bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative splicing of its 5′-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies
Authors: Ang Zhiwei , Paruzzo Luca , Hayer Katharina E. , Schmidt Carolin , Torres Diz Manuel , Xu Feng , Zankharia Urvi , Zhang Yunlin , Soldan Samantha , Zheng Sisi , Falkenstein Catherine D. , Loftus Joseph P. , Yang Scarlett Y. , Asnani Mukta , King Sainos Patricia , Pillai Vinodh , Chong Emeline , Li Marilyn M. , Tasian Sarah K. , Barash Yoseph , Lieberman Paul M. , Ruella Marco , Schuster Stephen J. , Thomas-Tikhonenko Andrei
Published: September 2023

Aberrant skipping of coding exons in CD19 and CD22 compromises the response to immunotherapy in B-cell malignancies. Here, we showed that the MS4A1 gene encoding human CD20 also produces several messenger RNA (mRNA) isoforms with distinct 5′ untranslated regions. Four variants (V1-4) were detected using RNA sequencing (RNA-seq) at distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma, only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform contained upstream open reading frames and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, whereas V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly, in vitro CD20-directed chimeric antigen receptor T cells were able to kill both V3- and V1-expressing cells, but the bispecific T-cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on 4 postmosunetuzumab follicular lymphoma relapses and discovered that in 2 of them, the downregulation of CD20 was accompanied by a V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies.
Risky health behaviors and subsequent late mortality after blood or marrow transplantation: a BMTSS report
Authors: Balas Nora , Richman Joshua , Landier Wendy , Shrestha Sadeep , Bruxvoort Katia J. , Hageman Lindsey , Meng Qingrui , Ross Elizabeth , Bosworth Alysia , Te Hok Sreng , Wong F. Lennie , Bhatia Ravi , Forman Stephen J. , Armenian Saro H. , Weisdorf Daniel J. , Bhatia Smita
Published: September 2023

We examined the association between risky health behaviors (smoking, heavy alcohol consumption, and lack of vigorous physical activity) and all-cause and cause-specific late mortality after blood or marrow transplantation (BMT) to understand the role played by potentially modifiable risk factors. Study participants were drawn from the BMT Survivor Study (BMTSS) and included patients who received transplantation between 1974 and 2014, had survived ≥2 years after BMT, and were aged ≥18 years at study entry. Survivors provided information on sociodemographic characteristics, chronic health conditions, and health behaviors. National Death Index was used to determine survival and cause of death. Multivariable regression analyses determined the association between risky health behaviors and all-cause mortality (Cox regression) and nonrecurrence-related mortality (NRM; subdistribution hazard regression), after adjusting for relevant sociodemographic, clinical variables and therapeutic exposures. Overall, 3866 participants completed the BMTSS survey and were followed for a median of 5 years to death or 31 December 2021; and 856 participants (22.1%) died after survey completion. Risky health behaviors were associated with increased hazard of all-cause mortality (adjusted hazard ratio [aHR] former smoker, 1.2; aHR current smoker, 1.7; reference, nonsmoker; aHR heavy drinker, 1.4; reference, nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity) and NRM (aHR former smoker, 1.3; aHR current smoker, 1.6; reference, nonsmoker; aHR heavy drinker, 1.4; reference: nonheavy drinker; and aHR no vigorous activity, 1.2; reference, vigorous activity). The association between potentially modifiable risky health behaviors and late mortality offers opportunities for development of interventions to improve both the quality and quantity of life after BMT.
Ecological correlates of cranial evolution in the megaradiation of dipsadine snakes
Authors: Pandelis Gregory G. , Grundler Michael C. , Rabosky Daniel L.
Published: September 2023

Background

Dipsadine snakes represent one of the most spectacular vertebrate radiations that have occurred in any continental setting, with over 800 species in South and Central America. Their species richness is paralleled by stunning ecological diversity, ranging from arboreal snail-eating and aquatic eel-eating specialists to terrestrial generalists. Despite the ecological importance of this clade, little is known about the extent to which ecological specialization shapes broader patterns of phenotypic diversity within the group. Here, we test how habitat use and diet have influenced morphological diversification in skull shape across 160 dipsadine species using micro-CT and 3-D geometric morphometrics, and we use a phylogenetic comparative approach to test the contributions of habitat use and diet composition to variation in skull shape among species.

Results

We demonstrate that while both habitat use and diet are significant predictors of shape in many regions of the skull, habitat use significantly predicts shape in a greater number of skull regions when compared to diet. We also find that across ecological groupings, fossorial and aquatic behaviors result in the strongest deviations in morphospace for several skull regions. We use simulations to address the robustness of our results and describe statistical anomalies that can arise from the application of phylogenetic generalized least squares to complex shape data.

