bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the toxicity of WS-5 in a 90-days nose-only exposure in sprague-dawley rats
Authors: Oldham Michael Jerome , Desai Rahat Wadhwa , Randazzo James , Lalonde Guy , Weil Roxana 
Published: April 2023

Introduction WS-5 is a flavor ingredient that provides a cooling sensation similar to that of menthol but without the characteristic menthol flavor. In the available toxicological evaluations of WS-5 there was no data specific to inhalation exposure. Methods A 90-days nose-only inhalation study was conducted using Sprague Dawley rats exposed to Filtered air, propylene glycol/glycerin (40/60 by weight; vehicle control), or one of three WS-5 concentrations (0.2, 0.4, or 0.8% by weight) to assess the inhalation toxicity of WS-5. The study design was consistent with the Organization for Economic Development and Cooperation test guideline 413 and included a 28-day and 6-week recovery sacrifices, in addition to the 13-week assessment. Results Food consumption and body weights were unaffected by WS-5 exposure compared to vehicle control or Filtered air. No WS-5 exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or bronchoalveolar lavage fluid cytology and clinical chemistry. Macroscopic examinations and terminal organ weights revealed no observations associated with exposure to WS-5. Discussion Histopathology findings of alveolar hemorrhage and mixed cell infiltration at the 28-day necropsy were either not present in the WS-5 exposed groups or were present at similar frequencies in the vehicle control and/or Filtered air groups at the 13-weeks necropsy and thus, were not considered to be vehicle control or WS-5 related. Conclusion Based on the absence of adverse effects, the no-observed-adverse effect concentration was considered to be 2.5 mg/L of aerosolized 0.8 w% WS-5 that achieved a mean measured exposure concentration of approximately 18 μg WS-5/L
Narrow and Stripe Leaf 2 Regulates Leaf Width by Modulating Cell Cycle Progression in Rice
Authors: Shen Wenqiang , Sun Jiajie , Xiao Zan , Feng Ping , Zhang Ting , He Guanghua , Sang Xianchun 
Published: April 2023

Abstract
Background
Leaf morphology is an important component of the idea plant architecture that extensively influences photosynthesis, transpiration, and ultimately grain yield in crops. However, the genetic and molecular mechanisms regulating this morphology remain largely unclear.

Results
In this study, a mutant showing a narrow and stripe leaf phonotype, designated nsl2, was obtained. Histological analysis revealed defects in the vascular system and reduced epidermal cell number in the nsl2, while the cell size remained unchanged. Map-based cloning and genetic complementation experiments revealed that NSL2, which encodes a small subunit of ribonucleotide reductases (RNRs), is a null allelic with ST1 and SDL. The NSL2 was expressed in variety of tissues, with the highest levels detected in leaves, and its protein was localized in the nucleus and cytoplasm. The dNTPs level was altered in the nsl2 mutant, and thereby affecting the dNTPs pool balance. In addition, flow cytometric analysis and the altered transcript level of genes related to cell cycle indicated that NSL2 affects cell cycle progression.

Conclusions
Our findings here suggest that NSL2 function in the synthesis of dNTP, the deficient of which leads to DNA synthesis block and in turn affects cell cycle progression, and ultimately decreased cell number and narrow leaf in the nsl2 plant.
Concomitant clear cell renal cell carcinoma with osseous metaplasia and papillary thyroid microcarcinoma: a case report with literature review
Authors: Fakhralddin Saman S. , Qader Deedar K. , Salih Abdulwahid M. , Abdullah Ari M. , Baba Hiwa O. , Tahir Soran H. , Qaradakhy Aras J. , Hiwa Dilan S. , Kakamad Fahmi H. 
Published: April 2023

Abstract
Backgrounds
Although calcifications have been observed in various renal masses, osseous metaplasia has very rarely been reported. Here, we present a case of concomitant clear cell renal cell carcinoma with osseous metaplasia and papillary thyroid microcarcinoma.

