001 and 0.001, respectively]. The other indices were not different between both subgroups. The multiple linear regression revealed that qat chewing and age, individually or together, as independent determinants for the dental decay, missing, DMFT and TI.

Conclusion
Qat chewing habit has a detrimental impact on dental health. It is associated with higher dental caries and missing teeth, and a lower treatment index.
Perceived guideline clarity impacts guideline-concordant care for breast cancer screening in women age 40–49
Authors: Nadler Michelle B. , Corrado Ann Marie , Wilson Brooke E. , Desnoyers Alexandra , Amir Eitan , Ivers Noah , Desveaux Laura 
Published: February 2023

Abstract
Background
Canadian and US Task Forces recommend against routine mammography screening for women age 40–49 at average breast cancer risk as harms outweigh benefits. Both suggest individualized decisions based on the relative value women place on potential screening benefits and harms. Population-based data reveal variation in primary care professionals (PCPs) mammography rates in this age group after adjusting for sociodemographic factors, highlighting the need to explore PCP screening perspectives and how this informs clinical behaviours. Results from this study will inform interventions that can improve guideline concordant breast screening for this age group.

Methods
Qualitative semi-structured interviews were performed with PCPs in Ontario, Canada. Interviews were structured using the theoretical domains framework (TDF) to explore determinants of breast cancer screening best-practice behaviours: (1) risk assessment; (2) discussion regarding benefits and harms; and (3) referral for screening.

Analysis
Interviews were transcribed and analyzed iteratively until saturation. Transcripts were coded deductively by behaviour and TDF domain. Data that did not fit within a TDF code were coded inductively. The research team met repeatedly to identify potential themes that influenced or were important consequences of the screening behaviours. The themes were tested against further data, disconfirming cases, and different PCP demographics.

Results
Eighteen physicians were interviewed. The theme of perceived guideline clarity (a lack of clarity on guideline-concordant practices) influenced all behaviours and moderated the extent to which the risk assessment and discussion occurred. Many were unaware of how risk-assessment factored into the guidelines and/or did not perceive that a shared-care discussion was guideline-concordant. Deferral to patient preference (screening referral without a complete discussion of benefits and harms) occurred when the PCPs had low knowledge regarding harms and/or if they experienced regret (TDF domain: emotion) resulting from prior clinical experiences. Older providers described patient’s influence impacting their decisions and physicians trained outside Canada, practicing in higher-resourced areas, and female physicians described being influenced by beliefs about consequences of benefits of screening.

Conclusion
Perceived guideline clarity is an important driver of physician behaviour. Improving guideline concordant care should start by clarifying the guideline itself. Thereafter, targeted strategies include building skills in identifying and overcoming emotional factors and communication skills important for evidence-based screening discussions.