Conclusions

Both habitat and dietary ecology are significantly correlated with skull shape in dipsadines; the strongest relationships involved skull shape in snakes with aquatic and fossorial lifestyles. This association between skull morphology and multiple ecological axes is consistent with a classic model of adaptive radiation and suggests that ecological factors were an important component in driving morphological diversification in the dipsadine megaradiation.
Pangenome analysis of Corynebacterium striatum: insights into a neglected multidrug-resistant pathogen
Authors: Nageeb Wedad M. , Hetta Helal F.
Published: September 2023

Background

Over the past two decades, Corynebacterium striatum has been increasingly isolated from clinical cultures with most isolates showing increased antimicrobial resistance (AMR) to last resort agents. Advances in the field of pan genomics would facilitate the understanding of the clinical significance of such bacterial species previously thought to be among commensals paving the way for identifying new drug targets and control strategies.

Methods

We constructed a pan-genome using 310 genome sequences of C. striatum. Pan-genome analysis was performed using three tools including Roary, PIRATE, and PEPPAN. AMR genes and virulence factors have been studied in relation to core genome phylogeny. Genomic Islands (GIs), Integrons, and Prophage regions have been explored in detail.

Results

The pan-genome ranges between a total of 5253–5857 genes with 2070 − 1899 core gene clusters. Some antimicrobial resistance genes have been identified in the core genome portion, but most of them were located in the dispensable genome. In addition, some well-known virulence factors described in pathogenic Corynebacterium species were located in the dispensable genome. A total of 115 phage species have been identified with only 44 intact prophage regions.

Conclusion

This study presents a detailed comparative pangenome report of C. striatum. The species show a very slowly growing pangenome with relatively high number of genes in the core genome contributing to lower genomic variation. Prophage elements carrying AMR and virulence elements appear to be infrequent in the species. GIs appear to offer a prominent role in mobilizing antibiotic resistance genes in the species and integrons occur at a frequency of 50% in the species. Control strategies should be directed against virulence and resistance determinants carried on the core genome and those frequently occurring in the accessory genome.
Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations
Authors: Gross Maya E. , Godecker Amy , Hughes Ainsley , Sampene Katherine
Published: September 2023

Objective

Aspirin (ASA) is recommended for patients at elevated risk of preeclampsia. Limited data exists on adherence to guidelines for ASA prescription. This project evaluates the implementation of a standardized approach to ASA prescription in an academic OB/Gyn practice.

Methods

We implemented a quality improvement project to evaluate compliance with the United States Preventative Services Task Force (USPSTF) recommendations for ASA to prevent preeclampsia. Pre-intervention, we analyzed prescription adherence at 201 New Obstetric (NOB) visits. A multi-step intervention was then implemented at 199 NOB visits. Nurses utilized a checklist created from USPSTF guidelines to identify high-risk patients, defined as having ≥1 high-risk factor or ≥2 moderate-risk factors. ASA orders were placed by physicians. A Plan-Do-Study-Act (PDSA) cycle was performed, and changes implemented. Primary outcome was percent of patients screened at RN intake visit (goal = 90%). Secondary outcomes were percent of patients who screened positive that received the ASA recommendation (goal = 80%) and percent screened and recommended by race.

Results

Pre-intervention, 47% of patients met criteria for ASA and 28% received a documented recommendation. Post-intervention, 99% were screened. Half (48%) met criteria for an ASA recommendation and 79% received a recommendation (p = < 0.001). Rates of appropriate recommendation did not differ by Black (80%) vs. non-Black (79%) status (p = 0.25). Subsequent PDSA cycles for 12 months neared 100% RN screening rates. Physicians correctly recommended ASA 80–100% of the time.

Conclusion

It is feasible, sustainable and equitable to standardize screening and implementation of ASA to patients at high risk for preeclampsia. Providers can easily reproduce our processes to improve delivery of equitable and reliable preventative obstetric care.
Adherence to the Mediterranean diet and risk of gestational diabetes: a prospective cohort study
Authors: Mohtashaminia Fatemeh , Hosseini Fatemeh , Jayedi Ahmad , Mirmohammadkhani Majid , Emadi Alireza , Takfallah Leila , Shab-Bidar Sakineh
Published: September 2023

Background

Limited data is available on the association between adherence to the Mediterranean diet during early pregnancy and risk of gestational diabetes (GDM) in countries located in the Middle East, one of the regions with the highest prevalence of GDM.

Methods

A total of 647 pregnant mothers were included in the present prospective birth cohort study in Iran. Dietary intake was assessed by a 90-item food frequency questionnaire during the first trimester of pregnancy. Cases of GDM were ascertained by a two-step approach with a 50-g screen followed by a 100-g oral glucose tolerance for those who tested positive. Cox proportional hazard model was used to calculate the hazard ratio and 95%CI of GDM across tertiles of the Mediterranean diet score, while controlling for a wide range of potential confounders.

Results

A total of 647 pregnant mothers were included, of whom 77 mothers were diagnosed with GDM during their pregnancy. The average age of the mothers was 28.8 ± 5.1 years. In the multivariable analysis, being in the third tertile of the score of adherence to the Mediterranean diet was associated with a 41% lower risk of developing GDM as compared to those in the first tertile (adjusted hazard ratio: 0.59, 95%CI: 0.35, 0.99).