Case presentation
A 52-year-old male was being investigated for having post-prandial gaseous abdominal distention. Computed tomography of the abdomen showed a heterogeneous mass lesion measuring 27 × 24 mm at the upper/mid pole of the right kidney. It also revealed two small (10 and 11 mm) benign bone islands in the body of the D4 and L4 vertebrae. The patient underwent a metastatic workup by computed tomography, which revealed a 93 × 35 mm mass in the left thyroid lobe with coarse calcification. A partial nephrectomy was planned for the renal mass, but the site of the mass deemed this impossible. Six months after the operation, the patient underwent total thyroidectomy. Histopathology of both tissue samples revealed concomitant clear cell renal cell carcinoma with heterotopic bone formation and papillary thyroid microcarcinoma.

Conclusion
Although rare, osseous metaplasia in renal cell carcinoma can occur and may indicate an early-stage carcinoma with a favorable prognosis.
Restoration of aberrant gene expression of monocytes in systemic lupus erythematosus via a combined transcriptome-reversal and network-based drug repurposing strategy
Authors: Nikolakis Dimitrios , Garantziotis Panagiotis , Sentis George , Fanouriakis Antonis , Bertsias George , Frangou Eleni , Nikolopoulos Dionysis , Banos Aggelos , Boumpas Dimitrios T 
Published: April 2023

Abstract
Background
Monocytes -key regulators of the innate immune response- are actively involved in the pathogenesis of systemic lupus erythematosus (SLE). We sought to identify novel compounds that might serve as monocyte-directed targeted therapies in SLE.

Results
We performed mRNA sequencing in monocytes from 15 patients with active SLE and 10 healthy individuals. Disease activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Leveraging the drug repurposing platforms iLINCS, CLUE and L1000CDS2, we identified perturbagens capable of reversing the SLE monocyte signature. We identified transcription factors and microRNAs (miRNAs) that regulate the transcriptome of SLE monocytes, using the TRRUST and miRWalk databases, respectively. A gene regulatory network, integrating implicated transcription factors and miRNAs was constructed, and drugs targeting central components of the network were retrieved from the DGIDb database. Inhibitors of the NF-κB pathway, compounds targeting the heat shock protein 90 (HSP90), as well as a small molecule disrupting the Pim-1/NFATc1/NLRP3 signaling axis were predicted to efficiently counteract the aberrant monocyte gene signature in SLE. An additional analysis was conducted, to enhance the specificity of our drug repurposing approach on monocytes, using the iLINCS, CLUE and L1000CDS2 platforms on publicly available datasets from circulating B-lymphocytes, CD4+ and CD8+ T-cells, derived from SLE patients. Through this approach we identified, small molecule compounds, that could potentially affect more selectively the transcriptome of SLE monocytes, such as, certain NF-κB pathway inhibitors, Pim-1 and SYK kinase inhibitors. Furthermore, according to our network-based drug repurposing approach, an IL-12/23 inhibitor and an EGFR inhibitor may represent potential drug candidates in SLE.

Conclusions
Application of two independent - a transcriptome-reversal and a network-based -drug repurposing strategies uncovered novel agents that might remedy transcriptional disturbances of monocytes in SLE.
Unravelling the genetic diversity and population structure of common walnut in the Iranian Plateau
Authors: Shahi Shavvon Robabeh , Qi Hai-Ling , Mafakheri Mohammad , Fan Pen-Zheng , Wu Hong-Yu , Bazdid Vahdati Fatemeh , Al-Shmgani Hanady S. , Wang Yue-Hua , Liu Jie 
Published: April 2023

Abstract
Background
Common walnut (Juglans regia L.) has a long cultivation history, given its highly valuable wood and rich nutritious nuts. The Iranian Plateau has been considered as one of the last glaciation refugia and a centre of origin and domestication for the common walnut. However, a prerequisite to conserve or utilize the genetic resources of J. regia in the plateau is a comprehensive evaluation of the genetic diversity that is conspicuously lacking. In this regard, we used 31 polymorphic simple sequence repeat (SSR) markers to delineate the genetic variation and population structure of 508 J. regia individuals among 27 populations from the Iranian Plateau.