Conclusions

Based on our findings, greater adherence to the Mediterranean diet during early pregnancy may be associated with a lower risk of developing GDM in Iranian women. Larger cohort studies are needed to confirm the findings.
Impact of estrogen receptor expression level on response to neoadjuvant chemotherapy and prognosis in HER2-negative breast cancers
Authors: Chen Hai-long , Huang Feng-bo , Chen Qiang , Deng Yong-chuan
Published: September 2023

Background

Breast cancers with 1–10% cell staining for estrogen receptor (ER) present particular clinical features. The clinical data of estrogen receptor expression level and treatment effect are limited, particularly regarding chemotherapy benefit. We evaluated the pathologic response to neoadjuvant chemotherapy (NAC) in ER low positive tumors (ER staining 1-10%) and compared it with ER > 10% positive tumors (ER staining > 10%) and ER-negative tumors. We further explored the differences in recurrence and survival with respect to the ER expression level.

Method

Patients with stages II and III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery were categorized according to their ER percentages into three groups: ER-negative, ER low positive, and ER > 10% positive. Logistic regression models were used to assess the association between each variable and pathologic complete response (pCR). Kaplan‒Meier analysis was used to estimate survival outcomes. Cox models were used to adjust for patient and tumor characteristics.

Results

A total of 241 patients were analyzed. Of all patients included, 22 (9.1%) had ER low positive tumors, 159 (66.0%) had ER > 10% positive tumors, and 60 (24.9%) were ER-negative. Low ER positivity was significantly associated with a higher pCR rate than ER > 10% positivity (OR, 0.249; 95% CI, 0.067–0.923; P = 0.038). After a median follow-up time of 32 months, the disease-free survival (DFS) and overall survival (OS) of the patients with ER low positive tumors were significantly worse than those of the patients with ER > 10% positive tumors but similar to those with ER-negative tumors. After adjustment for covariates, ER low positive tumors were significantly associated with worse DFS than ER > 10% positive tumors.

Conclusion

Our results indicated that ER low positive breast cancer presents a better response to neoadjuvant chemotherapy and significantly worse prognosis for patients than those with ER > 10% positive tumors, but similar to the ER-negative group. These data support that this category of patients behaves clinically like patients with ER-negative breast cancer and should be treated differently from patients with ER > 10% positive tumors. Further prospective study is needed.
Oxygen saturation levels and retinopathy of prematurity in extremely preterm infants - a case control study
Authors: Aggarwal Varnika , Bhatia Risha , Tan Kenneth
Published: September 2023

Purpose

To investigate the association of risk factors, including oxygen exposure, for developing retinopathy of prematurity (ROP) in preterm infants at increased risk of ROP.

Methods

A case-control study was conducted where each infant born at < 28 weeks gestation with ROP was matched with another without ROP over five years (July 2015 – June 2020). Clinical information about the infants was collected from electronic medical records, including method of oxygen delivery, oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) and mean airway pressure (MAP) measurements. MATLAB was used for a time-averaged analysis. Stata/SE 16.0 was used for statistical analysis.

Results

123 ROP/non-ROP pairs were included in this study. The time-averaged SpO2 analysis showed non-ROP group spent more time in hyperoxia than the ROP group (p < 0.001). The non-ROP group had lower respiratory severity scores and analysis when FiO2 > 21% showed that were was no difference in SpO2 between the two groups when the infants were receiving oxygen support. Conditional logistic regressions showed neonatal surgery significantly increased the risk of ROP (OR = 1.4347, p = 0.010), while the influence of birthweight (odds ratio of 0.9965, p = 0.001) and oxygen exposure (OR = 0.9983, p = 0.012) on ROP outcome was found to be negligible as their odds ratios indicated no influence.

Conclusions

At times when infants were receiving respiratory support (FiO2 > 21%) the SpO2 data indicated no difference in SpO2 between the ROP and non-ROP groups. Analysis of clinical variables found that neonatal surgery increased the odds of developing ROP.
Gender role attitudes and well-being of German and refugee adolescents—same or different?
Authors: Nilles Hannah , EL-Awad Usama , Kerkhoff Denny , Braig Johanna , Schmees Pia , Kilinc Yasemin , Rueth Jana-Elisa , Eschenbeck Heike , Lohaus Arnold
Published: September 2023

Background

Assumed differences in gender role attitudes (GRAs) of German adolescents and refugee adolescents from the Middle East are often discussed, but rarely investigated. Presumed differences in GRAs across cultures and genders are assumed to be involved in emerging gender differences in well-being and mental health symptoms. Overall, appropriate measurements for investigating GRAs of adolescents with different cultural backgrounds are scarce.

Methods

Hence, the present study exemplarily investigates (1) the measurement invariance (MI) of a German translation of the Social Role Questionnaire (SRQ) for German (n = 114) and German-speaking Middle Eastern refugee adolescents from Syria, Afghanistan, or Iraq (n = 115), using a Multiple Indicator Multiple Cause (MIMIC) model to account for age and gender. Moreover, (2) differences between GRAs of both groups, (3) relationships of GRAs with different facets of affective well-being, as well as (4) differences in these relationships between German and refugee adolescents are examined by extending the MIMIC-model to a full structural equation model (SEM).

Results

Results indicate (1) that scalar MI for the SRQ can be assumed. Furthermore, (2) German adolescents show less traditional gender-linked GRAs than refugee adolescents, but no further differences in GRAs. Furthermore, no differences between the relationships of GRAs with well-being and mental health symptoms were found between the groups (4). Also, (3) GRAs showed no relation with any of the outcomes, but gender and age predicted mental health symptoms.

Conclusion

The findings show that the SRQ is a useful measurement for investigating the GRAs of adolescents living in Germany and could be used in further cross-cultural research.
Consensus on the pharmacological treatment of acute stress disorder in Chinese pilots: a Delphi study
Authors: Gao Xing , Wang Zhenzhen , Guo Li , Gu Yanan , Song Lei , Wu Zhongying , Li Fengzhan , Jin Yinchuan , Yang Qun
Published: September 2023

Background

Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method.

Methods

Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots.

Results

A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall’s coefficient of concordance of indicators at all levels was 0.564–0.594 (p < 0.01). Based on the number of votes received, alprazolam tablets (16), eszopiclone tablets (15), and lorazepam tablets (14) were recommended for the treatment of excitatory psychomotor symptoms of acute stress disorder; paroxetine tablets (15) and sertraline tablets (15) were available for psychomotor depressive symptoms; olanzapine tablets (15), olanzapine orally disintegrating tablets (14), and quetiapine fumarate tablets (14) were selected for psychotic symptoms.

Conclusions

This study formed a consensus on rapid and effective pharmacological treatment for different symptoms of acute stress disorder pilots, which provides a reference for clinical treatment.
A study of temperature variability on admissions and deaths for cardiovascular diseases in Northwestern China
Authors: Zheng Shan , Zhang Xiaofei , Zhu Wenzhi , Nie Yonghong , Ke Ximeng , Liu Shaodong , Wang Xue , You Jinlong , Kang Feng , Bai Yana , Wang Minzhen
Published: September 2023

Objective

To explore the effect of temperature variability (TV) on admissions and deaths for cardiovascular diseases (CVDs).

Method

The admissions data of CVDs were collected in 4 general hospitals in Jinchang City, Gansu Province from 2013 to 2016. The monitoring data of death for CVDs from 2013 to 2017 were collected through the Jinchang City Center for Disease Control and Prevention. Distributed lag nonlinear model (DLNM) was combined to analyze the effects of TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) on the admissions and deaths for CVDs after adjusting confounding effects. Stratified analysis was conducted by age and gender. Then the attribution risk of TV was evaluated.

Results

There was a broadly linear correlation between TV and the admissions and deaths for CVDs, but only the association between TV and outpatient and emergency room (O&ER) visits for CVDs have statistically significant. DTV and HTV have similar lag effect. Every 1 ℃ increase in DTV and HTV was associated with a 3.61% (95% CI: 1.19% ~ 6.08%), 3.03% (95% CI: 0.27% ~ 5.86%) increase in O&ER visits for CVDs, respectively. There were 22.75% and 14.15% O&ER visits for CVDs can attribute to DTV and HTV exposure during 2013–2016. Males and the elderly may be more sensitive to the changes of TV. Greater effect of TV was observed in non-heating season than in heating season.

Conclusion

TV was an independent risk factor for the increase of O&ER visits for CVDs, suggesting effective guidance such as strengthening the timely prevention for vulnerable groups before or after exposure, which has important implications for risk management of CVDs.
Differences in smoking behaviors and readiness to change for patients with COPD and differing categories of depressive symptoms: a descriptive cross-sectional design
Authors: Floyd Jessica , Mallow Jennifer , Wang Kesheng , Davis Stephen M. , Carpenter Roger , Theeke Laurie
Published: September 2023

Background

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world with nearly 90% of cases caused by tobacco smoking. Nearly 40% of people with COPD are diagnosed with depression which impacts quality of life and smoking cessation. The purpose of this study was to describe factors influencing smoking behaviors and readiness to change in people with comorbid COPD and depression.

Methods

A descriptive cross-sectional design was used. A convenience sample of 222 participants self-reported and/or had a documented diagnosis of COPD. Participants completed study measures which included the PHQ-9 for depressive symptoms, assessment of smoking behaviors using The Cigarette Dependence Scale, report of readiness to change using The Smoking Stage of Change Questionnaire, The Smoking Decisional Balance Questionnaire, and The Processes of Change Questionnaire. Electronic and paper questionnaires were used. Data was stored in RedCap and analyzed using SPSS version 26. Based on variable type, descriptive and comparative analyses were conducted using ANOVA, t-test, chi-square, Pearson correlation, linear regression, and multiple linear regression to determine the relationships between smoking behaviors, COPD, and depressive symptoms.