Results
The SSR markers expressed a high level of genetic diversity (HO = 0.438, and HE = 0.437). Genetic differentiation among the populations was moderate (FST = 0.124), and genetic variation within the populations (79%) significantly surpassed among populations (21%). The gene flow (Nm = 1.840) may have remarkably influenced the population genetic structure of J. regia, which can be attributed to anthropological activities and wind dispersal of pollen. The STRUCTURE analysis divided the 27 populations into two main clusters. Comparing the neighbor-joining and principal coordinate analysis dendrograms and the Bayesian STRUCTURE analysis revealed the general agreement between the population subdivisions and the genetic relationships among the populations. However, a few geographically close populations dispersed into different clusters. Further, the low genetic diversity of the Sulaymaniyah (SMR) population of Iraq necessitates urgent conservation by propagation and seedling management or tissue culture methods; additionally, we recommend the indispensable preservation of the Gonabad (RGR) and Arak (AKR) populations in Iran.

Conclusions
These results reflected consistent high geographical affinity of the accession across the plateau. Our findings suggest that gene flow is a driving factor influencing the genetic structure of J. regia populations, whereas ecological and geological variables did not act as strong barriers. Moreover, the data reported herein provide new insights into the population structure of J. regia germplasm, which will help conserve genetic resources for the future, hence improving walnut breeding programs’ efficiency.
Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis
Authors: Yan Jisi , Zhao LiHua , Zhang Tongqiang , Wei Yupeng , Guo Detong , Guo Wei , Zheng Jun , Xu Yongsheng 
Published: April 2023

Abstract
Background
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection.

Methods
A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases. A prediction model was built on 227 cases and validated on 98 cases, which were divided by random sampling in R software. Relevant clinical, laboratory and imaging data were collected. Multivariate logistic regression models were used to determine optimal predictors and to construct nomograms. The performance of the nomogram was evaluated by the area under the characteristic curve (AUC), calibration ability and decision curve analysis (DCA).

Results
There were 137 (60.4%) mild and 90 (39.6%) severe RSV-associated bronchiolitis cases in the training group (n = 227) and 63 (64.3%) mild and 35 (35.7%) severe cases in the validation group (n = 98). Multivariate logistic regression analysis identified 5 variables as significant predictive factors to construct the nomogram for predicting severe RSV-associated bronchiolitis, including preterm birth (OR = 3.80; 95% CI, 1.39–10.39; P = 0.009), weight at admission (OR = 0.76; 95% CI, 0.63–0.91; P = 0.003), breathing rate (OR = 1.11; 95% CI, 1.05–1.18; P = 0.001), lymphocyte percentage (OR = 0.97; 95% CI, 0.95–0.99; P = 0.001) and outpatient use of glucocorticoids (OR = 2.27; 95% CI, 1.05–4.9; P = 0.038). The AUC value of the nomogram was 0.784 (95% CI, 0.722–0.846) in the training set and 0.832 (95% CI, 0.741–0.923) in the validation set, which showed a good fit. The calibration plot and Hosmer‒Lemeshow test indicated that the predicted probability had good consistency with the actual probability both in the training group (P = 0.817) and validation group (P = 0.290). The DCA curve shows that the nomogram has good clinical value.