Results

Only 18 participants were classified as having no depressive symptoms. Participants who smoked had high nicotine dependence and wanted to quit smoking. Overall, participants saw more cons to smoking and were engaged in the processes of change. The majority of participants were in the maintenance or contemplation stage. Cigarette dependence could decrease by 9% if depressive symptoms are treated.

Conclusions

There is a need to assess COPD patients for depression and to assess COPD patients’ smoking behaviors and readiness to change. Adequate treatment of depression could promote an individual to move through the stages of change from chronic contemplation to action, thus improving smoking cessation efforts for individuals with COPD. Understanding patients’ smoking behaviors and readiness to change can aid in developing personalized interventions to achieve smoking cessation and improve long-term outcomes.
Lower respiratory tract infections among newly diagnosed sleep apnea patients
Authors: Keto Jaana , Feuth Thijs , Linna Miika , Saaresranta Tarja
Published: September 2023

Background

Sleep apnea is associated with chronic comorbidities and acute complications. Existing data suggest that sleep apnea may predispose to an increased risk and severity of respiratory tract infections.

Methods

We investigated the incidence of lower respiratory tract infections in the first and second year before and after diagnosis of sleep apnea in a Finnish nationwide, population-based, retrospective case–control study based on linking data from the national health care registers for primary and secondary care from 2015–2019. Controls were matched for age, sex, hospital district, and multimorbidity status. We furthermore analysed the independent effect of comorbidities and other patient characteristics on the risk of lower respiratory tract infections, and their recurrence.

Results

Sleep apnea patients had a higher incidence of lower respiratory tract infections than their matched controls within one year before (hazard ratio 1.35, 95% confidence interval 1.16–1.57) and one year after (hazard ratio1.39, 95% confidence interval1.22–1.58) diagnosis of sleep apnea. However, we found no difference in the incidence of lower respiratory tract infections within the second year before or after diagnosis of sleep apnea in comparison with matched controls. In sleep apnea, history of lower respiratory tract infection prior to sleep apnea, multimorbidity, COPD, asthma, and age greater than 65 years increased the risk of incident and recurrent lower respiratory tract infections.

Conclusions

Sleep apnea patients are at increased risk of being diagnosed with a lower respiratory tract infection within but not beyond one year before and after diagnosis of sleep apnea. Among sleep apnea patients, chronic comorbidities had a significant impact on the risk of lower respiratory tract infections and their recurrence.
Development of short hairpin RNA expression vectors targeting the internal ribosomal entry site of the classical swine fever virus genomic RNA
Authors: Okamoto Riai , Ito Nobumasa , Ide Yutaro , Kitab Bouchra , Sakoda Yoshihiro , Tsukiyama-Kohara Kyoko
Published: September 2023

Background

Classical swine fever (CSF) is a fatal contagious disease affecting pigs caused by classical swine fever virus (CSFV). The disease can be transmitted by pigs and wild boars, and it is difficult to prevent and control. To obtain necessary information to establish the CSFV resistant animals in a future study, we designed lentiviral vector-delivered short hairpin RNAs (shRNAs) targeting the conserved domain III of the internal ribosomal entry site (IRES) of the CSFV genomic RNA.

Results

First, we confirmed the effects of siRNAs on CSFV-IRES activity. We observed significant inhibition of CSFV-IRES activity by si42 (domain IIIa), si107 (domain IIIc), and si198 (domain IIIf) in SK-L cells and si56 (domain IIIb), si142 (domain IIId1) and si198 in HEK293 cells without affecting the amount of luciferase RNA. Next, we constructed lentiviral vectors expressing shRNA based on siRNA sequences. Treatment with shRNA-expressing lentivirus was examined at 7 and 14 days post infection in SK-L cells and HEK293 cells, and CSFV-IRES was significantly suppressed at 14 days (sh42) post infection in HEK293 cells without significant cytotoxicity. Next, we examined the silencing effect of siRNA on CSFV replicon RNA and observed a significant effect by si198 after 2 days of treatment and by shRNA-expressing lentivirus (sh56, sh142, and sh198) infection after 14 days of treatment. Treatment of sh198-expressing lentivirus significantly suppressed CSFV infection at 3 days after infection.

Conclusion

The IRES targeting sh198 expressing lentivirus vector can be a candidate tool for CSFV infection control.
Criteria for early diagnosis of mandibular third molar agenesis based on the developmental stages of mandibular canine, first and second premolars, and second molar: a retrospective cohort study
Authors: Kim Hyuntae , Hyun Hong-Keun , Shin Teo Jeon , Kim Young-Jae , Kim Jung-Wook , Jang Ki-Taeg , Song Ji-Soo
Published: September 2023

Background

Permanent first molars with severe dental caries, developmental defects, or involved in oral pathologies are at risk of poor prognosis in children. Accordingly, using the third molar to replace the first molar can be a good treatment option when third molar agenesis is predicted early. Thus, this retrospective cohort study aimed to develop criteria for early detection of mandibular third molar (L8) agenesis based on the developmental stages of mandibular canine (L3), first premolar (L4), second premolar (L5), and second molar (L7).