Conclusion
A nomogram for predicting severe RSV-associated bronchiolitis in the early clinical stage was established and validated, which can help physicians identify severe RSV-associated bronchiolitis and then choose reasonable treatment.
Assessing the transmissibility of epidemics involving epidemic zoning
Authors: Yuan Baoyin , Liu Rui , Tang Sanyi 
Published: April 2023

AbstractBackgroundEpidemic zoning is an important option in a series of measures for the prevention and control of infectious diseases. We aim to accurately assess the disease transmission process by considering the epidemic zoning, and we take two epidemics with distinct outbreak sizes as an example, i.e., the Xi’an epidemic in late 2021 and the Shanghai epidemic in early 2022.MethodsFor the two epidemics, the total cases were clearly distinguished by their reporting zone and the Bernoulli counting process was used to describe whether one infected case in society would be reported in control zones or not. Assuming the imperfect or perfect isolation policy in control zones, the transmission processes are respectively simulated by the adjusted renewal equation with case importation, which can be derived on the basis of the Bellman-Harris branching theory. The likelihood function containing unknown parameters is then constructed by assuming the daily number of new cases reported in control zones follows a Poisson distribution. All the unknown parameters were obtained by the maximum likelihood estimation.ResultsFor both epidemics, the internal infections characterized by subcritical transmission within the control zones were verified, and the median control reproduction numbers were estimated as 0.403 (95% confidence interval (CI): 0.352, 0.459) in Xi’an epidemic and 0.727 (95% CI: 0.724, 0.730) in Shanghai epidemic, respectively. In addition, although the detection rate of social cases quickly increased to 100% during the decline period of daily new cases until the end of the epidemic, the detection rate in Xi’an was significantly higher than that in Shanghai in the previous period.ConclusionsThe comparative analysis of the two epidemics with different consequences highlights the role of the higher detection rate of social cases since the beginning of the epidemic and the reduced transmission risk in control zones throughout the outbreak. Strengthening the detection of social infection and strictly implementing the isolation policy are of great significance to avoid a larger-scale epidemic.
Prevalence of Mollicutes among men who have sex with men and transgender women aged 15 to 19 years in Salvador, North-eastern Brazil
Authors: de Jesus Salgado Valdiele , de Abreu Oliveira Caio Marcellus Pereira , da Silva Ágatha Morgana Bertoti , de Brito Henrique Inácio Lima , de Medeiros Danielle Souto , Soares Fabiane , Magno Laio , Dourado Inês , Campos Guilherme Barreto , Marques Lucas Miranda 
Published: April 2023

Abstract
Background
Some species of Mollicutes have been associated with different pathologies of the urogenital tract in humans, with a high prevalence among adult men who have sex with men (MSM) and transgender women (TGW). However, few studies have been performed to investigate its prevalence among adolescents. In this study, we estimated the initial prevalence of Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP); the rate of misdiagnosis at different anatomical sites; and the associated factors with positive tests for Mollicutes among MSM and TGW aged 15 to 19 years enrolled in the PrEP1519 study.

Methods
PrEP-1519 is the first study to investigate the effectiveness of pre-exposure prophylaxis for human immunodeficiency virus among adolescent MSM and TGW aged 15 to 19 in Latin America. Oral, anal, and urethral swabs were taken from 246 adolescents upon enrolment in the study to detect MG, MH, UU, and UP by quantitative polymerase chain reaction (qPCR). Bivariate and multivariate analyses were conducted by Poisson regression and 95% confidence intervals (95% CI) were estimated.

Results
The prevalence of Mollicutes was 32.1%. UU was the most prevalent species (20.7%), followed by MH (13.4%), MG (5.7%), and UP (3.2%); 67.3% of the positive samples would have been missed if only urethral samples had been taken. Receptive anal sex (prevalence ratio [PR] = 1.79; 95% CI = 1.07–3.01) and clinical suspicion of sexually transmitted infection (PR = 1.62; 95% CI = 1.01–2.61) were factors associated with the detection of Mollicutes in general. Group sex (PR = 1.98; 95% CI = 1.12–3.50) and receptive anal sex (PR = 2.36; 95% CI = 0.95–5.86) were associated with the detection of Mycoplasma spp. No sociodemographic, clinical, or behavioural variable was significantly associated with the detection of Ureaplasma spp.