Method

Overall, 1,044 and 919 panoramic radiographs of 343 males and 317 females, respectively, taken between the ages of 6 and 12 years were included. All developmental stages of L3, L4, L5, L7, and L8 were analyzed based on the dental age, as suggested by Demirjian et al. The independent t-test was used to assess age differences between males and females. The rank correlation coefficients were examined using Kendall’s tau with bootstrap analysis and Bonferroni’s correction to confirm the teeth showing developmental stages most similar to those of L8s. Finally, a survival analysis was performed to determine the criteria for the early diagnosis of mandibular third molar agenesis.

Results

Some age differences were found in dental developmental stages between males and females. Correlation coefficients between all stages of L3, L4, L5, and L7 and L8 were high. In particular, the correlation coefficient between L7 and L8 was the highest, whereas that between L3 and L8 was the lowest.

Conclusion

If at least two of the following criteria (F stage of L3, F stage of L4, F stage of L5, and E stage of L7) are met in the absence of L8 crypt, agenesis of L8 can be confirmed.
Antibiotic prescriptions among dentists across Norway and the impact of COVID-19 pandemic
Authors: Tousi Farnoush , Al Haroni Mohammed , Lie Stein Atle , Lund Bodil
Published: September 2023

Background

The prescription of antibiotics in dental practice contributes significantly to the total use of antibiotics in primary healthcare. This study aimed to evaluate antibiotic prescription in dental practice during the years 2016–2021 in Norway and their relative contribution to national outpatient consumption and to investigate the influence of age, gender, geographic region, and COVID-19. A further aim was to review differences in prescribing patterns to verify effect of governmental strategies to reduce over-prescribing of antibiotics.

Methods

This register study investigated the national antibiotic prescription between 2016 and 2021. Data was obtained from the Norwegian prescription register, the Norwegian Institute of Public Health and Statistics Norway. The consumption of 12 common antibiotics was measured using WHO defined daily doses (DDDs), DDD per 1000 inhabitants per day (DIDs 1000).

Results

A total of 6,049,445 antibiotic prescriptions of the 12 investigated compounds were issued in primary care during the study period. Dentists accounted for 942,350 prescriptions corresponding to 15.6% of the total. An overall decrease in the number of prescriptions by health professions other than dentists during the 5 years (IRR = 0.92, 95% CI:0.92–0.93, p < 0.001) was observed. For dentists a slight increase in the number of prescriptions (IRR = 1.01, 95% CI: 1.01–1.01, p < 0.001) was seen over the study period. The increase of antibiotic prescriptions in dentistry was more pronounced during the COVID-19 pandemic. The 4 most prescribed type of antibiotics based on average number of DDDs of the total period 2016–2021 were in descending order; phenoxymethylpenicillin (1,109,150) followed by amoxicillin (126,244), clindamycin (72,565), and metronidazole (64,599). An unexpected finding was that the prescription of the combination compound amoxicillin/clavulanic acid had significantly increased in dentistry during the last 5 years. Geographic, gender, and age differences in the rates of prescriptions were also seen. The data revealed that there are seasonal variations in dental prescriptions.

Conclusions

Noticeable differences exist in prescribing patterns of antibiotics in the last 5 years. Restricted access to dental care due to COVID-19 may have resulted in increased antibiotic prescribing in dentistry as opposed to an otherwise downward trend. Despite national guidelines there is still a need for improvement of antibiotic stewardship in dentistry and to define effective methods to disseminate information.
State of well-being among residents in a tertiary center in Riyadh, Saudi Arabia
Authors: AlAhmari Fatimah Saeed , Aloqail Alaa , Almansour Shahad , Bagha Mohammad
Published: September 2023

Background

Medical residency is a part of postgraduate medical education and involves clinical training in a selected specialty. It is a challenging step in a physician’s professional development. This study aims to estimate the impact of the residency training program and demographic factors on the trainee’s state of well-being (SOW).

Methods

This was an observational cross-sectional study carried out in the year 2019–2020, which aimed to measure the SOW of residents undergoing clinical training in Riyadh, Saudi Arabia. A total of 260 residents participated in the study. A self-administered validated online the World Health Organization, Quality of Life Scale questionnaire- BREF was distributed to collect the data. The collected information on four different domains was analysed and compared across the baseline characteristics and different specialties. When appropriate, the independent sample t-test, bivariate correlation analysis, and ANOVA tests were used.

Results

A total of 260 resident responses were included in the final analysis The results revealed a significant difference in physical health scores (p = 0.006), social relationship scores (p = 0.038), and environmental scores (p < 0.001) while no significant difference was found in psychological health scores among the physicians’ specialties (p = 0.053). Post hoc comparison found statistically significant variations in the physical health domain between the medical and emergency specialties (p = 0.007), as well as surgical and emergency specialties (p = 0.024). There was also a significant difference between medical and emergency specialties (p = 0.008) in the social relationship domain. In the environment domain, significant variation was reported between medical specialties and emergency specialties (p = 0.001), as well asbetween surgical specialties and emergency specialties (p = 0.045). Female residents reported significantly lower quality of life in the physical (p = 0.020) and psychological (p = 0.032) domains.