Conclusions
A high prevalence of Mollicutes was observed among adolescent MSM and TGW, especially at extragenital sites. Further research is required to understand the epidemiological profile of high-risk adolescents in different regions and contexts, and to investigate the pathogenesis of Mollicutes in the oral and anal mucosa before routine screening can be recommended in clinical practice.
Acute and subacute intraocular pressure and macular microvascular structure changes after intravitreal ranibizumab injection in eyes with branch retinal vein occlusion
Authors: Li Xiaoyu , Chen Qin , Yu Xiaobing 
Published: April 2023

Abstract
Purpose
To investigate early changes in the intraocular pressure (IOP) and macular microvascular structure in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal Ranibizumab injection.

Methods
This study enrolled 30 patients (one eye per patient) who received intravitreal injections (IVI) of ranibizumab for macular edema secondary to BRVO. IOP were measured before, 30 min (min) and 1 month following IVI. Changes in macular microvascular structure were examined via assessment of foveal avascular zone (FAZ) parameters, vascular density (VD) of superficial vascular complex (SVC), and deep vascular complex (DVC) in whole macula, central fovea and parafovea area which were measured automatically by optical coherence tomography angiography (OCTA) on the same time as IOP examinations. Paired t test and Wilcoxon test were used to compare pre- and post-injection values. The correlation between IOP and OCTA findings was assessed.

Results
IOP Measurements at 30 min post-IVI (17.91 ± 3.36 mmHg) increased significantly from baseline (15.07 ± 2.58 mmHg, p < 0.001), then became similar with baseline after 1 month (15.00 ± 3.16 mmHg, p = 0.925). 30 min past the injection, the parameters of VD of the SCP significantly decreased in comparison to baseline, then became similar with baseline after one month, while there were no significant changes in other OCTA parameters, including parameters of VD of the DCP and the FAZ. At 1 month after IVI, in comparison to baseline, no significant changes were observed in all of the OCTA parameters (P > 0.05). There were no significant correlations between IOP and OCTA findings no matter 30 min or 1 month post-IVI (P > 0.05).

Conclusions
Transient IOP elevation and decreased superficial macular capillary perfusion density were detected 30 min post-IVI, however, no potential continual macular microvascular damage was suspected.
Medical studies in times of a pandemic – concepts of digital teaching for Orthopaedics and Trauma at german universities
Authors: Mielke Anna-Maria , Ghanem Mohamed , Back David Alexander , Fröhlich Susanne , Herbstreit Stephanie , Seemann Ricarda Johanna 
Published: April 2023

Abstract
Background
Due to the Covid-19 pandemic, on-site classroom teaching became limited at most German medical universities. This caused a sudden demand for digital teaching concepts. How the transfer from classroom to digital teaching or digitally assisted teaching was conducted was decided by each university and/or department individually. As a surgical discipline, Orthopaedics and Trauma have a particular focus on hands-on teaching as well as direct contact to patients. Therefore, specific challenges in designing digital teaching concepts were expected to arise. Aim of this study was to evaluate medical teaching at German universities one year into the pandemic as well as to identify potentials and pitfalls in order to develop possible optimization approaches.

Methods
A questionnaire with 17 items was designed and sent to the professors in charge of organising the teaching in Orthopaedics and Trauma at each medical university. A differentiation between Orthopaedics and Trauma was not made to allow a general overview. We collected the answers and conducted a qualitative analysis.

Results
We received 24 replies. Each university reported a substantial reduction of their classroom teaching and efforts to transfer their teaching to digital formats. Three sites were able to switch to digital teaching concepts completely, whereas others tried to enable classroom and bedside teaching at least for students of higher edcuational levels. The online platforms used varied depending on the university as well as the format it was supposed to support.

Conclusion
One year into the pandemic significant differences concerning the proportions of classroom and digital teaching for Orthopaedics and Trauma can be observed. Simultaneously huge differences in concepts used to create digital teaching are present. Since a complete suspense of classroom teaching was never mandatory, several universities developed hygiene concepts to enable hands-on and bedside teaching. Despite these differences, some similarities were observed: the lack of time and personnel to generate adequate teaching material was reported as the leading challenge by all participants of this study.