Conclusions

A significant relationship was found between physical, social, and environmental domains according to residents’ specialties. The factors that affected one or more domains included age, female gender, marital status, disease status, the number of on-calls received, and workload. We emphasize the importance of implementing policies to regulate working hours and on-call schedules as well as prioritizing mental health support.
Integrating research in health professions education: a scoping review
Authors: Riiser Kirsti , Kalleson Runa , Holmen Heidi , Torbjørnsen Astrid
Published: September 2023

Background

Integrating teaching and research may boost students’ learning and improve future clinical practice when incorporated into education. Explorations of health professions students’ involvement in the research processes and their learning outcomes are sparse. Thus, the purpose of this scoping review is to explore the existing scientific literature on courses involving students from health professions education in research activities. The research questions are: Which parts of the research process are the health professions students involved in, and what are the students’ main learning outcomes related to the research process reported to be?

Methods

A scoping review following the six-step approach of Arksey and O’Malley was undertaken. We searched four electronic databases to identify studies focusing on research-based teaching in health professions education. Inspired by content analysis, we identified key concepts relating to the research process and learning outcomes.

Results

We screened 1084 abstracts, reviewed 95 full-text reports, and included 24 for analysis. Overall, the students were more involved in conducting and disseminating research than in the planning phases. Learning outcomes were most frequently reported as specific research skills, such as conducting literature reviews, writing academically, and presenting results, but also as improved understanding of research in general as well as improved motivation and confidence in conducting research.

Conclusions

The heterogeneity of educational programs, study designs, and measures makes it difficult to draw conclusions across the studies included in the review. More research is needed to conclude whether health professions students who actively engage in research gain a better understanding of the research process, become more likely to pursue research in their practice, or are more motivated to choose an academic career.
Associations of a current Australian model of dietetic care for women diagnosed with gestational diabetes and maternal and neonatal health outcomes
Authors: Absalom Gina , Zinga Julia , Margerison Claire , Abbott Gavin , O’Reilly Sharleen , van der Pligt Paige
Published: September 2023

Background

Gestational diabetes mellitus (GDM) is a significant public health burden in Australia. Subsequent strain on healthcare systems is widespread and current models of care may not be adequate to provide optimal healthcare delivery. This study aimed to assess a current model of dietetic care with maternal and neonatal outcomes.

Methods

Hospital medical record data from The Women’s Hospital, Melbourne, for women with GDM (n = 1,185) (July 2105-May 2017) was retrospectively analysed. Adjusted linear and logistic regression were used to analyse associations between the number of dietitian consultations and maternal and neonatal health outcomes.

Results

Half of all women (50%) received two consultations with a dietitian. 19% of women received three or more consultations and of these women, almost twice as many were managed by medical nutrition therapy (MNT) and pharmacotherapy (66%) compared with MNT alone (34%). Higher odds of any maternal complication among women receiving 3 + consultations compared to those receiving zero (OR = 2.33 [95% CI: 1.23, 4.41], p = 0.009), one (OR = 1.80 [95% CI: 1.09, 2.98], p = 0.02), or two (OR = 1.65 [95% CI: 1.04, 2.60], p = 0.03) consultations were observed. Lower odds of infant admission to the Neonatal Intensive Care Unit (NICU) were observed among women receiving one (OR = 0.38 [95% CI: 0.18, 0.78], p = 0.008), two (OR = 0.37 [95% CI: 15 0.19, 0.71], p = 0.003), or three + consultations (OR = 0.43 [95% CI: 0.21, 0.88], p = 0.02), compared to no consultations.

Conclusion

The optimal schedule of dietitian consultations for women with GDM in Australia remains largely unclear. Alternate delivery of education for women with GDM such as telehealth and utilisation of digital platforms may assist relieving pressures on the healthcare system and ensure optimal care for women during pregnancy.
Assessment of factors influencing physicians’ intention to prescribe transfusion using the theory of planned behavior
Authors: Liao Yu-Han , Tang Kung-Pei , Chou Chih-Yu , Kuo Chien-Feng , Tsai Shin-Yi
Published: September 2023

Background

Blood shortage is a persistent problem affecting Taiwan’s health-care system. The theory of planned behavior (TPB) has been commonly used in studies of health advocacy. The purpose of this study was to develop a questionnaire measuring clinicians’ intention to prescribe transfusion based on the TPB.

Method

A questionnaire comprising 15 items for assessing clinicians’ intention to prescribe blood transfusion was developed, and it collected demographic characteristics, tested patient blood management (PBM) and perceived knowledge of PBM. Furthermore, the questionnaire contained four subscales related to the TPB. A total of 129 clinicians participated in this pilot study between July and December2020. Item analysis and exploratory factor analysis were conducted to examine the validity and reliability of this measurement instrument.

Results

The results indicated no statistically significant correlations between the demographic characteristics and PBM test scores. Regarding perceived knowledge, the results of a one-way analysis of variance revealed that the effect of age, hierarchy of doctors, and education level were significant. In terms of subjective norms, a significant effect on education level was noted [t (129) = 2.28, p < 0.05], with graduate school graduates receiving higher scores than college graduates. An analysis of variance demonstrated the effects of hierarchy, education level, and medical specialty on perceived behavioral control. The results of the regression analyses revealed that perceived knowledge (β = 0.32, p < 0.01) and subjective norms (β = 0.22, p < 0.05) were significantly related to clinicians’ behavioral intentions.

Conclusions

This study revealed that factors affecting clinicians’ blood transfusion management can be explained using the TPB-based questionnaire. This study demonstrated that physicians’ perceptions of whether most people approve of PBM and their self-assessment of their PBM knowledge affect their intentions to proceed with PBM. According to this finding, a support system among physicians must be established and maintained to increase physicians’ confidence in promoting PBM.
Integrated epigenome, whole genome sequence and metabolome analyses identify novel multi-omics pathways in type 2 diabetes: a Middle Eastern study
Authors: Yousri Noha A. , Albagha Omar M. E. , Hunt Steven C.
Published: September 2023

Background

T2D is of high prevalence in the middle east and thus studying its mechanisms is of a significant importance. Using 1026 Qatar BioBank samples, epigenetics, whole genome sequencing and metabolomics were combined to further elucidate the biological mechanisms of T2D in a population with a high prevalence of T2D.

Methods

An epigenome-wide association study (EWAS) with T2D was performed using the Infinium 850K EPIC array, followed by whole genome-wide sequencing SNP-CpG association analysis (> 5.5 million SNPs) and a methylome-metabolome (CpG-metabolite) analysis of the identified T2D sites.

Results

A total of 66 T2D-CpG associations were identified, including 63 novel sites in pathways of fructose and mannose metabolism, insulin signaling, galactose, starch and sucrose metabolism, and carbohydrate absorption and digestion. Whole genome SNP associations with the 66 CpGs resulted in 688 significant CpG-SNP associations comprising 22 unique CpGs (33% of the 66 CPGs) and included 181 novel pairs or pairs in novel loci. Fourteen of the loci overlapped published GWAS loci for diabetes related traits and were used to identify causal associations of HK1 and PFKFB2 with HbA1c. Methylome-metabolome analysis identified 66 significant CpG-metabolite pairs among which 61 pairs were novel. Using the identified methylome-metabolome associations, methylation QTLs, and metabolic networks, a multi-omics network was constructed which suggested a number of metabolic mechanisms underlying T2D methylated genes. 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) – a triglyceride-associated metabolite, shared a common network with 13 methylated CpGs, including TXNIP, PFKFB2, OCIAD1, and BLCAP. Mannonate – a food component/plant shared a common network with 6 methylated genes, including TXNIP, BLCAP, THBS4 and PEF1, pointing to a common possible cause of methylation in those genes. A subnetwork with alanine, glutamine, urea cycle (citrulline, arginine), and 1-carboxyethylvaline linked to PFKFB2 and TXNIP revealed associations with kidney function, hypertension and triglyceride metabolism. The pathway containing STYXL1-POR was associated with a sphingosine-ceramides subnetwork associated with HDL-C and LDL-C and point to steroid perturbations in T2D.

Conclusions

This study revealed several novel methylated genes in T2D, with their genomic variants and associated metabolic pathways with several implications for future clinical use of multi-omics associations in disease and for studying therapeutic targets.
Effects of dietary Lactobacillus rhamnosus GG supplementation on the production performance, egg quality, eggshell ultrastructure, and lipid metabolism of late-phase laying hens
Authors: Liu Liming , Zhang Guoqing , Qu Ge , Liu Bin , Zhang Xiufeng , Li Gaoqian , Jin Ningyi , Li Chang , Bai Jieying , Zhao Cuiqing
Published: September 2023

Background

Toward the late phase of laying, the production performance of laying hens decreases, egg quality deteriorates, lipid metabolism weakens, and hepatic lipid accumulation is exacerbated. Probiotics as an alternative to antimicrobials have been employed in poultry-related industries. Lactobacillus rhamnosus GG (LGG) is currently the most researched and clinically validated probiotic, showing promising effects in multiple application areas. However, few studies have been conducted on livestock (including poultry) production.

Results

Compared with the CON group, the feed conversion ratio (P < 0.01) declined significantly in the LGG group. Eggshell strength (P < 0.001) and eggshell thickness (P < 0.001) were significantly increased by supplementation with LGG in the diet. The height (P < 0.001) and proportion (P < 0.05) of the effective layer and the mammillary knob density (P < 0.01) in the eggshell ultrastructure of the LGG group increased significantly, while the mammillary layer (P < 0.05) and knob width (P < 0.01) decreased significantly. The LGG-treated hens had significantly lower serum concentrations of low-density lipoprotein (P < 0.05), free fatty acids (P < 0.01), and liver triglyceride (P < 0.05) levels than those in the CON group.

Conclusions

LGG supplementation significantly decreases the feed conversion ratio, improves eggshell quality by altering the ultrastructure, and improves lipid metabolism in the late laying period.